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Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1
Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y., E-mail: firstname.lastname@example.com
Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF–Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 from phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrf1 attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. Highlights: • The effect of GSK3 on Nrf1 expression was examined. • GSK3 destabilizes Nrf1 protein via Fbw7 ubiquitin ligase. • GSK3 binds and phosphorylates Nrf1. • Protection from stress-induced apoptosis by Nrf1 is inhibited by GSK3.
Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells
Mattingly, Kathleen A.; Klinge, Carolyn M. [University of Louisville School of Medicine, Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, Louisville, KY (United States)
Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1-regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17{beta}-estradiol (E{sub 2}), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription, and this suppression was not ablated by concomitant treatment with E{sub 2}, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E{sub 2} increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects. (orig.)
Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells
Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S.; Rouchka, Eric C.; Hill, Bradford G.; Klinge, Carolyn M.
Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.
Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells
Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S. [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Rouchka, Eric C. [Bioinformatics and Biomedical Computing Laboratory, Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292 (United States); Hill, Bradford G. [Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Klinge, Carolyn M., E-mail: email@example.com [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States)
Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.
Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition.
Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro
Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 ( GluR2 ) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2 . This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT.
Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition
Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro
Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2. This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT. PMID:28800112
Nuclear respiratory factor 2 regulates the expression of the same NMDA receptor subunit genes as NRF-1: both factors act by a concurrent and parallel mechanism to couple energy metabolism and synaptic transmission.
Priya, Anusha; Johar, Kaid; Wong-Riley, Margaret T T
Neuronal activity and energy metabolism are tightly coupled processes. Previously, we found that nuclear respiratory factor 1 (NRF-1) transcriptionally co-regulates energy metabolism and neuronal activity by regulating all 13 subunits of the critical energy generating enzyme, cytochrome c oxidase (COX), as well as N-methyl-d-aspartate (NMDA) receptor subunits 1 and 2B, GluN1 (Grin1) and GluN2B (Grin2b). We also found that another transcription factor, nuclear respiratory factor 2 (NRF-2 or GA-binding protein) regulates all subunits of COX as well. The goal of the present study was to test our hypothesis that NRF-2 also regulates specific subunits of NMDA receptors, and that it functions with NRF-1 via one of three mechanisms: complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, in vivo chromatin immunoprecipitation of mouse neuroblastoma cells and rat visual cortical tissue, promoter mutations, real-time quantitative PCR, and western blot analysis, NRF-2 was found to functionally regulate Grin1 and Grin2b genes, but not any other NMDA subunit genes. Grin1 and Grin2b transcripts were up-regulated by depolarizing KCl, but silencing of NRF-2 prevented this up-regulation. On the other hand, over-expression of NRF-2 rescued the down-regulation of these subunits by the impulse blocker TTX. NRF-2 binding sites on Grin1 and Grin2b are conserved among species. Our data indicate that NRF-2 and NRF-1 operate in a concurrent and parallel manner in mediating the tight coupling between energy metabolism and neuronal activity at the molecular level. Copyright © 2012 Elsevier B.V. All rights reserved.
AMPK activation represses the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase: Role of nuclear respiratory factor-1
Adam, Tasneem; Opie, Lionel H. [Hatter Cardiovascular Research Institute, Faculty of Health Sciences, University of Cape Town, Observatory 7925 (South Africa); Essop, M. Faadiel, E-mail: email@example.com [Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600 (South Africa)
Research highlights: {yields} AMPK inhibits acetyl-CoA carboxylase beta gene promoter activity. {yields} Nuclear respiratory factor-1 inhibits acetyl-CoA carboxylase beta promoter activity. {yields} AMPK regulates acetyl-CoA carboxylase beta at transcriptional level. -- Abstract: The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC{beta}) produces malonyl-CoA, a potent inhibitor of carnitine palmitoyltransferase-1. AMPK inhibits ACC{beta} activity, lowering malonyl-CoA levels and promoting mitochondrial fatty acid {beta}-oxidation. Previously, AMPK increased promoter binding of nuclear respiratory factor-1 (NRF-1), a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins. We therefore hypothesized that NRF-1 inhibits myocardial ACC{beta} promoter activity via AMPK activation. A human ACC{beta} promoter-luciferase construct was transiently transfected into neonatal cardiomyocytes {+-} a NRF-1 expression construct. NRF-1 overexpression decreased ACC{beta} gene promoter activity by 71 {+-} 4.6% (p < 0.001 vs. control). Transfections with 5'-end serial promoter deletions revealed that NRF-1-mediated repression of ACC{beta} was abolished with a pPII{beta}-18/+65-Luc deletion construct. AMPK activation dose-dependently reduced ACC{beta} promoter activity, while NRF-1 addition did not further decrease it. We also investigated NRF-1 inhibition in the presence of upstream stimulatory factor 1 (USF1), a known transactivator of the human ACC{beta} gene promoter. Here NRF-1 blunted USF1-dependent induction of ACC{beta} promoter activity by 58 {+-} 7.5% (p < 0.001 vs. control), reversed with a dominant negative NRF-1 construct. NRF-1 also suppressed endogenous USF1 transcriptional activity by 55 {+-} 6.2% (p < 0.001 vs. control). This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACC{beta} gene promoter in the mammalian heart. Our data extends AMPK regulation of ACC{beta} to the transcriptional level.
Regulation of Na(+)/K(+)-ATPase by nuclear respiratory factor 1: implication in the tight coupling of neuronal activity, energy generation, and energy consumption.
Johar, Kaid; Priya, Anusha; Wong-Riley, Margaret T T
NRF-1 regulates mediators of neuronal activity and energy generation. NRF-1 transcriptionally regulates Na(+)/K(+)-ATPase subunits α1 and β1. NRF-1 functionally regulates mediators of energy consumption in neurons. NRF-1 mediates the tight coupling of neuronal activity, energy generation, and energy consumption at the molecular level. Energy generation and energy consumption are tightly coupled to neuronal activity at the cellular level. Na(+)/K(+)-ATPase, a major energy-consuming enzyme, is well expressed in neurons rich in cytochrome c oxidase, an important enzyme of the energy-generating machinery, and glutamatergic receptors that are mediators of neuronal activity. The present study sought to test our hypothesis that the coupling extends to the molecular level, whereby Na(+)/K(+)-ATPase subunits are regulated by the same transcription factor, nuclear respiratory factor 1 (NRF-1), found recently by our laboratory to regulate all cytochrome c oxidase subunit genes and some NMDA and AMPA receptor subunit genes. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, in vivo chromatin immunoprecipitation, promoter mutational analysis, and real-time quantitative PCR, NRF-1 was found to functionally bind to the promoters of Atp1a1 and Atp1b1 genes but not of the Atp1a3 gene in neurons. The transcripts of Atp1a1 and Atp1b1 subunit genes were up-regulated by KCl and down-regulated by tetrodotoxin. Atp1b1 is positively regulated by NRF-1, and silencing of NRF-1 with small interference RNA blocked the up-regulation of Atp1b1 induced by KCl, whereas overexpression of NRF-1 rescued these transcripts from being suppressed by tetrodotoxin. On the other hand, Atp1a1 is negatively regulated by NRF-1. The binding sites of NRF-1 on Atp1a1 and Atp1b1 are conserved among mice, rats, and humans. Thus, NRF-1 regulates key Na(+)/K(+)-ATPase subunits and plays an important role in mediating the tight coupling between
Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis
Hsieh, Pei-Fang [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Shu-Fen [Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan (China); Hung, Tsung-Jen [Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Hung, Chien-Ya [Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Guo-Zheng [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Chuang, Lea-Yea [Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Chen, Mei-Fen [Department of Acupressure Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Wang, Jue-Long [Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan (China); Shi, Ming-Der [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan (China); Hsu, Chen Hung [Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Shiue, Yow-Ling, E-mail: firstname.lastname@example.com [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Yang, Yu-Lin, E-mail: email@example.com [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China)
Background: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods: In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results: Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin
Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.
Dhar, Shilpa S; Liang, Huan Ling; Wong-Riley, Margaret T T
Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts down-regulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.
The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.
Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang
The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.
CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.
Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo
The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.
The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia.
Chepelev, Nikolai L; Bennitz, Joshua D; Huang, Ting; McBride, Skye; Willmore, William G
Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is a transcription factor mediating cellular responses to xenobiotic and pro-oxidant stress. Nrf1 regulates the transcription of many stress-related genes through the electrophile response elements (EpREs) located in their promoter regions. Despite its potential importance in human health, the mechanisms controlling Nrf1 have not been addressed fully. We found that proteasomal inhibitors MG-132 and clasto-lactacystin-β-lactone stabilized the protein expression of full-length Nrf1 in both COS7 and WFF2002 cells. Concomitantly, proteasomal inhibition decreased the expression of a smaller, N-terminal Nrf1 fragment, with an approximate molecular weight of 23 kDa. The EpRE-luciferase reporter assays revealed that proteasomal inhibition markedly inhibited the Nrf1 transactivational activity. These results support earlier hypotheses that the 26 S proteasome processes Nrf1 into its active form by removing its inhibitory N-terminal domain anchoring Nrf1 to the endoplasmic reticulum. Immunoprecipitation demonstrated that Nrf1 is ubiquitinated and that proteasomal inhibition increased the degree of Nrf1 ubiquitination. Furthermore, Nrf1 protein had a half-life of approximately 5 hours in COS7 cells. In contrast, hypoxia (1% O(2)) significantly increased the luciferase reporter activity of exogenous Nrf1 protein, while decreasing the protein expression of p65, a shorter form of Nrf1, known to act as a repressor of EpRE-controlled gene expression. Finally, the protein phosphatase inhibitor okadaic acid activated Nrf1 reporter activity, while the latter was repressed by the PKC inhibitor staurosporine. Collectively, our data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status. © 2011 Chepelev et al.
NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis.
Widenmaier, Scott B; Snyder, Nicole A; Nguyen, Truc B; Arduini, Alessandro; Lee, Grace Y; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S
Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity. In Nrf1 deficiency, in vivo cholesterol challenges induce massive hepatic cholesterol accumulation and damage, which is rescued by replacing Nrf1 exogenously. This Nrf1-mediated mechanism involves the suppression of CD36-driven inflammatory signaling and derepression of liver X receptor activity. These findings reveal Nrf1 as a guardian of cholesterol homeostasis and a core component of adaptive responses to excess cellular cholesterol. Copyright © 2017. Published by Elsevier Inc.
The Relationship Between Transcript Expression Levels of Nuclear Encoded (TFAM, NRF1 and Mitochondrial Encoded (MT-CO1 Genes in Single Human Oocytes During Oocyte Maturation
Ghaffari Novin M.
Full Text Available In some cases of infertility in women, human oocytes fail to mature when they reach the metaphase II (MII stage. Mitochondria plays an important role in oocyte maturation. A large number of mitochondrial DNA (mtDNA, copied in oocytes, is essential for providing adenosine triphosphate (ATP during oocyte maturation. The purpose of this study was to identify the relationship between transcript expression levels of the mitochondrial encoded gene (MT-CO1 and two nuclear encoded genes, nuclear respiratory factor 1 (NRF1 and mitochondrial transcription factor A (TFAM in various stages of human oocyte maturation. Nine consenting patients, age 21-35 years old, with male factors were selected for ovarian stimulation and intracytoplasmic sperm injection (ICSI procedures. mRNA levels of mitochondrial- related genes were performed by singlecell TaqMan® quantitative real-time polymerase chain reaction (qRT-PCR. There was no significant relationship between the relative expression levels in germinal vesicle (GV stage oocytes (p = 0.62. On the contrary, a significant relationship was seen between the relative expression levels of TFAM and NRF1 and the MT-CO1 genes at the stages of metaphase I (MI and MII (p = 0.03 and p = 0.002. A relationship exists between the transcript expression levels of TFAM and NRF1, and MT-CO1 genes in various stages of human oocyte maturation.
Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis.
Han, Weinong; Ming, Mei; Zhao, Rui; Pi, Jingbo; Wu, Chunli; He, Yu-Ying
Skin cancer is the most common cancer in the United States. Its major environmental risk factor is UVB radiation in sunlight. In response to UVB damage, epidermal keratinocytes activate a specific repair pathway, i.e. nucleotide excision repair, to remove UVB-induced DNA lesions. However, the regulation of UVB response is not fully understood. Here we show that the long isoform of the nuclear factor erythroid 2-related factor 1 (Nrf1, also called NFE2L1), a cytoprotective transcription factor critical for the expression of multiple antioxidant response element-dependent genes, plays an important role in the response of keratinocytes to UVB. Nrf1 loss sensitized keratinocytes to UVB-induced apoptosis by up-regulating the expression of the proapoptotic Bcl-2 family member Bik through reducing glutathione levels. Knocking down Bik reduced UVB-induced apoptosis in Nrf1-inhibited cells. In UVB-irradiated surviving cells, however, disruption of Nrf1 impaired nucleotide excision repair through suppressing the transcription of xeroderma pigmentosum C (XPC), a factor essential for initiating the global genome nucleotide excision repair by recognizing the DNA lesion and recruiting downstream factors. Nrf1 enhanced XPC expression by increasing glutathione availability but was independent of the transcription repressor of XPC. Adding XPC or glutathione restored the DNA repair capacity in Nrf1-inhibited cells. Finally, we demonstrate that Nrf1 levels are significantly reduced by UVB radiation in mouse skin and are lower in human skin tumors than in normal skin. These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin.
Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.
Preciados, Mark; Yoo, Changwon; Roy, Deodutta
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of
Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases
Mark Preciados
Full Text Available During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA, polychlorinated biphenyls (PCBs, phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1 signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2 and
Increase of mitochondrial DNA content and transcripts in early bovine embryogenesis associated with upregulation of mtTFA and NRF1 transcription factors
Heyman Yvan
Full Text Available Abstract Background Recent work has shown that mitochondrial biogenesis and mitochondrial functions are critical determinants of embryonic development. However, the expression of the factors controlling mitochondrial biogenesis in early embryogenesis has received little attention so far. Methods We used real-time quantitative PCR to quantify mitochondrial DNA (mtDNA in bovine oocytes and in various stages of in vitro produced embryos. To investigate the molecular mechanisms responsible for the replication and the transcriptional activation of mtDNA, we quantified the mRNA corresponding to the mtDNA-encoded cytochrome oxidase 1 (COX1, and two nuclear-encoded factors, i.e. the Nuclear Respiratory Factor 1 (NRF1, and the nuclear-encoded Mitochondrial Transcription Factor A (mtTFA. Results Unlike findings reported in mouse embryos, the mtDNA content was not constant during early bovine embryogenesis. We found a sharp, 60% decrease in mtDNA content between the 2-cell and the 4/8-cell stages. COX1 mRNA was constant until the morula stage after which it increased dramatically. mtTFA mRNA was undetectable in oocytes and remained so until the 8/16-cell stage; it began to appear only at the morula stage, suggesting de novo synthesis. In contrast, NRF1 mRNA was detectable in oocytes and the quantity remained constant until the morula stage. Conclusion Our results revealed a reduction of mtDNA content in early bovine embryos suggesting an active process of mitochondrial DNA degradation. In addition, de novo mtTFA expression associated with mitochondrial biogenesis activation and high levels of NRF1 mRNA from the oocyte stage onwards argue for the essential function of these factors during the first steps of bovine embryogenesis.
Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury
Hernandez-Montes, Eva; Pollard, Susan E.; Vauzour, David; Jofre-Montseny, Laia; Rota, Cristina; Rimbach, Gerald; Weinberg, Peter D.; Spencer, Jeremy P.E.
Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of γ-glutamylcysteine synthetase-heavy subunit (γ-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis
The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.
Zhang, Yiguo; Hayes, John D
The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.
The words "respiratory" and "respiration" refer to the lungs and breathing. ... Boron WF. Organization of the respiratory system. In: Boron WF, Boulpaep EL, eds. Medical Physiology . 3rd ed. Philadelphia, PA: Elsevier; 2017:chap 26.
The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells
Schultz, Michelle A. [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Abdel-Mageed, Asim B. [Department of Urology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Mondal, Debasis, E-mail: firstname.lastname@example.com [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States)
Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa.
Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.
Zhang, Yiguo; Ren, Yonggang; Li, Shaojun; Hayes, John D
The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.
Exercise increases hyper-acetylation of histones on the Cis-element of NRF-1 binding to the Mef2a promoter: Implications on type 2 diabetes.
Joseph, Jitcy S; Ayeleso, Ademola O; Mukwevho, Emmanuel
Exercise brings changes on the chromatin ensuing the upregulation of many genes that confer protection from type 2 diabetes. In type-2 diabetes, critical genes are down-regulated such as those involved in glucose transport (GLUT4, MEF2A) and also oxidative phosphorylation (NRF-1 and its target genes). Recent reports have shown that NRF-1 not only regulate mitochondrial oxidative genes but also controls MEF2A, the main transcription factor for glucose transporter, GLUT4. Such dual control of the two pathways by NRF-1 place it as critical gene in the design of therapeutic modalities much needed to cure or better manage type 2 diabetes. Although it is known that NRF-1 controls these dual pathways (glucose transport and oxidative phosphorylation), the actual molecular mechanisms involved surrounding this regulation remains elusive. NRF-1 itself is regulated through posttranslational modifications (acetylation, methylation and phosphorylation) resulting in enhanced binding to its target genes. This study is therefore aimed at assessing whether CaMKII, a kinase activated by exercise brings about hyper-acetylation of histones in the vicinity of NRF-1 target gene, Mef2a. Five to six weeks old male Wistar rats were used in this study. Chromatin immunoprecipitation (ChIP) assay was used to investigate the extent through which NRF-1 is bound to the Mef2a gene and if this was associated with hyper-acetylation of histones in the region of NRF-1 binding site of the Mef2a gene. Quantitative real time PCR (qPCR) was used to determine the gene expression of MEF2A and NRF-1. Results from this study indicated that exercise-induced CaMKII activation increased hyper-acetylation of histones in the region of NRF-1 binding site on vicinity of Mef2a gene and this was associated with the increased binding of NRF-1 to Mef2a gene. Exercise also increased the expression of NRF-1 and MEF2A genes. Administration of CaMKII inhibitor (KN93) prior to exercise attenuated the observed exercise
Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response
Wan, Xianxiu; Gupta, Shivali; Zago, Maria P.; Davidson, Mercy M.; Dousset, Pierre; Amoroso, Alejandro; Garg, Nisha Jain
Background Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for
The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo
Karilyn E. Sant
Full Text Available Redox signaling is important for embryogenesis, guiding pathways that govern processes crucial for embryo patterning, including cell polarization, proliferation, and apoptosis. Exposure to pro-oxidants during this period can be deleterious, resulting in altered physiology, teratogenesis, later-life diseases, or lethality. We previously reported that the glutathione antioxidant defense system becomes increasingly robust, including a doubling of total glutathione and dynamic shifts in the glutathione redox potential at specific stages during embryonic development in the zebrafish, Danio rerio. However, the mechanisms underlying these changes are unclear, as is the effectiveness of the glutathione system in ameliorating oxidative insults to the embryo at different stages. Here, we examine how the glutathione system responds to the model pro-oxidants tert-butylhydroperoxide and tert-butylhydroquinone at different developmental stages, and the role of Nuclear factor erythroid 2-related factor (Nrf proteins in regulating developmental glutathione redox status. Embryos became increasingly sensitive to pro-oxidants after 72 h post-fertilization (hpf, after which the duration of the recovery period for the glutathione redox potential was increased. To determine whether the doubling of glutathione or the dynamic changes in glutathione redox potential are mediated by zebrafish paralogs of Nrf transcription factors, morpholino oligonucleotides were used to knock down translation of Nrf1 and Nrf2 (nrf1a, nrf1b, nrf2a, nrf2b. Knockdown of Nrf1a or Nrf1b perturbed glutathione redox state until 72 hpf. Knockdown of Nrf2 paralogs also perturbed glutathione redox state but did not significantly affect the response of glutathione to pro-oxidants. Nrf1b morphants had decreased gene expression of glutathione synthesis enzymes, while hsp70 increased in Nrf2b morphants. This work demonstrates that despite having a more robust glutathione system, embryos become more
Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...
Alkalosis - respiratory ... leads to shortness of breath can also cause respiratory alkalosis (such as pulmonary embolism and asthma). ... Treatment is aimed at the condition that causes respiratory alkalosis. Breathing into a paper bag -- or using ...
Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...
Bartlett, R. G., Jr.
The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.
Wilson, Theodore A
This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...
... Us Home > Healthy Living > Living With Lung Disease > Respiratory Home Health Care Font: Aerosol Delivery Oxygen Resources ... Teenagers Living With Lung Disease Articles written by Respiratory Experts Respiratory Home Health Care Respiratory care at ...
Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition
Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro
Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability ...
... Videos for Educators Search English Español Lungs and Respiratory System KidsHealth / For Parents / Lungs and Respiratory System ... ll have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't ...
Neonatal respiratory distress syndrome
Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... improves slowly after that. Some infants with severe respiratory distress syndrome will die. This most often occurs ...
Middle East Respiratory Syndrome
This podcast discusses Middle East Respiratory Syndrome, or MERS, a viral respiratory illness caused by Middle East Respiratory Syndrome CoronavirusâMERS-CoV. Created: 7/7/2014 by National Center for Immunization and Respiratory Diseases (NCIRD). Date Released: 7/7/2014.
The respiratory microbiome and respiratory infections
Unger, Stefan A.; Bogaert, Debby
Despite advances over the past ten years lower respiratory tract infections still comprise around a fifth of all deaths worldwide in children under five years of age with the majority in low- and middle-income countries. Known risk factors for severe respiratory infections and poor chronic
... with facebook share with twitter share with linkedin Respiratory Syncytial Virus (RSV) Credit: CDC This is the ... the United States. Why Is the Study of Respiratory Syncytial Virus (RSV) a Priority for NIAID? In ...
Respiratory syncytial virus (RSV)
RSV; Palivizumab; Respiratory syncytial virus immune globulin; Bronchiolitis - RSV ... Crowe JE. Respiratory syncytial virus. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ...
Respiratory Issues in Osteogenesis Imperfecta \\ Introduction The respiratory system's job is to bring oxygen into the body and remove carbon dioxide, the waste product of breathing. Because oxygen is the fuel ...
Acute respiratory distress syndrome
Upper respiratory tract (image)
The major passages and structures of the upper respiratory tract include the nose or nostrils, nasal cavity, mouth, throat (pharynx), and voice box (larynx). The respiratory system is lined with a mucous membrane that ...
Avian respiratory system disorders
Olsen, Glenn H.
Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.
What Is Respiratory Distress Syndrome?
... Home / Respiratory Distress Syndrome Respiratory Distress Syndrome Also known as What Is Respiratory ... This condition is called apnea (AP-ne-ah). Respiratory Distress Syndrome Complications Depending on the severity of ...
Severe acute respiratory syndrome (SARS)
SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...
The effect of vascular endothelial growth factor-1 expression on ...
Riyad Bendardaf
Feb 28, 2017 ... The effect of vascular endothelial growth factor-1 expression on survival of ... Sharjah, Sharjah, United Arab Emirates; cFaculty of Medicine, Suez Canal University, ..... interleukin-6, and C-reactive protein level in colorectal.
Neurological Respiratory Failure
Mohan Rudrappa
Full Text Available West Nile virus infection in humans is mostly asymptomatic. Less than 1% of neuro-invasive cases show a fatality rate of around 10%. Acute flaccid paralysis of respiratory muscles leading to respiratory failure is the most common cause of death. Although the peripheral nervous system can be involved, isolated phrenic nerve palsy leading to respiratory failure is rare and described in only two cases in the English literature. We present another case of neurological respiratory failure due to West Nile virus-induced phrenic nerve palsy. Our case reiterates the rare, but lethal, consequences of West Nile virus infection, and the increase of its awareness among physicians.
Tetratrichomonads from the oral cavity and respiratory tract of humans
Kutišová, K.; Kulda, J.; Čepička, I.; Flegr, J.; Koudela, Břetislav; Teras, J.; Tachezy, J.
Roč. 131, č. 1 (2005), s. 1-11 ISSN 0031-1820 Grant - others:Grantová agentura Karlovy univerzity v Praze(CZ) 264/1999 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tetratrichomonas spp. * human respiratory tract * oral cavity Subject RIV: EE - Microbiology, Virology Impact factor: 1.703, year: 2005
Stromal cell-derived factor 1α (SDF-1α)
Li, Dana; Bjørnager, Louise; Langkilde, Anne
OBJECTIVES: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated...
Association between Insulin Like Growth Factor-1 (IGF-1) gene ...
The insulin-like growth factor-1 (IGF1) is a key regulator of muscle development and metabolism in birds and other vertebrate. Our objective was to determine the association between IGF1 gene polymorphism and carcass traits in FUNAAB Alpha chicken. Genomic DNA was extracted from the blood of 50 normal feathered ...
49 CFR 325.73 - Microphone distance correction factors. 1
... 49 Transportation 5 2010-10-01 2010-10-01 false Microphone distance correction factors. 1 325.73 Section 325.73 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR... MOTOR CARRIER NOISE EMISSION STANDARDS Correction Factors § 325.73 Microphone distance correction...
Respiratory medicine of reptiles.
Schumacher, Juergen
Noninfectious and infectious causes have been implicated in the development of respiratory tract disease in reptiles. Treatment modalities in reptiles have to account for species differences in response to therapeutic agents as well as interpretation of diagnostic findings. Data on effective drugs and dosages for the treatment of respiratory diseases are often lacking in reptiles. Recently, advances have been made on the application of advanced imaging modalities, especially computed tomography for the diagnosis and treatment monitoring of reptiles. This article describes common infectious and noninfectious causes of respiratory disease in reptiles, including diagnostic and therapeutic regimen. Copyright © 2011 Elsevier Inc. All rights reserved.
Insulin-Like Growth Factor-1 and Neuroinflammation
Labandeira-Garcia, Jose L.; Costa-Besada, Maria A.; Labandeira, Carmen M.; Villar-Cheda, Begoña; Rodríguez-Perez, Ana I.
Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results o...
Respiratory Syncytial Virus (RSV)
Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDCâs Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread. Created: 2/4/2013 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases (DVD). Date Released: 2/13/2013.
Obesity and respiratory diseases
Zammit, Christopher; Liddicoat, Helen; Moonsie, Ian; Makker, Himender
Christopher Zammit, Helen Liddicoat, Ian Moonsie, Himender MakkerSleep and Ventilation Unit, Department of Respiratory Medicine, North Middlesex University Hospital, London, UKAbstract: The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ produ...
Acute respiratory distress syndrome
Confalonieri, Marco; Salton, Francesco; Fabiano, Francesco
Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foste...
Respiratory Syncytial Virus Vaccines
Dudas, Robert A.; Karron, Ruth A.
Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...
Managing respiratory problems in athletes.
Hull, James H; Ansley, Les; Robson-Ansley, Paula; Parsons, Jonathan P
Respiratory problems are common in athletes of all abilities and can significantly impact upon their health and performance. In this article, we provide an overview of respiratory physiology in athletes. We also discuss the assessment and management of common clinical respiratory conditions as they pertain to athletes, including airways disease, respiratory tract infection and pneumothorax. We focus on providing a pragmatic approach and highlight important caveats for the physician treating respiratory conditions in this highly specific population.
Obesity and respiratory diseases
Christopher Zammit
Full Text Available Christopher Zammit, Helen Liddicoat, Ian Moonsie, Himender MakkerSleep and Ventilation Unit, Department of Respiratory Medicine, North Middlesex University Hospital, London, UKAbstract: The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population.Keywords: obesity, lung function, obstructive sleep apnea, obesity hypoventilation syndrome, anesthesia
Respiratory manifestations of hypothyroidism
Sorensen, Jesper Roed; Winther, Kristian Hillert; Bonnema, Steen Joop
BACKGROUND: Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. We conducted a systematic review to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. METHODS: PubMed and EMBASE databases were...... searched for relevant literature from January 1950 through January 2015 with study eligibility criteria: English-language publications; Adult subclinical or overt hypothyroid patients; Intervention, observational or retrospective studies; and respiratory manifestations. We followed the PRISMA statement...... and used the Cochrane's risk of bias tool. RESULTS: A total of 1699 papers were screened by two independent authors for relevant titles. Of 109 relevant abstracts, 28 papers underwent full text analyses, of which 22 were included in the review. We identified possible mechanisms explaining respiratory...
Respiratory care manpower issues.
Mathews, Paul; Drumheller, Lois; Carlow, John J
Although respiratory care is a relatively new profession, its practitioners are deeply involved in providing patient care in the critical care. In preparation for writing this article, we sought to explore the respiratory therapy manpower needs and activities designed to fulfill those needs in critical care practice. We began by delineating the historical development of respiratory care as a profession, the development of its education, and the professional credentialing system. We then conducted several literature reviews with few articles generated. We requested and received data from the American Association for Respiratory Care (AARC), The National Board for Respiratory Care (NBRC), and the Committee on Accreditation of Respiratory Care education (CoARC) relative to their membership, number of credentialed individuals, and educational program student and graduate data for 2000 through 2004. We then conducted two electronic surveys. Survey 1 was a six-item survey that examined the use of mandatory overtime in respiratory care departments. We used a convenience sample of 30 hospitals stratified by size (or=500 beds). Survey 2 was a five-item instrument distributed by blast E-mail to the Society of Critical Care Medicine's Respiratory Care Section members and members of the RC_World list serve. This survey elicited 51 usable and non-duplicative responses from geographically and size-varied institutions. We analyzed these data in several ways from distribution analysis to one-way analysis of variance procedure and appropriate post hoc analysis techniques. Where appropriate, a matched-pairs analysis was performed and these were compared across the variables intensive care unit (ICU) beds per actual number of respiratory care practitioners (RCPs) and ICU beds per preferred number of RCPs. The data gathered from the professional organizations indicated a relatively stable attrition rate (35.2%+/-1.7-3.1%), even in the face of varying enrollments (6,231 in 2004 vs. 4
The microbiota of the respiratory tract : Gatekeeper to respiratory health
Man, Wing Ho; De Steenhuijsen Piters, Wouter A.A.; Bogaert, Debby
The respiratory tract is a complex organ system that is responsible for the exchange of oxygen and carbon dioxide. The human respiratory tract spans from the nostrils to the lung alveoli and is inhabited by niche-specific communities of bacteria. The microbiota of the respiratory tract probably acts
Adult respiratory distress syndrome
Svendsen, J.; Jespersen, J.; Skjoedt, T.
Our present-day knowledge concerning the clinico-chemical and radiological findings in adult respiratory distress syndrome are described. Three typical case histories have been selected to illustrate this condition; they were due to multiple trauma or sepsis. It is stressed that radiology is in a key position for making the diagnosis and for observing the course of the illness. (orig) [de
European Respiratory Society statement
Miravitlles, Marc; Dirksen, Asger; Ferrarotti, Ilaria
lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment.The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has...
Respiratory Syncytial Virus (RSV)
Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDCâs Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.
Respiratory problems in foals.
Beech, J
Despite major advances in our knowledge and ability to treat respiratory diseases in neonatal foals, neonatal respiratory medicine is still in its infancy. It is hoped that this article may serve as a guideline for diagnosis and treatment. Specific antibiotic regimens and emergency procedures are covered in other articles in this symposium. Because management factors play a critical role in the pathogenesis of respiratory disease, education of clients as to their importance would help both prophylactically and therapeutically. The necessity of very careful monitoring of neonates, which is critical to early detection of disease, should be stressed. As respiratory diseases can be fulminant and rapidly fatal, it is imperative not to delay diagnosis and therapy. Thorough examination and implementation of appropriate diagnostic techniques, as well as prompt early referral to a more sophisticated facility when indicated, would prevent many deaths. Although sophisticated support systems are vital for survival of some of these foals, good basic intensive nursing care combined with selection of appropriate drug therapy very early in the course of the disease is all that many foals require and can significantly improve survival rates.
Respiratory Symptoms in Firefighters
Greven, Frans E.; Rooyackers, Jos M.; Kerstjens, Huib A. M.; Heederik, Dick J.
Background The aim of the present study was to determine the prevalence and risk factors associated with respiratory symptoms in common firefighters in the Netherlands. Methods A total of 1,330 firefighters from the municipal fire brigades of three provinces of the Netherlands were included in the
Textbook of respiratory medicine
Murray, J.F.; Nadel, J.
This book presents a clinical reference of respiratory medicine. It also details basic science aspects of pulmonary physiology and describes recently developed, sophisticated diagnostic tools and therapeutic methods. It also covers anatomy, physiology, pharmacology, and pathology; microbiologic, radiologic, nuclear medicine, and biopsy methods for diagnosis
Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM
Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim
Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations
ARDS (Acute Respiratory Distress Syndrome)
... Also known as What Is ARDS, or acute respiratory distress syndrome, is a lung condition that leads ... treat ARDS. Other Names Acute lung injury Adult respiratory distress syndrome Increased-permeability pulmonary edema Noncardiac pulmonary ...
Respiratory gating in cardiac PET
Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E
BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...... of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent. METHODS AND RESULTS: Forty-eight patients were randomized to adenosine or dipyridamole cardiac...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4...
Middle East Respiratory Syndrome (MERS)
Middle East Respiratory Syndrome Coronavirus; MERS-CoV; Novel coronavirus; nCoV ... for Disease Control and Prevention website. Middle East Respiratory Syndrome (MERS): Frequently asked questions and answers. www. ...
Acute respiratory infections at children
Delyagin, V.
The common signs of virus respiratory diseases, role of pathological inclination to infections, value of immunodeficiency are presented at lecture. Features of most often meeting respiratory virus infections are given.
Dexamethasone impairs hypoxia-inducible factor-1 function
Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of α- and β-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1α levels in the cytosol of HepG2 cells, while nuclear HIF-1α levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients
Climate change and respiratory disease: European Respiratory Society position statement.
Ayres, J G; Forsberg, B; Annesi-Maesano, I; Dey, R; Ebi, K L; Helms, P J; Medina-Ramón, M; Windt, M; Forastiere, F
Climate change will affect individuals with pre-existing respiratory disease, but the extent of the effect remains unclear. The present position statement was developed on behalf of the European Respiratory Society in order to identify areas of concern arising from climate change for individuals with respiratory disease, healthcare workers in the respiratory sector and policy makers. The statement was developed following a 2-day workshop held in Leuven (Belgium) in March 2008. Key areas of concern for the respiratory community arising from climate change are discussed and recommendations made to address gaps in knowledge. The most important recommendation was the development of more accurate predictive models for predicting the impact of climate change on respiratory health. Respiratory healthcare workers also have an advocatory role in persuading governments and the European Union to maintain awareness and appropriate actions with respect to climate change, and these areas are also discussed in the position statement.
Evaluation of respiratory pattern during respiratory-gated radiotherapy
Dobashi, Suguru; Mori, Shinichiro
The respiratory cycle is not strictly regular, and generally varies in amplitude and period from one cycle to the next. We evaluated the characteristics of respiratory patterns acquired during respiratory gating treatment in more than 300 patients. A total 331 patients treated with respiratory-gated carbon-ion beam therapy were selected from a group of patients with thoracic and abdominal conditions. Respiratory data were acquired for a total of 3,171 fractions using an external respiratory sensing monitor and evaluated for respiratory cycle, duty cycle, magnitude of baseline drift, and intrafractional/interfractional peak inhalation/exhalation positional variation. Results for the treated anatomical sites and patient positioning were compared. Mean ± SD respiratory cycle averaged over all patients was 4.1 ± 1.3 s. Mean ± SD duty cycle averaged over all patients was 36.5 ± 7.3 %. Two types of baseline drift were seen, the first decremental and the second incremental. For respiratory peak variation, the mean intrafractional variation in peak-inhalation position relative to the amplitude in the first respiratory cycle (15.5 ± 9.3 %) was significantly larger than that in exhalation (7.5 ± 4.6 %). Interfractional variations in inhalation (17.2 ± 18.5 %) were also significantly greater than those in exhalation (9.4 ± 10.0 %). Statistically significant differences were observed between patients in the supine position and those in the prone position in mean respiratory cycle, duty cycle, and intra-/interfractional variations. We quantified the characteristics of the respiratory curve based on a large number of respiratory data obtained during treatment. These results might be useful in improving the accuracy of respiratory-gated treatment.
Respiratory guiding system for respiratory motion management in respiratory gated radiotherapy
Kang, Seong Hee; Kim, Dong Su; Kim, Tae Ho; Suh, Tae Suk
Respiratory guiding systems have been shown to improve the respiratory regularity. This, in turn, improves the efficiency of synchronized moving aperture radiation therapy, and it reduces the artifacts caused by irregular breathing in imaging techniques such as four-dimensional computed tomography (4D CT), which is used for treatment planning in RGRT. We have previously developed a respiratory guiding system that incorporates an individual-specific guiding waveform, which is easy to follow for each volunteer, to improve the respiratory regularity. The present study evaluates the application of this system to improve the respiratory regularity for respiratory-gated radiation therapy (RGRT). In this study, we evaluated the effectiveness of an in-house-developed respiratory guiding system incorporating an individual specific guiding waveform to improve the respiratory regularity for RGRT. Most volunteers showed significantly less residual motion at each phase during guided breathing owing to the improvement in respiratory regularity. Therefore, the respiratory guiding system can clearly reduce the residual, or respiratory, motion in each phase. From the result, the CTV and the PTV margins during RGRT can be reduced by using the respiratory guiding system, which reduces the residual motions, thus improving the accuracy of RGRT
Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure
Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.
Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of
Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure
Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.
Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of
Ocular Tropism of Respiratory Viruses
Rota, Paul A.; Tumpey, Terrence M.
SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620
Nanotechnology in respiratory medicine.
Omlor, Albert Joachim; Nguyen, Juliane; Bals, Robert; Dinh, Quoc Thai
Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task.
Adult respiratory distress syndrome
Murphy, C.H.; Colvin, R.S.
Due to improved emergency resuscitation procedures, and with advancing medical technology in the field of critical care, an increasing number of patients survive the acute phase of shock and catastrophic trauma. Patients who previously died of massive sepsis, hypovolemic or hypotensive shock, multiple fractures, aspiration, toxic inhalation, and massive embolism are now surviving long enough to develop previously unsuspected and unrecognized secondary effects. With increasing frequency, clinicians are recognizing the clinical and radiographic manifestations of pathologic changes in the lungs occurring secondary to various types of massive insult. This paper gives a list of diseases that have been shown to precipitate or predispose to diffuse lung damage. Various terms have been used to describe the lung damage and respiratory failure secondary to these conditions. The term adult respiratory distress syndrome (ARDS) is applied to several cases of sudden respiratory failure in patients with previously healthy lungs following various types of trauma or shock. Numerous investigations and experiments have studied the pathologic changes in ARDS, and, while there is still no clear indication of why it develops, there is now some correlation of the sequential pathologic developments with the clinical and radiographic changes
Submersion and acute respiratory failure
Yu-Jang Su
Conclusions: Submersion patients who are hypothermic on arrival of emergency department (ED are risky to respiratory failure and older, more hypothermic, longer hospital stay in suicidal submersion patients.
Management of Postoperative Respiratory Failure.
Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V
Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.
Mostert, J.W. (Pretoria Univ. (South Africa). Dept. of Anesthesiology)
The high degree of technical perfection of the respiratory mass spectrometer has rendered the instrument feasible for routine monitoring of anesthetized patients. It is proposed that the difference between inspired and expired oxygen tension in mm Hg be equated with whole body oxygen consumption in ml/min/M/sup 2/ body-surface area at STPD, by the expedient of multiplying tension-differences by a factor of 2. Years of experience have confirmed the value of promptly recognizing sudden drops in this l/E tension difference below 50 mm Hg indicative of metabolic injury from hypovolemia or respiratory depression. Rises in l/E tension-differences were associated with shivering as well as voluntary muscle activity. Tension differences of less than 25 mm Hg (equated with a whole-body O/sub 2/ consumption of less than 50 ml O/sub 2//min/M/sup 2/) occurred in a patient in the sitting position for posterior fossa exploration without acidosis, hypoxia or hypotension for several hours prior to irreversible cardiac arrest. The value of clinical monitoring by mass spectrometry is especially impressive in open-heart surgery.
The respiratory mass spectrometer
Mostert, J.W.
The high degree of technical perfection of the respiratory mass spectrometer has rendered the instrument feasible for routine monitoring of anesthetized patients. It is proposed that the difference between inspired and expired oxygen tension in mm Hg be equated with whole body oxygen consumption in ml/min/M 2 body-surface area at STPD, by the expedient of multiplying tension-differences by a factor of 2. Years of experience have confirmed the value of promptly recognizing sudden drops in this l/E tension difference below 50 mm Hg indicative of metabolic injury from hypovolemia or respiratory depression. Rises in l/E tension-differences were associated with shivering as well as voluntary muscle activity. Tension differences of less than 25 mm Hg (equated with a whole-body O 2 consumption of less than 50 ml O 2 /min/M 2 ) occurred in a patient in the sitting position for posterior fossa exploration without acidosis, hypoxia or hypotension for several hours prior to irreversible cardiac arrest. The value of clinical monitoring by mass spectrometry is especially impressive in open-heart surgery
Acute Respiratory Distress Syndrome
Carmen Sílvia Valente Barbas
Full Text Available This paper, based on relevant literature articles and the authors' clinical experience, presents a goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome (ARDS that can help improve clinicians' ability to care for these patients. Early recognition of ARDS modified risk factors and avoidance of aggravating factors during hospital stay such as nonprotective mechanical ventilation, multiple blood products transfusions, positive fluid balance, ventilator-associated pneumonia, and gastric aspiration can help decrease its incidence. An early extensive clinical, laboratory, and imaging evaluation of "at risk patients" allows a correct diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic indices, so that a careful treatment can be planned. Rapid administration of antibiotics and resuscitative measures in case of sepsis and septic shock associated with protective ventilatory strategies and early short-term paralysis associated with differential ventilatory techniques (recruitment maneuvers with adequate positive end-expiratory pressure titration, prone position, and new extracorporeal membrane oxygenation techniques in severe ARDS can help improve its prognosis. Revaluation of ARDS patients on the third day of evolution (Sequential Organ Failure Assessment (SOFA, biomarkers and response to infection therapy allows changes in the initial treatment plans and can help decrease ARDS mortality.
Respiratory symptoms of megaesophagus
Fabio Di Stefano
Full Text Available Megaesophagus as the end result of achalasia is the consequence of disordered peristalsis and the slow decompensation of the esophageal muscular layer. The main symptoms of achalasia are dysphagia, regurgitation, chest pain and weight loss, but respiratory symptoms, such as coughing, particularly when patients lie in a horizontal position, may also be common due to microaspiration. A 70-year old woman suffered from a nocturnal cough and shortness of breath with stridor. She reported difficulty in swallowing food over the past ten years, but had adapted by eating a semi-liquid diet. Chest X-ray showed right hemithorax patchy opacities projecting from the posterior mediastinum. Chest computed tomography scan showed a marked dilatation of the esophagus with abundant food residues. Endoscopy confirmed the diagnosis of megaesophagus due to esophageal achalasia, excluding other causes of obstruction, such as secondary esophagitis, polyps, leiomyoma or leiomyosarcoma. In the elderly population, swallowing difficulties due to esophageal achalasia are often underestimated and less troublesome than the respiratory symptoms that are caused by microaspiration. The diagnosis of esophageal achalasia, although uncommon, should be considered in patients with nocturnal chronic coughs and shortness of breath with stridor when concomitant swallowing difficulties are present.
Acute respiratory distress syndrome
Marco Confalonieri
Full Text Available Since its first description, the acute respiratory distress syndrome (ARDS has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.
10 CFR 850.28 - Respiratory protection.
... 10 Energy 4 2010-01-01 2010-01-01 false Respiratory protection. 850.28 Section 850.28 Energy... Respiratory protection. (a) The responsible employer must establish a respiratory protection program that complies with the respiratory protection program requirements of 29 CFR 1910.134, Respiratory Protection...
Doping and respiratory system.
Casali, L; Pinchi, G; Puxeddu, E
Historically many different drugs have been used to enhance sporting performances. The magic elixir is still elusive and the drugs are still used despite the heavy adverse effects. The respiratory system is regularly involved in this research probably because of its central location in the body with several connections to the cardiovascular system. Moreover people are aware that O2 consumption and its delivery to mitochondria firstly depend on ventilation and on the respiratory exchanges. The second step consists in the tendency to increase V'O2 max and to prolong its availability with the aim of improving the endurance time and to relieve the fatigue. Many methods and substances had been used in order to gain an artificial success. Additional oxygen, autologous and homologous transfusion and erythropoietin, mainly the synthetic type, have been administered with the aim of increasing the amount of oxygen being delivered to the tissues. Some compounds like stimulants and caffeine are endowed of excitatory activity on the CNS and stimulate pulmonary ventilation. They did not prove to have any real activity in supporting the athletic performances. Beta-adrenergic drugs, particularly clenbuterol, when administered orally or parenterally develop a clear illicit activity on the myosin fibres and on the muscles as a whole. Salbutamol, terbutaline, salmeterol and formoterol are legally admitted when administrated by MDI in the treatment of asthma. The prevalence of asthma and bronchial hyperactivity is higher in athletes than amongst the general population. This implies that clear rules must be provided to set a correct diagnosis of asthma in the athletes and a correct therapy to align with the actual guidelines according to the same rights of the "other" asthmatic patients.
Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis
... Home » Health Info » Voice, Speech, and Language Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis On this page: What ... find additional information about RRP? What is recurrent respiratory papillomatosis? Recurrent respiratory papillomatosis (RRP) is a disease ...
Is recurrent respiratory infection associated with allergic respiratory disease?
de Oliveira, Tiago Bittencourt; Klering, Everton Andrei; da Veiga, Ana Beatriz Gorini
Respiratory infections cause high morbidity and mortality worldwide. This study aims to estimate the relationship between allergic respiratory diseases with the occurrence of recurrent respiratory infection (RRI) in children and adolescents. The International Study of Asthma and Allergies in Childhood questionnaire and a questionnaire that provides data on the history of respiratory infections and the use of antibiotics were used to obtain data from patients. The relationship between the presence of asthma or allergic rhinitis and the occurrence of respiratory infections in childhood was analyzed. We interviewed the caregivers of 531 children aged 0 to 15 years. The average age of participants was 7.43 years, with females accounting for 52.2%. This study found significant relationship between: presence of asthma or allergic rhinitis with RRI, with prevalence ratio (PR) of 2.47 (1.51-4.02) and 1.61 (1.34-1.93), respectively; respiratory allergies with use of antibiotics for respiratory problems, with PR of 5.32 (2.17-13.0) for asthma and of 1.64 (1.29-2.09) for allergic rhinitis; asthma and allergic rhinitis with diseases of the lower respiratory airways, with PR of 7.82 (4.63-13.21) and 1.65 (1.38-1.96), respectively. In contrast, no relationship between upper respiratory airway diseases and asthma and allergic rhinitis was observed, with PR of 0.71 (0.35-1.48) and 1.30 (0.87-1.95), respectively. RRI is associated with previous atopic diseases, and these conditions should be considered when treating children.
Dysrhythmias of the respiratory oscillator
Paydarfar, David; Buerkel, Daniel M.
Breathing is regulated by a central neural oscillator that produces rhythmic output to the respiratory muscles. Pathological disturbances in rhythm (dysrhythmias) are observed in the breathing pattern of children and adults with neurological and cardiopulmonary diseases. The mechanisms responsible for genesis of respiratory dysrhythmias are poorly understood. The present studies take a novel approach to this problem. The basic postulate is that the rhythm of the respiratory oscillator can be altered by a variety of stimuli. When the oscillator recovers its rhythm after such perturbations, its phase may be reset relative to the original rhythm. The amount of phase resetting is dependent upon stimulus parameters and the level of respiratory drive. The long-range hypothesis is that respiratory dysrhythmias can be induced by stimuli that impinge upon or arise within the respiratory oscillator with certain combinations of strength and timing relative to the respiratory cycle. Animal studies were performed in anesthetized or decerebrate preparations. Neural respiratory rhythmicity is represented by phrenic nerve activity, allowing use of open-loop experimental conditions which avoid negative chemical feedback associated with changes in ventilation. In animal experiments, respiratory dysrhythmias can be induced by stimuli having specific combinations of strength and timing. Newborn animals readily exhibit spontaneous dysrhythmias which become more prominent at lower respiratory drives. In human subjects, swallowing was studied as a physiological perturbation of respiratory rhythm, causing a pattern of phase resetting that is characterized topologically as type 0. Computational studies of the Bonhoeffer-van der Pol (BvP) equations, whose qualitative behavior is representative of many excitable systems, supports a unified interpretation of these experimental findings. Rhythmicity is observed when the BvP model exhibits recurrent periods of excitation alternating with
Respiratory muscle involvement in sarcoidosis.
Schreiber, Tina; Windisch, Wolfram
In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.
Respiratory effort from the photoplethysmogram.
Addison, Paul S
The potential for a simple, non-invasive measure of respiratory effort based on the pulse oximeter signal - the photoplethysmogram or 'pleth' - was investigated in a pilot study. Several parameters were developed based on a variety of manifestations of respiratory effort in the signal, including modulation changes in amplitude, baseline, frequency and pulse transit times, as well as distinct baseline signal shifts. Thirteen candidate parameters were investigated using data from healthy volunteers. Each volunteer underwent a series of controlled respiratory effort maneuvers at various set flow resistances and respiratory rates. Six oximeter probes were tested at various body sites. In all, over three thousand pleth-based effort-airway pressure (EP) curves were generated across the various airway constrictions, respiratory efforts, respiratory rates, subjects, probe sites, and the candidate parameters considered. Regression analysis was performed to determine the existence of positive monotonic relationships between the respiratory effort parameters and resulting airway pressures. Six of the candidate parameters investigated exhibited a distinct positive relationship (poximeter probe and an ECG (P2E-Effort) and the other using two pulse oximeter probes placed at different peripheral body sites (P2-Effort); and baseline shifts in heart rate, (BL-HR-Effort). In conclusion, a clear monotonic relationship was found between several pleth-based parameters and imposed respiratory loadings at the mouth across a range of respiratory rates and flow constrictions. The results suggest that the pleth may provide a measure of changing upper airway dynamics indicative of the effort to breathe. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.
Auscultation of the respiratory system
Sarkar, Malay; Madabhavi, Irappa; Niranjan, Narasimhalu; Dogra, Megha
Auscultation of the lung is an important part of the respiratory examination and is helpful in diagnosing various respiratory disorders. Auscultation assesses airflow through the trachea-bronchial tree. It is important to distinguish normal respiratory sounds from abnormal ones for example crackles, wheezes, and pleural rub in order to make correct diagnosis. It is necessary to understand the underlying pathophysiology of various lung sounds generation for better understanding of disease processes. Bedside teaching should be strengthened in order to avoid erosion in this age old procedure in the era of technological explosion. PMID:26229557
Auscultation of the respiratory system
Malay Sarkar
Full Text Available Auscultation of the lung is an important part of the respiratory examination and is helpful in diagnosing various respiratory disorders. Auscultation assesses airflow through the trachea-bronchial tree. It is important to distinguish normal respiratory sounds from abnormal ones for example crackles, wheezes, and pleural rub in order to make correct diagnosis. It is necessary to understand the underlying pathophysiology of various lung sounds generation for better understanding of disease processes. Bedside teaching should be strengthened in order to avoid erosion in this age old procedure in the era of technological explosion.
Respiratory Viruses in Febrile Neutropenic Patients with Respiratory Symptoms
Mohsen Meidani
Full Text Available Background: Respiratory infections are a frequent cause of fever in neutropenic patients, whereas respiratory viral infections are not frequently considered as a diagnosis, which causes high morbidity and mortality in these patients. Materials and Methods: This prospective study was performed on 36 patients with neutropenia who admitted to hospital were eligible for inclusion with fever (single temperature of >38.3°C or a sustained temperature of >38°C for more than 1 h, upper and lower respiratory symptoms. Sampling was performed from the throat of the patient by the sterile swab. All materials were analyzed by quantitative real-time multiplex polymerase chain reaction covering the following viruses; influenza, parainfluenza virus (PIV, rhinovirus (RV, human metapneumovirus, and respiratory syncytial virus (RSV. Results: RV was the most frequently detected virus and then RSV was the most. PIV was not present in any of the tested samples. Furthermore, no substantial differences in the distribution of specific viral species were observed based on age, sex, neutropenia duration, hematological disorder, and respiratory tract symptoms and signs (P > 0.05. Conclusion: Our prospective study supports the hypothesis that respiratory viruses play an important role in the development of neutropenic fever, and thus has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised patients with neutropenia.
House Dust Mite Respiratory Allergy
Calderón, Moisés A; Kleine-Tebbe, Jörg; Linneberg, Allan
Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence on the e......Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence...... not extend beyond the end of treatment. Finally, allergen immunotherapy has a poor but improving evidence base (notably on sublingual tablets) and its benefits last after treatment ends. This review identifies needs for deeper physician knowledge on the extent and impact of HDM allergy in respiratory disease...... and therapy of HDM respiratory allergy in practice....
Employee guide to respiratory protection
Wright, E.M.
This employee guide discusses use of respiratory protective equipment for particulates, gases, vapors, supplied air, and self-contained breathing apparatus. It also covers equipment selection medical factors, fitting criteria; care; and employee responsibilities
Climate Change and Respiratory Infections.
Mirsaeidi, Mehdi; Motahari, Hooman; Taghizadeh Khamesi, Mojdeh; Sharifi, Arash; Campos, Michael; Schraufnagel, Dean E
The rate of global warming has accelerated over the past 50 years. Increasing surface temperature is melting glaciers and raising the sea level. More flooding, droughts, hurricanes, and heat waves are being reported. Accelerated changes in climate are already affecting human health, in part by altering the epidemiology of climate-sensitive pathogens. In particular, climate change may alter the incidence and severity of respiratory infections by affecting vectors and host immune responses. Certain respiratory infections, such as avian influenza and coccidioidomycosis, are occurring in locations previously unaffected, apparently because of global warming. Young children and older adults appear to be particularly vulnerable to rapid fluctuations in ambient temperature. For example, an increase in the incidence in childhood pneumonia in Australia has been associated with sharp temperature drops from one day to the next. Extreme weather events, such as heat waves, floods, major storms, drought, and wildfires, are also believed to change the incidence of respiratory infections. An outbreak of aspergillosis among Japanese survivors of the 2011 tsunami is one such well-documented example. Changes in temperature, precipitation, relative humidity, and air pollution influence viral activity and transmission. For example, in early 2000, an outbreak of Hantavirus respiratory disease was linked to a local increase in the rodent population, which in turn was attributed to a two- to threefold increase in rainfall before the outbreak. Climate-sensitive respiratory pathogens present challenges to respiratory health that may be far greater in the foreseeable future.
33 CFR 142.39 - Respiratory protection.
... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Respiratory protection. 142.39... Respiratory protection. (a) Personnel in an atmosphere specified under ANSI Z88.2, requiring the use of respiratory protection equipment shall wear the type of respiratory protection equipment specified in ANSI Z88...
Respiratory care management information systems.
Ford, Richard M
Hospital-wide computerized information systems evolved from the need to capture patient information and perform billing and other financial functions. These systems, however, have fallen short of meeting the needs of respiratory care departments regarding work load assessment, productivity management, and the level of outcome reporting required to support programs such as patient-driven protocols. The respiratory care management information systems (RCMIS) of today offer many advantages over paper-based systems and hospital-wide computer systems. RCMIS are designed to facilitate functions specific to respiratory care, including assessing work demand, assigning and tracking resources, charting, billing, and reporting results. RCMIS incorporate mobile, point-of-care charting and are highly configurable to meet the specific needs of individual respiratory care departments. Important and substantial benefits can be realized with an RCMIS and mobile, wireless charting devices. The initial and ongoing costs of an RCMIS are justified by increased charge capture and reduced costs, by way of improved productivity and efficiency. It is not unusual to recover the total cost of an RCMIS within the first year of its operation. In addition, such systems can facilitate and monitor patient-care protocols and help to efficiently manage the vast amounts of information encountered during the practitioner's workday. Respiratory care departments that invest in RCMIS have an advantage in the provision of quality care and in reducing expenses. A centralized respiratory therapy department with an RCMIS is the most efficient and cost-effective way to monitor work demand and manage the hospital-wide allocation of respiratory care services.
[Respiratory treatments in neuromuscular disease].
Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A
In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Respiratory tract infection during Hajj
Alzeer Abdulaziz
Full Text Available Respiratory tract infection during Hajj (pilgrimage to Mecca is a common illness, and it is responsible for most of the hospital admissions. Influenza virus is the leading cause of upper respiratory tract infection during Hajj, and pneumonia can be serious. Taking into account the close contacts among the pilgrims, as well as the crowding, the potential for transmission of M. tuberculosis is expected to be high. These pilgrims can be a source for spreading infection on their return home. Although vaccination program for influenza is implemented, its efficacy is uncertain in this religious season. Future studies should concentrate on prevention and mitigation of these infections.
Respiratory correlated cone beam CT
Sonke, Jan-Jakob; Zijp, Lambert; Remeijer, Peter; Herk, Marcel van
A cone beam computed tomography (CBCT) scanner integrated with a linear accelerator is a powerful tool for image guided radiotherapy. Respiratory motion, however, induces artifacts in CBCT, while the respiratory correlated procedures, developed to reduce motion artifacts in axial and helical CT are not suitable for such CBCT scanners. We have developed an alternative respiratory correlated procedure for CBCT and evaluated its performance. This respiratory correlated CBCT procedure consists of retrospective sorting in projection space, yielding subsets of projections that each corresponds to a certain breathing phase. Subsequently, these subsets are reconstructed into a four-dimensional (4D) CBCT dataset. The breathing signal, required for respiratory correlation, was directly extracted from the 2D projection data, removing the need for an additional respiratory monitor system. Due to the reduced number of projections per phase, the contrast-to-noise ratio in a 4D scan reduced by a factor 2.6-3.7 compared to a 3D scan based on all projections. Projection data of a spherical phantom moving with a 3 and 5 s period with and without simulated breathing irregularities were acquired and reconstructed into 3D and 4D CBCT datasets. The positional deviations of the phantoms center of gravity between 4D CBCT and fluoroscopy were small: 0.13±0.09 mm for the regular motion and 0.39±0.24 mm for the irregular motion. Motion artifacts, clearly present in the 3D CBCT datasets, were substantially reduced in the 4D datasets, even in the presence of breathing irregularities, such that the shape of the moving structures could be identified more accurately. Moreover, the 4D CBCT dataset provided information on the 3D trajectory of the moving structures, absent in the 3D data. Considerable breathing irregularities, however, substantially reduces the image quality. Data presented for three different lung cancer patients were in line with the results obtained from the phantom study. In
Thresholds in chemical respiratory sensitisation.
Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian
There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the
Stem cells and respiratory diseases
Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Investigacao]. E-mail: email@example.com
Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)
Stem cells and respiratory diseases
Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo
Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)
Activation of respiratory muscles during respiratory muscle training.
Walterspacher, Stephan; Pietsch, Fabian; Walker, David Johannes; Röcker, Kai; Kabitz, Hans-Joachim
It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order. Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax). 41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05). IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL. Copyright © 2017 Elsevier B.V. All rights reserved.
The role of serial measurements of serum insulin-like growth factor 1 levels in the development of retinopathy of prematurity.
Dorum, Bayram Ali; Yılmaz, Cansu Canbolat; Köksal, Nilgün; Özkan, Hilal; Yıldız, Meral; Özmen, Ahmet Tuncer
To determine the role of serum insulin-like growth factor-1 levels in the development of retinopathy of prematurity, which is a major cause of childhood blindness worldwide. We prospectively studied newborn infants born at a postmenstrual age of prematurity screening and follow-up. Retinopathy of prematurity was classified according to the international classification of retinopathy of prematurity. Serum Insulin like growth factor 1 levels were measured serially in blood samples on the 1 st , 3 rd , 7 th , 21 st , and 28 th day. Among the 40 infants, 11 (27.5%) constituted the retinopathy of prematurity group and 29 comprised the non-retinopathy of prematurity group. In the retinopathy of prematurity group, the mean gestational age and birth weight was significantly lower. The demographic features of the study cohort were similar. The duration of mechanical ventilation was significantly greater in the retinopathy of prematurity group compared with the non-retinopathy of prematurity group (p=0.036). In terms of neonatal morbidities such as respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, patent ductus arteriosus, and necrotizing enterocolitis, no differences were detected between the groups. The mean serum insulin-like growth factor-1 levels in retinopathy of prematurity group were significantly lower than those in the non-retinopathy of prematurity group at each time point (1 st , 3 rd , 7 th , 21 st , and 28 th day of postnatal life) (p=0.001). This study demonstrated the low serum insulin-like growth factor-1 levels was associated with retinopathy of prematurity development.
Climate change and respiratory health.
Gerardi, Daniel A; Kellerman, Roy A
To discuss the nature of climate change and both its immediate and long-term effects on human respiratory health. This review is based on information from a presentation of the American College of Chest Physicians course on Occupational and Environmental Lung Disease held in Toronto, Canada, June 2013. It is supplemented by a PubMed search for climate change, global warming, respiratory tract diseases, and respiratory health. It is also supplemented by a search of Web sites including the Environmental Protection Agency, National Oceanic and Atmospheric Administration, World Meteorological Association, National Snow and Ice Data Center, Carbon Dioxide Information Analysis Center, Inter-Governmental Panel on Climate Change, and the World Health Organization. Health effects of climate change include an increase in the prevalence of certain respiratory diseases, exacerbations of chronic lung disease, premature mortality, allergic responses, and declines in lung function. Climate change, mediated by greenhouse gases, causes adverse health effects to the most vulnerable patient populations-the elderly, children, and those in distressed socioeconomic strata.
[Undernutrition in chronic respiratory diseases].
Zielonka, Tadeusz M; Hadzik-Błaszczyk, Małgorzata
Respiratory diseases such as asthma, COPD, lung cancer, infections, including also tuberculosis constitute the most frequent diseases in the word. Undernutrition frequently accompanies these diseases. Early diagnosis of malnutrition and implementation of appropriate treatment is very important. A nutritional interview and anthropometric examinations, such as body mass index, fat free mass and fat mass are used to diagnose it. Nutritional therapy affects the course and prognosis of these diseases. Diet should be individually adjusted to the calculated caloric intake that increases during exacerbation of disease, because of increased respiratory effort. Too large supply of energy can cause increase metabolism, higher oxygen consumption and PaCO2 increase each dangerous for patients with respiratory insufficiency. Main source of carbohydrates for these patients should be products with low glycemic index and with high dietary fiber contents. Large meals should be avoided since they cause rapid satiety, abdominal discomfort and have negative impact on the work of the respiratory muscles, especially of the diaphragm. Dietary supplements can be used in case of ineffectiveness of diet or for the patients with severe undernutrition.
Respiratory effects of borax dust.
Garabrant, D H; Bernstein, L; Peters, J M; Smith, T J; Wright, W E
The relation of respiratory symptoms, pulmonary function, and abnormalities of chest radiographs to estimated exposures of borax dust has been investigated in a cross sectional study of 629 actively employed borax workers. Ninety three per cent of the eligible workers participated in the study and exposures ranged from 1.1 mg/m3 to 14.6 mg/m3. Symptoms of acute respiratory irritation such as dryness of the mouth, nose, or throat, dry cough, nose bleeds, sore throat, productive cough, shortness of breath, and chest tightness were related to exposures of 4.0 mg/m3 or more, and were infrequent at exposures of 1.1 mg/m3. Symptoms of persistent respiratory irritation meeting the definition of chronic simple bronchitis were related to exposure among non-smokers. Decrements in the FEV1 as a percentage of predicted were seen among smokers who had heavy cumulative borax exposures (greater than or equal to 80 mg/m3 years) but were not seen among less exposed smokers or among non-smokers. Radiographic abnormalities were uncommon and were not related to dust exposure. Borax dust appears to act as a simple respiratory irritant and perhaps causes small changes in the FEV1 among smokers who are heavily exposed.
Guide to industrial respiratory protection
Pritchard, J.A.
The Occupational Safety and Health Act of 1970 has increased the emphasis on proper selection and use of respirators in situations where engineering controls are not feasible or are being implemented. Although a great deal of information on respiratory protection has been published, most of it is more technical than necessary for the average user faced with day-to-day problems of respiratory protection in industrial environments. This Guide is to provide the industrial user a single reference source containing enough information for establishing and maintaining a respirator program that meets the OSHA requirements outlined in 29 CFR Part 1910.134. It includes chapters on respirator selection, use, maintenance, and inspection, a complete description of all types of respirators and their advantages and limitations, and chapters on respirator fitting and wearer training, respiratory physiology, respiratory hazards, and physiological and psychological limitations. Also included are samples of the decision logic used in respirator selection, guidance on setting up an adequate respirator program through formulation of written standard operating procedures, and discussion of the meaning of the approved respirator
[Respiratory diseases in metallurgy production workers].
Shliapnikov, D M; Vlasova, E M; Ponomareva, T A
The authors identified features of respiratory diseases in workers of various metallurgy workshops. Cause-effect relationships are defined between occupational risk factors and respiratory diseases, with determining the affection level.
Assessment of respiratory involvement in children with ...
Background: Mucopolysaccharidosis (MPS) are classified into seven clinical types based on eleven known lysosomal enzyme deficiencies of glycosaminoglycan (GAG) metabolism. Respiratory involvement seen in most MPS types includes recurrent respiratory infections, upper and lower airway obstruction, tracheomalacia ...
Coal Mining-Related Respiratory Diseases
... Topics Publications and Products Programs Contact NIOSH NIOSH COAL WORKERS' HEALTH SURVEILLANCE PROGRAM Recommend on Facebook Tweet Share Compartir Coal Mining-Related Respiratory Diseases Coal mining-related respiratory ...
Respiratory physiology during early life.
Stocks, J
Despite the rapid adaptation to extrauterine life, the respiratory system of an infant is not simply a miniaturized version of that of an adult, since the rapid somatic growth that occurs during the first year of life is accompanied by major developmental changes in respiratory physiology. The highly compliant chest wall of the infant results in relatively low transpulmonary pressures at end expiration with increased tendency of the small peripheral airways to close during tidal breathing. This not only impairs gas exchange and ventilation-perfusion balance, particularly in dependent parts of the lung, but, together with the small absolute size of the airways, renders the infant and young child particularly susceptible to airway obstruction. Premature airways are highly compliant structures compared with those of mature newborns or adults. This increased compliance can cause airway collapse, resulting in increased airways resistance, flow limitation, poor gas exchange and increased work of breathing. Although there is clear evidence that airway reactivity is present from birth, its role in wheezing lower respiratory tract illnesses in young infants may be overshadowed by pre-existing abnormalities of airway geometry and lung mechanics, or by pathological changes such as airway oedema and mucus hypersecretion. Attempts to assess age-related changes in airway reactivity or response to aerosol therapy in the very young is confounded by changes in breathing patterns and the fact that infants are preferential nose breathers. There is increasing evidence that pre-existing abnormalities of respiratory function, associated with adverse events during foetal life (including maternal smoking during pregnancy), and familial predisposition to wheezing are important determinants of wheezing illnesses during the first years of life. This emphasizes the need to identify and minimize any factors that threaten the normal development of the lung during this critical period if
Respiratory symptoms in insect breeders.
Harris-Roberts, J; Fishwick, D; Tate, P; Rawbone, R; Stagg, S; Barber, C M; Adisesh, A
A number of specialist food suppliers in the UK breed and distribute insects and insect larvae as food for exotic pets, such as reptiles, amphibians and invertebrates. To investigate the extent of work-related (WR) symptoms and workplace-specific serum IgE in workers potentially exposed to a variety of biological contaminants, including insect and insect larvae allergens, endotoxin and cereal allergens at a UK specialist insect breeding facility. We undertook a study of respiratory symptoms and exposures at the facility, with subsequent detailed clinical assessment of one worker. All 32 workers were assessed clinically using a respiratory questionnaire and lung function. Eighteen workers consented to provide serum for determination of specific IgE to workplace allergens. Thirty-four per cent (11/32) of insect workers reported WR respiratory symptoms. Sensitization, as judged by specific IgE, was found in 29% (4/14) of currently exposed workers. Total inhalable dust levels ranged from 1.2 to 17.9 mg/m(3) [mean 4.3 mg/m(3) (SD 4.4 mg/m(3)), median 2.0 mg/m(3)] and endotoxin levels of up to 29435 EU/m(3) were recorded. Exposure to organic dusts below the levels for which there are UK workplace exposure limits can result in respiratory symptoms and sensitization. The results should alert those responsible for the health of similarly exposed workers to the potential for respiratory ill-health and the need to provide a suitable health surveillance programme.
Dosimetry of the respiratory tract
Roy, M.
A new dosimetric model of the human respiratory tract has been recently recommended by the International Commission on Radiological Protection, in ICRP Publication 66. This model was intended to update the previous lung model of the Task Group on Lung Dynamics that was adopted by ICRP in Publication 30. With this aim, extensive reviews of the available knowledge were made for anatomy and physiology of the respiratory tract and for deposition, clearance and biological effects of inhaled radionuclides. Finally, expanded dosimetry requirements resulted in a widely different approach from the former model. The main features of the new model are the followings: instead of calculating the average dose to the total mass of blood filled lung, the model takes account of differences in radiosensitivity of the venous respiratory tract tissues. It applies not only to adult workers but also to all members of the population, and provides reference values for children aged 3 months, 1, 5, 10, and 15 years, and adults. Deposition modelling of airborne gases and aerosols associates age dependent breathing rates, airway dimensions and physical activity, to particle size, density and chemical form of inhaled material. Clearance results of competition between mechanical transport clearance and absorption to blood. At each step of the calculation, adjustment guidance is provided to account for use of exact values of particle sizes and specific dissolution rates of inhaled material in order to calculate their own parameter of retention in the airways, and to assess accurately doses to the respiratory tract. Possible influence of smoking, of respiratory tract diseases and of eventual exposure to airborne toxicants is also addressed. (author)
Prevention of Respiratory Distress After Laparoscopic Cholecystectomy
O. A. Dolina
Full Text Available The paper presents the results of a comparative study of different methods for preventing respiratory distress after laparoscopic cholecystectomy. It shows the advantages of use of noninvasive assisted ventilation that ensures excessive positive pressure in the respiratory contour, its impact on external respiratory function, arterial blood gases, oxygen transport and uptake. A scheme for the prevention of respiratory diseases applying noninvasive assisted ventilation is given.
Effects of Aging on the Respiratory System.
Levitzky, Michael G.
Relates alterations in respiratory system functions occurring with aging to changes in respiratory system structure during the course of life. Main alterations noted include loss of alveolar elastic recoil, alteration in chest wall structure and decreased respiratory muscle strength, and loss of surface area and changes in pulmonary circulation.…
46 CFR 154.1405 - Respiratory protection.
... 46 Shipping 5 2010-10-01 2010-10-01 false Respiratory protection. 154.1405 Section 154.1405... Equipment § 154.1405 Respiratory protection. When Table 4 references this section, a vessel carrying the listed cargo must have: (a) Respiratory protection equipment for each person on board that protects the...
46 CFR 197.550 - Respiratory protection.
... 46 Shipping 7 2010-10-01 2010-10-01 false Respiratory protection. 197.550 Section 197.550 Shipping... GENERAL PROVISIONS Benzene § 197.550 Respiratory protection. (a) General. When the use of respirators in... section that is appropriate for the exposure. Table 197.550(b)—Respiratory Protection for Benzene Airborne...
29 CFR 1915.154 - Respiratory protection.
... 29 Labor 7 2010-07-01 2010-07-01 false Respiratory protection. 1915.154 Section 1915.154 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... (PPE) § 1915.154 Respiratory protection. Respiratory protection for shipyard employment is covered by...
33 CFR 127.1209 - Respiratory protection.
... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Respiratory protection. 127.1209... Waterfront Facilities Handling Liquefied Hazardous Gas Equipment § 127.1209 Respiratory protection. Each waterfront facility handling LHG must provide equipment for respiratory protection for each employee of the...
Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.
Haeri, Sina; Devers, Patricia L; Kaiser-Rogers, Kathleen A; Moylan, Vincent J; Torchia, Beth S; Horton, Amanda L; Wolfe, Honor M; Aylsworth, Arthur S
Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension. Copyright Thieme Medical Publishers.
Partnering for optimal respiratory home care: physicians working with respiratory therapists to optimally meet respiratory home care needs.
Spratt, G; Petty, T L
The need for respiratory care services continues to increase, reimbursement for those services has decreased, and cost-containment measures have increased the frequency of home health care. Respiratory therapists are well qualified to provide home respiratory care, reduce misallocation of respiratory services, assess patient respiratory status, identify problems and needs, evaluate the effect of the home setting, educate the patient on proper equipment use, monitor patient response to and complications of therapy, monitor equipment functioning, monitor for appropriate infection control procedures, make recommendations for changes to therapy regimen, and adjust therapy under the direction of the physician. Teamwork benefits all parties and offers cost and time savings, improved data collection and communication, higher job satisfaction, and better patient monitoring, education, and quality of life. Respiratory therapists are positioned to optimize treatment efficacy, maximize patient compliance, and minimize hospitalizations among patients receiving respiratory home care.
A Quick Reference on Respiratory Acidosis.
Johnson, Rebecca A
Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco 2 , decreases in pH and compensatory increases in blood HCO 3 - concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO 3 - concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO 3 - . Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O 2 ). Copyright © 2016 Elsevier Inc. All rights reserved.
Respiratory challenge MRI: Practical aspects
Fiona C. Moreton
Full Text Available Respiratory challenge MRI is the modification of arterial oxygen (PaO2 and/or carbon dioxide (PaCO2 concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques.
Hypnosis in paediatric respiratory medicine.
McBride, Joshua J; Vlieger, Arine M; Anbar, Ran D
Hypnotherapy is an often misunderstood yet effective therapy. It has been reported to be useful within the field of paediatric respiratory medicine as both a primary and an adjunctive therapy. This article gives a brief overview of how hypnotherapy is performed followed by a review of its applications in paediatric patients with asthma, cystic fibrosis, dyspnea, habit cough, vocal cord dysfunction, and those requiring non-invasive positive pressure ventilation. As the available literature is comprised mostly of case series, retrospective studies, and only a single small randomized study, the field would be strengthened by additional randomized, controlled trials in order to better establish the effectiveness of hypnosis as a treatment, and to identify the processes leading to hypnosis-induced physiologic changes. As examples of the utility of hypnosis and how it can be taught to children with respiratory disease, the article includes videos that demonstrate its use for patients with cystic fibrosis. Copyright © 2013 Elsevier Ltd. All rights reserved.
Vitamin D and respiratory disorder
Mahnaz Hushmand
Full Text Available The active form of vitamin D is synthesized in some body organs following sun exposure and dietary intake. Vitamin D exhibits its major and critical effects not only through regulation of calcium and phosphate metabolism but also by influencing on respiratory and immune system. Serum concentrations of 25-hydroxyvitamin D below the optimum limit lead to vitamin D insufficiency or maybe deficiency. These inappropriate concentrations of vitamin D lead to different types of pulmonary diseases such as viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. In this review we described the association between vitamin D deficiency and severe therapy resistant asthma. We also reviewed the underlying molecular mechanism of vitamin D deficiency in children with severe- therapy resistant asthma. Based on current information, future clinical trial are needed to study the role of vitamin D supplementation on different groups of patients with severe asthma including infants, children of school age, and ethnic minorities.
Extensive upper respiratory tract sarcoidosis
Soares, Mafalda Trindade; Sousa, Carolina; Garanito, Luísa; Freire, Filipe
Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It can affect any part of the organism, although the lung is the most frequently affected organ. Upper airway involvement is rare, particularly if isolated. Sarcoidosis is a diagnosis of exclusion, established by histological evidence of non-caseating granulomas and the absence of other granulomatous diseases. The authors report a case of a man with sarcoidosis manifesting as a chronic inflammatory stenotic condition of the upper respiratory tract and trachea. PMID:27090537
Recurrent Respiratory Infections in Children
F. Yurochko
Full Text Available The paper covers a problem of recurrent respiratory infections (RRI in children. Their description, risk factors, diagnostic algorithm have been dwelt. A special attention is paid to the treatment. An optimal antibiotic in RRI of bacterial genesis is a high-dose amoxicillin/clavulanate (registered as Augmentin™ ES in Ukraine, the efficacy of which is 94.6–96.3 % according to different data.
Acute respiratory failure in asthma
Soubra Said; Guntupalli Kalapalatha
Although asthma is a condition that is managed in the outpatient setting in most patients, the poorly controlled and severe cases pose a major challenge to the health-care team. Recognition of the more common insidious and the less common rapid onset "acute asphyxic" asthma are important. The intensivist needs to be familiar with the factors that denote severity of the exacerbation. The management of respiratory failure in asthma, including pharmacologic and mechanical ventilation, are discus...
Zonography in acute respiratory diseases
Druzhinina, V.S.; Fetisova, V.M.; Kozorez, A.G.
Radiography was performed in 94 patients whose initial condition was assessed as acute respiratory disease. Radioscopy with x-ray image amplifier, roentgenography and zonography were used. Pulmonary changes were found in 61 persons. In 45 of them acute pneumonia was revealed, in 16 changes in the pulmonary pattern assessed as residual manifestations of pneumonia. Changes in 30 patients with pneumonia and 16 patients with residual manifestations were detected by zonography only
Respiratory failure due to tracheobronchomalacia.
Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.
A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair. PMID:8711665
Respiratory failure due to tracheobronchomalacia.
Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.
A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair.
Respiratory manifestations in endocrine diseases
The control mechanisms of respiration as a vital function are complex: voluntary ? cortical, and involuntary ? metabolic, neural, emotional and endocrine. Hormones and hypothalamic neuropeptides (that act as neurotrasmitters and neuromodulators in the central nervous system) play a role in the regulation of respiration and in bronchopulmonary morphology. This article presents respiratory manifestations in adult endocrine diseases that evolve with hormone deficit or hypersecretion. In hyperthy...
A Review on Human Respiratory Modeling.
Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza
Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.
Sulfur mustard and respiratory diseases.
Tang, Feng Ru; Loke, Weng Keong
Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.
Respiratory analysis system and method
Liu, F. F. (Inventor)
A system is described for monitoring the respiratory process in which the gas flow rate and the frequency of respiration and expiration cycles can be determined on a real time basis. A face mask is provided with one-way inlet and outlet valves where the gas flow is through independent flowmeters and through a mass spectrometer. The opening and closing of a valve operates an electrical switch, and the combination of the two switches produces a low frequency electrical signal of the respiratory inhalation and exhalation cycles. During the time a switch is operated, the corresponsing flowmeter produces electric pulses representative of the flow rate; the electrical pulses being at a higher frequency than that of the breathing cycle and combined with the low frequency signal. The high frequency pulses are supplied to conventional analyzer computer which also receives temperature and pressure inputs and computes mass flow rate and totalized mass flow of gas. From the mass spectrometer, components of the gas are separately computed as to flow rate. The electrical switches cause operation of up-down inputs of a reversible counter. The respective up and down cycles can be individually monitored and combined for various respiratory measurements.
Synchrony - Cyberknife Respiratory Compensation Technology
Ozhasoglu, Cihat; Saw, Cheng B.; Chen Hungcheng; Burton, Steven; Komanduri, Krishna; Yue, Ning J.; Huq, Saiful M.; Heron, Dwight E.
Studies of organs in the thorax and abdomen have shown that these organs can move as much as 40 mm due to respiratory motion. Without compensation for this motion during the course of external beam radiation therapy, the dose coverage to target may be compromised. On the other hand, if compensation of this motion is by expansion of the margin around the target, a significant volume of normal tissue may be unnecessarily irradiated. In hypofractionated regimens, the issue of respiratory compensation becomes an important factor and is critical in single-fraction extracranial radiosurgery applications. CyberKnife is an image-guided radiosurgery system that consists of a 6-MV LINAC mounted to a robotic arm coupled through a control loop to a digital diagnostic x-ray imaging system. The robotic arm can point the beam anywhere in space with 6 degrees of freedom, without being constrained to a conventional isocenter. The CyberKnife has been recently upgraded with a real-time respiratory tracking and compensation system called Synchrony. Using external markers in conjunction with diagnostic x-ray images, Synchrony helps guide the robotic arm to move the radiation beam in real time such that the beam always remains aligned with the target. With the aid of Synchrony, the tumor motion can be tracked in three-dimensional space, and the motion-induced dosimetric change to target can be minimized with a limited margin. The working principles, advantages, limitations, and our clinical experience with this new technology will be discussed
Undifferentiated Embryonic Cell Transcription Factor 1 Regulates ESC Chromatin Organization and Gene Expression
Kooistra, Susanne M.; van den Boom, Vincent; Thummer, Rajkumar P.; Johannes, Frank; Wardenaar, Rene; Tesson, Bruno M.; Veenhoff, Liesbeth M.; Fusetti, Fabrizia; O'Neill, Laura P.; Turner, Bryan M.; de Haan, Gerald; Eggen, Bart J. L.; O'Neill, Laura P.
Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES
A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth
Greenberger, Lee M; Horak, Ivan D; Filpula, David
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth facto...
Structure and role of neutrophil cytosol factor 1 (NCF1) gene in ...
Dec 27, 2010 ... The neutrophil cytosol factor 1 (NCF1) gene consists of 11 exons and is found in two forms; one is wild ... granulomatous disease, multiple sclerosis, arthritis and parasitic infection. ... TCR, T cell receptor; AhR, aryl hydrocarbon receptor; RA, .... During malaria, ROS production can contribute to both.
Fas-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction
Guerra, B; Boldyreff, B; Issinger, O G
We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging...
Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy
Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K.; van Wijk, Albert C.; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C.; van Gulik, Thomas M.; Storm, Gert; Heger, Michal
Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of
Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy
Weijer, R.; Broekgaarden, M.; Krekorian, M.; Alles, L.K.; van Wijk, A.C; Mackaaij, C.; Verheij, J.; van der Wal, A.C.; van Gullik, T.M.; Storm, Gerrit; Heger, M.
Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression
Role of multiprotein bridging factor 1 in archaea: bridging the domains?
Koning, de B.; Blombach, F.; Wu Hao,; Brouns, S.J.J.; Oost, van der J.
MBF1 (multiprotein bridging factor 1) is a highly conserved protein in archaea and eukaryotes. It was originally identified as a mediator of the eukaryotic transcription regulator BmFTZ-F1 (Bombyx mori regulator of fushi tarazu). MBF1 was demonstrated to enhance transcription by forming a bridge
Effect of hypoxia-inducible factor 1-alpha (HIF-1α) on proliferation ...
Jul 25, 2011 ... Full Length Research Paper. Effect of hypoxia-inducible factor 1-alpha ... 1Department of Neurosurgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025,. China. 2Department of Neurosurgery, Chaoyang Hospital, Huainan, Anhui, China. 3Department of Neurosurgery ...
Preadipocyte factor-1 is associated with metabolic profile in severe obesity.
O'Connell, J
Dysfunctional adipose tissue has been proposed as a key pathological process linking obesity and metabolic disease. Preadipocyte factor-1 (Pref-1) has been shown to inhibit differentiation in adipocyte precursor cells and could thereby play a role in determining adipocyte size, adipose tissue functioning, and metabolic profile in obese individuals.
Surfactant Protein D in Respiratory and Non-Respiratory Diseases
Sorensen, Grith L.
Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases
Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1α and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.
Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu
Hypoxia of the human endometrium is a physiologic event occurring during the perimenstrual period and the local stimulus for angiogenesis. The aim of this study was to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1/CXCL12), and the potential role of hypoxia-inducible factor-1α (HIF-1α) in the endometrium. Human endometrial stromal cells (ESCs, n= 22 samples) were studied in vitro. ESCs were cultured under hypoxic and normoxic conditions and treated with cobalt chloride (CoCl₂; a hypoxia-mimicking agent) and/or echinomycin, a small-molecule inhibitor of HIF-1α activity. The mRNA levels and production of VEGF and SDF-1 were assessed by real-time PCR and ELISA, respectively. The HIF-1α protein levels were measured using western blot analysis. Hypoxia simultaneously induced the expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 from ESCs in a time-dependent manner. Similar changes were observed in the ESCs after stimulation with CoCl₂ in a dose-dependent manner. CoCl₂ significantly induced the expression of HIF-1α protein, and its highest expression was observed at 6 h. Echinomycin inhibited hypoxia-induced VEGF production without affecting the HIF-1α protein level and cell toxicity and had no effect on SDF-1 secretion (P hypoxic conditions that could influence angiogenesis in the human endometrium.
Air pollution and multiple acute respiratory outcomes.
Faustini, Annunziata; Stafoggia, Massimo; Colais, Paola; Berti, Giovanna; Bisanti, Luigi; Cadum, Ennio; Cernigliaro, Achille; Mallone, Sandra; Scarnato, Corrado; Forastiere, Francesco
Short-term effects of air pollutants on respiratory mortality and morbidity have been consistently reported but usually studied separately. To more completely assess air pollution effects, we studied hospitalisations for respiratory diseases together with out-of-hospital respiratory deaths. A time-stratified case-crossover study was carried out in six Italian cities from 2001 to 2005. Daily particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)) and nitrogen dioxide (NO2) associations with hospitalisations for respiratory diseases (n = 100 690), chronic obstructive pulmonary disease (COPD) (n = 38 577), lower respiratory tract infections (LRTI) among COPD patients (n = 9886) and out-of-hospital respiratory deaths (n = 5490) were estimated for residents aged ≥35 years. For an increase of 10 μg·m(-3) in PM10, we found an immediate 0.59% (lag 0-1 days) increase in hospitalisations for respiratory diseases and a 0.67% increase for COPD; the 1.91% increase in LRTI hospitalisations lasted longer (lag 0-3 days) and the 3.95% increase in respiratory mortality lasted 6 days. Effects of NO2 were stronger and lasted longer (lag 0-5 days). Age, sex and previous ischaemic heart disease acted as effect modifiers for different outcomes. Analysing multiple rather than single respiratory events shows stronger air pollution effects. The temporal relationship between the pollutant increases and hospitalisations or mortality for respiratory diseases differs.
Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.
Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy
PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.
Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.
Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U
Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.
Visual aided pacing in respiratory maneuvers
Rambaudi, L R [Laboratorio de Biofisica y Fisiologia ' Antonio Sadi Frumento' (Argentina); Rossi, E [Catedra de Bioingenieria II (Argentina); Mantaras, M C [Catedra de Bioingenieria II (Argentina); Perrone, M S [Laboratorio de Biofisica y Fisiologia ' Antonio Sadi Frumento' (Argentina); Siri, L Nicola [Catedra de Bioingenieria II (Argentina)
A visual aid to pace self-controlled respiratory cycles in humans is presented. Respiratory manoeuvres need to be accomplished in several clinic and research procedures, among others, the studies on Heart Rate Variability. Free running respiration turns to be difficult to correlate with other physiologic variables. Because of this fact, voluntary self-control is asked from the individuals under study. Currently, an acoustic metronome is used to pace respiratory frequency, its main limitation being the impossibility to induce predetermined timing in the stages within the respiratory cycle. In the present work, visual driven self-control was provided, with separate timing for the four stages of a normal respiratory cycle. This visual metronome (ViMet) was based on a microcontroller which power-ON and -OFF an eight-LED bar, in a four-stage respiratory cycle time series handset by the operator. The precise timing is also exhibited on an alphanumeric display.
Visual aided pacing in respiratory maneuvers
Rambaudi, L R; Rossi, E; Mantaras, M C; Perrone, M S; Siri, L Nicola
A visual aid to pace self-controlled respiratory cycles in humans is presented. Respiratory manoeuvres need to be accomplished in several clinic and research procedures, among others, the studies on Heart Rate Variability. Free running respiration turns to be difficult to correlate with other physiologic variables. Because of this fact, voluntary self-control is asked from the individuals under study. Currently, an acoustic metronome is used to pace respiratory frequency, its main limitation being the impossibility to induce predetermined timing in the stages within the respiratory cycle. In the present work, visual driven self-control was provided, with separate timing for the four stages of a normal respiratory cycle. This visual metronome (ViMet) was based on a microcontroller which power-ON and -OFF an eight-LED bar, in a four-stage respiratory cycle time series handset by the operator. The precise timing is also exhibited on an alphanumeric display
Year in Review 2015: Neonatal Respiratory Care.
Courtney, Sherry E
Neonatal respiratory care practices have changed with breathtaking speed in the past few years. It is critical for the respiratory therapist and others caring for neonates to be up to date with current recommendations and evolving care practices. The purpose of this article is to review papers of particular note that were published in 2015 and address important aspects of newborn respiratory care. Copyright © 2016 by Daedalus Enterprises.
Measurements of respiratory illness among construction painters.
White, M C; Baker, E L
The prevalence of different measurements of respiratory illness among construction painters was examined and the relation between respiratory illness and employment as a painter assessed in a cross sectional study of current male members of two local affiliates of a large international union of painters. Respiratory illness was measured by questionnaire and spirometry. Longer employment as a painter was associated with increased prevalence of chronic obstructive disease and an interactive eff...
Respiratory disease mortality among uranium miners
Archer, V.E.; Gillam, J.D.; Wagoner, J.K.
A mortality analysis of a group of white and Indian uranium miners was done by a life-table method. A significant excess of respiratory cancer among both whites and Indians was found. Nonmalignant respiratory disease deaths among the whites are approaching cancer in importance as a cause of death, probably as a result of diffuse parenchymal radiation damage. Exposure-response curves for nonsmokers are linear for both respiratory cancer and ''other respiratory disease''. Cigaret smoking elevates and distorts that curve. Light cigaret smokers appear to be most vulnerable to lung parenchymal damage. The predominant histologic cancer among nonsmokers is small-cell undifferentiated, just as it is among cigaret smokers
Bovine respiratory syncytial virus (BRSV): A review
Larsen, Lars Erik
Bovine respiratory syncytial virus (BRSV) infection is the major cause of respiratory disease in calves during the first year of life. The study of the virus has been difficult because of its lability and very poor growth in cell culture. However, during the last decade, the introduction of new...... complex and unpredictable which makes the diagnosis and subsequent therapy very difficult. BRSV is closely related to human respiratory syncytial virus (HRSV) which is an important cause of respiratory disease in young children. In contrast to BRSV, the recent knowledge of HRSV is regularly extensively...
Respiratory monitoring with an acceleration sensor
Ono, Tomohiro; Takegawa, Hideki; Ageishi, Tatsuya; Takashina, Masaaki; Numasaki, Hodaka; Matsumoto, Masao; Teshima, Teruki
Respiratory gating radiotherapy is used to irradiate a local area and to reduce normal tissue toxicity. There are certain methods for the detection of tumor motions, for example, using internal markers or an external respiration signal. However, because some of these respiratory monitoring systems require special or expensive equipment, respiratory monitoring can usually be performed only in limited facilities. In this study, the feasibility of using an acceleration sensor for respiratory monitoring was evaluated. The respiratory motion was represented by means of a platform and measured five times with the iPod touch (registered) at 3, 4 and 5 s periods of five breathing cycles. For these three periods of the reference waveform, the absolute means ± standard deviation (SD) of displacement were 0.45 ± 0.34 mm, 0.33 ± 0.24 mm and 0.31 ± 0.23 mm, respectively. On the other hand, the corresponding absolute means ± SD for the periods were 0.04 ± 0.09 s, 0.04 ± 0.02 s and 0.06 ± 0.04 s. The accuracy of respiratory monitoring using the acceleration sensor was satisfactory in terms of the absolute means ± SD. Using the iPod touch (registered) for respiratory monitoring does not need special equipment and makes respiratory monitoring easier. For these reasons, this system is a viable alternative to other respiratory monitoring systems.
A Quick Reference on Respiratory Alkalosis.
Johnson, Rebecca A
Respiratory alkalosis, or primary hypocapnia, occurs when alveolar ventilation exceeds that required to eliminate the carbon dioxide produced by tissues. Concurrent decreases in Paco 2 , increases in pH, and compensatory decreases in blood HCO 3 - levels are associated with respiratory alkalosis. Respiratory alkalosis can be acute or chronic, with metabolic compensation initially consisting of cellular uptake of HCO 3 - and buffering by intracellular phosphates and proteins. Chronic respiratory alkalosis results in longer-lasting decreases in renal reabsorption of HCO 3 - ; the arterial pH can approach near-normal values. Copyright © 2016 Elsevier Inc. All rights reserved.
Human Respiratory Syncytial Virus and Human Metapneumovirus
Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns
The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide. hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...
Insulin-like growth factor-1 levels in children with Beta-thalassemia minor
Mehran Karimi; Hamdollah Karamifar; Nargrs Sobhani
Objective: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH) / insulin growth factor-1 (IGF-1) axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in he...
Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.
Weigent, Douglas A; Arnold, Robyn E
Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.
Postperfusion lung syndrome: Respiratory mechanics, respiratory indices and biomarkers
Shi-Min Yuan
Full Text Available Postperfusion lung syndrome is rare but lethal. Secondary inflammatory response was the popularly accepted theory for the underlying etiology. Respiratory index (RI and arterial oxygen tension/fractional inspired oxygen can be reliable indices for the diagnosis of this syndrome as X-ray appearance is always insignificant at the early stage of the onset. Evaluations of extravascular lung water content and pulmonary compliance are also helpful in the definite diagnosis. Multiorgan failure and triple acid-base disturbances that might develop secondary to postperfusion lung syndrome are responsible for the poor prognosis and increased mortality rather than postperfusion lung syndrome itself. Mechanical ventilation with low tidal volume (TV and proper positive end-expiratory pressure can be an effective treatment strategy. Use of ulinastatin and propofol may benefit the patients through different mechanisms.
Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus
White, Mitchell R; Crouch, Erika; Vesona, Jenny
of IAV with SP-D in vitro strongly increases neutrophil respiratory burst responses to the virus. Several factors are shown to modify this apparent proinflammatory effect of SP-D. Although multimeric forms of SP-D show dose-dependent augmentation of respiratory burst responses, trimeric, single-arm forms...... of IAV while reducing the respiratory burst response to virus....
Quantitation of respiratory viruses in relation to clinical course in children with acute respiratory tract infections
Jansen, Rogier R.; Schinkel, Janke; dek, Irene; Koekkoek, Sylvie M.; Visser, Caroline E.; de Jong, Menno D.; Molenkamp, Richard; Pajkrt, Dasja
Quantitation of respiratory viruses by PCR could potentially aid in clinical interpretation of PCR results. We conducted a study in children admitted with acute respiratory tract infections to study correlations between the clinical course of illness and semiquantitative detection of 14 respiratory
Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells.
Mahendran Botlagunta
Full Text Available DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region.
Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1{alpha}
Ueda, Masashi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kudo, Takashi; Konishi, Hiroaki; Miyano, Azusa; Ono, Masahiro; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kuge, Yuji [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Mukai, Takahiro [Kyushu University, Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto (Japan)
Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-{sup 123}I-iodobenzoyl)norbiotinamide ({sup 123}I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and {sup 123}I-IBB for rapid imaging of HIF-1-active tumours. Tumour-implanted mice were pretargeted with POS. After 24 h, {sup 125}I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between {sup 125}I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of {sup 125}I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1{alpha} immunohistochemistry. {sup 125}I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from {sup 125}I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of {sup 125}I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of {sup 125}I-IBB was heterogeneous and was significantly correlated with HIF-1{alpha}-positive regions (R=0.58, p<0.0001). POS pretargeting with {sup 123}I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours. (orig.)
Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin-like growth factor-1 resistance in cardiomyocytes.
Patrizia Fabbi
Full Text Available Insulin-like growth factor-1 (IGF-1 promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R. Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3, which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes.Besides inducing apoptosis, concentrations of doxorubicin comparable to those observed in patients after bolus infusion (0.1-1 µM caused a progressive decrease in IGF-1R and increase in IGFBP-3 expression. Exogenous IGF-1 was capable to rescue cardiomyocytes from apoptosis triggered by 0.1 and 0.5 µM, but not 1 µM doxorubicin. The loss of response to IGF-1 was paralleled by a significant reduction in IGF-1 availability and signaling, as assessed by free hormone levels in conditioned media and Akt phosphorylation in cell lysates, respectively. Doxorubicin also dose-dependently induced p53, which is known to repress the transcription of IGF1R and induce that of IGFBP3. Pre-treatment with the p53 inhibitor, pifithrin-α, prevented apoptosis and the changes in IGF-1R and IGFBP-3 elicited by doxorubicin. The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol.Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to doxorubicin-initiated apoptosis. Further studies are needed to confirm these findings in human cardiomyocytes and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity.
Respiratory muscle training in Duchenne muscular dystrophy.
Rodillo, E; Noble-Jamieson, C M; Aber, V; Heckmatt, J Z; Muntoni, F; Dubowitz, V
Twenty two boys with Duchenne muscular dystrophy were entered into a randomised double blind crossover trial to compare respiratory muscle training with a Triflow II inspirometer and 'placebo' training with a mini peak flow meter. Supine posture was associated with significantly impaired lung function, but respiratory muscle training showed no benefit.
Housing and respiratory health at older ages.
Webb, E; Blane, D; de Vries, Robert
A large proportion of the population of England live in substandard housing. Previous research has suggested that poor-quality housing, particularly in terms of cold temperatures, mould, and damp, poses a health risk, particularly for older people. The present study aimed to examine the association between housing conditions and objectively measured respiratory health in a large general population sample of older people in England. Data on housing conditions, respiratory health and relevant covariates were obtained from the second wave of the English Longitudinal Study of Ageing. Multivariate regression methods were used to test the association between contemporary housing conditions and respiratory health while accounting for the potential effect of other factors; including social class, previous life-course housing conditions and childhood respiratory health. Older people who were in fuel poverty or who did not live in a home they owned had significantly worse respiratory health as measured by peak expiratory flow rates. After accounting for covariates, these factors had no effect on any other measures of respiratory health. Self-reported housing problems were not consistently associated with respiratory health. The housing conditions of older people in England, particularly those associated with fuel poverty and living in rented accommodation, may be harmful to some aspects of respiratory health. This has implications for upcoming UK government housing and energy policy decisions.
Respiratory difficulties and breathing disorders in achondroplasia.
Afsharpaiman, S; Saburi, A; Waters, Karen A
Respiratory difficulties and breathing disorders in achondroplasia are thought to underlie the increased risk for sudden infant death and neuropsychological deficits seen in this condition. This review evaluates literature regarding respiratory dysfunctions and their sequelae in patients with achondroplasia. The limited number of prospective studies of respiratory disease in achondroplasia means that observational studies and case series provide a large proportion of the data regarding the spectrum of respiratory diseases in achondroplasia and their treatments. Amongst clinical respiratory problems described, snoring is the commonest observed abnormality, but the reported incidence of obstructive sleep apnoea (OSA) shows wide variance (10% to 75%). Reported treatments of OSA include adenotonsillectomy, the use of CPAP, and surgical improvement of the airway, including mid-face advancement. Otolaryngologic manifestations are also common. Respiratory failure due to small thoracic volumes is reported, but uncommon. Mortality rate at all ages was 2.27 (CI: 1.7-3.0) with age-specific mortality increased at all ages. Sudden death was most common in infants and children. Cardiovascular events are the main cause of mortality in adults. Despite earlier recognition and treatment of respiratory complications of achondroplasia, increased mortality rates and other complications remain high. Future and ongoing evaluation of the prevalence and impact of respiratory disorders, particularly OSA, in achondroplasia is recommended. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
Nanotechnology: Advancing the translational respiratory research
Dua, Kamal; Shukla, Shakti Dhar; de Jesus Andreoli Pinto, Terezinha; Hansbro, Philip Michael
Considering the various limitations associated with the conventional dosage forms, nanotechnology is gaining increased attention in drug delivery particularly in respiratory medicine and research because of its advantages like targeting effects, improved pharmacotherapy, and patient compliance. This paper provides a quick snapshot about the recent trends and applications of nanotechnology to various translational and formulation scientists working on various respiratory diseases, which can he...
Fabry disease, respiratory symptoms, and airway limitation
Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke
. The remaining 27 articles were relevant for this review. RESULTS: The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory...
Respiratory bacterial infections in cystic fibrosis
Ciofu, Oana; Hansen, Christine R; Høiby, Niels
PURPOSE OF REVIEW: Bacterial respiratory infections are the main cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa remains the main pathogen in adults, but other Gram-negative bacteria such as Achromobacter xylosoxidans and Stenotrophomonas maltophilia...... respiratory tract (nasal sampling) should be investigated and both infection sites should be treated....
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)
Kvisgaard, Lise Kirstine
This PhD thesis presents the diversity of Porcine Reproductive and Respiratory Syndrome viruses (PRRSV) circulating in the Danish pig population. PRRS is a disease in pigs caused by the PRRS virus resulting in reproductive failures in sows and gilts and respiratory diseases in pigs . Due to genetic...
29 CFR 1917.92 - Respiratory protection.
... 29 Labor 7 2010-07-01 2010-07-01 false Respiratory protection. 1917.92 Section 1917.92 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Personal Protection § 1917.92 Respiratory protection. (See § 1917.1(a)(2)(x...
29 CFR 1926.103 - Respiratory protection.
... 29 Labor 8 2010-07-01 2010-07-01 false Respiratory protection. 1926.103 Section 1926.103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1926.103 Respiratory protection. Note: The requirements applicable to construction work under this...
29 CFR 1918.102 - Respiratory protection.
... 29 Labor 7 2010-07-01 2010-07-01 false Respiratory protection. 1918.102 Section 1918.102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Respiratory protection. (See § 1918.1(b)(8)). [65 FR 40946, June 30, 2000] ...
Perceived Competence and Comfort in Respiratory Protection
Burgel, Barbara J.; Novak, Debra; Burns, Candace M.; Byrd, Annette; Carpenter, Holly; Gruden, MaryAnn; Lachat, Ann; Taormina, Deborah
In response to the Institute of Medicine (2011) report Occupational Health Nurses and Respiratory Protection: Improving Education and Training, a nationwide survey was conducted in May 2012 to assess occupational health nurses' educational preparation, roles, responsibilities, and training needs in respiratory protection. More than 2,000 occupational health nurses responded; 83% perceived themselves as competent, proficient, or expert in respiratory protection, reporting moderate comfort with 12 respiratory program elements. If occupational health nurses had primary responsibility for the respiratory protection program, they were more likely to perceive higher competence and more comfort in respiratory protection, after controlling for occupational health nursing experience, highest education, occupational health nursing certification, industry sector, Association of Occupational Health Professionals in Healthcare membership, taking a National Institute for Occupational Safety and Health spirometry course in the prior 5 years, and perceiving a positive safety culture at work. These survey results document high perceived competence and comfort in respiratory protection. These findings support the development of targeted educational programs and interprofessional competencies for respiratory protection. PMID:23429638
Air pollution and respiratory illness
Indra, G. [DIET, Uttamasolapuram, Salem (India)
This presentation provides an overview of air pollution and impacts on public health. It provides a definition of pollution according to the Oxford English dictionary and categorizes the different types of pollution according to air, water, land and noise. It discusses air pollution and its pollutants (gaseous and particulate pollutants) as well as the diameter of the pollutant (dust, smoke, and gas). The paper also illustrates the formation of acid rain and discusses the amount of pollutants in the atmosphere per year. It presents occupational diseases, discusses radio active pollutants, respiratory illnesses as well as pollution prevention and control. The paper concluded that more research is needed to obtain information on ways to reduce the quantity of pollutants being discharged from special processes. 3 refs., 2 figs., 2 tabs.
Perioperative modifications of respiratory function.
Duggan, Michelle
Postoperative pulmonary complications contribute considerably to morbidity and mortality, especially after major thoracic or abdominal surgery. Clinically relevant pulmonary complications include the exacerbation of underlying chronic lung disease, bronchospasm, atelectasis, pneumonia and respiratory failure with prolonged mechanical ventilation. Risk factors for postoperative pulmonary complications include patient-related risk factors (e.g., chronic obstructive pulmonary disease (COPD), tobacco smoking and increasing age) as well as procedure-related risk factors (e.g., site of surgery, duration of surgery and general vs. regional anaesthesia). Careful history taking and a thorough physical examination may be the most sensitive ways to identify at-risk patients. Pulmonary function tests are not suitable as a general screen to assess risk of postoperative pulmonary complications. Strategies to reduce the risk of postoperative pulmonary complications include smoking cessation, inspiratory muscle training, optimising nutritional status and intra-operative strategies. Postoperative care should include lung expansion manoeuvres and adequate pain control.
The respiratory system in equations
Maury, Bertrand
The book proposes an introduction to the mathematical modeling of the respiratory system. A detailed introduction on the physiological aspects makes it accessible to a large audience without any prior knowledge on the lung. Different levels of description are proposed, from the lumped models with a small number of parameters (Ordinary Differential Equations), up to infinite dimensional models based on Partial Differential Equations. Besides these two types of differential equations, two chapters are dedicated to resistive networks, and to the way they can be used to investigate the dependence of the resistance of the lung upon geometrical characteristics. The theoretical analysis of the various models is provided, together with state-of-the-art techniques to compute approximate solutions, allowing comparisons with experimental measurements. The book contains several exercises, most of which are accessible to advanced undergraduate students.
Prevention of Nosocomial Respiratory Infections
N. A. Karpun
Full Text Available Objective: to evaluate the efficiency of an extended package of preventive measures on the incidence of nosocomial respiratory infections in surgical patients at an intensive care unit (ICU. Subjects and methods. The study included 809 patients aged 35 to 80 years. A study group comprised 494 patients in whom an extended package of preventive measures was implemented during 7 months (March-September. A control group consisted of 315 patients treated in 2004 in the same period of time (March-September. The groups were stratified by age, gender, underlying diseases, and APACHE-2 and SOFA scores. The extended package of anti-infectious measures involved a high air purification in ICUs («Flow-M» technology, routine use of ventilatory filters, closed aspiration systems with a built-in antibacterial filter under artificial ventilation for over 2 days. Results. The proposed technologies could reduce the frequency of tracheobronchitis and ventilator-associated pneumonias in the groups of patients at high risk for nosocomial infections substantially (by more than twice. Conclusion. The findings have led to the conclusion that the extended package of preventive measures is effective in preventing respiratory infections in ICU patients. Of special note is the proper prevention of upper airway contamination with pathogenic microorganisms, by employing the closed aspiration systems with a built-in antibacterial filter. The routine use of high-tech consumables in the intensive care of surgical patients causes a considerable decrease in the incidence of nosocomial pneumonia, ventilator-associated pneumonia, and purulent tracheobronchitis and a reduction in the number of microbiological studies. Key words: ventilator-associated pneumonia, prevention of nosocomial infections, closed aspiration system.
Stem cells and respiratory diseases
Soraia Carvalho Abreu
Full Text Available Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases.As células-tronco têm uma infinidade de implicações clínicas no pulmão. Este artigo é uma revisão crítica que inclui estudos clínicos e experimentais advindos do banco de dados do MEDLINE e SciElo nos últimos 10 anos, onde foram destacados os efeitos da terapia celular na síndrome do desconforto respiratório agudo ou doenças mais crônicas, como fibrose pulmonar e enfisema. Apesar de muitos estudos demonstrarem os efeitos benéficos das células-tronco no desenvolvimento, reparo e remodelamento pulmonar; algumas questões ainda precisam ser respondidas para um melhor entendimento dos mecanismos que controlam a divisão celular e diferenciação, permitindo o uso da terapia celular nas doenças respiratórias.
Respiratory neuroplasticity - Overview, significance and future directions.
Fuller, David D; Mitchell, Gordon S
Neuroplasticity is an important property of the neural system controlling breathing. However, our appreciation for its importance is still relatively new, and we have much to learn concerning different forms of plasticity, their underlying mechanisms, and their biological and clinical significance. In this brief review, we discuss several well-studied models of respiratory plasticity, including plasticity initiated by inactivity in the respiratory system, intermittent and sustained hypoxia, and traumatic injury to the spinal cord. Other aspects of respiratory plasticity are considered in other contributions to this special edition of Experimental Neurology on respiratory plasticity. Finally, we conclude with discussions concerning the biological and clinical significance of respiratory motor plasticity, and areas in need of future research effort. Copyright © 2016. Published by Elsevier Inc.
The measurement of insulin-like growth factor 1 in sheep plasma.
Bruce, L A; Atkinson, T; Hutchinson, J S; Shakespear, R A; MacRae, J C
A method is described for the radioimmunoassay (RIA) of insulin-like growth factor 1 (IGF-1) in neutralised formic acid-ethanol extracts of sheep plasma. The ability of the acid-ethanol pretreatment to remove the IGF-1 binding proteins (BPs), which interfere in the assay has been examined. Comparative plasma IGF-1 concentrations determined by the method correlated closely (P less than 0.001) with corresponding values where BPs were removed by acid gel filtration. The method has been applied to studies in which sheep were given exogenous growth hormone and indicated that plasma IGF-1 levels respond rapidly to the onset and termination of treatment.
Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation
Jakobsson, Magnus E; Małecki, Jędrzej; Falnes, Pål Ø
Lysine methylation is a frequent post-translational protein modification, which has been intensively studied in the case of histone proteins. Lysine methylations are also found on many non-histone proteins, and one prominent example is eukaryotic elongation factor 1 alpha (eEF1A). Besides its...... essential role in the protein synthesis machinery, a number of non-canonical functions have also been described for eEF1A, such as regulation of the actin cytoskeleton and the promotion of viral replication. The functional significance of the extensive lysine methylations on eEF1A, as well as the identity...
Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans
Heintz, Caroline; Doktor, Thomas K; Lanjuin, Anne
via splicing factor 1 (SFA-1; the C. elegans homologue of SF1, also known as branchpoint binding protein, BBP). We show that SFA-1 is specifically required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also...... homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or subjected to dietary restriction, we find defects in global pre-mRNA splicing with age that are reduced by dietary restriction...
Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells
Li, Yangxin; Yu, XiYong; Lin, ShuGuang; Li, XiaoHong; Zhang, Saidan; Song, Yao-Hua
Mesenchymal stem cells (MSCs) are attractive candidates for cell based therapies. However, the mechanisms responsible for stem cell migration and homing after transplantation remain unknown. It has been shown that insulin-like growth factor-1 (IGF-1) induces proliferation and migration of some cell types, but its effects on stem cells have not been investigated. We isolated and cultured MSC from rat bone marrow, and found that IGF-1 increased the expression levels of the chemokine receptor CXCR4 (receptor for stromal cell-derived factor-1, SDF-1). Moreover, IGF-1 markedly increased the migratory response of MSC to SDF-1. The IGF-1-induced increase in MSC migration in response to SDF-1 was attenuated by PI3 kinase inhibitor (LY294002 and wortmannin) but not by mitogen-activated protein/ERK kinase inhibitor PD98059. Our data indicate that IGF-1 increases MSC migratory responses via CXCR4 chemokine receptor signaling which is PI3/Akt dependent. These findings provide a new paradigm for biological effects of IGF-1 on MSC and have implications for the development of novel stem cell therapeutic strategies
Management of respiratory symptoms in ALS.
Hardiman, Orla
Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
Management of respiratory symptoms in ALS.
Hardiman, Orla
Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
SMART phones and the acute respiratory patient.
Gleeson, L
Definition of Respiratory Failure using PaO2 alone is confounded when patients are commenced on oxygen therapy prior to arterial blood gas (ABG) measurement. Furthermore, classification of Respiratory Failure as Type 1 or Type 2 using PaCO2 alone can give an inaccurate account of events as both types can co-exist. 100 consecutive presentations of acute respiratory distress were assessed initially using PaO2, and subsequently PaO2\\/FiO2 ratio, to diagnose Respiratory Failure. Respiratory Failure cases were classified as Type 1 or Type 2 initially using PaCO2, and subsequently alveolar-arterial (A-a) gradient. Any resultant change in management was documented. Of 100 presentations, an additional 16 cases were diagnosed as Respiratory Failure using PaO2\\/FiO2 ratio in place of PaO2 alone (p = 0.0338). Of 57 cases of Respiratory Failure, 22 cases classified as Type 2 using PaCO2 alone were reclassified as Type 1 using A-a gradient (p < 0.001). Of these 22 cases, management changed in 18.
Human Respiratory Syncytial Virus and Human Metapneumovirus
Luciana Helena Antoniassi da Silva
Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide. hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms. The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.
Respiratory Depression Caused by Heroin Use
Kadir Hakan Cansiz
Full Text Available Summary Heroin is a semisynthetic narcotic analgesic and heroin abuse is common due to its pleasure-inducing effect. For the last 30 years heroin abuse has become an important worldwide public health problem. Heroin can be administered in many different ways as preferred. Heroin affects many systems including respiratory system, cardiovascular system and particulary the central nervous system. Overdose use of heroin intravenously can be fatal due to respiratory depression. In this letter, we wanted to engage attention to respiratory depression caused by heroin abuse and potential benefits of using naloxone. [TAF Prev Med Bull 2012; 11(2.000: 248-250
Evaluation and treatment of respiratory alkalosis.
Palmer, Biff F
Respiratory alkalosis is the most frequent acid-base disturbance encountered in clinical practice. This is particularly true in critically ill patients, for whom the degree of hypocapnia directly correlates with adverse outcomes. Although this acid-base disturbance often is considered benign, evidence suggests that the alkalemia of primary hypocapnia can cause clinically significant decreases in tissue oxygen delivery. Mild respiratory alkalosis often serves as a marker of an underlying disease and may not require therapeutic intervention. In contrast, severe respiratory alkalosis should be approached with a sense of urgency and be aggressively corrected. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.
Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F
To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.
Chaotic dynamics of respiratory sounds
Ahlstrom, C.; Johansson, A.; Hult, P.; Ask, P.
There is a growing interest in nonlinear analysis of respiratory sounds (RS), but little has been done to justify the use of nonlinear tools on such data. The aim of this paper is to investigate the stationarity, linearity and chaotic dynamics of recorded RS. Two independent data sets from 8 + 8 healthy subjects were recorded and investigated. The first set consisted of lung sounds (LS) recorded with an electronic stethoscope and the other of tracheal sounds (TS) recorded with a contact accelerometer. Recurrence plot analysis revealed that both LS and TS are quasistationary, with the parts corresponding to inspiratory and expiratory flow plateaus being stationary. Surrogate data tests could not provide statistically sufficient evidence regarding the nonlinearity of the data. The null hypothesis could not be rejected in 4 out of 32 LS cases and in 15 out of 32 TS cases. However, the Lyapunov spectra, the correlation dimension (D 2 ) and the Kaplan-Yorke dimension (D KY ) all indicate chaotic behavior. The Lyapunov analysis showed that the sum of the exponents was negative in all cases and that the largest exponent was found to be positive. The results are partly ambiguous, but provide some evidence of chaotic dynamics of RS, both concerning LS and TS. The results motivate continuous use of nonlinear tools for analysing RS data
Chaotic dynamics of respiratory sounds
Ahlstrom, C. [Department of Biomedical Engineering, Linkoepings Universitet, IMT/LIU, Universitetssjukhuset, S-58185 Linkoeping (Sweden) and Biomedical Engineering, Orebro University Hospital, S-70185 Orebro (Sweden)]. E-mail: firstname.lastname@example.com; Johansson, A. [Department of Biomedical Engineering, Linkoepings Universitet, IMT/LIU, Universitetssjukhuset, S-58185 Linkoeping (Sweden); Hult, P. [Department of Biomedical Engineering, Linkoepings Universitet, IMT/LIU, Universitetssjukhuset, S-58185 Linkoeping (Sweden); Biomedical Engineering, Orebro University Hospital, S-70185 Orebro (Sweden); Ask, P. [Department of Biomedical Engineering, Linkoepings Universitet, IMT/LIU, Universitetssjukhuset, S-58185 Linkoeping (Sweden); Biomedical Engineering, Orebro University Hospital, S-70185 Orebro (Sweden)
There is a growing interest in nonlinear analysis of respiratory sounds (RS), but little has been done to justify the use of nonlinear tools on such data. The aim of this paper is to investigate the stationarity, linearity and chaotic dynamics of recorded RS. Two independent data sets from 8 + 8 healthy subjects were recorded and investigated. The first set consisted of lung sounds (LS) recorded with an electronic stethoscope and the other of tracheal sounds (TS) recorded with a contact accelerometer. Recurrence plot analysis revealed that both LS and TS are quasistationary, with the parts corresponding to inspiratory and expiratory flow plateaus being stationary. Surrogate data tests could not provide statistically sufficient evidence regarding the nonlinearity of the data. The null hypothesis could not be rejected in 4 out of 32 LS cases and in 15 out of 32 TS cases. However, the Lyapunov spectra, the correlation dimension (D {sub 2}) and the Kaplan-Yorke dimension (D {sub KY}) all indicate chaotic behavior. The Lyapunov analysis showed that the sum of the exponents was negative in all cases and that the largest exponent was found to be positive. The results are partly ambiguous, but provide some evidence of chaotic dynamics of RS, both concerning LS and TS. The results motivate continuous use of nonlinear tools for analysing RS data.
Metformin-associated respiratory alkalosis.
Bryant, Sean M; Cumpston, Kirk; Lipsky, Martin S; Patel, Nirali; Leikin, Jerrold B
We present an 84-year-old man with a history of chronic obstructive pulmonary disease, type 2 diabetes, hypertension, glaucoma, and bladder cancer who presented to the emergency department after the police found him disoriented and confused. Metformin therapy began 3 days before, and he denied any overdose or suicidal ideation. Other daily medications included glipizide, fluticasone, prednisone, aspirin, furosemide, insulin, and potassium supplements. In the emergency department, his vital signs were significant for hypertension (168/90), tachycardia (120 bpm), and Kussmaul respirations at 24 breaths per minute. Oxygen saturation was 99% on room air, and a fingerstick glucose was 307 mg/dL. He was disoriented to time and answered questions slowly. Metformin was discontinued, and by day 3, the patient's vital signs and laboratory test results normalized. He has been asymptomatic at subsequent follow-up visits. Metformin-associated lactic acidosis is a well-known phenomenon. Respiratory alkalosis may be an early adverse event induced by metformin prior to the development of lactic acidosis.
Respiratory signal analysis of liver cancer patients with respiratory-gated radiation therapy
Kang, Dong Im; Jung, Sang Hoon; Kim, Chul Jong; Park, Hee Chul; Choi, Byung Ki
External markers respiratory movement measuring device (RPM; Real-time Position Management, Varian Medical System, USA) Liver Cancer Radiation Therapy Respiratory gated with respiratory signal with irradiation time and the actual research by analyzing the respiratory phase with the breathing motion measurement device respiratory tuning evaluate the accuracy of radiation therapy May-September 2014 Novalis Tx. (Varian Medical System, USA) and liver cancer radiotherapy using respiratory gated RPM (Duty Cycle 20%, Gating window 40%-60%) of 16 patients who underwent total when recording the analyzed respiratory movement. After the breathing motion of the external markers recorded on the RPM was reconstructed by breathing through the acts phase analysis, for Beam-on Time and Duty Cycle recorded by using the reconstructed phase breathing breathing with RPM gated the prediction accuracy of the radiation treatment analysis and analyzed the correlation between prediction accuracy and Duty Cycle in accordance with the reproducibility of the respiratory movement. Treatment of 16 patients with respiratory cycle during the actual treatment plan was analyzed with an average difference -0.03 seconds (range -0.50 seconds to 0.09 seconds) could not be confirmed statistically significant difference between the two breathing (p = 0.472). The average respiratory period when treatment is 4.02 sec (0.71 sec), the average value of the respiratory cycle of the treatment was characterized by a standard deviation 7.43% (range 2.57 to 19.20%). Duty Cycle is that the actual average 16.05% (range 13.78 to 17.41%), average 56.05 got through the acts of the show and then analyzed% (range 39.23 to 75.10%) is planned in respiratory research phase (40% to 60%) in was confirmed. The investigation on the correlation between the ratio Duty Cycle and planned respiratory phase and the standard deviation of the respiratory cycle was analyzed in each -0.156 (p = 0.282) and -0.385 (p = 0.070). This study is
Effect of transoral tracheal wash on respiratory mechanics in dogs with respiratory disease.
Vaught, Meghan E; Rozanski, Elizabeth A; deLaforcade, Armelle M
The purpose of this study was to determine the impact of a transoral tracheal wash (TOTW) on respiratory mechanics in dogs and to describe the use of a critical care ventilator (CCV) to determine respiratory mechanics. Fourteen client-owned dogs with respiratory diseases were enrolled. Respiratory mechanics, including static compliance (C stat ) and static resistance (R stat ), were determined before and after TOTW. Pre- and post-wash results were compared, with a P -value of mechanics, as observed by a reduction in C stat , presumably due to airway flooding and collapse. While no long-lasting effects were noted in these clinical patients, this effect should be considered when performing TOTW on dogs with respiratory diseases. Respiratory mechanics testing using a CCV was feasible and may be a useful clinical testing approach.
X-Ray structure and biophysical properties of rabbit fibroblast growth factor 1
Lee, Jihun; Blaber, Sachiko I.; Irsigler, Andre; Aspinwall, Eric; Blaber, Michael; (FSU)
The rabbit is an important and de facto animal model in the study of ischemic disease and angiogenic therapy. Additionally, fibroblast growth factor 1 (FGF-1) is emerging as one of the most important growth factors for novel pro-angiogenic and pro-arteriogenic therapy. However, despite its significance, the fundamental biophysical properties of rabbit FGF-1, including its X-ray structure, have never been reported. Here, the cloning, crystallization, X-ray structure and determination of the biophysical properties of rabbit FGF-1 are described. The X-ray structure shows that the amino-acid differences between human and rabbit FGF-1 are solvent-exposed and therefore potentially immunogenic, while the biophysical studies identify differences in thermostability and receptor-binding affinity that distinguish rabbit FGF-1 from human FGF-1.
Napsin A and Thyroid Transcription Factor-1-Positive Cerebellar Tumor with Epidermal Growth Factor Receptor Mutation
Taiji Kuwata
Full Text Available We present a very rare case of cerebellar metastasis of unknown origin, in which a primary lung adenocarcinoma was diagnosed by pathological examination of a cerebellar metastatic tumor, using immunohistochemical markers and epidermal growth factor receptor (EGFR mutation of primary lung cancer. A 69-year-old woman was admitted to our hospital because of a hemorrhagic cerebellar tumor and multiple small brain tumors. She underwent cerebellar tumor resection. On pathological examination, the tumor was diagnosed as adenocarcinoma. However, the primary tumor site was unidentifiable even with several imaging inspections. On immunohistochemical analysis, the resected tumor was positive for napsin A and thyroid transcription factor-1. In addition, an EGFR mutation was detected in the tumor. Therefore, primary lung cancer was diagnosed and the patient was started on gefitinib (250 mg/day therapy.
Serum insulin-like growth factor 1 in the aging horse
Lygren, Tone; Hansen, Sanni; Langberg, Henning
BACKGROUND: Insulin-like growth factor 1 (IGF-1) has important roles in anabolic processes in the musculoskeletal system and has been reported to decrease with age in both people and horses. OBJECTIVES: The objective of this study was to determine serum IGF-1 levels in the aging horse from early...... was found between serum IGF-1 levels and age in the cross-sectional study. In the longitudinal study, a latent variable model fitted to the data revealed that horses in general experienced a 5.2% increase of serum IGF-1 levels over a 5-year period, but horses crossing a change point around 9 years of age...... between the 2 samples experienced an 11.0% decrease. CONCLUSIONS: In this study, there was no evidence for aging being a factor in changes of IGF-1 levels in an adult and old horse population....
Undifferentiated embryonic cell transcription factor 1 regulates ESC chromatin organization and gene expression
Kooistra, Susanne M; van den Boom, Vincent; Thummer, Rajkumar P
Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES...... cell chromatin structure. Using chromatin immunoprecipitation-on-chip analysis, we identified >1,700 UTF1 target genes that significantly overlap with previously identified Nanog, Oct4, Klf-4, c-Myc, and Rex1 targets. Gene expression profiling showed that UTF1 knock down results in increased expression...... of a large set of genes, including a significant number of UTF1 targets. UTF1 knock down (KD) ES cells are, irrespective of the increased expression of several self-renewal genes, Leukemia inhibitory factor (LIF) dependent. However, UTF1 KD ES cells are perturbed in their differentiation in response...
Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.
El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun
Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.
Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.
Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki
Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.
Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.
Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen
The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.
Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.
Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D
Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.
Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum.
Gupta, Mohit Kumar; Agarawal, Meetu; Banu, Khadija; Reddy, K Sony; Gaur, Deepak; Dhar, Suman Kumar
Nucleosome assembly in P. falciparum could be the key process in maintaining its genomic integrity as DNA replicates more than once per cell cycle during several stages of its life cycle. Here, we report the functional characterization of P. falciparum chromatin assembly factor 1 (CAF1), which interacts with several proteins namely PfCAF2, Histones, PfHP1 and others. Consistent with the above findings, we demonstrate the presence of PfCAF1 at the telomeric repeat regions, central and subtelomeric var genes of multiple var gene family along with PfHP1. Further, we report the upregulation of PfCAF1 after treatment with genotoxic agents like MMS and HU. Together, these findings establish role of PfCAF1 in heterochromatin maintenance and as histone chaperone in nucleosome assembly and DNA damage repair. Copyright © 2017 Elsevier Inc. All rights reserved.
Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties.
Krastel, Philipp; Roggo, Silvio; Schirle, Markus; Ross, Nathan T; Perruccio, Francesca; Aspesi, Peter; Aust, Thomas; Buntin, Kathrin; Estoppey, David; Liechty, Brigitta; Mapa, Felipa; Memmert, Klaus; Miller, Howard; Pan, Xuewen; Riedl, Ralph; Thibaut, Christian; Thomas, Jason; Wagner, Trixie; Weber, Eric; Xie, Xiaobing; Schmitt, Esther K; Hoepfner, Dominic
Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF-1α) as the primary target for this compound class. Nannocystin A (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti-cancer compound didemnin B on EF-1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Retinopathy of prematurity and serum level of insulin-like growth factor-1.
Banjac, Lidija; Bokan, Vesna
The aim of our study was to measure and compare serum insulin-like growth factor-1 (IGF-1) levels at postmenstrual age of 33 weeks between preterm infants with and without retinopathy of prematurity (ROP). ROP occurs in two phases. Low serum levels of IGF-1 during ROP phase 1 have been found to correlate with the severity of ROP. ROP phase 2 begins around postmenstrual week 33. We conducted a prospective cohort study to measure serum IGF-1 levels in premature infants at postmenstrual age of 33 weeks. The study included all premature infants (N = 74), gestational age large controlled study with repeated measurement of IGF-1 level in the neonatal period is needed to confirm that restoration of IGF-I level occurs in ROP phase 2, i.e. that the low level of IGF-1 is only a feature of ROP phase 1.
Insulin like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation
Zhang, Hongbin; Nøhr, Jane; Jensen, Charlotte Harken
that forced expression of the soluble form, FA1, or full-length Pref-1 did not inhibit adipocyte differentiation of 3T3-L1 cells when differentiation was induced by standard treatment with methylisobutylxanthine, dexamethasone, and high concentrations of insulin. However, forced expression of either form...... of Pref-1/FA1 in 3T3-L1 or 3T3-F442A cells inhibited adipocyte differentiation when insulin or insulin-like growth factor-1 (IGF-1) was omitted from the differentiation mixture. We demonstrate that the level of the mature form of the IGF-1 receptor is reduced and that IGF-1-dependent activation of p42/p44...... mitogen-activated protein kinases (MAPKs) is compromised in preadipocytes with forced expression of Pref-1. This is accompanied by suppression of clonal expansion and terminal differentiation. Accordingly, supplementation with insulin or IGF-1 rescued p42/p44 MAPK activation, clonal expansion...
FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs
Schwartz, Carol J.E.; Sampson, Heidi M.; Hlousek, Daniela; Percival-Smith, Anthony; Copeland, John W.R.; Simmonds, Andrew J.; Krause, Henry M.
To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We also show that FTZ contains an AF2-interacting nuclear receptor box, the first to be found in a homeodomain protein. Both interaction motifs are shown to be necessary for physical interactions in vitro and for functional interactions in developing embryos. These unexpected findings have important implications for the conserved homologs of the two proteins. PMID:11157757
Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation
Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens
Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...
Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma
Liu NQ
Full Text Available Naiqing Liu,1,2,* Jingyu Zhang,2,* Shuxiang Sun,2 Liguang Yang,2 Zhongjin Zhou,2 Qinli Sun,2 Jun Niu11Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, People's Republic of China; 2Department of General Surgery, Yishui Central Hospital, Linyi, People's Republic of China*These authors contributed equally to this workBackground: The clinical significance of fibroblast growth factor 1 (FGF1 has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored.Patients and methods: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan–Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma.Results: Higher FGF1 expression rate is 56.7% (101/178 in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001. Expression of FGF1 is significantly associated with lymph node invasion (P<0.001, distant metastasis (P=0.013, and differentiation (P=0.015. Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021, and can be identified to be an independent unfavorable prognostic factor (P=0.004.Conclusion: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.Keywords: fibroblast growth factor 1, gastric adenocarcinoma, prognosis, biomarker, lymph node, gene fusion
Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells
Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko
Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.
Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells
Matsukura, Hiroshi, E-mail: email@example.com [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: firstname.lastname@example.com [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)
Highlights: {yields} Genistein (GEN) is a phytoestrogen found in soy products. {yields} GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. {yields} GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. {yields} A high-resolution melting assay was used to screen for epigenetic change. {yields} We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.
Effects of global warming on respiratory diseases
Abe Olugbenga
and tuberculosis), parasitic lung diseases, chronic obstructive pulmonary disease ... Methods: A literature search on global warming and respiratory diseases was carried out through the internet .... (COPD) The main factor to consider here is.
Respiratory muscle training for multiple sclerosis
Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.
Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and
Severe acute respiratory syndrome: lessons and uncertainties.
Kullberg, B.J.; Voss, A.
The outbreak of severe acute respiratory syndrome (SARS) has produced scientific and epidemiological discoveries with unprecedented speed, and this information has been spread instantaneously to the global health community through the internet. Within a few weeks, the coronavirus associated with
Respiratory function in facioscapulohumeral muscular dystrophy 1
Wohlgemuth, M.; Horlings, G.C.; Kooi, E.L. van der; Gilhuis, H.J.; Hendriks, J.C.M.; Maarel, S.M. van der; Engelen, B.G.M. van; Heijdra, Y.F.; Padberg, G.W.A.M.
To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory
Respiratory Health Effects of Passive Smoking
This report concludes that exposure to environmental tobacco smoke (ETS), commonly known as secondhand smoke, is responsible for approximately 3,000 lung cancer deaths each year in nonsmoking adults and impairs respiratory health.
Investigations of respiratory control systems simulation
Gallagher, R. R.
The Grodins' respiratory control model was investigated and it was determined that the following modifications were necessary before the model would be adaptable for current research efforts: (1) the controller equation must be modified to allow for integration of the respiratory system model with other physiological systems; (2) the system must be more closely correlated to the salient physiological functionings; (3) the respiratory frequency and the heart rate should be expanded to illustrate other physiological relationships and dependencies; and (4) the model should be adapted to particular individuals through a better defined set of initial parameter values in addition to relating these parameter values to the desired environmental conditions. Several of Milhorn's respiratory control models were also investigated in hopes of using some of their features as modifications for Grodins' model.
Automated respiratory support in newborn infants.
Claure, Nelson; Bancalari, Eduardo
A considerable proportion of premature infants requires mechanical ventilatory support and supplemental oxygen. Due to their immaturity, exposure to these forms of respiratory support contributes to the development of lung injury, oxidative stress and abnormal retinal development. These conditions are associated with poor long-term respiratory and neurological outcome. Mechanically ventilated preterm infants present with frequent fluctuations in ventilation and gas exchange. Currently available ventilatory modes and manual adjustment to the ventilator or supplemental oxygen cannot effectively adapt to these recurrent fluctuations. Moreover, the respiratory support often exceeds the infant's real needs. Techniques that adapt the mechanical ventilatory support and supplemental oxygen to the changing needs of preterm infants are being developed in order to improve stability of gas exchange, to minimise respiratory support and to reduce personnel workload. This article describes the preliminary evidence on the application of these new techniques in preterm infants and animal models.
Respiratory Disorders Among Workers in Slaughterhouses
Abbasali Kasaeinasab
Conclusion: The prevalence of respiratory disorders was significantly higher among workers in slaughterhouses. Thus, the significant reduction in the percentage predicted lung function among workers in slaughterhouses might be associated with exposure to bioaerosols in their work environment.
M M Karambin
Full Text Available "nThere is a lack of large, prospective epidemiologic studies concerning acute lung injury (ALI and acute respiratory distress syndrome (ARDS in pediatric population. To determine the different causes of respiratory distress in children, we prepared a retrospective study and included the whole 567 children with respiratory distress referred to 17-Shahrivar Hospital, Rasht, Guilan. Using their medical files, data including age, sex, and causes of respiratory distress were collected. SPSS 13.0 (statistical software applied for statistical analysis. Pneumonia, asthma, and croup were the major causes of ARDS in children with a rate of 38.4, 19.04, and 16.5 percent, respectively. It seems that infectious factors are at the top of the list of ARDS causing factors which can be helpful to approach and manage such patients. We suggest vaccinating these at risk groups against common infectious factors such as H. Influenza and RSV which can cause either pneumonia or inducing asthma.
Learn about Respiratory Syncytial Virus (RSV)
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Effects of air pollution on respiratory health
Hasan Bayram
In conclusion, air pollutants can induce respiratory mortality and morbidity by leading to airway and lung inflammation and impairing the airway defence system against noxious agents and microorganisms such as mycobacteria TB.
LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells.
Sato, Mariko; Hirose, Katsumi; Kashiwakura, Ikuo; Aoki, Masahiko; Kawaguchi, Hideo; Hatayama, Yoshiomi; Akimoto, Hiroyoshi; Narita, Yuichiro; Takai, Yoshihiro
Hypoxia‑inducible factor 1 (HIF‑1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF‑1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF‑1α. A clear anti‑tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF‑1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF‑1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel‑Lindau protein. In addition, at this concentration, LW6 induced hypoxia‑selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6‑treated hypoxic A549 cells and LW6 induced a hypoxia‑selective increase of mitochondrial O2•‑. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.
Treatment of respiratory failure in COPD
Stephan Budweiser
Full Text Available Stephan Budweiser1, Rudolf A Jörres2, Michael Pfeifer1,31Center for Pneumology, Hospital Donaustauf, Donaustauf, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany; 3Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, GermanyAbstract: Patients with advanced COPD and acute or chronic respiratory failure are at high risk for death. Beyond pharmacological treatment, supplemental oxygen and mechanical ventilation are major treatment options. This review describes the physiological concepts underlying respiratory failure and its therapy, as well as important treatment outcomes. The rationale for the controlled supply of oxygen in acute hypoxic respiratory failure is undisputed. There is also a clear survival benefit from long-term oxygen therapy in patients with chronic hypoxia, while in mild, nocturnal, or exercise-induced hypoxemia such long-term benefits appear questionable. Furthermore, much evidence supports the use of non-invasive positive pressure ventilation in acute hypercapnic respiratory failure. It application reduces intubation and mortality rates, and the duration of intensive care unit or hospital stays, particularly in the presence of mild to moderate respiratory acidosis. COPD with chronic hypercapnic respiratory failure became a major indication for domiciliary mechanical ventilation, based on pathophysiological reasoning and on data regarding symptoms and quality of life. Still, however, its relevance for long-term survival has to be substantiated in prospective controlled studies. Such studies might preferentially recruit patients with repeated hypercapnic decompensation or a high risk for death, while ensuring effective ventilation and the patients' adherence to therapy.Keywords: respiratory failure, COPD, mechanical ventilation, non-invasive ventilation long-term oxygen therapy, chronic
Obesity and common respiratory diseases in children.
Xanthopoulos, Melissa; Tapia, Ignacio E
Obesity has become an important public health problem worldwide that disproportionally affects the underserved. Obesity has been associated with many diseases and unfortunately has not spared the respiratory system. Specifically, the prevalence of common respiratory problems, such as asthma and obstructive sleep apnoea, is higher in obese children. Further, the treatment outcomes of these frequent conditions is also worse in obese children compared to lean controls. Copyright © 2016 Elsevier Ltd. All rights reserved.
Acute hypoxemic respiratory failure in immunocompromised patients
Azoulay, Elie; Pickkers, Peter; Soares, Marcio
BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational.......54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2
[Immunomodulators in Therapy of Respiratory Infections].
Isakov, V A; Isakov, D V
Viral infections provoke dysbalance in the interferon system and inhibition of the cellular and phagocytic responses of the host. Long-term persistence of pathogenic viruses and bacteria induce atopy and could aggravate chronic respiratory diseases. The up-to-date classification of immunomodulators is described. High efficacy of interferon inductors, such as cycloferon and some others as auxiliary means in therapy or prophylaxis (immunorehabilitation) of viral respiratory infections in adults and children was shown.
Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection
von Linstow, Marie-Louise; Henrik Larsen, Hans; Koch, Anders
The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p respiratory support. hMPV is present in young...
Incidence of respiratory viruses in Peruvian children with acute respiratory infections.
del Valle Mendoza, Juana; Cornejo-Tapia, Angela; Weilg, Pablo; Verne, Eduardo; Nazario-Fuertes, Ronald; Ugarte, Claudia; del Valle, Luis J; Pumarola, Tomás
Acute respiratory infections are responsible for high morbi-mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses. © 2015 Wiley Periodicals, Inc.
Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.
Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka
Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.
The effect of aging on respiratory synergy.
Kweon, Migyoung; Son, Sung Min; Kwon, Yong Hyun
[Purpose] The purpose of this study was to investigate the effect of aging on respiratory synergy, through the comparison of an elderly group and a young group, to help further understanding of postural control in the elderly. [Subjects and Methods] Ten community-dwelling elderly subjects and ten young subjects performed standing under two different respiratory conditions: quiet breathing and apnea. Center of foot pressure displacement and joint angular movements of the head, trunk, pelvis, hips, knees and ankles were measured. [Results] The results of this study showed that the elderly group had a respiratory synergy different from that of the young group. The elderly group in quiet stance used significantly more hip and pelvis movements when compensating for respiratory disturbance than standing with apnea, while the young group used significantly more whole body segments. There were no differences in angular displacements in the quiet stance between the elderly and the young groups. [Conclusion] The elderly group demonstrated a respiratory synergy pattern different from that of the young group. The findings indicate that aging changes the respiratory synergy pattern and this change is not due to decreased functioning of the ankle joint alone.
Respiratory processes in non-photosynthetic plastids
Renato, Marta; Boronat, Albert; Azcón-Bieto, Joaquín
Chlororespiration is a respiratory process located in chloroplast thylakoids which consists in an electron transport chain from NAD(P)H to oxygen. This respiratory chain involves the NAD(P)H dehydrogenase complex, the plastoquinone pool and the plastid terminal oxidase (PTOX), and it probably acts as a safety valve to prevent the over-reduction of the photosynthetic machinery in stress conditions. The existence of a similar respiratory activity in non-photosynthetic plastids has been less studied. Recently, it has been reported that tomato fruit chromoplasts present an oxygen consumption activity linked to ATP synthesis. Etioplasts and amyloplasts contain several electron carriers and some subunits of the ATP synthase, so they could harbor a similar respiratory process. This review provides an update on the study about respiratory processes in chromoplasts, identifying the major gaps that need to be addressed in future research. It also reviews the proteomic data of etioplasts and amyloplasts, which suggest the presence of a respiratory electron transport chain in these plastids. PMID:26236317
Respiratory processes in non-photosynthetic plastids
Marta eRenato
Full Text Available Chlororespiration is a respiratory process located in chloroplast thylakoids which consists in an electron transport chain from NAD(PH to oxygen. This respiratory chain involves the NAD(PH dehydrogenase complex, the plastoquinone pool and the plastid terminal oxidase (PTOX, and it probably acts as a safety valve to prevent the over-reduction of the photosynthetic machinery in stress conditions. The existence of a similar respiratory activity in non-photosynthetic plastids has been less studied. Recently, it has been reported that tomato fruit chromoplasts present an oxygen consumption activity linked to ATP synthesis. Etioplasts and amyloplasts contain several electron carriers and some subunits of the ATP synthase, so they could harbor a similar respiratory process. This review provides an update on the study about respiratory processes in chromoplasts, identifying the major gaps that need to be addressed in future research. It also reviews the proteomic data of etioplasts and amyloplasts, which suggest the presence of a respiratory electron transport chain in these plastids.
Environmental exposure to pesticides and respiratory health
Ali Mamane
Full Text Available Respiratory effects of environmental exposure to pesticides are debated. Here we aimed to review epidemiological studies published up until 2013, using the PubMed database. 20 studies dealing with respiratory health and non-occupational pesticide exposure were identified, 14 carried out on children and six on adults. In four out of nine studies in children with biological measurements, mothers' dichlorodiphenyldichloroethylene (DDE blood levels during pregnancy were associated with asthma and wheezing in young children. An association was also found between permethrin in indoor air during pregnancy and wheezing in children. A significant association between asthma and DDE measured in children's blood (aged 7–10 years was observed in one study. However, in three studies, no association was found between asthma or respiratory infections in children and pesticide levels in breast milk and/or infant blood. Lastly, in three out of four studies where post-natal pesticide exposure of children was assessed by parental questionnaire an association with respiratory symptoms was found. Results of the fewer studies on pesticide environmental exposure and respiratory health of adults were much less conclusive: indeed, the associations observed were weak and often not significant. In conclusion, further studies are needed to confirm whether there is a respiratory risk associated with environmental exposure to pesticides.
Biology of human respiratory syncytial virus: a review | Aliyu | Bayero ...
Acute lower respiratory tract infection is one of the major causes of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) is the single most important viral cause of lower respiratory tract infection during infancy and early childhood worldwide. Respiratory syncytial virus belongs to the ...
Evaluation of the Usefulness of the Respiratory Guidance System in the Respiratory Gating Radiation Therapy
Lee, Yeong Cheol; Kim, Sun Myung; Do, Gyeong Min; Park, Geun Yong; Kim, Gun Oh; Kim, Young Bum [Dept. of Radiation Oncology, Guro Hospital, Korea Univeristy, Seoul (Korea, Republic of)
The respiration is one of the most important factors in respiratory gating radiation therapy (RGRT). We have developed an unique respiratory guidance system using an audio-visual system in order to support and stabilize individual patient's respiration and evaluated the usefulness of this system. Seven patients received the RGRT at our clinic from June 2011 to April 2012. After breathing exercise standard deviations by the superficial contents of respiratory cycles and functions, and analyzed them to examine changes in their breathing before and with the audio-visual system, we measured their spontaneous respiration and their respiration with the audio-visual system respectively. With the measured data, we yielded after the therapy. The PTP (peak to peak) of the standard deviations of the free breathing, the audio guidance system, and the respiratory guidance system were 0.343, 0.148, and 0.078 respectively. The respiratory cycles were 0.645, 0.345, and 0.171 respectively and the superficial contents of the respiratory functions were 2.591, 1.008, and 0.877 respectively. The average values of the differences in the standard deviations among the whole patients at the CT room and therapy room were 0.425 for the PTP, 1.566 for the respiratory cycles, and 3.671 for the respiratory superficial contents. As for the standard deviations before and after the application of the PTP respiratory guidance system, that of the PTP was 0.265, that of the respiratory cycles was 0.474, and that of the respiratory superficial contents. The results of t-test of the values before and after free breathing and the audio-visual guidance system showed that the P-value of the PTP was 0.035, that of the cycles 0.009, and that of the respiratory superficial contents 0.010. The respiratory control could be one of the most important factors in the RGRT which determines the success or failure of a treatment. We were able to get more stable breathing with the audio-visual respiratory
Evaluation of the Usefulness of the Respiratory Guidance System in the Respiratory Gating Radiation Therapy
Lee, Yeong Cheol; Kim, Sun Myung; Do, Gyeong Min; Park, Geun Yong; Kim, Gun Oh; Kim, Young Bum
The respiration is one of the most important factors in respiratory gating radiation therapy (RGRT). We have developed an unique respiratory guidance system using an audio-visual system in order to support and stabilize individual patient's respiration and evaluated the usefulness of this system. Seven patients received the RGRT at our clinic from June 2011 to April 2012. After breathing exercise standard deviations by the superficial contents of respiratory cycles and functions, and analyzed them to examine changes in their breathing before and with the audio-visual system, we measured their spontaneous respiration and their respiration with the audio-visual system respectively. With the measured data, we yielded after the therapy. The PTP (peak to peak) of the standard deviations of the free breathing, the audio guidance system, and the respiratory guidance system were 0.343, 0.148, and 0.078 respectively. The respiratory cycles were 0.645, 0.345, and 0.171 respectively and the superficial contents of the respiratory functions were 2.591, 1.008, and 0.877 respectively. The average values of the differences in the standard deviations among the whole patients at the CT room and therapy room were 0.425 for the PTP, 1.566 for the respiratory cycles, and 3.671 for the respiratory superficial contents. As for the standard deviations before and after the application of the PTP respiratory guidance system, that of the PTP was 0.265, that of the respiratory cycles was 0.474, and that of the respiratory superficial contents. The results of t-test of the values before and after free breathing and the audio-visual guidance system showed that the P-value of the PTP was 0.035, that of the cycles 0.009, and that of the respiratory superficial contents 0.010. The respiratory control could be one of the most important factors in the RGRT which determines the success or failure of a treatment. We were able to get more stable breathing with the audio-visual respiratory guidance
Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice.
Devine, Raymond D; Bicer, Sabahattin; Reiser, Peter J; Wold, Loren E
Cancer cachexia is a progressive wasting disease resulting in significant effects on the quality of life and high mortality. Most studies on cancer cachexia have focused on skeletal muscle; however, the heart is now recognized as a major site of cachexia-related effects. To elucidate possible mechanisms, a proteomic study was performed on the left ventricles of colon-26 (C26) adenocarcinoma tumor-bearing mice. The results revealed several changes in proteins involved in metabolism. An integrated pathway analysis of the results revealed a common mediator in hypoxia-inducible factor-1α (HIF-1α). Work by other laboratories has shown that extensive metabolic restructuring in the C26 mouse model causes changes in gene expression that may be affected directly by HIF-1α, such as glucose metabolic genes. M-mode echocardiography showed progressive decline in heart function by day 19 , exhibited by significantly decreased ejection fraction and fractional shortening, along with posterior wall thickness. Using Western blot analysis, we confirmed that HIF-1α is significantly upregulated in the heart, whereas there were no changes in its regulatory proteins, prolyl hydroxylase domain-containing protein 2 (PHD2) and von Hippel-Lindau protein (VHL). PHD2 requires both oxygen and iron as cofactors for the hydroxylation of HIF-1α, marking it for ubiquination via VHL and subsequent destruction by the proteasome complex. We examined venous blood gas values in the tumor-bearing mice and found significantly lower oxygen concentration compared with control animals in the third week after tumor inoculation. We also examined select skeletal muscles to determine whether they are similarly affected. In the diaphragm, extensor digitorum longus, and soleus, we found significantly increased HIF-1α in tumor-bearing mice, indicating a hypoxic response, not only in the heart, but also in skeletal muscle. These results indicate that HIF-1α may contribute, in part, to the metabolic changes
Respiratory Syncytial Virus Bronchiolitis in Children.
Smith, Dustin K; Seales, Sajeewane; Budzik, Carol
Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause of this infection. RSV is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. Patients with RSV bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower respiratory tract symptoms such as increasing cough, wheezing, and increased respiratory effort. In 2014, the American Academy of Pediatrics updated its clinical practice guideline for diagnosis and management of RSV bronchiolitis to minimize unnecessary diagnostic testing and interventions. Bronchiolitis remains a clinical diagnosis, and diagnostic testing is not routinely recommended. Treatment of RSV infection is mainly supportive, and modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and antibiotics are generally not useful. Evidence supports using supplemental oxygen to maintain adequate oxygen saturation; however, continuous pulse oximetry is no longer required. The other mainstay of therapy is intravenous or nasogastric administration of fluids for infants who cannot maintain their hydration status with oral fluid intake. Educating parents on reducing the risk of infection is one of the most important things a physician can do to help prevent RSV infection, especially early in life. Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.
Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression.
Ball, Mark W; Bezerra, Stephania M; Chaux, Alcides; Faraj, Sheila F; Gonzalez-Roibon, Nilda; Munari, Enrico; Sharma, Rajni; Bivalacqua, Trinity J; Netto, George J; Burnett, Arthur L
To evaluate insulin-like growth factor-1 receptor (IGF1R) expression in penile cancer and its association with oncologic outcomes. Tissue microarrays were constructed from 53 patients treated at our institution. Expression of IGF1R was evaluated using a Her2-like scoring system. Overexpression was defined as 1+ or greater membranous staining. Association of IGF1R expression with pathologic features was assessed with comparative statistics, and association with local recurrence, progression to nodal or distance metastases, or death was assessed with Kaplan-Meier survival analysis and Cox proportional hazard regression models. Overall, IGF1R overexpression was seen in 33 (62%) cases. With a median follow-up of 27.8 months, IGF1R overexpression was associated with inferior progression-free survival (PFS) (P = .003). In a multivariable model controlling for grade, T stage, perineural invasion, and lymphovascular invasion, IGF1R expression was independently associated with disease progression (hazard ratio 2.3, 95% confidence interval 1.1-5.1, P = .03. Comparing patients without IGF1R overexpression to those with overexpression, 5-year PFS was 94.1% vs 45.8%. IGF1R overexpression was associated with inferior PFS in penile cancer. Drugs that target IGF1R and downstream messengers may have a therapeutic benefit in patients that exhibit IGF1R overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.
Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury
Mushfiquddin Khan
Full Text Available Mild traumatic brain injury (TBI, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide (NO, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.
Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis
Kim, Hyo Jung; Cha, Jiyoung Y.; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae-woo
Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis. PMID:27345868
Osteocalcin and serum insulin-like growth factor-1 as biochemical skeletal maturity indicators
Tulika Tripathi
Full Text Available Abstract Background With change in concepts of growth determination methods, there is a surge in the measurement of biomarkers for appraisal of growth status. Osteocalcin is a bone-specific protein and was observed to parallel the normal growth curve. Hence, the present study was intended to assess the levels of serum osteocalcin and serum insulin-like growth factor-1 (IGF-1 and compare them with cervical vertebral maturation index (CVMI stages. Methods The cross-sectional study was performed on 150 subjects (75 males and 75 females in the age group of 8–20 years and segregated into six CVMI stages. Serum osteocalcin and IGF-1 were estimated by ELISA. Mann-Whitney U test was used to compare the mean ranks of serum osteocalcin and serum IGF-1 with different CVMI stages. Spearman correlation was performed to find association between serum osteocalcin and serum IGF-1 across six CVMI stages. Results Peak serum IGF-1 levels were obtained at CVMI stages 4 and 3 for males and females, respectively, with insignificant difference between stages 3 and 4 in females. Peak serum osteocalcin levels were found at stage 5 and 3 for males and females with insignificant difference from other stages except stages 5 and 6 in males. A statistically significant correlation was seen between serum IGF-1 and serum osteocalcin across six CVMI stages (P < 0.01. Conclusions Osteocalcin followed IGF-1 across all CVMI stages but showed insignificant interstage differences.
Elongation Factor-1α Accurately Reconstructs Relationships Amongst Psyllid Families (Hemiptera: Psylloidea), with Possible Diagnostic Implications.
Martoni, Francesco; Bulman, Simon R; Pitman, Andrew; Armstrong, Karen F
The superfamily Psylloidea (Hemiptera: Sternorrhyncha) lacks a robust multigene phylogeny. This impedes our understanding of the evolution of this group of insects and, consequently, an accurate identification of individuals, of their plant host associations, and their roles as vectors of economically important plant pathogens. The conserved nuclear gene elongation factor-1 alpha (EF-1α) has been valuable as a higher-level phylogenetic marker in insects and it has also been widely used to investigate the evolution of intron/exon structure. To explore evolutionary relationships among Psylloidea, polymerase chain reaction amplification and nucleotide sequencing of a 250-bp EF-1α gene fragment was applied to psyllids belonging to five different families. Introns were detected in three individuals belonging to two families. The nine genera belonging to the family Aphalaridae all lacked introns, highlighting the possibility of using intron presence/absence as a diagnostic tool at a family level. When paired with cytochrome oxidase I gene sequences, the 250 bp EF-1α sequence appeared to be a very promising higher-level phylogenetic marker for psyllids. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: firstname.lastname@example.com.
Targeted selected reaction monitoring mass spectrometric immunoassay for insulin-like growth factor 1.
Eric E Niederkofler
Full Text Available Insulin-like growth factor 1 (IGF1 is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM mode. The resulting quantitative mass spectrometric immunoassay (MSIA exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories.
Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.
Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa
Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.
Pharmacokinetic properties of 2nd-generation fibroblast growth factor-1 mutants for therapeutic application.
Xue Xia
Full Text Available Fibroblast growth factor-1 (FGF-1 is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK study in rabbits of human FGF-1 in the presence and absence of heparin, as well as three mutant forms having differential effects upon thermostability, buried reactive thiols, and heparin affinity. The results support the hypothesis that heparan sulfate proteoglycan (HSPG in the vasculature of liver, kidney and spleen serves as the principle peripheral compartment in the distribution kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like properties of distribution. Mutant forms of FGF-1 that enhance thermostability or eliminate buried reactive thiols demonstrate a shorter distribution half-life, a longer elimination half-life, and a longer mean residence time (MRT in comparison to wild-type FGF-1. The results show how such mutations can produce useful 2nd-generation forms with tailored PK profiles for specific therapeutic application.
Growth hormone and insulin-like growth factor 1 affect the severity of Graves' disease.
Di Cerbo, Alfredo; Pezzuto, Federica; Di Cerbo, Alessandro
Graves' disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves' disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves' disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves' disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves' disease and synergize the stimulatory activity of Graves' IgGs. Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.The coexistence of acromegaly and Graves' disease is a very unusual event, the prevalence being Graves' disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves' disease.
Insulin-like growth factor-1 protects preimplantation embryos from anti-developmental actions of menadione.
Moss, James I; Pontes, Eduardo; Hansen, Peter James
Menadione is a naphthoquinone used as a vitamin K source in animal feed that can generate reactive oxygen species (ROS) and cause apoptosis. Here, we examined whether menadione reduces development of preimplantation bovine embryos in a ROS-dependent process and tested the hypothesis that actions of menadione would be reduced by insulin-like growth factor-1 (IGF-1). Menadione caused a concentration-dependent decrease in the proportion of embryos that became blastocysts. All concentrations tested (1, 2.5, and 5.0 microM) inhibited development. Treatment with 100 ng/ml IGF-1 reduced the magnitude of the anti-developmental effects of the two lowest menadione concentrations. Menadione also caused a concentration-dependent increase in the percent of cells positive for the TUNEL reaction. The response was lower for IGF-1-treated embryos. The effects of menadione were mediated by ROS because (1) the anti-developmental effect of menadione was blocked by the antioxidants dithiothreitol and Trolox and (2) menadione caused an increase in ROS generation. Treatment with IGF-1 did not reduce ROS formation in menadione-treated embryos. In conclusion, concentrations of menadione as low as 1.0 muM can compromise development of bovine preimplantation embryos to the blastocyst stage of development in a ROS-dependent mechanism. Anti-developmental actions of menadione can be blocked by IGF-1 through effects downstream of ROS generation.
Insulin-like growth factor-1 levels in children with Beta-thalassemia minor
Mehran Karimi
Full Text Available Objective: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH / insulin growth factor-1 (IGF-1 axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in healthy children. Material and Methods: Fifty children aged 6 months to 15 years with b-thalassemia minor (32 males, 18 females and 50 age- and sex-matched normal healthy children were selected. Medical history was taken and complete physical examination was done in each case; IGF-1 level was checked in all cases. This study was done in Shiraz, southern Iran, during 2005.Results: IGF-1 levels were significantly lower in b-thalassemia minor children than normal children (P = 0.015. This result demonstrates that some etiologies of growth failure in b-thalassemia major other than those described to date can exist, which may be shared with b-thalassemia minor in feature or may be transformed by genes that are either expressed or not.Conclusion: We conclude that in addition to that observed in b-thalassemia major, IGF-1 level is also decreased in b-thalassemia minor, and these two may have similar etiologies.
Bone mineral density and insulin-like growth factor-1 in children with spastic cerebral palsy.
Nazif, H; Shatla, R; Elsayed, R; Tawfik, E; Osman, N; Korra, S; Ibrahim, A
Children with cerebral palsy (CP) have significant decrease linear growth rate and low bone mineral density (BMD). This study is to evaluate BMD in children with CP and its relation to the levels of insulin-like growth factor-1 (IGF-1). This cross-sectional study was carried out on 58 children suffering from spastic CP with the age range 4-12 years compared to 19 controls. All assessed by dual energy x-ray absorptiometry (DXA) to measure BMD, serum level of IGF-1, and serum vitamin D. The patients were classified according to their GMFCS. Fractures were reported in seven (12.1%) of cases. Our study demonstrated that, IGF-1 level and BMD decrease in correlation with the severity of CP. IGF-1correlates positively with serum vitamin D, BMI, and BMD. CP children with severe GMFCS level or who use anticonvulsive drugs are at a high risk for low BMD and low levels of IGF-1. Both BMD and IGF-1 were significantly in low children with spastic CP; IGF-1 negatively correlates with the severity of osteopenia in children with spastic. Children with CP who are not independently ambulant or with severe GMFCS level or who use anticonvulsive drugs are at a high risk for developing low BMD.
A quantitative assay measuring the function of lipase maturation factor 1
Yin, Fen; Doolittle, Mark H.; Péterfy, Miklós
Newly synthesized lipoprotein lipase (LPL) and related members of the lipase gene family require an endoplasmic reticulum maturation factor for attainment of enzyme activity. This factor has been identified as lipase maturation factor 1 (Lmf1), and mutations affecting its function and/or expression result in combined lipase deficiency (cld) and hypertriglyceridemia. To assess the functional impact of Lmf1 sequence variations, both naturally occurring and induced, we report the development of a cell-based assay using LPL activity as a quantitative reporter of Lmf1 function. The assay uses a cell line homozygous for the cld mutation, which renders endogenous Lmf1 nonfunctional. LPL transfected into the mutant cld cell line fails to attain activity; however, cotransfection of LPL with wild-type Lmf1 restores its ability to support normal lipase maturation. In this report, we describe optimized conditions that ensure the detection of a complete range of Lmf1 function (full, partial, or complete loss of function) using LPL activity as the quantitative reporter. To illustrate the dynamic range of the assay, we tested several novel mutations in mouse Lmf1. Our results demonstrate the ability of the assay to detect and analyze Lmf1 mutations having a wide range of effects on Lmf1 function and protein expression. PMID:19471043
Decay-accelerating factor 1 deficiency exacerbates Trypanosoma cruzi-induced murine chronic myositis.
Solana, María E; Ferrer, María F; Novoa, María Mercedes; Song, Wen-Chao; Gómez, Ricardo M
Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T-cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance murine T-cell responses and autoimmunity. To determine whether Daf1 deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice were inoculated with 5 × 10(4) trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T-cell expansion were studied in the acute and chronic stages. DAF(-/-) mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells. An enhanced CD8(+) T-cell immune-specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a useful model to study T-cell mediated immunity in skeletal muscle tissues. Copyright © 2012 Wiley Periodicals, Inc.
Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene
Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu
Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT
Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.
Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter
Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.
Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.
Domingo-Gonzalez, Racquel; Das, Shibali; Griffiths, Kristin L; Ahmed, Mushtaq; Bambouskova, Monika; Gopal, Radha; Gondi, Suhas; Muñoz-Torrico, Marcela; Salazar-Lezama, Miguel A; Cruz-Lagunas, Alfredo; Jiménez-Álvarez, Luis; Ramirez-Martinez, Gustavo; Espinosa-Soto, Ramón; Sultana, Tamanna; Lyons-Weiler, James; Reinhart, Todd A; Arcos, Jesus; de la Luz Garcia-Hernandez, Maria; Mastrangelo, Michael A; Al-Hammadi, Noor; Townsend, Reid; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B; Kaplan, Gilla; Horne, William; Kolls, Jay K; Artyomov, Maxim N; Rangel-Moreno, Javier; Zúñiga, Joaquín; Khader, Shabaana A
Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.
Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.
Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah
Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.
Hypoxia-Inducible Factor-1 in Physiological and Pathophysiological Angiogenesis: Applications and Therapies
Zimna, Agnieszka; Kurpisz, Maciej
The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy. PMID:26146622
Radiolabeled Probes Targeting Hypoxia-Inducible Factor-1-Active Tumor Microenvironments
Masashi Ueda
Full Text Available Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1 expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α, which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of 18F-FDG or 18F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.
Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance
Harada, Hiroshi
Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1–mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed
Diacetoxyscirpenol as a new anticancer agent to target hypoxia-inducible factor 1
Choi, Yong-Joon; Shin, Hyun-Woo; Chun, Yang-Sook; Leutou, Alain Simplice; Son, Byeng Wha; Park, Jong-Wan
Hypoxia activates hypoxia-inducible factor 1, which promotes the progression of malignancy by stimulating angiogenesis and by augmenting the ability of tumors to survive. Thus, HIF-1 is one of the most compelling targets for treating cancers. The aim of this study was to find a small molecule that inhibits HIF-1 under hypoxia in cancer cells. 7,280 compounds in a chemical library were tested in a cancer cell line expressing luciferase HIF-dependently. Through three rounds of screening, we finally picked up a compound that originates from a marine bacterium parasitizing red alga. The antibiotic potently inhibited HIF-1 expression and its transcriptional activity in cancer cells exposed to hypoxia. Through two-step fractionation, diacetoxyscirpenol was purified and identified as a HIF-inhibiting ingredient. Mechanistically, diacetoxyscirpenol inhibits the synthesis of HIF-1α protein and also interferes with the dimerization of HIF-1α and ARNT. It attenuates HIF-mediated gene expression in cancer cells exposed to hypoxia, and by doing so reduces tumorigenic and angiogenic potentials of cancer cells. More importantly, diacetoxyscirpenol retarded tumor growth in mice, and reduced HIF-1α expression and vascular formation in the tumors. Overall, diacetoxyscirpenol is considered a potential drug deregulating the HIF-1 signaling pathway, and it could be beneficially employed for treating malignant tumors with hypoxic microenvironment. PMID:27613833
Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1.
Xie, Xiayang; Tang, Shou-Ching; Cai, Yafei; Pi, Wenhu; Deng, Libin; Wu, Guangyu; Chavanieu, Alain; Teng, Yong
Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis.
Saururus cernuus lignans-Potent small molecule inhibitors of hypoxia-inducible factor-1
Hossain, Chowdhury Faiz; Kim, Yong-Pil; Baerson, Scott R.; Zhang Lei; Bruick, Richard K.; Mohammed, Kaleem A.; Agarwal, Ameeta K.; Nagle, Dale G.; Zhou Yudong
Hypoxia-inducible factor-1 (HIF-1) represents an important tumor-selective therapeutic target for solid tumors. In search of novel small molecule HIF-1 inhibitors, 5400 natural product-rich extracts from plants, marine organisms, and microbes were examined for HIF-1 inhibitory activities using a cell-based reporter assay. Bioassay-guided fractionation and isolation, followed by structure elucidation, yielded three potent natural product-derived HIF-1 inhibitors and two structurally related inactive compounds. In a T47D cell-based reporter assay, manassantin B 1 , manassantin A, and 4-O-methylsaucerneol inhibited hypoxia-induced HIF-1 activation with IC 50 values of 3, 3, and 20 nM, respectively. All three compounds are relatively hypoxia-specific inhibitors of HIF-1 activation, in comparison to other stimuli. The hypoxic induction of HIF-1 target genes CDKN1A, VEGF, and GLUT-1 were also inhibited. These compounds inhibit HIF-1 by blocking hypoxia-induced nuclear HIF-1α protein accumulation without affecting HIF-1α mRNA levels. In addition, preliminary structure-activity studies suggest specific structural requirements for this class of HIF-1 inhibitors
Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage
Logan, Ian R.; McNeill, Hesta V.; Cook, Susan; Lu, Xiaohong; Meek, David W.; Fuller-Pace, Frances V.; Lunec, John; Robson, Craig N.
Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents. PMID:19295133
Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression
Currie Margaret J
Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.
The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress
Murphy, Brian J.; Sato, Barbara G.; Dalton, Timothy P.; Laderoute, Keith R.
Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1α protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis-glutamate cysteine ligase catalytic subunit-than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1α protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity
The Therapeutic Potential of Insulin-Like Growth Factor-1 in Central Nervous System Disorders
Costales, Jesse; Kolevzon, Alexander
Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD. PMID:26780584
Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.
Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia
To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.
Hypoxia-Inducible Factor-1 as a Therapeutic Target in Endometrial Cancer Management
Laura M. S. Seeber
Full Text Available In the Western world, endometrial cancer (EC is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1 (HIF-1 plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1 protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials.
Differentiation-inducing factor-1 suppresses gene expression of cyclin D1 in tumor cells
Yasmin, Tania; Takahashi-Yanaga, Fumi; Mori, Jun; Miwa, Yoshikazu; Hirata, Masato; Watanabe, Yutaka; Morimoto, Sachio; Sasaguri, Toshiyuki
To determine the mechanism by which differentiation-inducing factor-1 (DIF-1), a morphogen of Dictyostelium discoideum, inhibits tumor cell proliferation, we examined the effect of DIF-1 on the gene expression of cyclin D1. DIF-1 strongly reduced the expression of cyclin D1 mRNA and correspondingly decreased the amount of β-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3β (GSK-3β) and inhibition of GSK-3β attenuated the DIF-1-induced β-catenin degradation, indicating the involvement of GSK-3β in this effect. Moreover, DIF-1 reduced the activities of T-cell factor (TCF)/lymphoid enhancer factor (LEF) reporter plasmid and a reporter gene driven by the human cyclin D1 promoter. Eliminating the TCF/LEF consensus site from the cyclin D1 promoter diminished the effect of DIF-1. These results suggest that DIF-1 inhibits Wnt/β-catenin signaling, resulting in the suppression of cyclin D1 promoter activity
Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.
Bortvedt, Sarah F; Lund, P Kay
To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.
Are Ichthyosporea animals or fungi? Bayesian phylogenetic analysis of elongation factor 1alpha of Ichthyophonus irregularis.
Ragan, Mark A; Murphy, Colleen A; Rand, Thomas G
Ichthyosporea is a recently recognized group of morphologically simple eukaryotes, many of which cause disease in aquatic organisms. Ribosomal RNA sequence analyses place Ichthyosporea near the divergence of the animal and fungal lineages, but do not allow resolution of its exact phylogenetic position. Some of the best evidence for a specific grouping of animals and fungi (Opisthokonta) has come from elongation factor 1alpha, not only phylogenetic analysis of sequences but also the presence or absence of short insertions and deletions. We sequenced the EF-1alpha gene from the ichthyosporean parasite Ichthyophonus irregularis and determined its phylogenetic position using neighbor-joining, parsimony and Bayesian methods. We also sequenced EF-1alpha genes from four chytrids to provide broader representation within fungi. Sequence analyses and the presence of a characteristic 12 amino acid insertion strongly indicate that I. irregularis is a member of Opisthokonta, but do not resolve whether I. irregularis is a specific relative of animals or of fungi. However, the EF-1alpha of I. irregularis exhibits a two amino acid deletion heretofore reported only among fungi.
Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists.
Mochizuki, Michiyo; Kori, Masakuni; Kobayashi, Katsumi; Yano, Takahiko; Sako, Yuu; Tanaka, Maiko; Kanzaki, Naoyuki; Gyorkos, Albert C; Corrette, Christopher P; Cho, Suk Young; Pratt, Scott A; Aso, Kazuyoshi
Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.
Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1
Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.
Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866
The cauliflower Orange gene enhances petiole elongation by suppressing expression of eukaryotic release factor 1.
Zhou, Xiangjun; Sun, Tian-Hu; Wang, Ning; Ling, Hong-Qing; Lu, Shan; Li, Li
The cauliflower (Brassica oleracea var. botrytis) Orange (Or) gene affects plant growth and development in addition to conferring β-carotene accumulation. This study was undertaken to investigate the molecular basis for the effects of the Or gene mutation in on plant growth. The OR protein was found to interact with cauliflower and Arabidopsis eukaryotic release factor 1-2 (eRF1-2), a member of the eRF1 family, by yeast two-hybrid analysis and by bimolecular fluorescence complementation (BiFC) assay. Concomitantly, the Or mutant showed reduced expression of the BoeRF1 family genes. Transgenic cauliflower plants with suppressed expression of BoeRF1-2 and BoeRF1-3 were generated by RNA interference. Like the Or mutant, the BoeRF1 RNAi lines showed increased elongation of the leaf petiole. This long-petiole phenotype was largely caused by enhanced cell elongation, which resulted from increased cell length and elevated expression of genes involved in cell-wall loosening. These findings demonstrate that the cauliflower Or gene controls petiole elongation by suppressing the expression of eRF1 genes, and provide new insights into the molecular mechanism of leaf petiole regulation. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.
The histone deacetylase inhibitor, Vorinostat, represses hypoxia inducible factor 1 alpha expression through translational inhibition.
Darren M Hutt
Full Text Available Hypoxia inducible factor 1α (HIF-1α is a master regulator of tumor angiogenesis being one of the major targets for cancer therapy. Previous studies have shown that Histone Deacetylase Inhibitors (HDACi block tumor angiogenesis through the inhibition of HIF-1α expression. As such, Vorinostat (Suberoylanilide Hydroxamic Acid/SAHA and Romidepsin, two HDACis, were recently approved by the Food and Drug Administration (FDA for the treatment of cutaneous T cell lymphoma. Although HDACis have been shown to affect HIF-1α expression by modulating its interactions with the Hsp70/Hsp90 chaperone axis or its acetylation status, the molecular mechanisms by which HDACis inhibit HIF-1α expression need to be further characterized. Here, we report that the FDA-approved HDACi Vorinostat/SAHA inhibits HIF-1α expression in liver cancer-derived cell lines, by a new mechanism independent of p53, prolyl-hydroxylases, autophagy and proteasome degradation. We found that SAHA or silencing of HDAC9 mechanism of action is due to inhibition of HIF-1α translation, which in turn, is mediated by the eukaryotic translation initiation factor--eIF3G. We also highlighted that HIF-1α translation is dramatically inhibited when SAHA is combined with eIF3H silencing. Taken together, we show that HDAC activity regulates HIF-1α translation, with HDACis such as SAHA representing a potential novel approach for the treatment of hepatocellular carcinoma.
Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations
David Olmos
Full Text Available Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response.
Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations
Olmos, David; Martins, Ana Sofia; Jones, Robin L.; Alam, Salma; Scurr, Michelle; Judson, Ian R.
Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response. PMID:21647361
Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection
Bont, L.; Steijn, M.; van Aalderen, W. M. C.; Brus, F.; Th Draaisma, J. M.; van Diemen-Steenvoorde, R. A. A. M.; Pekelharing-Berghuis, M.; Kimpen, J. L. L.
Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of
Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection
Bont, L; Steijn, M; van Aalderen, WMC; Brus, F; Draaisma, JMT; Van Diemen-Steenvoorde, RAAM; Pekelharing-Berghuis, M; Kimpen, JLL
Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of
Prediction of tonic parasympathetic cardiac control using respiratory sinus arrhythmia: the need for respiratory control
GROSSMAN, P.; Karemaker, J.; Wieling, W.
Respiratory sinus arrhythmia (RSA) has received much attention in recent years due to the large body of evidence indicating that variations in this phenomenon represent alterations in parasympathetic cardiac control. Although it appears that respiratory sinus arrhythmia is mediated by vagal
Human herpesviruses respiratory infections in patients with acute respiratory distress (ARDS).
Bonizzoli, Manuela; Arvia, Rosaria; di Valvasone, Simona; Liotta, Francesco; Zakrzewska, Krystyna; Azzi, Alberta; Peris, Adriano
Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype.
Evaluation of exercise-respiratory system modifications and preliminary respiratory-circulatory system integration scheme
Gallagher, R. R.
The respiratory control system, functioning as an independent system, is presented with modifications of the exercise subroutine. These modifications illustrate an improved control of ventilation rates and arterial and compartmental gas tensions. A very elementary approach to describing the interactions of the respiratory and circulatory system is presented.
Lower respiratory tract infection caused by respiratory syncytial virus : current management and new therapeutics
Mazur, Natalie; Martinon-Torres, Federico; Baraldi, Eugenio; Fauroux, Brigitte; Greenough, Anne; Heikkinen, Terho; Manzoni, Paolo; Mejias, Asuncion; Nair, Harish; Papadopoulos, Nikolaos G.; Polack, Fernando P.; Ramilo, Octavio; Sharland, Mike; Stein, Renato; Madhi, Shabir A.; Bont, Louis
Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and
[Respiratory symptoms and atmospheric pollution and respiratory symptoms in the general population].
Simon, I; Charpin, D
Epidemiological studies on air pollution have mainly been interested in the effects of short- or long-term exposure on patients suffering from respiratory illnesses. Fewer studies have addressed the acute effects of air pollution on respiratory symptoms in the general population. We conducted a review of the literature over the last 16years that has addressed the impact of atmospheric pollution on respiratory symptoms in the general population to estimate the magnitude of effect. The majority of studies demonstrated a significant association between exposure to air pollutants and the occurrence of respiratory symptoms, without any threshold. Although a link between atmospheric pollution and respiratory symptoms has been demonstrated, knowledge of the effects of specific air pollutants and the effect of pollution on particular vulnerable groups (infants, young children, the elderly) is still limited. There is a need for further studies in this area. Copyright 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Respiratory muscle training for cystic fibrosis.
Hilton, Nathan; Solis-Moya, Arturo
Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review. To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 17 April 2018.A hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases up until 07 May 2018. Randomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis. Review authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system MAIN RESULTS: Authors identified 19 studies, of which nine studies with 202 participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the nine included studies were published as abstracts only and lacking concise details, thus limiting the information available. Seven studies were parallel studies and two of a cross-over design. Respiratory
Occupational exposure to pesticides and respiratory health
Ali Mamane
Full Text Available This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspnoea, breathlessness or chest tightness. All four studies on asthma found a relationship with occupational exposure, as did all three studies on chronic bronchitis. The four studies that performed spirometry reported impaired respiratory function linked to pesticide exposure, suggestive of either obstructive or restrictive syndrome according to the chemical class of pesticide. 12 papers reported results from cohort studies. Three out of nine found a significant relationship with increased risk of wheeze, five out of nine with asthma and three out of three with chronic bronchitis. In workers employed in pesticide production, elevated risks of chronic obstructive pulmonary disease (two studies out of three and impaired respiratory function suggestive of an obstructive syndrome (two studies out of two were reported. In conclusion, this article suggests that occupational exposure to pesticides is associated with an increased risk of respiratory symptoms, asthma and chronic bronchitis, but the causal relationship is still under debate.
[Late respiratory function complications following burns].
Ernesto, S; Marduel, Y; Freymond, N; Pacheco, Y; Devouassoux, G
Twenty five per cent of thermal injuries are associated with secondary respiratory events linked to several mechanisms. In the acute phase of the accident oedema of the airways, the fume inhalation syndrome and ARDS are the most common causes responsible for death in 60% of cases. Late respiratory complications are little known and neglected. They comprise obstructive ventilatory defects due to the inhalation syndrome and restrictive defects secondary to ARDS or to dermal injury. We report the case of a female patient, extensively burnt 2 years previously, admitted to hospital with severe acute respiratory failure complicating COPD. The presence of both restrictive and obstructive defects led to the suggestion of alternative underlying mechanisms such as the pulmonary consequences of ARDS and extensive dermal scars. The latter were responsible for an armour like thickening of the skin of the thorax compatible with the restrictive defect. These functional abnormalities and the potential severity of acute respiratory failure are indications for regular pulmonary follow-up of patients with severe circumferential scarring of the thorax who are at high risk for respiratory complications.
Respiratory adaptations in different types of sport.
Lazovic, B; Mazic, S; Suzic-Lazic, J; Djelic, M; Djordjevic-Saranovic, S; Durmic, T; Zikic, D; Zugic, V
Recent studies demonstrated that current European Respiratory Society/American Thoracic Society spirometric reference equations, used in general population, may not be applicable in population of elite athletes. Althought it is well known that physical activity may affect lung volumes, the effect of sporting activity on pulmonary function testing indices was never examined. The aim of this study was to examine the differences in functional respiratory parameters in various types of sports by measuring lung volumes and to extend the existing factors as well as sport disciplines which affect respiratory function the most. A total of 1639 elite male athletes, aged 18-35 years were divided in 4 groups according to the predominant characteristics of training: skill, power, mixed and endurance athletes. They performed basic anthropometric measurements and spirometry. Groups were compared, and Pearson's simple correlation was performed to test the relation between anthropometric and spirometric characteristics of athletes. All anthropometric characteristics significantly differed among groups and correlate with respiratory parameters. The highest correlation was found for body height and weight. Sports participation is associated with respiratory adaptation, and the extent of adaptation depends on type of activity. Endurance sports athletes have higher lung volumes in comparison with skill, mixed and power group of sport.
Dynamics of human respiratory system mycoflora
Anna Biedunkiewicz
Full Text Available The study aimed at determing the prevalence of individual species of fungi in the respiratory systems of women and men, analysis of the dynamics of the fungi in individual sections of the respiratory system as concerns their quantity and identification of phenology of the isolated fungi coupled with an attempt at identifying their possible preferences for appearing during specific seasons of thc year. During 10 years of studies (1989- 1998. 29 species of fungi belonging: Candida, Geolrichum, Saccharomyces, Saccharomycopsis, Schizosaccharomyces, Torulopsis, Trichosporon and Aspergillus were isolated from the ontocenoses of the respiratory systems of patients at the Independent Public Center for Pulmonology and Oncology in Olsztyn. Candida albicans was a clearly dominating fungus. Individual species appeared individually, in twos or threes in a single patient, they were isolated more frequently in the spring and autumn, less frequently during the winter and summer. The largest number of fungi species were isolated from sputum (29 species, bronchoscopic material (23 species and pharyngeal swabs (15 species. Sacchoromycopsis capsularis and Trichosporon beigelii should be treated as new for the respiratory system. Biodiversity of fungi, their numbers and continous fluctuations in frequency indicate that the respiratory system ontocenose offers the optimum conditions for growth and development of the majority of the majority of yeasts - like fungi.
Inhaled Antibiotic Therapy in Chronic Respiratory Diseases
Diego J. Maselli
Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.
Respiratory exercise in amyotrophic lateral sclerosis.
Pinto, Susana; Swash, Michael; de Carvalho, Mamede
We have evaluated the potential role of respiratory exercise by implementing specific inspiratory muscle training in a selected population of early-affected amyotrophic lateral sclerosis (ALS) patients. We studied 26 patients with ALS with normal respiratory function using two groups of patients in a parallel, control-group, randomized, delayed-start design. Patients in the first group (G1) started the active inspiratory exercise programme at entry and were followed for eight months, while the second group (G2) of patients followed a placebo exercise programme for the first four months and then active exercise for the second four-month period. The primary outcome measure was the ALSFRS. Respiratory tests, neurophysiological measurements, fatigue and quality of life scales were secondary outcomes. Analysis of covariance was used to compare changes between and within groups. Results showed that there was no significant difference between the two patient groups. Within-group analysis suggested that inspiratory exercise promotes a transient improvement in the respiratory subscore and in the maximal voluntary ventilation, peak expiratory flow, and sniff inspiratory pressure. In conclusion, there was no clear positive or negative outcome of the respiratory exercise protocol we have proposed, but we cannot rule out a minor positive effect. Exercise regimes merit more detailed clinical evaluation in ALS.
Viral respiratory diseases: vaccines and antivirals.
Lennette, E H
Acute respiratory diseases, most of which are generally attributed to viruses, account for about 6% of all deaths and for about 60% of the deaths associated with all respiratory disease. The huge cost attributable to viral respiratory infections as a result of absenteeism and the disruption of business and the burden of medical care makes control of these diseases an important objective. The viruses that infect the respiratory tract fall taxonomically into five viral families. Although immunoprophylaxis would appear to be the logical approach, the development of suitable vaccines has been confronted with numerous obstacles, including antigenic drift and shift in the influenzaviruses, the large number of antigenically distinct immunotypes among rhinoviruses, the occurrence after immunization of rare cases of a severe form of the disease following subsequent natural infection with respiratory syncytial virus, and the risk of oncogenicity of adenoviruses for man. Considerable expenditure on the development of new antiviral drugs has so far resulted in only three compounds that are at present officially approved and licensed for use in the USA. Efforts to improve the tools available for control should continue and imaginative and inventive approaches are called for. However, creativity and ingenuity must operate within the constraints imposed by economic, political, ethical, and legal considerations.
Spinal Metaplasticity in Respiratory Motor Control
Gordon S Mitchell
Full Text Available A hallmark feature of the neural system controlling breathing is its ability to exhibit plasticity. Less appreciated is the ability to exhibit metaplasticity, a change in the capacity to express plasticity (ie. plastic plasticity. Recent advances in our understanding of cellular mechanisms giving rise to respiratory motor plasticity lay the groundwork for (ongoing investigations of metaplasticity. This detailed understanding of respiratory metaplasticity will be essential as we harness metaplasticity to restore breathing capacity in clinical disorders that compromise breathing, such as cervical spinal injury, motor neuron disease and other neuromuscular diseases. In this brief review, we discuss key examples of metaplasticity in respiratory motor control, and our current understanding of mechanisms giving rise to spinal plasticity and metaplasticity in phrenic motor output; particularly after pre-conditioning with intermittent hypoxia. Progress in this area has led to the realization that similar mechanisms are operative in other spinal motor networks, including those governing limb movement. Further, these mechanisms can be harnessed to restore respiratory and non-respiratory motor function after spinal injury.
Metagenomic analysis of viral diversity in respiratory samples from patients with respiratory tract infections in Kuwait.
Madi, Nada; Al-Nakib, Widad; Mustafa, Abu Salim; Habibi, Nazima
A metagenomic approach based on target independent next-generation sequencing has become a known method for the detection of both known and novel viruses in clinical samples. This study aimed to use the metagenomic sequencing approach to characterize the viral diversity in respiratory samples from patients with respiratory tract infections. We have investigated 86 respiratory samples received from various hospitals in Kuwait between 2015 and 2016 for the diagnosis of respiratory tract infections. A metagenomic approach using the next-generation sequencer to characterize viruses was used. According to the metagenomic analysis, an average of 145, 019 reads were identified, and 2% of these reads were of viral origin. Also, metagenomic analysis of the viral sequences revealed many known respiratory viruses, which were detected in 30.2% of the clinical samples. Also, sequences of non-respiratory viruses were detected in 14% of the clinical samples, while sequences of non-human viruses were detected in 55.8% of the clinical samples. The average genome coverage of the viruses was 12% with the highest genome coverage of 99.2% for respiratory syncytial virus, and the lowest was 1% for torque teno midi virus 2. Our results showed 47.7% agreement between multiplex Real-Time PCR and metagenomics sequencing in the detection of respiratory viruses in the clinical samples. Though there are some difficulties in using this method to clinical samples such as specimen quality, these observations are indicative of the promising utility of the metagenomic sequencing approach for the identification of respiratory viruses in patients with respiratory tract infections. © 2017 Wiley Periodicals, Inc.
Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification
Wang, Shouyi; Bowen, Stephen R.; Chaovalitwongse, W. Art; Sandison, George A.; Grabowski, Thomas J.; Kinahan, Paul E.
The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUVpeak) over lesions of interest. Relative differences in SUVpeak between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUVpeak values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation
Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification
Wang, Shouyi; Chaovalitwongse, W Art; Bowen, Stephen R; Kinahan, Paul E; Sandison, George A; Grabowski, Thomas J
The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUV peak ) over lesions of interest. Relative differences in SUV peak between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUV peak values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion
Interaction between nucleotide binding sites on chloroplast coupling factor 1 during ATP hydrolysis
Leckband, D.; Hammes, G.G.
The initial hydrolysis of radioactively-labelled CaATP by chloroplast coupling factor 1 was studied with the quenched-flow method. The time course of hydrolysis can be described as a first-order conversion of the enzyme to an active form followed by steady-state formation of product. The rate constant for the first-order process is independent of substrate concentration but increased hyperbolically to a limiting value of 0.43 s/sup -1/ with increasing concentrations of free Ca/sup 2 +/. A mechanism involving a Ca/sup 2 +/-triggered conversion to an active form of the enzyme is consistent with the data. The steady-state rate varied sigmoidally with the CaATP concentration. Initial exchange of tightly bound ADP is complex: approx. 50% of the bound nucleotide is lost within 30 s, with complete exchange requiring several minutes. The first-order rate constant characterizing the rapid phase of the reaction increases hyperbolically to a limiting value of 0.26 s/sup -1/ as the concentration of CaATP is increased, indicating that the binding of CaATP to the enzyme promotes the exchange process. Modification of the quenched-flow apparatus permitted measurement of the rate of nucleotide exchange during steady-state catalysis. The value of the first-order rate constant characterizing this process is similar to the catalytic rate constant determined under identical conditions. When MgATP is tightly bound to the enzyme, none of the kinetic properties of the enzyme described above were significantly changes. The results obtained suggest a mechanism in which two sites on the enzyme participate in catalysis. Several possible mechanisms consistent with the data are discussed.
Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium
Polosukhin, Vasiliy V; Cates, Justin M; Lawson, William E; Milstone, Aaron P; Matafonov, Anton G; Massion, Pierre P; Lee, Jae Woo; Randell, Scott H; Blackwell, Timothy S
Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65 – 100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O2) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD. PMID:21557221
MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1.
Luo, Rongcan; Shao, Xuan; Xu, Peng; Liu, Yanlei; Wang, Yongqing; Zhao, Yangyu; Liu, Ming; Ji, Lei; Li, Yu-Xia; Chang, Cheng; Qiao, Jie; Peng, Chun; Wang, Yan-Ling
Preeclampsia is a pregnancy-specific syndrome manifested by the onset of hypertension and proteinuria after the 20th week of gestation. Abnormal placenta development has been generally accepted as the initial cause of the disorder. Recently, microRNA-210 (miR-210) has been found to be upregulated in preeclamptic placentas compared with normal placentas, indicating a possible association of this small molecule with the placental pathology of preeclampsia. However, the function of miR-210 in the development of the placenta remains elusive. The aim of this study was to characterize the molecular mechanism of preeclampsia development by examining the role of miR-210. In this study, miR-210 and potassium channel modulatory factor 1 (KCMF1) expressions were compared in placentas from healthy pregnant individuals and patients with preeclampsia, and the role of miR-210 in trophoblast cell invasion via the downregulation of KCMF1 was investigated in the immortal trophoblast cell line HTR8/SVneo. The levels of KCMF1 were significantly lower in preeclamptic placenta tissues than in gestational week-matched normal placentas, which was inversely correlated with the level of miR-210. KCMF1 was validated as the direct target of miR-210 using real-time polymerase chain reaction, Western blotting, and dual luciferase assay in HTR8/SVneo cells. miR-210 inhibited the invasion of trophoblast cells, and this inhibition was abrogated by the overexpression of KCMF1. The inflammatory factor tumor necrosis factor-α could upregulate miR-210 while suppressing KCMF1 expression in HTR8/SVneo cells. This is the first report on the function of KCMF1 in human placental trophoblast cells, and the data indicate that aberrant miR-210 expression may contribute to the occurrence of preeclampsia by interfering with KCMF1-mediated signaling in the human placenta. © 2014 American Heart Association, Inc.
Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans
Wang Xiaoqin
Full Text Available Abstract Background Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM. The β-cell specific transcription factor, insulin promoter factor 1 gene (IPF1, is essential to pancreatic development and the maintenance of β-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM. Methods We screened 71 Caucasian and 69 African American individuals for genetic variants in the promoter region, three highly conserved upstream regulatory sequences (PH1, PH2 and PH3, the human β-cell specific enhancer, and the two exons with adjacent introns. We tested for an association of each variant with T2DM Caucasians (192 cases and 192 controls and African Americans (341 cases and 186 controls. Results We identified 8 variants in the two populations, including a 3 bp insertion in exon 2 (InsCCG243 in African Americans that resulted in an in-frame proline insertion in the transactivation domain. No variant was associated with T2DM in Caucasians, but polymorphisms at -3766 in the human β-cell enhancer, at -2877 bp in the PH1 domain, and at -108 bp in the promoter region were associated with T2DM in African American subjects (p Conculsion The common alleles of regulatory variants in the 5' enhancer and promoter regions of the IPF1 gene increase susceptibility to type 2 diabetes among African American individuals, likely as a result of gene-gene or gene-environment interactions. In contrast, IPF1 is not a cause of type 2 diabetes in Caucasians. A previously described InsCCG243 variant may contribute to diabetes susceptibility in African American individuals, but is of low penetrance.
Changes in Insulin-like Growth Factor-1 Level in Patients with Sepsis and Septic Shock
Sang Hoon Lee
Full Text Available Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1 has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA. Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively. Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029. Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038. IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.
Association Between Omentin, Visfatin and Insulin-Like Growth Factor-1 in Women With Metabolic Syndrome
Full Text Available Background Adipokines that are produced by adipose tissue have extensive effects on carbohydrate and lipid metabolism and also on the pathogenesis of the metabolic syndrome (MetS. Objectives This study aimed to measure the concentrations of omentin-1, visfatin and insulin-like growth factor-1 (IGF-1 as likely markers of metabolic syndrome and also to demonstrate their associations in women with MetS. Materials and Methods Eighty women with MetS and eighty healthy women as controls participated in this study. Blood pressure, waist circumference, body mass index (BMI, and serum biochemical parameters were determined in all subjects. The serum level of IGF-1, omentin-1 and visfatin were assessed using the enzyme linked immunosorbent assay (ELISA. The association between omentin, visfatin and IGF-1 was also determined in these women. Results Significantly lower levels of omentin-1 and IGF-1 were observed in MetS subjects compared to the controls (P = 0.009 and < 0.001 respectively. However, a significant difference was not observed in visfatin concentration between the two studied groups (P = 0.67. A positive association was observed between omentin-1, visfatin and IGF-1 in the MetS group. Conclusions Our findings indicated a lower level of both omentin-1 and IGF-1 in women with MetS; this might play a role in the pathogenesis of MetS. Furthermore, the main finding of the current investigation was the association between omentin, visfatin and IGF-1; however determining the molecular mechanism of the observed relationships needs further studies.
Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.
Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A
We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.
Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.
Koichi Murata
Full Text Available Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/- mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/- mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/- mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/- mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/- mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/- mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/- mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/- mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.
Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.
Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy; Awara, Mahmoud A; Moniz, Caje; le Roux, Carel W
Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.
Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats
Ji-Min Wang
Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.
Impact of insulin like growth factor-1 in development of coronary artery ectasia
Ibrahim Faruk Akturk
Full Text Available Coronary artery ectasia (CAE is characterized by inappropriate dilatation of the coronary vasculature. The mechanisms of CAE are not well known. Insulin-like growth factor-1 (IGF-1 may make endothelial cells and smooth muscle cells more sensitive to the effects of growth hormone. In the present study, we hypothesized that IGF-1 may have an impact on the formation of ectasia and aneurysm in arterial system, and aimed to investigate the associations between the presence of CAE and serum IGF-1 levels in patients undergoing coronary angiography. The study included 2.980 subjects undergoing elective diagnostic coronary angiography. We selected 40 patients diagnosed with CAE as CAE group and 44 subjects with absolutely normal coronary arteries were assigned as normal control group. IGF-1 levels were measured in both groups of patients. Groups were similar in terms of age, sex and coronary artery disease risk factors. The serum IGF-1 levels were significantly higher in CAE patients with 109.64±54.64 ng/mL than in controls with 84.76±34.01 ng/mL (p=0.016. HDL levels were lower in ectasia group with 41.5±10.7 mg/dL than controls with 47.7±10.4 mg/dL (p=0.018. By means of logistic regression analysis, high IGF-1 and low HDL levels were found to be independent risk factors for the presence of CAE (p<0.02, p<0.016, respectively. The study revealed that there was a positive correlation between serum IGF-1 levels and presence of CAE, and high IGF-1 levels and low HDL levels were independent risk factors for the presence of CAE. Future studies are needed to confirm these results.
Effect of Hypoxia-Inducible Factor 1α on Early Healing in Extraction Sockets
Hyun-Chang Lim
Full Text Available The aim of the present study was to investigate the effect of hypoxia-inducible factor 1α (HIF1A on the early healing (4 weeks of extraction sockets exhibiting partial loss of the labial bone. Two extraction sockets of the maxillary incisors from each of six dogs were assigned to two treatment modalities: deproteinized bovine bone mineral (i with 10% collagen (DBBM-C soaked with HIF1A and covered by a collagen membrane (CM (HIF group or (ii treated with DBBM-C only and covered by a CM (control group. Microcomputed tomography revealed some degree of collapse of the labial contour. The totally augmented volume and new bone volume did not differ significantly between two groups (P>0.05. The histological analysis revealed that the apical area of the socket was mostly filled with newly formed bone, while there was less newly formed bone in the coronal area and incomplete cortex formation. The histomorphometric analysis revealed that the area of newly formed bone was significantly larger in the HIF group than the control group (12.16±3.04 versus 9.48±2.01 mm2, P<0.05, while there was no significant intergroup difference in the total augmented area. In conclusion, even though DBBM-C soaked with HIF1A enhanced histomorphometric bone formation, this intervention did not demonstrate superiority in preventing ridge shrinkage compared to DBBM-C alone. Clinical relevance of these findings should be further studied.
Stromal cell-derived factor 1 regulates the actin organization of chondrocytes and chondrocyte hypertrophy.
Murata, Koichi; Kitaori, Toshiyuki; Oishi, Shinya; Watanabe, Naoki; Yoshitomi, Hiroyuki; Tanida, Shimei; Ishikawa, Masahiro; Kasahara, Takashi; Shibuya, Hideyuki; Fujii, Nobutaka; Nagasawa, Takashi; Nakamura, Takashi; Ito, Hiromu
Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF) plays important roles in the biological and physiological functions of haematopoietic and mesenchymal stem cells. This chemokine regulates the formation of multiple organ systems during embryogenesis. However, its roles in skeletal development remain unclear. Here we investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic chondrocytes in the newly formed endochondral callus of rib fracture as well as in the growth plate of normal mouse tibia by immunohistochemical analysis. Using SDF-1(-/-) mouse embryo, we histologically showed that the total length of the whole humeri of SDF-1(-/-) mice was significantly shorter than that of wild-type mice, which was contributed mainly by shorter hypertrophic and calcified zones in SDF-1(-/-) mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/-) mouse humeri showed less F-actin and rounder shape than that of wild-type mice. Primary chondrocytes from SDF-1(-/-) mice showed the enhanced formation of philopodia and loss of F-actin. The administration of SDF-1 to primary chondrocytes of wild-type mice and SDF-1(-/-) mice promoted the formation of actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/-) mice showed the growth delay, which was recovered by an exogenous administration of SDF-1. mRNA expression of type X collagen in metatarsals and in primary chondrocytes of SDF-1(-/-) mouse embryo was down-regulated while the administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1 regulates the actin organization and stimulates bone growth by mediating chondrocyte hypertrophy.
Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.
Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K; van Wijk, Albert C; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C; van Gulik, Thomas M; Storm, Gert; Heger, Michal
Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.
Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia
Pei Wang
Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.
Hypoxia-inducible factor 1α mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia.
Zhu, Tingna; Zhan, Lixuan; Liang, Donghai; Hu, Jiaoyue; Lu, Zhiwei; Zhu, Xinyong; Sun, Weiwen; Liu, Liu; Xu, En
Hypoxia administered after transient global cerebral ischemia (tGCI) has been shown to induce neuroprotection in adult rats, but the underlying mechanisms for this protection are unclear. Here, we tested the hypothesis that hypoxic postconditioning (HPC) induces neuroprotection through upregulation of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), and that this involves phosphatidylinositol-3-kinase (PI3K), p38 mitogen-activated protein kinase (p38 MAPK), and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) pathways. The expression of HIF-1α, VEGF, and cleaved caspase-9 were determined by immunohistochemistry and Western blot. As pharmacologic interventions, the HIF-1α inhibitor 2-methoxyestradiol (2ME2), PI3K inhibitor LY294002, p38 MAPK inhibitor SB203580, and MEK inhibitor U0126 were administered before HPC or after tGCI. We found that HPC maintained the higher expression of HIF-1α and VEGF and decreased cleaved caspase-9 levels in CA1 after tGCI. These effects were reversed by 2ME2 administered before HPC, and the neuroprotection of HPC was abolished. LY294002 and SB203580 decreased the expression of HIF-1α and VEGF after HPC, whereas U0126 increased HIF-1α and VEGF after tGCI. These findings suggested that HIF-1α exerts neuroprotection induced by HPC against tGCI through VEGF upregulation and cleaved caspase-9 downregulation, and that the PI3K, p38 MAPK, and MEK pathways are involved in the regulation of HIF-1α and VEGF.
Insulin-like growth factor 1 (IGF-1): a growth hormone
Laron, Z
Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173
Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne.
Ben-Amitai, D; Laron, Z
The role of growth hormone, insulin, and insulin-like growth factor-1 (IGF-1) in the development of acne is incompletely understood. To study the effect of the absence of IGF-1 and its pharmacologic replacement on the occurrence of acne vulgaris. Laron syndrome (LS) is characterized by congenital IGF-1 deficiency. The study group consisted of 21 patients with classical LS, who underwent puberty: 13 (8 male, 5 female) untreated and under regular follow-up until age 20?48 years; and 8 (2 male, 6 female) treated with IGF-1 (70-200 μg/kg/day), including 6 adults (2 male, treated at age 14.5-29 years and 4 female, treated at age 30-37 years) and 2 adolescents (2 female, treated at age 3.5-16 years). The medical files were reviewed for occurrence of acne and the corresponding sex hormone levels, and the findings were compared between the treated and untreated patients. Puberty was delayed in all untreated patients. Only one patient had slight acne at age 22 years, when he reached full puberty. Among the 2 IGF-1 treated male patients, none acquired acne. Among the 6 treated female patients, 3 had signs of hyperandrogenism (oligo-amenorrhea) and acne during IGF-1 over-dosage. On reduction of the IGF-1 dose (to 50 μg/kg/day) or cessation of treatment, the acne disappeared in all 3 patients. This study demonstrates for the first time that serum IGF-1 deficiency prevents the occurrence of acne. The findings suggest that an interaction between IGF-1 and androgens is necessary for the development of acne. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.
Effects of spaceflight and Insulin-like Growth Factor-1 on rat bone properties
Bateman, T.A.; Ayers, R.A.; Spetzler, M.L.; Simske, S.J. [BioServe Space Technologies University of Colorado Boulder, Colorado80309-0429 (United States); Zimmerman, R.J. [Chiron Corporation 4560 Horton Street Emeryville, California94608-2916 (United States)
Spaceflight induces bone degradation which is analogous to an accelerated onset of osteoporosis in humans (Tilton {ital et al.}, 1980). In rats, decreased bone formation is indicative of reduced osteoblast activity (Morey and Baylink, 1978). Chiron Corporation (Emeryville, CA) is interested in using the microgravity environment of low-Earth-orbit to test its therapeutic drug, Insulin-like Growth Factor-1 (IGF-1). This pharmaceutic is known to promote osteoblast activity (Schmid {ital et al.}, 1984) and therefore may encourage bone growth in rats. Chiron sponsored the Immune.3 payload on STS-73 (May 19{endash}29, 1996) through its Center for Space Commercialization (CSC) partner BioServe Space Technologies (University of Colorado and Kansas State University) to investigate the effects of IGF-1 on mitigating the skeletal degradation that affects rats and humans during spaceflight. Twelve rats were flown for 10 days using two Animal Enclosure Modules (AEMs) provided by NASA Ames Research Center. Of the twelve, six received 1.4 mg/day of IGF-1; the other six saline. Sixteen vivarium ground controls received the same treatment on a one day delay. Rat femora and tibiae were examined for bone mineral density via DXA scan. Femora and humeri were measured for physical and compositional properties, as well as mechanically tested in three point flexure. Quantitative histomorphometric examination of tibiae, humeri, fibulae, ribs and cranial bone; and microhardness testing on tibiae and humeri are currently in progress. Flight humeri and vivarium femora were significantly larger than their counterparts; however, significant differences in mechanical properties and mineral density were not concurrent to these mass changes. {copyright} {ital 1997 American Institute of Physics.}
Glutamine's protection against cellular injury is dependent on heat shock factor-1.
Morrison, Angela L; Dinges, Martin; Singleton, Kristen D; Odoms, Kelli; Wong, Hector R; Wischmeyer, Paul E
Glutamine (GLN) has been shown to protect cells, tissues, and whole organisms from stress and injury. Enhanced expression of heat shock protein (HSP) has been hypothesized to be responsible for this protection. To date, there are no clear mechanistic data confirming this relationship. This study tested the hypothesis that GLN-mediated activation of the HSP pathway via heat shock factor-1 (HSF-1) is responsible for cellular protection. Wild-type HSF-1 (HSF-1(+/+)) and knockout (HSF-1(-/-)) mouse fibroblasts were used in all experiments. Cells were treated with GLN concentrations ranging from 0 to 16 mM and exposed to heat stress injury in a concurrent treatment model. Cell viability was assayed with phenazine methosulfate plus tetrazolium salt, HSP-70, HSP-25, and nuclear HSF-1 expression via Western blot analysis, and HSF-1/heat shock element (HSE) binding via EMSA. GLN significantly attenuated heat-stress induced cell death in HSF-1(+/+) cells in a dose-dependent manner; however, the survival benefit of GLN was lost in HSF-1(-/-) cells. GLN led to a dose-dependent increase in HSP-70 and HSP-25 expression after heat stress. No inducible HSP expression was observed in HSF-1(-/-) cells. GLN increased unphosphorylated HSF-1 in the nucleus before heat stress. This was accompanied by a GLN-mediated increase in HSF-1/HSE binding and nuclear content of phosphorylated HSF-1 after heat stress. This is the first demonstration that GLN-mediated cellular protection after heat-stress injury is related to HSF-1 expression and cellular capacity to activate an HSP response. Furthermore, the mechanism of GLN-mediated protection against injury appears to involve an increase in nuclear HSF-1 content before stress and increased HSF-1 promoter binding and phosphorylation.
Hypoxia-inducible factor-1α induces multidrug resistance protein in colon cancer
Lv Y
Full Text Available Yingqian Lv, Shan Zhao, Jinzhu Han, Likang Zheng, Zixin Yang, Li Zhao Department of Oncology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China Abstract: Multidrug resistance is the major cause of chemotherapy failure in many solid tumors, including colon cancer. Hypoxic environment is a feature for all solid tumors and is important for the development of tumor resistance to chemotherapy. Hypoxia-inducible factor (HIF-1α is the key transcription factor that mediates cellular response to hypoxia. HIF-1α has been shown to play an important role in tumor resistance; however, the mechanism is still not fully understood. Here, we found that HIF-1α and the drug resistance-associated gene multidrug resistance associated protein 1 (MRP1 were induced by treatment of colon cancer cells with the hypoxia-mimetic agent cobalt chloride. Inhibition of HIF-1α by RNA interference and dominant-negative protein can significantly reduce the induction of MRP1 by hypoxia. Bioinformatics analysis showed that a hypoxia response element is located at -378 to -373 bp upstream of the transcription start site of MRP1 gene. Luciferase reporter assay combined with mutation analysis confirmed that this element is essential for hypoxia-mediated activation of MRP gene. Furthermore, RNA interference revealed that HIF-1α is necessary for this hypoxia-driven activation of MRP1 promoter. Importantly, chromatin immunoprecipitation analysis demonstrated that HIF-1α could directly bind to this HRE site in vivo. Together, these data suggest that MRP1 is a downstream target gene of HIF-1α, which provides a potential novel mechanism for HIF-1α-mediated drug resistance in colon cancer and maybe other solid tumors as well. Keywords: hypoxia, hypoxia-inducible factor-1α, multidrug resistance associated protein, transcriptional regulation, chemotherapy tolerance
Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation
Retamales, A.; Zuloaga, R.; Valenzuela, C.A.; Gallardo-Escarate, C.; Molina, A.; Valdés, J.A.
Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast
Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice
Zhao, Yan-Ying, E-mail: firstname.lastname@example.com [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Huang, Xin-Yuan [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China); Chen, Zheng-Wang [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)
Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.
Effects of insulin-like growth factor-1 (IGF-1) and amifostine in spinal cord reirradiation
Nieder, C.; Andratschke, N.; Price, R.E.; Rivera, B.; Ang, K. Kian
Purpose: To test whether insulin-like growth factor-1 (IGF-1) and amifostine modulate the reirradiation tolerance of rat cervical spinal cord. Initial experiments by the authors' group suggested that administration of each agent alone significantly increased the median latent time to radiation myelopathy (RM) in previously unirradiated animals but did not change the dose-response relationship. Because of different modes of action, a follow-up study was undertaken to test the combined treatment. Material and Methods: The cervical spinal cord of 51 adult Fisher F-344 rats received a single fraction of 16 Gy, which corresponds to approximately 75% of the median paresis dose (ED 50 ), followed 5 months later by a second radiation dose, which ranged from 17 to 21 Gy. The study animals received a single intrathecal injection of 0.3 mg amifostine into the cisterna magna 30-60 min before reirradiation plus three subcutaneous doses of IGF-1 (700 μg) starting from 24 h before to 24 h after reirradiation. Control animals received saline injections via the same routes. Animals were followed until RM developed or until 12 months from reirradiation. Histopathologic examinations were performed post mortem. Results: No animals showed any neurologic abnormalities before reirradiation. RM occurred in controls versus treated rats after a mean latency of 218 versus 314 days (19 Gy; p=0.11) and 104 versus 186 days (21 Gy; p=0.002) from second dose (Figure 1). ED 50 was 18.2 versus 19.4 Gy (p=0.15; Figure 2). Treatment with IGF-1 and amifostine did not significantly influence the rates of tumor induction or intercurrent death. Conclusion: IGF-1 and amifostine significantly reduced RM rates after 21 Gy. The shift of the dose-response curve suggests an increase of the ED 50 for single-dose treatment by approximately 7%. Thus, brief therapeutic intervention might slightly decrease radiation-induced neurotoxicity in a retreatment situation. (orig.)
Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation
Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Li, Zhiguo [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Department of Immunology, Duke University Medical Center, Durham, North Carolina (United States); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Chen, Benny J., E-mail: email@example.com [Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States)
Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.
Investigations of labeling insulin-like growth factor-1 analogue with 188Re
Zhang Bin; Wu Yiwei; Fan Wo
Objective: To establish a stable method for labeling insulin-like growth factor-1 analogue (IGF-1A) with 188 Re. Methods: The directly labeling method was adopted. Several labeling conditions were tested, such as the volume of Tween-80, the concentration of SnCl 2 ·2H 2 O, the amount of IGF-1A, and the volume of 188 Re perrhenate. The labeling efficiency was determined from 15 min to 8 h after labeling. The in vitro stability of 188 Re-IGF-1A was analyzed by using human serum or sodium chloride as challenging agent, and the labeling efficiency was determined from 2 to 24 h after added challenging agent. Results: The optimum labeling conditions were 10 μl 0.1% Tween-80, 100 μl SnCl 2 · 2H 2 O (10 mg/ml), 50 μl IGF-1A (2 mg/ml), and 50 μl 188 Re perrhenate, incubated 30 min at room temperature. The labeling efficiency of 188 Re-IGF-1A could reach (94.07 ± 0.32)% and the amount of radiocolloid was (5.50 ± 1.50)%. It was (89.07 ± 0.74)% after incubation for 6 h at room temperature, and was (76.57 ± 9.96)% after incubation for 24 h with human serum. Conclusion: This method of labeling IGF- 1A with 188 Re using SnCl 2 ·2H 2 O is stable and high labeling efficiency can be obtained. (authors)
Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation
Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.
Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells
Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation
Limesand, Kirsten H.; Avila, Jennifer L.; Victory, Kerton; Chang, Hui-Hua; Shin, Yoon Joo; Grundmann, Oliver; Klein, Rob R.
Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.
Extensive proteomic remodeling is induced by eukaryotic translation elongation factor 1Bγ deletion in Aspergillus fumigatus.
O'Keeffe, Grainne; Jöchl, Christoph; Kavanagh, Kevin; Doyle, Sean
The opportunistic pathogen Aspergillus fumigatus is ubiquitous in the environment and predominantly infects immunocompromised patients. The functions of many genes remain unknown despite sequencing of the fungal genome. A putative translation elongation factor 1Bγ (eEF1Bγ, termed elfA; 750 bp) is expressed, and exhibits glutathione S-transferase activity, in A. fumigatus. Here, we demonstrate the role of ElfA in the oxidative stress response, as well as a possible involvement in translation and actin cytoskeleton organization, respectively. Comparative proteomics, in addition to phenotypic analysis, under basal and oxidative stress conditions, demonstrated a role for A. fumigatus elfA in the oxidative stress response. An elfA-deficient strain (A. fumigatus ΔelfA) was significantly more sensitive to the oxidants H2O2, diamide, and 4,4'-dipyridyl disulfide (DPS) than the wild-type. This was further supported with the identification of differentially expressed proteins of the oxidative stress response, including; mitochondrial peroxiredoxin Prx1, molecular chaperone Hsp70 and mitochondrial glycerol-3-phosphate dehydrogenase. Phenotypic analysis also revealed that A. fumigatus ΔelfA was significantly more tolerant to voriconazole than the wild-type. The differential expression of two aminoacyl-tRNA synthetases suggests a role for A. fumigatus elfA in translation, while the identification of actin-bundling protein Sac6 and vacuolar dynamin-like GTPase VpsA link A. fumigatus elfA to the actin cytoskeleton. Overall, this work highlights the diverse roles of A. fumigatus elfA, with respect to translation, oxidative stress and actin cytoskeleton organization. In addition to this, the strategy of combining targeted gene deletion with comparative proteomics for elucidating the role of proteins of unknown function is further revealed. © 2013 The Protein Society.
Insulin-Like Growth Factor-1 Levels in Term Newborns with Hypoxic-Ischemic Encephalopathy.
Umran, Raid M R; Al-Tahir, Mahir; Jagdish, Desai; Chouthai, Nitin
Objective This study aims to evaluate the correlation of changes in serum insulin-like growth factor-1 (IGF-1) levels with the clinical staging of hypoxic-ischemic encephalopathy (HIE) in term newborns. Study Design A prospective study of 29 newborns with HIE (stage I = 15, stage II + III = 14) and 28 healthy term newborns as the control group was performed in the neonatal intensive care unit. IGF-1 levels were obtained within 6 hours after birth from HIE and control groups and again on day 3 from HIE group. HIE was classified using the Sarnat staging I to III. Results IGF-1 levels were significantly lower in the HIE group than in the control group (p = 0.024). It was lower in the HIE stage II to III group compared with HIE stage I group at birth (p < 0.0001) and on day 3 (p = 0.009). The mean IGF-1 levels were significantly higher on day 3 than on day 1 among stage II to III HIE (p = 0.006) and it was inversely correlated with staging (R = - 0.475, p = 0.009). There was a significant correlation between IGF-1 levels and Apgar score at 5 (R = 0.39, p = 0.042) and 10 minutes (R = 0.38, p = 0.035). Conclusions IGF-1 was lower in HIE and inversely correlated with clinical staging. It was increased with clinical improvement in the subsequent days. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Suckling induced insulin-like growth factor-1 (IGF-1) release in mother rats.
Lékó, András H; Cservenák, Melinda; Dobolyi, Árpád
Lactation involves significant neuroendocrine changes. The elevated prolactin (PRL) release from the pituitary, induced markedly by suckling, is the most relevant example. Suckling also causes a significant and rapid elevation in growth hormone (GH) levels. GH is necessary for milk synthesis as milk yield is stopped completely in the absence of PRL and GH, while the absence of PRL alone causes only a 50% reduction. Insulin-like growth factor-1 (IGF-1) plays an important role in the GH axis. GH exerts its effects through IGF-1 in the periphery, for example in the mammary gland. In addition, IGF-1 is responsible for the long-loop feedback control of GH secretion. IGF-1 secretion has not been established yet in mothers. Therefore, in the present study, we investigated the effect of suckling on serum IGF-1 level in rat mothers and correlated it with serum PRL levels. We examined a potential mechanism of the regulation of IGF-1 level during suckling by administering IGF-1 into the lateral ventricle of rat mothers continuously for 12days, or acutely, right before the start of suckling. We described that suckling affected IGF-1 release based on one-way repeated measures ANOVA (F=10.8 and pIGF-1 level 30min after the start of suckling (pIGF-1 release. The prolonged central IGF-1 administration diminished the suckling-induced IGF-1 surge (F=9.19 and pIGF-1 release either by elevating PRL or GH. Long-loop feedback via IGF-1 in the GH axis can diminish this action. Copyright © 2017 Elsevier Ltd. All rights reserved.
Hydrogen-deuterium exchange studies of the rat thyroid transcription factor 1 homeodomain
Esposito, Gennaro; Fogolari, Federico; Damante, Giuseppe; Formisano, Silvestro; Tell, Gianluca; Leonardi, Antonio; Di Lauro, Roberto; Viglino, Paolo
The 1 H NMR solution structure of the rat thyroid transcription factor 1 homeodomain (TTF-1 HD) showed that the molecule folds like classical homeodomains. The C-terminal extension of helix III (fragment 51-59) appeared to adopt a helical geometry, albeit not as rigid as the preceding portion, but the hydrogen-deuterium exchange of backboneamides and the NOE data provided evidence of a discontinuity between the two moieties of helix III at the highly conserved fragmentAsn 51 -His 52 -Arg 53 .Analysis of quantitative measurements of isotope exchange rates allows one to recognize the general occurrence, in that region of HD motifs, of opposite effects to helix III stability. Asparagine, histidine and arginine residues occur most frequently at the beginning and end of protein helices.In TTF-1 HD a local fluctuation is observed in the fragment 51-53 which either kinks or tightens the α-helix. A search through the protein structure database reveals that the three most common variants of HD fragments 51-53 are often involved in helices and, frequently, in helix initiation or termination. For homeodomains in general, the nature of the fragment 51-53 may be related to the conformational dynamics of their DNA-recognition helix (helix III). Besides the specific results on fragment 51-53, the complete isotope exchange analysis of TTF-1 HD data shows that the partially solvent-exposed recognition helix is stabilized by hydrophobic interactions, like most of the structured regions of the molecule. Hydrophobic stabilization of the contacting regions meets the requirements of a DNA-interaction mechanism which, as shown with other DNA-protein complexes, should entail negative heat capacity variations due to changes in solvent exposure of the nonpolar protein surface
Diversification of the insulin-like growth factor 1 gene in mammals.
Peter Rotwein
Full Text Available Insulin-like growth factor 1 (IGF1, a small, secreted peptide growth factor, is involved in a variety of physiological and patho-physiological processes, including somatic growth, tissue repair, and metabolism of carbohydrates, proteins, and lipids. IGF1 gene expression appears to be controlled by several different signaling cascades in the few species in which it has been evaluated, with growth hormone playing a major role by activating a pathway involving the Stat5b transcription factor. Here, genes encoding IGF1 have been evaluated in 25 different mammalian species representing 15 different orders and ranging over ~180 million years of evolutionary diversification. Parts of the IGF1 gene have been fairly well conserved. Like rat Igf1 and human IGF1, 21 of 23 other genes are composed of 6 exons and 5 introns, and all 23 also contain recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are similar in most species, and DNA sequence conservation is moderately high in orthologous exons and proximal promoter regions. In contrast, putative growth hormone-activated Stat5b-binding enhancers found in analogous locations in rodent Igf1 and in human IGF1 loci, have undergone substantial variation in other mammals, and a processed retro-transposed IGF1 pseudogene is found in the sloth locus, but not in other mammalian genomes. Taken together, the fairly high level of organizational and nucleotide sequence similarity in the IGF1 gene among these 25 species supports the contention that some common regulatory pathways had existed prior to the beginning of mammalian speciation.
Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation
Retamales, A.; Zuloaga, R.; Valenzuela, C.A. [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Gallardo-Escarate, C. [Laboratory of Biotechnology and Aquatic Genomics, Universidad de Concepción, Concepción (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile); Molina, A. [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile); Valdés, J.A., E-mail: email@example.com [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile)
Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.
Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.
Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha
Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.
Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.
Hidekazu Kuwayama
Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.
AZD5363 inhibits inflammatory synergy between interleukin-17 and insulin/insulin-like growth factor 1
Chong eChen
Full Text Available In the United States, one third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1 and interleukin-17 (IL-17. Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-kappa B (NF-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase GSK3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1, C-C motif ligand 20 (Ccl20 and interleukin-6 (Il-6 in wild-type, GSK3α-/-, and GSK3β-/- mouse embryonic fibroblast (MEF cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17- induced expression of Cxcl1, Ccl20 and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.
Expression and purification of recombinant truncated human keratinocyte growth factor-1
Deng Lin; Ma Jisheng; Liu Xiaoju; Wang Xiaojie; Li Xiaokun; Gong Shouliang; Wang Huiyan; Tian Haishan
Objective: To construct the genetic engineering bacteria highly expressing 23 amino acids human keratinocyte growth factor-1 (rhKGF1 dest23 ) missing N terminal, and provide experimental data for development of new drug for treatment of oral mucositis after radiotherapy and chemotherapy. Methods: PCR was used to synthese 23 amino acids rhKGF1 dest23 missing N terminal and sumo gene fragments, and construct four kinds of recombinant prokaryotic expression vectors: pET22b-rhKGF1 dest23 , pET22b-sumo-rhKGF1 dest23 , pET3c-rhKGF1 dest23 and pET3c-sumo-rhKGF1 dest23 , then they were transformed into prokaryotic expression host bacteria: Rosetta (DE3) plysS, BL21 (DE3), BL21 (DE3) Star plysS, origima(DE3) and BL21AI, the best expression combination of plasmid and host strain of rhKGF1 dest23 protein was screened and purified by CM ion-exchange and heparin affinity chromatography and identified with Western blotting. Results: pET22b-rhKGF1 dest23 plasmid and the BL21AI host bacteria was the best combination of expression, after induced by IPTG and arabinose, the majority of recombinant protein was expressed in soluble form, accounting for about 12% of the total bacterial proteins. Its purity reached to more than 95% of the protein after two steps chromatography, then conformed with Western blotting. Conclusion: Human genetic engineering bacteria of KGF1 dest23 is successfully constructed and induced by IPTG and arabinose, then after CM weak cation exchange and heparin affinity chromatography, the purified rhKGF1 dest23 protein is obtained. (authors)
Fluvastatin increases insulin-like growth factor-1 gene expression in rat model of metabolic syndrome
Mansy, Wael H.; Sourour, Doaa A.; Shaker, Olfat G.; Mahfouz, Mahmoud M.
Insulin-like growth factor-1 (IGF-1) was found to have a role in both glucose homeostasis and cardiovascular diseases. The present study was designed to compare the effects of fluvastatin and metformin on IGF-1 mRNA expression within the liver and other individual components of the metabolic syndrome induced in rats by high fructose feeding. Rats fed 60% fructose in diet for 6 weeks were treated daily with fluvastatin (3.75 mg/kg/day) during the last two weeks and were compared with untreated fructose fed group. Fasting levels of plasma cholesterol, triglyceride, glucose, insulin, nitric oxide products, IGF-1 mRNA within the liver as well as systolic blood pressure and body weight were determined. Compared to control rats, the fructose fed group developed hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia and endothelial dysfunction as well as decreased levels of plasma IGF-1 and its mRNA within the liver. Fructose fed rats treated with fluvastatin or metformin for 2 weeks showed significant decrease in plasma cholesterol, triglyceride, insulin and glucose levels compared to untreated fructose fed group. Also, both drugs increased significantly plasma levels of nitric oxide products and IGF-1 together with significant increase in IGF-1 mRNA within the liver. However, only metformin treated rats showed significant decrease in systolic blood pressure compared to fructose fed group. This study showed that in a rat model of insulin resistance, fluvastatin improves the metabolic profile and increases plasma level of IGF-1 and its gene expression as effective as metformin. (author)
Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression
Ma, Qi-lin; Yang, Tian-lun [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yin, Ji-ye [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Peng, Zhen-yu [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yu, Min [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: firstname.lastname@example.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Chen, Fang-ping, E-mail: email@example.com [Department of Haematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China)
Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 {mu}g/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT{sub 1}) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 {mu}mol/L) induced HUVECs arrested at G{sub 0}/G{sub 1}, enhanced the expression level of AT{sub 1} mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT{sub 1} mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G{sub 0}/G{sub 1} and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.
Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression
Ma, Qi-lin; Yang, Tian-lun; Yin, Ji-ye; Peng, Zhen-yu; Yu, Min; Liu, Zhao-qian; Chen, Fang-ping
Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 μg/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT 1 ) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 μmol/L) induced HUVECs arrested at G 0 /G 1 , enhanced the expression level of AT 1 mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT 1 mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G 0 /G 1 and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.
Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia.
McCall-Hosenfeld, Jennifer S; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K
To determine activity of the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis in women with fibromyalgia (FM). Premenopausal women with FM (n = 24) and premenopausal healthy women (n = 27) were studied. IGF-1 was measured in 23 patients with FM and 25 controls. GH was measured during a stepped hypoglycemic hyperinsulinemic clamp procedure (blood glucose decreased from 90 to 40 mg/dl every 30 min in 10 mg/dl decrements) in 12 FM and 13 control subjects. IGF-1 concentrations were similar in the FM (200 +/- 71 ng/ml, mean +/- SD) and control (184 +/- 70 ng/ml) groups. By multiple variable analysis, IGF-1 was negatively associated with age (p = 0.0006), body mass index (BMI) (p = 0.006), and 24 h urinary free cortisol (p = 0.007) in healthy controls. Even after accounting for these factors, there was no association between FM and IGF-1. The average peak GH achieved during hypoglycemia was lower in patients with FM (range 5 to 58 ng/ml, median 13 ng/ml) versus controls (6 to 68 ng/ml, median 21 ng/ml) (p = 0.04). However, BMI was a significant predictor of average peak GH in FM (r = -0.62, p BMI, there was no significant association between FM subjects and the average peak GH (p = 0.20). In this sample of premenopausal women with FM, the activity of the GH-IGF-1 axis was similar to that of healthy controls. Increases in age and obesity were both strongly associated with lower activity of this axis, suggesting that these factors must be considered when studying activity of the GH-IGF-1 axis in FM.
Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion
Ying Yang
Full Text Available Hypoxia inducible factor 1α (HIF-1α, a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs, were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.
How best to capture the respiratory consequences of prematurity?
Ciuffini, Francesca; Robertson, Colin F; Tingay, David G
Chronic respiratory morbidity is a common complication of premature birth, generally defined by the presence of bronchopulmonary dysplasia, both clinically and in trials of respiratory therapies. However, recent data have highlighted that bronchopulmonary dysplasia does not correlate with chronic respiratory morbidity in older children born preterm. Longitudinally evaluating pulmonary morbidity from early life through to childhood provides a more rational method of defining the continuum of chronic respiratory morbidity of prematurity, and offers new insights into the efficacy of neonatal respiratory interventions. The changing nature of preterm lung disease suggests that a multimodal approach using dynamic lung function assessment will be needed to assess the efficacy of a neonatal respiratory therapy and predict the long-term respiratory consequences of premature birth. Our aim is to review the literature regarding the long-term respiratory outcomes of neonatal respiratory strategies, the difficulties of assessing dynamic lung function in infants, and potential new solutions. Copyright ©ERS 2018.
Airway Reflux, Cough and Respiratory Disease
Molyneux, Ian D.; Morice, Alyn H.
It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752
Measurements of respiratory illness among construction painters.
White, M C; Baker, E L
The prevalence of different measurements of respiratory illness among construction painters was examined and the relation between respiratory illness and employment as a painter assessed in a cross sectional study of current male members of two local affiliates of a large international union of painters. Respiratory illness was measured by questionnaire and spirometry. Longer employment as a painter was associated with increased prevalence of chronic obstructive disease and an interactive effect was observed for smoking and duration of employment as a painter. Multiple regression analysis showed a significant association between years worked as a painter and a decrement in FEV1 equal to about 11 ml for each year worked. This association was larger among painters who had smoked. The prevalence of chronic bronchitis was significantly associated with increased use of spray application methods.
Extracorporeal respiratory support in adult patients
Thiago Gomes Romano
Full Text Available ABSTRACT In patients with severe respiratory failure, either hypoxemic or hypercapnic, life support with mechanical ventilation alone can be insufficient to meet their needs, especially if one tries to avoid ventilator settings that can cause injury to the lungs. In those patients, extracorporeal membrane oxygenation (ECMO, which is also very effective in removing carbon dioxide from the blood, can provide life support, allowing the application of protective lung ventilation. In this review article, we aim to explore some of the most relevant aspects of using ECMO for respiratory support. We discuss the history of respiratory support using ECMO in adults, as well as the clinical evidence; costs; indications; installation of the equipment; ventilator settings; daily care of the patient and the system; common troubleshooting; weaning; and discontinuation.
New ICRP human respiratory tract model
Bailey, M.R.
The new ICRP dosimetric model for the human respiratory tract is based on the premise that the large differences in radiation sensitivity of respiratory tract tissues, and the wide range of doses they receive argue for calculating specific tissue doses rather than average lung doses. The model is also directly applicable to the worldwide population of both workers and the public. The requirement to describe intake, and deposition, clearance and dosimetry in each respiratory tract region, for a wide range of subjects at various levels of exercise necessarily means that the model is more complex than that of ICRP Publication 30. The widespread use of powerful personal computers, and the availability of user-friendly software to implement the model, however, will make it widely and readily accessible when the report is published. (Author)
Respiratory hypersensitivity reactions to NSAIDs in Europe
Makowska, J S; Burney, P; Jarvis, D
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... and lower respiratory tract disorders. METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...
Maja Nikolić
Full Text Available Air pollution has very important influence on human health. Earlier investigations were not employed with estimation of influence of air pollution, which spring from traffic, on people health who live near busy cross – road.The aim of this paper was to determine how living near busy cross – road influences on appearance of respiratory symptoms and illness.400 adult people between 18-76 age who live five year least on this location at took a part in investigation. One group (200 live in Nis near the busiest cross-road, another group live in Niska Banja near cross-road with the smallest concentration of pollutants in last five years.We have determined that examines, who live near busy cross – road had statistical signify greater prevalence of all respiratory symptoms and pneumonia.Our investigation showed that living near busy cross road present risk factor for appearance of respiratory symptoms and pneumonia.
Endocan and the respiratory system: a review
Kechagia M
Full Text Available Maria Kechagia,1,2 Ioannis Papassotiriou,2 Konstantinos I Gourgoulianis1 1Respiratory Medicine Department, University of Thessaly Medical School, Larissa, 2Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece Abstract: Endocan, formerly called endothelial cell-specific molecule 1, is an endothelial cell-associated proteoglycan that is preferentially expressed by renal and pulmonary endothelium. It is upregulated by proangiogenic molecules as well as by pro-inflammatory cytokines, and since it reflects endothelial activation and dysfunction, it is regarded as a novel tissue and blood-based relevant biomarker. As such, it is increasingly being researched and evaluated in a wide spectrum of healthy and disease pathophysiological processes. Here, we review the present scientific knowledge on endocan, with emphasis on the evidence that underlines its possible clinical value as a prognostic marker in several malignant, inflammatory and obstructive disorders of the respiratory system. Keywords: endocan, endothelial dysfunction, inflammation, respiratory disorders
[Respiratory handicap. Recognition, evaluation and social benefits].
Marsac, J; Pujet, J C
The medico-social aspects of respiratory handicap pose some perplexing problems, notably in their recognition, rigorous evaluation and in the granting of social security benefits. The clinical and respiratory function data should be standardised and classified according to type and significance of respiratory disease and also according to the degree of co-operation and understanding of the patient. The respiratory handicap should be evaluated after considering the functional disability engendered by the disorder and their socio-professional repercussions. The abnormality in the lungs should be measured by resting tests; the degree of disability by exercise studies; the socio-professional handicap by ergonometric tests to assess the scale of the demands and requirements of family and social and professional life, indeed the cultural and economic style of the individual concerned. Such combined studies would enable recognition of severe chronic respiratory handicap leading to decisions for exemption certificates, such as cases of severe respiratory failure in patients requiring supplementary treatment for oxygen therapy or assisted ventilation. The benefits and grants offered to those with respiratory handicaps would involve a number of rights relating to: care, work, costs of replacement of workers in the event of prolonged sick leave or the benefits of an invalidity pension. There will be other allowances such as invalidity cards, lodging special studies and other rights particularly relating to lodging and special equipment. The present scale is difficult to use both because of its lack of specificity and its ill-chosen terminology. For better balance between the handicap and the benefits offered, a common and more flexible system, with a printed table should be at hand for the doctor to use for certain decisions: long term illness, period of invalidity or early retirement because of medical incapacity. Within each table a sub-section should exist to allow for
Quality verification for respiratory gated proton therapy
Kim, Eun Sook; Jang, Yo Jong; Park, Ji Yeon; Kang, Dong Yun; Yeom, Doo Seok
To verify accuracy of respiratory gated proton therapy by measuring and analyzing proton beam delivered when respiratory gated proton therapy is being performed in our institute. The plan data of 3 patients who took respiratory gated proton therapy were used to deliver proton beam from proton therapy system. The manufactured moving phantom was used to apply respiratory gating system to reproduce proton beam which was partially irradiated. The key characteristics of proton beam, range, spreat-out Bragg peak (SOBP) and output factor were measured 5 times and the same categories were measured in the continuous proton beam which was not performed with respiratory gating system. Multi-layer ionization chamber was used to measure range and SOBP, and Scanditronix Wellhofer and farmer chamber was used to measure output factor. The average ranges of 3 patients (A, B, C), who had taken respiratory gated proton therapy or not, were (A) 7.226, 7.230, (B) 12.216, 12.220 and (C) 19.918, 19.920 g/cm 2 and average SOBP were (A) 4.950, 4.940, (B) 6.496, 6.512 and (C) 8.486, 8.490 g/cm 2 . And average output factor were (A) 0.985, 0.984 (B) 1.026, 1.027 and (C) 1.138, 1.136 cGy/MU. The differences of average range were -0.004, -0.004, -0.002 g/cm 2 , that of SOBP were 0.010, -0.016, -0.004 g/cm 2 and that of output factor were 0.001, -0.001, 0.002 cGy/MU. It is observed that the range, SOBP and output factor of proton beam delivered when respiratory gated proton therapy is being performed have the same beam quality with no significant difference compared to the proton beam which was continuously irradiated. Therefore, this study verified the quality of proton beam delivered when respiratory gated proton therapy and confirmed the accuracy of proton therapy using this
Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.
Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago
Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.
T.A. Shemyakina
Full Text Available The researchers analyzed the efficacy of the new medical technology aimed at rehabilitation of the preschool children with the respiratory pathology. 177 children aged between 2 and 7 with recurrent respiratory diseases, bronchial asthma or chronic pathology of the end organs have been examined for 9 months. It was uncovered that among children (n = 90, who performed the sets of the therapeutic physical training and respiratory gymnastics according to the methods developed by the authors, the recurrence of the acute respiratory diseases and exacerbations of bronchial asthma was lower by 1,83 and 1,86 timers respectively. Besides, among children of this group the researchers noted the significant improvement of the physical qualities, spirometric indices and cytological picture of the substance removed from the nasal cavity if compared with the children from the screening group (n = 87, who performed the sets of the conventional gymnastics at the physical training lessons. Thus, the researchers proved the high efficacy of the proposed technology for the rehabilitation of the children, suffering from the chronic respiratory pathology.Key words: acute respiratory diseases, asthma, therapeutic physical training, respiratory gymnastics, children.
Radiological features of lower respiratory infection by respiratory syncytial virus in infants and young children
Kim, Woo Sun; Kim, In One; Yeon, Kyung Mo; Jang, Seong Hee; Lee, Hoan Jong
Respiratory syncytial virus is the most common cause of lower respiratory infection (bronchiolitis and pneumonia) of infancy and early childhood. We analyzed clinical and radiological features of 76 patients with lower respiratory infections by respiratory syncytial virus, which were diagnosed by indirect immunofluorescent test or culture of nasal aspirate in Hep-2-cell monolayer, during the period of January- December, 1991. There were peaks of incidences in March-May and November- December, accounting for 87% of eases. Sixty-two cases (82%) were under 1 year of age. Fifty cases (66%) had underlying diseases. Major radiographical findings were overaeration (83%), parahilar peribronchial infiltrates (67%), segmental or subsegmental atelectasis (32%), and segmental or lobar consolidation (16%). In 15 cases (20%), overaeration was the only radiological findings. There was no evidence of pleural effusion or lymph node enlargement in all cases. By considering clinical features (symptoms, age, underlying diseases, epidemic seasons) in addition to the radiological findings, radiologists would be familiar with lower respiratory infection by respiratory syncytial virus. Air space consolidation, which is generally thought to represent bacterial pneumonia, is also observed not infrequently in respiratory syncytial virus infection
Respiratory viral infections in infancy and school age respiratory outcomes and healthcare costs.
MacBean, Victoria; Drysdale, Simon B; Yarzi, Muska N; Peacock, Janet L; Rafferty, Gerrard F; Greenough, Anne
To determine the impact of viral lower respiratory tract infections (LRTIs) in infancy including rhinovirus (RV) and infancy respiratory syncytial virus (RSV), on school age pulmonary function and healthcare utilization in prematurely born children. School age respiratory outcomes would be worse and healthcare utilization greater in children who had viral LRTIs in infancy. Prospective study. A cohort of prematurely born children who had symptomatic LRTIs during infancy documented, was recalled. Pulmonary function was assessed at 5 to 7 years of age and health related costs of care from aged one to follow-up determined. Fifty-one children, median gestational age 33 +6 weeks, were assessed at a median (IQR) age 7.03 (6.37-7.26) years. Twenty-one children had no LRTI, 14 RV LRTI, 10 RSV LRTI, and 6 another viral LRTI (other LRTI). Compared to the no LRTI group, the RV group had a lower FEV 1 (P = 0.033) and the other LRTI group a lower FVC (P = 0.006). Non-respiratory medication costs were higher in the RV (P = 0.018) and RSV (P = 0.013) groups. Overall respiratory healthcare costs in the RV (£153/year) and RSV (£27/year) groups did not differ significantly from the no LRTI group (£56/year); the other LRTI group (£431/year) had higher respiratory healthcare costs (P = 0.042). In moderately prematurely born children, RV and RSV LRTIs in infancy were not associated with higher respiratory healthcare costs after infancy. Children who experienced LRTIs caused by other respiratory viruses (including RV) had higher respiratory healthcare costs and greater pulmonary function impairment. © 2018 Wiley Periodicals, Inc.
Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana.
Kwofie, Theophilus B; Anane, Yaw A; Nkrumah, Bernard; Annan, Augustina; Nguah, Samuel B; Owusu, Michael
Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.
Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana
Kwofie Theophilus B
Full Text Available Abstract Background Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Method Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Results Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2% were positive for one or more viruses. Respiratory Syncytial Virus (RSV was detected in 18(14.1%, 95%CI: 8.5% to 21.3% patients followed by Adenoviruses (AdV in 13(10.2%, 95%CI: 5.5% to 16.7%, Parainfluenza (PIV type: 1, 2, 3 in 4(3.1%, 95%CI: 0.9% to 7.8% and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3. Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36 of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. Conclusion The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.
Effect of respiratory function training on respiratory function of patients with severe cerebrovascular disease
Ming GUO
Full Text Available Objective To investigate the effect of respiratory function training on respiratory function and conscious state of patients with severe cerebrovascular disease (SCVD. Methods A total of 27 patients with SCVD were divided into control group (N = 17 and observation group (N = 10. Control group received routine drug and rehabilitation treatment, and observation group was added respiratory function training based on routine treatment. The respiratory rate, tidal volume (TV, heart rate, blood pressure and artery oxygen saturation (SaO2 of patients were monitored by breathing machine before and after 4-week treatment. Meanwhile, arterial blood gas analysis was used to detect arterial partial pressure of oxygen (PaO2, oxygenation index, partial pressure of carbon dioxide (PaCO2 and pH value. At the same time, Glasgow Coma Scale (GCS was used to evaluate the conscious state of patients. Results All patients successfully completed 4-week rehabilitation training, without asphyxia, arrhythmia or other adverse events. Compared with before training, the respiratory rate (P = 0.006 and pH value (P = 0.010 were significantly decreased, while SaO2 (P = 0.001, oxygenation index (P = 0.000 and GCS scores (P = 0.004, 0.017 were significantly increased in both groups of patients after training. There was no statistically significant difference between 2 groups on respiratory function indexes and GCS scores after training (P > 0.05, for all. Conclusions Respiratory function training did not significantly improve the respiratory function and conscious state of patients with SCVD, yet to be further studied. Randomized controlled clinical trials with larger, layered samples and long-term prognosis observation are needed. Examination method of respiratory function of SCVD patients is also a topic to be explored. DOI: 10.3969/j.issn.1672-6731.2017.04.007
The role of hypoxia inducible factor-1 alpha in bypassing oncogene-induced senescence.
Mehtap Kilic Eren
Full Text Available Oncogene induced senescence (OIS is a sustained anti-proliferative response acutely induced in primary cells via activation of mitogenic oncogenes such as Ras/BRAF. This mechanism acts as an initial barrier preventing normal cells transformation into malignant cell. Besides oncogenic activation and DNA damage response (DDR, senescence is modulated by a plethora of other factors, and one of the most important one is oxygen tension of the tissue. The aim of this study was to determine the impact of hypoxia on RasV12-induced senescence in human diploid fibroblasts (HDFs. We showed here that hypoxia prevents execution of oncogene induced senescence (OIS, through a strong down-regulation of senescence hallmarks, such as SA- β-galactosidase, H3K9me3, HP1γ, p53, p21CIP1 and p16INK4a in association with induction of hypoxia inducible factor-1α (HIF-1α. In addition, hypoxia also decreased marks of H-RasV12-induced DDR in both cell lines through down-regulation of ATM/ATR, Chk1 and Chk2 phosphorylation as well as decreased γ-H2AX positivity. Utilizing shRNA system targeting HIF-1α we show that HIF-1α is directly involved in down regulation of p53 and its target p21CIP1 but not p16INK4a. In line with this finding we found that knock down of HIF-1α leads to a strong induction of apoptotic response, but not restoration of senescence in Ras expressing HDFs in hypoxia. This indicates that HIF-1α is an important player in early steps of tumorigenesis, leading to suppression of senescence through its negative regulation of p53 and p21CIP1. In our work we describe a mechanism through which hypoxia and specifically HIF-1α preclude cells from maintaining senescence-driven anti proliferative response. These findings indicate the possible mechanism through which hypoxic environment helps premalignant cells to evade impingement of cellular failsafe pathways.
Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation
Yan, You-e [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Department of Pharmacology, Medical School of Yangtze University, Jingzhou 434000 (China); Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Wang, Hui, E-mail: firstname.lastname@example.com [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)
This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased
Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts.
Massicotte, Frédéric; Fernandes, Julio Cesar; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lajeunesse, Daniel
Human osteoarthritis (OA) is characterized by cartilage loss, bone sclerosis, osteophyte formation and inflammation of the synovial membrane. We previously reported that OA osteoblasts (Ob) show abnormal phenotypic characteristics possibly responsible for bone sclerosis and that two subgroups of OA patients can be identified by low or high endogenous production of prostaglandin E2 (PGE2) by OA Ob. Here, we determined that the elevated PGE2 levels in the high OA subgroup were linked with enhanced cyclooxygenase-2 (COX-2) protein levels compared to normal and low OA Ob. A linear relationship was observed between endogenous PGE2 levels and insulin-like growth factor 1 (IGF-1) levels in OA Ob. As parathyroid hormone (PTH) and PGE2 are known stimulators of IGF-1 production in Ob, we next evaluated their effect in OA Ob. Both subgroups increased their IGF-1 production similarly in response to PGE2, while the high OA subgroup showed a blunted response to PTH compared to the low OA group. Conversely, only the high OA group showed a significant inhibition of IGF-1 production when PGE2 synthesis was reduced with Naproxen, a non-steroidal antiinflammatory drug (NSAID) that inhibits cyclooxygenases (COX). The PGE2-dependent stimulation of IGF-1 synthesis was due in part to the cAMP/protein kinase A pathway since both the direct inhibition of this pathway with H-89 and the inhibition of EP2 or EP4 receptors, linked to cAMP production, reduced IGF-1 synthesis. The production of the most abundant IGF-1 binding proteins (IGFBPs) in bone tissue, IGFBP-3, -4, and -5, was lower in OA compared to normal Ob independently of the OA group. Under basal condition, OA Ob expressed similar IGF-1 mRNA to normal Ob; however, PGE2 stimulated IGF-1 mRNA expression more in OA than normal Ob. These data suggest that increased IGF-1 levels correlate with elevated endogenous PGE2 levels in OA Ob and that higher IGF-1 levels in OA Ob could be important for bone sclerosis in OA.
Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation
Yan, You-e; Liu, Lian; Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan; Wang, Hui
This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased
Effects of insulin-like growth factor-1 (IGF-1) and amifostine in spinal cord reirradiation
Nieder, C.; Andratschke, N. [TU Muenchen (Germany). Dept. of Radiation Oncology; Price, R.E.; Rivera, B. [University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Veterinary Medicine and Surgery; Ang, K. Kian [University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Radiation Oncology
Purpose: To test whether insulin-like growth factor-1 (IGF-1) and amifostine modulate the reirradiation tolerance of rat cervical spinal cord. Initial experiments by the authors' group suggested that administration of each agent alone significantly increased the median latent time to radiation myelopathy (RM) in previously unirradiated animals but did not change the dose-response relationship. Because of different modes of action, a follow-up study was undertaken to test the combined treatment. Material and Methods: The cervical spinal cord of 51 adult Fisher F-344 rats received a single fraction of 16 Gy, which corresponds to approximately 75% of the median paresis dose (ED{sub 50}), followed 5 months later by a second radiation dose, which ranged from 17 to 21 Gy. The study animals received a single intrathecal injection of 0.3 mg amifostine into the cisterna magna 30-60 min before reirradiation plus three subcutaneous doses of IGF-1 (700 {mu}g) starting from 24 h before to 24 h after reirradiation. Control animals received saline injections via the same routes. Animals were followed until RM developed or until 12 months from reirradiation. Histopathologic examinations were performed post mortem. Results: No animals showed any neurologic abnormalities before reirradiation. RM occurred in controls versus treated rats after a mean latency of 218 versus 314 days (19 Gy; p=0.11) and 104 versus 186 days (21 Gy; p=0.002) from second dose (Figure 1). ED{sub 50} was 18.2 versus 19.4 Gy (p=0.15; Figure 2). Treatment with IGF-1 and amifostine did not significantly influence the rates of tumor induction or intercurrent death. Conclusion: IGF-1 and amifostine significantly reduced RM rates after 21 Gy. The shift of the dose-response curve suggests an increase of the ED{sub 50} for single-dose treatment by approximately 7%. Thus, brief therapeutic intervention might slightly decrease radiation-induced neurotoxicity in a retreatment situation. (orig.)
Insulin-like growth factor 1 (IGF-1 enhances the protein expression of CFTR.
Ha Won Lee
Full Text Available Low levels of insulin-like growth factor 1 (IGF-1 have been observed in the serum of cystic fibrosis (CF patients. However, the effects of low serum IGF-1 on the cystic fibrosis transmembrane conductance regulator (CFTR, whose defective function is the primary cause of cystic fibrosis, have not been studied. Here, we show in human cells that IGF-1 increases the steady-state levels of mature wildtype CFTR in a CFTR-associated ligand (CAL- and TC10-dependent manner; moreover, IGF-1 increases CFTR-mediated chloride transport. Using an acceptor photobleaching fluorescence resonance energy transfer (FRET assay, we have confirmed the binding of CAL and CFTR in the Golgi. We also show that CAL overexpression inhibits forskolin-induced increases in the cell-surface expression of CFTR. We found that IGF-1 activates TC10, and active TC10 alters the functional association between CAL and CFTR. Furthermore, IGF-1 and active TC10 can reverse the CAL-mediated reduction in the cell-surface expression of CFTR. IGF-1 does not increase the expression of ΔF508 CFTR, whose processing is arrested in the ER. This finding is consistent with our observation that IGF-1 alters the functional interaction of CAL and CFTR in the Golgi. However, when ΔF508 CFTR is rescued with low temperature or the corrector VRT-325 and proceeds to the Golgi, IGF-1 can increase the expression of the rescued ΔF508 CFTR. Our data support a model indicating that CAL-CFTR binding in the Golgi inhibits CFTR trafficking to the cell surface, leading CFTR to the degradation pathway instead. IGF-1-activated TC10 changes the interaction of CFTR and CAL, allowing CFTR to progress to the plasma membrane. These findings offer a potential strategy using a combinational treatment of IGF-1 and correctors to increase the post-Golgi expression of CFTR in cystic fibrosis patients bearing the ΔF508 mutation.
Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis
Ren HY
Full Text Available Hai-Yong Ren,1 Yin-Hua Zhang,1,2 Heng-Yuan Li,1 Tao Xie,1 Ling-Ling Sun,1 Ting Zhu,1 Sheng-Dong Wang,1 Zhao-Ming Ye1 1Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2The First Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, People's Republic of China Background: Hypoxia-inducible factor-1α (HIF-1α plays an important role in tumor progression and metastasis. A number of studies have investigated the association of HIF-1α with prognosis and clinicopathological characteristics of osteosarcoma but yielded inconsistent results. Method: Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and odds ratios (ORs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of HIF-1α expression. The standard mean difference was used to analyze the continuous variable. Results: Finally, nine studies comprising 486 patients were subjected to final analysis. Protein expression level of HIF-1α was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46–6.15, disease-free survival (HR =2.23; 95% CI: 1.26–3.92, pathologic grade (OR =21.33; 95% CI: 4.60–98.88, tumor stage (OR =10.29; 95% CI: 3.55–29.82, chemotherapy response (OR =9.68; 95% CI: 1.87–50.18, metastasis (OR =5.06; 95% CI: 2.87–8.92, and microvessel density (standard mean difference =2.83; 95% CI: 2.28–3.39. Conclusion: This meta-analysis revealed that overexpression of HIF-1α is a predictive factor of poor outcomes for osteosarcoma. HIF-1α appeared to play an important role in prognostic evaluation and may be a potential target in antitumoral therapy. Keywords: HIF-1α, osteosarcoma, prognosis, meta-analysis
Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression
Simiantonaki, Nektaria; Taxeidis, Marios; Jayasinghe, Caren; Kurzik-Dumke, Ursula; Kirkpatrick, Charles James
Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in non-metastatic and metastatic colorectal adenocarcinomas. Eight colorectal carcinoma cell lines are tested for their HIF-1α inducibility after lipopolysaccharide (LPS) stimulation using western blot and immunocytochemistry. In normal mucosa, HPP and TA-LGD HIF-1α was not expressed. In contast, perinuclear protein accumulation and nuclear expression of HIF-1α were shown in half of the examined SSA and TA-HGD. In all investigated colorectal carcinomas a significant nuclear HIF-1α overexpression compared to the premalignant lesions was observed but a significant correlation with the metastatic status was not found. Nuclear HIF-1α expression was strongly accumulated in perinecrotic regions. In these cases HIF-1α activation was seen in viable cohesive tumor epithelia surrounding necrosis and in dissociated tumor cells, which subsequently die. Enhanced distribution of HIF-1α was also seen in periiflammatory regions. In additional in vitro studies, treatment of diverse colorectal carcinoma cell lines with the potent pro-inflammatory factor lipopolysaccharide (LPS) led to HIF-1α expression and nuclear translocation. We conclude that HIF-1α expression occurs in early stages of colorectal carcinogenesis and achieves a maximum in the invasive stage independent of the metastatic status. Perinecrotic
A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels
Yeşim Coşkun
Full Text Available AIM: To detect the impact of insulin-like growth factor-1 (IGF-1 and other risk factors for the early prediction of retinopathy of prematurity (ROP and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels. METHODS: The study was conducted with 127 preterm infants. IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was analyzed. The score was established after logistic regression analysis, considering the impact of each variable on the occurrences of any stage ROP. A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated. RESULTS: Birth weights (BW, gestational weeks (GW and the prevalence of breast milk consumption were lower, respiratory distress syndrome (RDS, bronchopulmonary dysplasia (BPD and necrotizing enterocolitis (NEC were more frequent, the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP (P<0.05. Initial serum IGF-1 levels tended to be lower in newborns who developed ROP. Logistic regression analysis revealed that low BW (<1250 g, presence of intraventricular hemorrhage (IVH and formula feeding increased the risk of ROP. Afterwards, the scoring system was validated on 107 infants. The negative predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while positive predictive values were 76.3%, 65.5% and 71.6% respectively. CONCLUSION: In addition to BW <1250 g and IVH, formula consumption was detected as a risk factor for the development of ROP. Breastfeeding is important for prevention of ROP in preterm infants.
Respiratory pattern changes during costovertebral joint movement.
Shannon, R
Experiments were conducted to determine if costovertebral joint manipulation (CVJM) could influence the respiratory pattern. Phrenic efferent activity (PA) was monitored in dogs that were anesthetized with Dial-urethane, vagotomized, paralyzed, and artificially ventilated. Ribs 6-10 (bilaterally) were cut and separated from ribs 5-11. Branches of thoracic nerves 5-11 were cut, leaving only the joint nerve supply intact. Manual joint movement in an inspiratory or expiratory direction had an inhibitory effect on PA. Sustained displacement of the ribs could inhibit PA for a duration equal to numerous respiratory cycles. CVJM in synchrony with PA resulted in an increased respiratory rate. The inspiratory inhibitory effect of joint receptor stimulation was elicited with manual chest compression in vagotomized spontaneously breathing dogs, but not with artificial lung inflation or deflation. It is concluded that the effect of CVJM on the respiratory pattern is due to stimulation of joint mechanoreceptors, and that they exert their influence in part via the medullary-pontine rhythm generator.
An interdisciplinary approach to occupational respiratory disorders
van Rooy, G.B.G.J.
The World Health Organization estimates that worldwide about 50 million new cases of occupational respiratory diseases emerge every year. Without preventative action, the burden of occupational diseases is expected to increase. In this thesis an alternative approach to deliver occupational health
Childhood respiratory morbidity and cooking practices among ...
Background: Household air pollution is a leading risk factor for respiratory morbidity and mortality in developing countries where biomass fuel is mainly used for cooking. Materials and Method: A household cross-sectional survey was conducted in a predominantly rural area of Ghana in 2007 to determine the prevalence of ...
Attentional Demands on Motor-Respiratory Coordination
Hessler, Eric E.; Amazeen, Polemnia G.
Athletic performance requires the pacing of breathing with exercise, known as motor-respiratory coordination (MRC). In this study, we added cognitive and physical constraints while participants intentionally controlled their breathing locations during rhythmic arm movement. This is the first study to examine a cognitive constraint on MRC.…
Respiratory Symptoms and Pulmonary Function Impairment among ...
Background: The industrial process of detergent production could be deleterious to lung function. This study describes respiratory symptoms and ventilatory function impairment among detergent workers in Jos, Northern Nigeria. Methods: Two hundred detergent plant workers and controls were studied for the presence of ...
Transmission of Middle East respiratory syndrome coronavirus ...
... hand hygiene, and cough etiquette, would minimize the infection rate among HCPs. The required consumables for maintaining hand hygiene should be readily available to all HCPs. Keywords: Middle East respiratory syndrome coronavirus (MERS-CoV), Systematic review, healthcareassociated infections, Coronaviruses ...
Respiratory risks in broiler production workers
M do CB de Alencar
Full Text Available There are many situations that involve health risks to the Brazilian rural worker, and animal production is just one of them. Inhalation of organic dust, which has many microorganisms, leads in general to respiratory allergic reactions in some individuals, "asthma-like syndrome", and mucous membrane inflammation syndrome, that is a complex of nasal, eye, and throat complaints. Furthermore, workers might have farmer's hypersensitivity pneumonia, that is a respiratory health risk along the years. The objective of this study was to evaluate the potential pulmonary health risks in poultry production workers in the region of Curitiba, PR, Brazil. Interviews using a pre-elaborated questionnaire with 40 questions were made with 37 broiler production workers, which were submitted to a pulmonary function test. Results of restrictive function with lower FEV1 (the maximum respiratory potential, the forced expiratory volume in the first second of exhalation and FVC (forced vital capacity represented 24.32% of the total of workers, and severe obstruction represented 2.70%. Other symptoms were found in 67.57% of the workers as well. The results showed that those who work more than 4 years and within more than one poultry house, exceeding 5 hours per day of work, presented higher pulmonary health risks. It is concluded that the activities within broiler houses may induce allergic respiratory reaction in workers. The use of IPE (individual protection equipment besides special attention to the air quality inside the housing may be advised in a preventive way.
The European Respiratory Society spirometry tent
Maio, Sara; Sherrill, Duane L; MacNee, William
In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing...
Respiratory allergy caused by house dust mites
Calderón, Moisés A; Linneberg, Allan; Kleine-Tebbe, Jörg
consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using "house dust mite" as a key search...
Cellular immune responses to respiratory viruses
van Helden, M.J.G.
When a respiratory virus successfully infects the lungs, cascades of immune responses are initiated aimed to remove the pathogen. Immediate non-specific protection is provided by the innate immune system and this reduces the viral load during the first days of infection. The adaptive immune response
Imaging in severe acute respiratory syndrome (SARS)
Antonio, G.E.; Wong, K.T.; Chu, W.C.W.; Hui, D.S.C.; Cheng, F.W.T.; Yuen, E.H.Y.; Chung, S.S.C.; Fok, T.F.; Sung, J.J.Y.; Ahuja, A.T.
Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review
State of the art. Neonatal respiratory failure.
Parker, L A
Advances in ventilatory management of respiratory distress in the newborn have made dramatic strides during the last decade. Innovative treatments such as PTV, HFV, liquid ventilation, and NO therapy are just beginning to have an impact on the care of neonates in the NICU. These treatment modalities should continue to have an effect on the care of the newborn infant well into the future.
Sarcopenia and frailty in chronic respiratory disease
Bone, Anna E; Hepgul, Nilay; Kon, Samantha
Sarcopenia and frailty are geriatric syndromes characterized by multisystem decline, which are related to and reflected by markers of skeletal muscle dysfunction. In older people, sarcopenia and frailty have been used for risk stratification, to predict adverse outcomes and to prompt intervention aimed at preventing decline in those at greatest risk. In this review, we examine sarcopenia and frailty in the context of chronic respiratory disease, providing an overview of the common assessments tools and studies to date in the field. We contrast assessments of sarcopenia, which consider muscle mass and function, with assessments of frailty, which often additionally consider social, cognitive and psychological domains. Frailty is emerging as an important syndrome in respiratory disease, being strongly associated with poor outcome. We also unpick the relationship between sarcopenia, frailty and skeletal muscle dysfunction in chronic respiratory disease and reveal these as interlinked but distinct clinical phenotypes. Suggested areas for future work include the application of sarcopenia and frailty models to restrictive diseases and population-based samples, prospective prognostic assessments of sarcopenia and frailty in relation to common multidimensional indices, plus the investigation of exercise, nutritional and pharmacological strategies to prevent or treat sarcopenia and frailty in chronic respiratory disease. PMID:27923981
Lung Surfactant - The Indispensable Component of Respiratory ...
Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 8. Lung Surfactant - The Indispensable Component of Respiratory Mechanics. Shweta Saxena. Research News Volume 10 Issue 8 August 2005 pp 91-96. Fulltext. Click here to view fulltext PDF. Permanent link:
Diagnostic approaches to respiratory sleep disorders
Riha, Renata L.
Sleep disordered breathing (SDB) comprises a number of breathing disturbances occurring during sleep including snoring, the obstructive sleep apnoea/hypopnea syndrome (OSAHS), central sleep apnoea (CSA) and hypoventilation syndromes. This review focuses on sleep disordered breathing and diagnostic approaches in adults, in particular clinical assessment and overnight assessment during sleep. Although diagnostic approaches to respiratory sleep disorders are reasonably straightforward, they do r...
Respiratory system. Part 2: Gaseous exchange.
McLafferty, Ella; Johnstone, Carolyn; Hendry, Charles; Farley, Alistair
This article, which isthe last in the life sciences series and the second of two articles on the respiratory system, describes gaseous exchange in the lungs, transport of oxygen and carbon dioxide, and internal and external respiration. The article concludes with a brief consideration of two conditions that affect gas exchange and transport: carbon monoxide poisoning and chronic obstructive pulmonary disease.
Potential impact of fireworks on respiratory health
Gouder, Caroline; Montefort, Stephen
The world-wide use of fireworks with their consequent detrimental effect on the air quality is widely recognized with elevated ambient air levels of particulate matter and its several metallic components and gases identified in several studies carried out during such events. Exposed individuals may be at risk following inhalation of such produced pollutants. This review focuses on the impact of fireworks on air quality and the potential effect of fireworks on the respiratory system of healthy individuals as well as those suffering from underlying respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This applies not only to spectators including children but also to pyrotechnicians themselves. An extensive Medline search revealed that a strong evidence of the impact of fireworks on respiratory health is lacking in susceptible as well as healthy individuals with no formal studies on COPD or asthma, other than a few case reports in the latter. The implementation of global strategies to control the use of fireworks and hence improve air quality could possibly reduce their likely detrimental effect on human respiratory health in exposed individuals, but clearly a more targeted research is needed. PMID:25378846
membrane of the eyes, mouth, or nose and possibly through the ... transmembrane anchor near the C terminus. It is cleaved into two ... immunity induced by previous strains (Hall, 2001). Fluctuations in the .... isolation, and other serological techniques. Antigen .... Respiratory syncytial virus in B.N. fields, D.M. Knipe and.
Respiratory symptoms and ventilatory function impairment among ...
Both upper and lower respiratory tract diseaes have been noticed and described. Several publications are found in the literature on these but no such report has come from the Savannah belt with its peculiar climatic conditions. Methods: One hundred and forty (140) workers in a wood furniture factory in Kaduna, a city within ...
Neonatal respiratory depression associated with epidural analgesia
Alberto Gálvez Toro
Full Text Available Background: Epidural analgesia is the most effective analgesics used during childbirth but is not without its problems.In the Hospital San Juan de la Cruz of Ubeda from November 2011 we have detected 3 cases of newborn infants with signs of respiratory depression. Appeared in them: normal cardiotocographic records during childbirth, use of epidural associated with fentanyl, termination by vacuum and elevated temperature in one case.ObjectivesKnow if the neonatal adaptation to extrauterine life may be influenced by the use of epidural analgesia in childbirth. Review what role can have the rise in maternal temperature and the use of epidural fentanyl with the appearance of newborn respiratory distress.MethodsLiterature Review conducted in February of 2012 in Pubmed and the Cochrane Library, using the key words: childbirth, epidural analgesia, neonatal respiratory depression.ResultsOn the respiratory depression associated with fentanyl, a Cochrane review found indicating that newborns of mothers with an epidural, had a lower pH and were less need for administration of naloxone.On PubMed we find a review study that indicates that the respiratory depression caused by the administration of opioids via neuroaxial is rare, placing it below 1 per 1000, and a clinical case that concluded that doses of fentanyl exceeding 300 µg (approx. 5 µg/kg for 4 hours previous to childbirth, have a high risk of neonatal respiratory depression at birth.The same Cochrane review indicates that the women with epidural analgesia had increased risk of maternal fever of at least 38 ° C and a recent cohort study relates this increase in temperature with a greater likelihood of neonatal adverse events (from 37.5 ° C.ConclusionsThe studies found considered safe epidurals to the neonate and the mother, except when certain conditions are met. The literature and our clinical experience have been reports linking neonatal respiratory depression with increasing temperature (37
Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention
Face mask spirometry and respiratory pressures in normal subjects.
Wohlgemuth, M.; Kooi, E.L. van der; Hendriks, J.C.M.; Padberg, G.W.A.M.; Folgering, H.T.M.
Spirometry and maximal respiratory pressures are pulmonary function parameters commonly used to evaluate respiratory function. Prediction values are available for conventional lung function devices using a standard tube or flanged type of mouthpiece connection. This equipment is not suitable for
Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies.
Sasaki, Nobuo; Meyer, Matthew J; Eikermann, Matthias
Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible.
Meditation or Exercise May Help Acute Respiratory Infections
... Legislation Advisory Council Job Opportunities All About NCCIH Health Topics A-Z ... to a recent study, exercising or practicing meditation may be effective in reducing acute respiratory infections. Acute respiratory infections, ...
History of mechanical ventilation may affect respiratory mechanics evolution in acute respiratory distress syndrome.
Koutsoukou, Antonia; Perraki, Helen; Orfanos, Stylianos E; Koulouris, Nikolaos G; Tromaropoulos, Andreas; Sotiropoulou, Christina; Roussos, Charis
The aim of this study was to investigate the effect of mechanical ventilation (MV) before acute respiratory distress syndrome (ARDS) on subsequent evolution of respiratory mechanics and blood gases in protectively ventilated patients with ARDS. Nineteen patients with ARDS were stratified into 2 groups according to ARDS onset relative to the onset of MV: In group A (n = 11), MV was applied at the onset of ARDS; in group B (n = 8), MV had been initiated before ARDS. Respiratory mechanics and arterial blood gas were assessed in early (protectively ventilated patients with ARDS, late alteration of respiratory mechanics occurs more commonly in patients who have been ventilated before ARDS onset, suggesting that the history of MV affects the subsequent progress of ARDS even when using protective ventilation.
Respiratory gated beam delivery cannot facilitate margin reduction, unless combined with respiratory correlated image guidance
Korreman, S.S.; Boyer, A.L.; Juhler-Nøttrup, Trine
PURPOSE/OBJECTIVE: In radiotherapy of targets moving with respiration, beam gating is offered as a means of reducing the target motion. The purpose of this study is to evaluate the safe magnitude of margin reduction for respiratory gated beam delivery. MATERIALS/METHODS: The study is based on data...... for 17 lung cancer patients in separate protocols at Rigshospitalet and Stanford Cancer Center. Respiratory curves for external optical markers and implanted fiducials were collected using equipment based on the RPM system (Varian Medical Systems). A total of 861 respiratory curves represented external...... measurements over 30 fraction treatment courses for 10 patients, and synchronous external/internal measurements in single sessions for seven patients. Variations in respiratory amplitude (simulated coaching) and external/internal phase shifts were simulated by perturbation with realistic values. Variations...
Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze
Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim
BACKGROUND: Respiratory syncytial virus (RSV) hospitalization is associated with wheeze. OBJECTIVE: To examine the influence of maternally derived RSV neutralizing antibodies in cord blood on RSV hospitalization and recurrent wheeze in infancy. METHODS: Among children from the Danish National Birth...
Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection
von Linstow, Marie-Louise; Larsen, Hans Henrik; Eugen-Olsen, Jesper
The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p infected children required respiratory support. hMPV is present in young.......6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young...
Patient training in respiratory-gated radiotherapy
Kini, Vijay R.; Vedam, Subrahmanya S.; Keall, Paul J.; Patil, Sumukh; Chen, Clayton; Mohan, Radhe
Respiratory gating is used to counter the effects of organ motion during radiotherapy for chest tumors. The effects of variations in patient breathing patterns during a single treatment and from day to day are unknown. We evaluated the feasibility of using patient training tools and their effect on the breathing cycle regularity and reproducibility during respiratory-gated radiotherapy. To monitor respiratory patterns, we used a component of a commercially available respiratory-gated radiotherapy system (Real Time Position Management (RPM) System, Varian Oncology Systems, Palo Alto, CA 94304). This passive marker video tracking system consists of reflective markers placed on the patient's chest or abdomen, which are detected by a wall-mounted video camera. Software installed on a PC interfaced to this camera detects the marker motion digitally and records it. The marker position as a function of time serves as the motion signal that may be used to trigger imaging or treatment. The training tools used were audio prompting and visual feedback, with free breathing as a control. The audio prompting method used instructions to 'breathe in' or 'breathe out' at periodic intervals deduced from patients' own breathing patterns. In the visual feedback method, patients were shown a real-time trace of their abdominal wall motion due to breathing. Using this, they were asked to maintain a constant amplitude of motion. Motion traces of the abdominal wall were recorded for each patient for various maneuvers. Free breathing showed a variable amplitude and frequency. Audio prompting resulted in a reproducible frequency; however, the variability and the magnitude of amplitude increased. Visual feedback gave a better control over the amplitude but showed minor variations in frequency. We concluded that training improves the reproducibility of amplitude and frequency of patient breathing cycles. This may increase the accuracy of respiratory-gated radiation therapy
Respiratory cancer database: An open access database of respiratory cancer gene and miRNA
Jyotsna Choubey
Results and Conclusions: RespCanDB is expected to contribute to the understanding of scientific community regarding respiratory cancer biology as well as developments of new way of diagnosing and treating respiratory cancer. Currently, the database consist the oncogenomic information of lung cancer, laryngeal cancer, and nasopharyngeal cancer. Data for other cancers, such as oral and tracheal cancers, will be added in the near future. The URL of RespCanDB is http://ridb.subdic-bioinformatics-nitrr.in/.
Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.
Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong
Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (C c O), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 ( P <0.05). The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.
Respiratory cancer database: An open access database of respiratory cancer gene and miRNA.
Choubey, Jyotsna; Choudhari, Jyoti Kant; Patel, Ashish; Verma, Mukesh Kumar
Respiratory cancer database (RespCanDB) is a genomic and proteomic database of cancer of respiratory organ. It also includes the information of medicinal plants used for the treatment of various respiratory cancers with structure of its active constituents as well as pharmacological and chemical information of drug associated with various respiratory cancers. Data in RespCanDB has been manually collected from published research article and from other databases. Data has been integrated using MySQL an object-relational database management system. MySQL manages all data in the back-end and provides commands to retrieve and store the data into the database. The web interface of database has been built in ASP. RespCanDB is expected to contribute to the understanding of scientific community regarding respiratory cancer biology as well as developments of new way of diagnosing and treating respiratory cancer. Currently, the database consist the oncogenomic information of lung cancer, laryngeal cancer, and nasopharyngeal cancer. Data for other cancers, such as oral and tracheal cancers, will be added in the near future. The URL of RespCanDB is http://ridb.subdic-bioinformatics-nitrr.in/.
42 CFR 84.52 - Respiratory hazards; classification.
... 42 Public Health 1 2010-10-01 2010-10-01 false Respiratory hazards; classification. 84.52 Section... SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Classification of Approved Respirators; Scope of Approval; Atmospheric Hazards; Service Time § 84.52 Respiratory...
Respiratory mechanics in ventilated preterm infants : early determinants and outcome
Snepvangers, Dimphn Adriana Cornelia Maria
The studies in this thesis show that in the current surfactant era, the majority of ventilated preterm infants are still suffering from respiratory morbidity and substantial respiratory function abnormalities throughout the early years of life. Since respiratory function testing during mechanical
Respiratory Belt Transducer Constructed Using a Singing Greeting Card Beeper
Bhaskar, Anand; Subramani, Selvam; Ojha, Rajdeep
An article by Belusic and Zupancic described the construction of a finger pulse sensor using a singing greeting card beeper. These authors felt that this beeper made of piezoelectric material could be easily modified to function as a respiratory belt transducer to monitor respiratory movements. Commercially available respiratory belt transducers,…
[Measurement of the passive compliance of the total respiratory system in newborn after respiratory insufficiency for risk assessment of respiratory disorders during the first 6 month of life].
Olechowski, Wiesław; Majorek-Olechowska, Bernadetta
To evaluate the relationships between postnatal passive respiratory compliance (Crs) and development of respiratory disorders during the first 6 month of life in preterm and full-term infants after respiratory insufficiency. The purpose of this study was to investigate whether other relevant neonatal factors, like degree of prematurity, birth weigh, ventilatory conditions, sepsis, and respiratory disease severity affected this relationship. The passive respiratory compliance was measured by the single occlusion technique in 73 preterm infants after respiratory distress syndrome (RDS), 19 full-term infants after congenital pneumonia and 33 healthy full-term infants. Respiratory function measurements were performed by single occlusion technique, during natural sleep, after acute phase of illness, before discharge from neonatal department. Crs was significantly lower in premature newborns newborns who have suffered from a congenital pneumonia (p = 0.0411), than in healthy full-term newborn infants. Premature infants who have undergone sepsis have significantly decreased Crs in relationship with those who did not have this complication (p = 0.0334). Preterm newborns who have suffered pneumonia during treatment of RDS have significantly frequent respiratory problems during the first 6 month of age (p = 0.043). Full-term infants after congenital pneumonia have more but not significantly frequent respiratory problems than healthy term newborns (p = 0.055) in this period. Decreased neonatal Crs wasn't significantly related to respiratory disorders in age of 6 month of life. Prematurity under 36 week of gestational age, low birth weight and suffering from sepsis in premature infants significantly decreased Crs in newborn. Decreased neonatal Crs in premature and full term infants after respiratory insufficiency wasn't significantly related to respiratory disorders during first 6 month of life. This study has showed significantly increase of respiratory problems in this
Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice
Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.
Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,
Management of respiratory motion in radiation oncology
Vedam, Subrahmanya Sastry
Respiration affects the instantaneous position of almost all thoracic and abdominal structures (lung, breast, liver, pancreas, etc.), posing significant problems in the radiotherapy of tumors located at these sites. The diaphragm, for example, has been shown to move approximately 1.5 cm in the superior-inferior direction during normal breathing. During radiotherapy, margin expansion around the tumor, based on an estimate of the expected range of tumor motion, is commonly employed to ensure adequate dose coverage. Such a margin estimate may or may not encompass the 'current' extent of motion exhibited by the tumor, resulting in either a higher dose to the surrounding normal tissue or a cold spot in the tumor volume, leading to poor prognosis. Accounting for respiratory motion by active management during radiotherapy can, however, potentiate a reduction in the amount of high dose to normal tissue. Active management of respiratory motion forms the primary theme of this dissertation. Among the various techniques available to manage respiratory motion, our research focused on respiratory gated and respiration synchronized radiotherapy, with an external marker to monitor respiratory motion. Multiple session recordings of diaphragm and external marker motion revealed a consistent linear relationship, validating the use of external marker motion as a 'surrogate' for diaphragm motion. The predictability of diaphragm motion based on such external marker motion both within and between treatment sessions was also determined to be of the order of 0.1 cm. Gating during exhalation was found to be more reproducible than gating during inhalation. Although, a reduction in the 'gate' width achieved a modest reduction in the margins added around the tumor further reduction was limited by setup error. A motion phantom study of the potential gains from respiratory gating indicated margin reduction of 0.2-1.1 cm while employing gating. In addition, gating also improved the quality of
Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.
Nizet, T.A.C.; Heijdra, Y.F.; Elshout, F.J.J. van den; Ven, M.J.T. van de; Bosch, F.H.; Mulder, P.H.M. de; Folgering, H.T.M.
Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish
Heat-induced accumulation of protein synthesis elongation factor 1A indicates an important role in heat tolerance in potato
Heat stress substantially reduces crop productivity worldwide, and will become more severe due to global warming. Identification of proteins involved in heat stress response may help develop varieties for heat tolerance. Eukaryotic elongation factor 1A (eEF1A) is a cytosolic, multifunctional protei...
Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus
The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not wel...
Advances toward DNA-based identification and phylogeny of North American Armillaria species using elongation factor-1 alpha gene
Amy L. Ross-Davis; John W. Hanna; Mee-Sook Kim; Ned B. Klopfenstein
The translation elongation factor-1 alpha gene was used to examine the phylogenetic relationships among 30 previously characterized isolates representing ten North American Armillaria species: A. solidipes (=A. ostoyae), A. gemina, A. calvescens, A. sinapina, A. mellea, A. gallica, A. nabsnona, North American biological species X, A. cepistipes, and A. tabescens. The...
Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast
Kuijper, Arno; Groep, P. van der; Wall, E. van der; Diest, P.J. van
INTRODUCTION Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance
Relationship between insulin-like growth factor-1 and radiographic disease in patients with primary osteoarthritis: a systematic review.
Claessen, K.M.; Ramautar, S.R.; Pereira, A.M.; Smit, J.W.A.; Biermasz, N.R.; Kloppenburg, M.
OBJECTIVE: To evaluate the association between radiographic osteoarthritis (OA) and either serum insulin-like growth factor-1 (IGF-1) levels or IGF-1 gene polymorphisms in patients with primary OA. METHODS: We conducted a systematic review of reported associations between circulating IGF-1 and/or
Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness
Ameri, P.; Canepa, M.; Fabbi, P.; Leoncini, G.; Milaneschi, Y.; Mussap, M.; AlGhatrif, M.; Balbi, M.; Viazzi, F.; Murialdo, G.; Pontremoli, R.; Brunelli, C.; Ferrucci, L.
Objective: Experimental evidence indicates that circulating insulin-like growth factor-1 (IGF-1) counteracts vascular aging and atherosclerosis, for which increased carotid artery intima-media thickness (IMT) is a marker. Yet, IGF-1 concentrations have been inconsistently associated with carotid IMT
Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians
Meex, S.J.; Vliet-Ostaptchouk, J.V.; Kallen, van der C.J.H.; Greevenbroek, M.M.; Schalkwijk, C.G.; Feskens, E.J.M.; Blaak, E.E.; Wijmenga, C.; Hofker, M.H.; Stehouwer, C.D.; Bruin, T.W.
Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF1), a well-established susceptibility gene for familial combined hyperlipidemia, is postulated to be such a shared genetic determinant. We evaluated two
Stromal cell-derived factor-1 alpha (SDF-1 alpha) improves neural recovery after spinal cord contusion in rats
Zendedel, A.; Nobakht, M.; Bakhtiyari, M.; Beyer, C.; Kipp, M.; Baazm, M.; Joghataie, M.T.
Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also
Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1
Serup, P; Jensen, J; Andersen, F G
Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London...
Longitudinal modelling of respiratory symptoms in children
Schlink, Uwe; Fritz, Gisela; Herbarth, Olf; Richter, Matthias
A panel of 277 children, aged 3-7 years, was used to study the association between air pollution (O3, SO2, NO2, and total suspended particles), meteorological factors (global radiation, maximum daytime temperature, daily averages of vapour pressure and air humidity) and respiratory symptoms. For 759 days the symptoms were recorded in a diary and modelling was based on a modification of the method proposed by Korn and Whittemore (Biometrics 35: 795-798, 1979). This approach (1) comprises an extension using environmental parameters at different time scales, (2) addresses the suitability of using the daily fraction of symptomatic individuals to account for inter-individual interactions and (3) enables the most significant weather effects to be identified. The resulting model consisted of (1) an individual specific intercept that takes account of the population's heterogeneity, (2) the individual's health status the day before, (3) a long-term meteorological effect, which may be either the squared temperature or global radiation in interaction with temperature, (4) the short-term effect of sulfur dioxide, and (5) the short-term effect of an 8-h ozone concentration above 60 µg/m3. Using the estimated parameters as input to a simulation study, we checked the quality of the model and demonstrate that the annual cycle of the prevalence of respiratory symptoms is associated to atmospheric covariates. Individuals suffering from allergy have been identified as a group of a particular susceptibility to ozone. The duration of respiratory symptoms appears to be free of scale and follows an exponential distribution function, which confirms that the symptom record of each individual follows a Poisson point-process. This supports the assumption that not only respiratory diseases, but also respiratory symptoms can be considered an independent measure for the health status of a population sample. Since a point process is described by only one parameter (namely the intensity of the
Respiratory Disorders in Complicated Cervical Spine Injury
S. A. Pervukhin
Full Text Available Objective. Evaluating the results of respiratory therapy in patients with complicated traumatic injury of the cervical spine.Materials and methods. A retrospective comparative analysis of the clinical course was carried out in 52 patients with complicated traumatic injury of the cervical spine: group A: complete spinal cord injury (ASIA A, 37 patients and group B: incomplete injury (ASIA B, 15 patients. The severity of patients' status on integral scales, parameters of the respiratory pattern and thoracopulmonary compliance, gas composition, and acidbase status of the blood were assessed. Data on patients who required prolonged mechanical ventilation, duration of mechanical ventilation, incidence of nosocomial pneumonia, duration of stay in the ICU, time of hospital treatment, and mortality were included in the analysis. Results. The average APACHE II and SOFA scores were higher in group A patients. The development of the acute respiratory failure required longterm mechanical ventilation (more than 48 hours in 91.4% of group A patients and in 53.3% of group B patients. Ventilatorassociated pneumonia complicated the disease in 81.3% of group A patients and 62.5% of group B patients and was accompanied by sepsis in 25% and 12.5% of cases, respectively. Statistically significant deterioration of biomechanical properties and gas exchange function of the lungs was observed in patients complicated with septic pneumonia.Conclusion. Patients with complicated ASIA A and ASIA B cervical spine injuries demonstrate the presence of respiratory failure of neurogenic origin. In addition, the infectious bronchopulmonary complications aggravated respiratory failure in patients with ASIA A injury in 70.3% versus 33.3% in patients with ASIA B. Developmentof pulmonogenic sepsis led to deterioration of the biomechanical and gas exchange functions of the lungs and increased the likelihood of unfavorable outcome of the disease in 77.8% of cases. The high
Cellular defense of the avian respiratory system: effects of Pasteurella multocida on respiratory burst activity of avian respiratory tract phagocytes.
Ochs, D L; Toth, T E; Pyle, R H; Siegel, P B
The respiratory tract of healthy chickens contain few free-residing phagocytic cells. Intratracheal inoculation with Pasteurella multocida stimulated a significant (P less than 0.05) migration of cells to the lungs and air sacs of White Rock chickens within 2 hours after inoculation. We found the maximal number of avian respiratory tract phagocytes (22.9 +/- 14.0 x 10(6] at 8 hours after inoculation. Flow cytometric analysis of these cells revealed 2 populations on the basis of cell-size and cellular granularity. One of these was similar in size and granularity to those of blood heterophils. Only this population was capable of generating oxidative metabolites in response to phorbol myristate acetate. The ability of the heterophils to produce hydrogen peroxide, measured as the oxidation of intracellularly loaded 2',7'-dichlorofluorescein, decreased with time after inoculation. These results suggest that the migration of heterophils, which are capable of high levels of oxidative metabolism, to the lungs and air sacs may be an important defense mechanism of poultry against bacterial infections of the respiratory tract.
Intensity cut-points for the Respiratory Distress Observation Scale
Campbell, Margaret L; Templin, Thomas N
Background The Respiratory Distress Observation Scale© is an innovative solution to assessment when a dyspnea report cannot be elicited. The Respiratory Distress Observation Scale has acceptable reliability and validity psychometrics. Aim To identify distress-intensity cut-points of the Respiratory Distress Observation Scale. Design Receiver operating characteristic curve analysis was conducted with inpatients stratified by four levels of respiratory distress—none, mild, moderate, or severe. Patients provided three self-report measures of dyspnea: dichotomous (yes/no); a ranking of none, mild, moderate, or severe; and a numerical rating scale. Respiratory distress was assessed using the Respiratory Distress Observation Scale instrument. Setting/participants Participants were 136 adult inpatients, mean age 61.8 years (standard deviation = 13.18 years), 89.7% African American, and 56.6% female, who were recruited from an urban, tertiary care hospital in the Midwest of the United States. Results In all, 47% (n = 64) self-reported dyspnea (yes/no). Ranking was distributed as follows: none = 36, mild = 35, moderate = 40, and severe = 25. Numerical rating scale scores ranged from 0 to 10, mean = 4.99 (standard deviation = 2.9). Respiratory Distress Observation Scale scores ranged from 0 to 7, median (interquartile range) = 2 (1–3). Receiver operating characteristic curve analysis–determined Respiratory Distress Observation Scale score of 0–2 suggests little or no respiratory distress; score ≥3 signified moderate to severe distress. Conclusion A Respiratory Distress Observation Scale score ≥3 signifies a patient's need for palliation of respiratory distress. An end-point for identifying responsiveness to treatment, in other words, respiratory comfort, is Respiratory Distress Observation Scale <3. Because patients with imminent respiratory failure, as typified by dying patients, were not represented yielding lower than expected Respiratory Distress
Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children
Bisgaard, H.; Flores-Nunez, A.; Goh, A.
RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial viru...
Realistic respiratory motion margins for external beam partial breast irradiation
Conroy, Leigh; Quirk, Sarah [Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta T2N 4N2 (Canada); Department of Physics and Astronomy, University of Calgary, Calgary, Alberta T2N 1N4 (Canada); Smith, Wendy L., E-mail: firstname.lastname@example.com [Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta T2N 4N2 (Canada); Department of Physics and Astronomy, University of Calgary, Calgary, Alberta T2N 1N4 (Canada); Department of Oncology, University of Calgary, Calgary, Alberta T2N 1N4 (Canada)
Purpose: Respiratory margins for partial breast irradiation (PBI) have been largely based on geometric observations, which may overestimate the margin required for dosimetric coverage. In this study, dosimetric population-based respiratory margins and margin formulas for external beam partial breast irradiation are determined. Methods: Volunteer respiratory data and anterior–posterior (AP) dose profiles from clinical treatment plans of 28 3D conformal radiotherapy (3DCRT) PBI patient plans were used to determine population-based respiratory margins. The peak-to-peak amplitudes (A) of realistic respiratory motion data from healthy volunteers were scaled from A = 1 to 10 mm to create respiratory motion probability density functions. Dose profiles were convolved with the respiratory probability density functions to produce blurred dose profiles accounting for respiratory motion. The required margins were found by measuring the distance between the simulated treatment and original dose profiles at the 95% isodose level. Results: The symmetric dosimetric respiratory margins to cover 90%, 95%, and 100% of the simulated treatment population were 1.5, 2, and 4 mm, respectively. With patient set up at end exhale, the required margins were larger in the anterior direction than the posterior. For respiratory amplitudes less than 5 mm, the population-based margins can be expressed as a fraction of the extent of respiratory motion. The derived formulas in the anterior/posterior directions for 90%, 95%, and 100% simulated population coverage were 0.45A/0.25A, 0.50A/0.30A, and 0.70A/0.40A. The differences in formulas for different population coverage criteria demonstrate that respiratory trace shape and baseline drift characteristics affect individual respiratory margins even for the same average peak-to-peak amplitude. Conclusions: A methodology for determining population-based respiratory margins using real respiratory motion patterns and dose profiles in the AP direction was
Realistic respiratory motion margins for external beam partial breast irradiation
Conroy, Leigh; Quirk, Sarah; Smith, Wendy L.
Purpose: Respiratory margins for partial breast irradiation (PBI) have been largely based on geometric observations, which may overestimate the margin required for dosimetric coverage. In this study, dosimetric population-based respiratory margins and margin formulas for external beam partial breast irradiation are determined. Methods: Volunteer respiratory data and anterior–posterior (AP) dose profiles from clinical treatment plans of 28 3D conformal radiotherapy (3DCRT) PBI patient plans were used to determine population-based respiratory margins. The peak-to-peak amplitudes (A) of realistic respiratory motion data from healthy volunteers were scaled from A = 1 to 10 mm to create respiratory motion probability density functions. Dose profiles were convolved with the respiratory probability density functions to produce blurred dose profiles accounting for respiratory motion. The required margins were found by measuring the distance between the simulated treatment and original dose profiles at the 95% isodose level. Results: The symmetric dosimetric respiratory margins to cover 90%, 95%, and 100% of the simulated treatment population were 1.5, 2, and 4 mm, respectively. With patient set up at end exhale, the required margins were larger in the anterior direction than the posterior. For respiratory amplitudes less than 5 mm, the population-based margins can be expressed as a fraction of the extent of respiratory motion. The derived formulas in the anterior/posterior directions for 90%, 95%, and 100% simulated population coverage were 0.45A/0.25A, 0.50A/0.30A, and 0.70A/0.40A. The differences in formulas for different population coverage criteria demonstrate that respiratory trace shape and baseline drift characteristics affect individual respiratory margins even for the same average peak-to-peak amplitude. Conclusions: A methodology for determining population-based respiratory margins using real respiratory motion patterns and dose profiles in the AP direction was
Respiratory therapies for amyotrophic lateral sclerosis: a primer.
Gruis, Kirsten L; Lechtzin, Noah
Respiratory complications are a common cause of morbidity and mortality in amyotrophic lateral sclerosis (ALS). Treatment of respiratory insufficiency with noninvasive ventilation (NIV) improves ALS patients' quality of life and survival. Evidence-based practice guidelines for the management of ALS patients recommend treatment of respiratory insufficiency with NIV as well as consideration of insufflation/exsufflation to improve clearance of airway secretions. Despite these recommendations respiratory therapies remain underused. In this review we provide a practical guide for the clinician to prescribe and manage respiratory therapies for the patient with ALS. Copyright © 2012 Wiley Periodicals, Inc.
Respiratory Acid-Base Disorders in the Critical Care Unit.
Hopper, Kate
The incidence of respiratory acid-base abnormalities in the critical care unit (CCU) is unknown, although respiratory alkalosis is suspected to be common in this population. Abnormal carbon dioxide tension can have many physiologic effects, and changes in Pco 2 may have a significant impact on outcome. Monitoring Pco 2 in CCU patients is an important aspect of critical patient assessment, and identification of respiratory acid-base abnormalities can be valuable as a diagnostic tool. Treatment of respiratory acid-base disorders is largely focused on resolution of the primary disease, although mechanical ventilation may be indicated in cases with severe respiratory acidosis. Published by Elsevier Inc.
Didactic tools for understanding respiratory physiology
Kehoe, P Donnelly; Bratovich, C; Perrone, Ms; Castells, L Mendez
The challenges in Bioengineering are not only the application of engineering knowledge to the measurement of physiological variables, but also the simulation of biological systems. Experience has shown that the physiology of the respiratory system involves a set of concepts that cannot be effectively taught without the help of a group of didactic tools that contribute to the measurement of characteristic specific variables and to the simulation of the system itself. This article describes a series of tools designed to optimize the teaching of the respiratory system, including the use of spirometers and software developed entirely by undergraduate Bioengineering students from Universidad Nacional de Entre Rios (UNER). The impact these resources have caused on the understanding of the topic and how each of them has facilitated the interpretation of the concepts by the students is also discussed
Recurrent respiratory papillomatosis with pulmonary involvement
Ikawa, Marcos Hiroyuki
A five-year-old girl developed hoarseness with gradual worsening at the age of eight months. Three months later, she underwent bronchoscopy in which papillomas in the vocal cords, larynx and trachea were observed. Because of serious bronchospasm crises and respiratory failure, she needed several hospitalizations, definitive tracheostomy and multiple endoscopic procedures for papilloma excision. The most recent chest radiography (Figure A) and computed tomography (CT) scans (Figures B and C) showed a nodule inside the trachea and multiple pulmonary nodules, cysts and consolidations. The anatomopathological findings from curettage of the lesions revealed benign squamous-cell papillomas. Recurrent respiratory papillomatosis (RRP) is directly related to the human papillomavirus (HPV). Its spread to the lower airways is uncommon, with involvement of trachea and/or proximal bronchi in 5% of the patients, and extension to the lungs in only 1% of the cases. (author)
Noninvasive ventilation in hypoxemic respiratory failure
Raja Dhar
Full Text Available Noninvasive ventilation (NIV refers to positive pressure ventilation delivered through a noninvasive interface (nasal mask, facemask, or nasal plugs etc. Over the past decade its use has become more common as its benefits are increasingly recognized. This review will focus on the evidence supporting the use of NIV in various conditions resulting in acute hypoxemic respiratory failure (AHRF, that is, non-hypercapnic patients having acute respiratory failure in the absence of a cardiac origin or underlying chronic pulmonary disease. Outcomes depend on the patient's diagnosis and clinical characteristics. Patients should be monitored closely for signs of noninvasive ventilation failure and promptly intubated before a crisis develops. The application of noninvasive ventilation by a trained and experienced team, with careful patient selection, should optimize patient outcomes.
Maintaining Respiratory Health in Cystic Fibrosis Patients
MR Modaresi
Full Text Available Cystic fibrosis (CF is an inherited disease that primarily affects the lungs and the digestive system, however, it also affects a number of other organs and systems. More than 90% of mortality of CF patients is due to lung complications. Healthy lungs are important for a long life for people with CF, We will discuss two important topics for maintaining respiratory health. Chronic use of drugs for maintaining respiratory health There are a number of drugs available to keep CF lungs healthy. We will discuss the science behind the recommendations for use of: Inhaled antibiotics Dornase alfa Azithromycin Hypertonic saline High-dose ibuprofen Ivacaftor CF Airway Clearance Therapies Airway Clearance therapy is very important to keeping CF lungs healthy. Our discussions cover the following topics such as the: Daily airway clearance Different techniques of airway clearance Effect of aerobic exercise on airway clearance
[Pneumococcal vaccine recommendations in chronic respiratory diseases].
Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A
Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Hilar enlargement in respiratory syncytial virus pneumonia
Odita, J.C.; Aghahowa, J.E.; Nwankwo, M.
The clinical and radiographic features of ten children with hilar enlargement in association with proven Respiratory Syncytial Virus (RSV) infection are described. Hilar enlargement was seen in 10/35 children with RSV infection, and was invariably unilateral and right sided. It is recommended that RSV pneumonia be considered in children with unilateral hilar enlargement if tuberculosis has been excluded, and the onset of disease is rapid. (orig.)
Respiratory Manifestations of Hypothyroidism: A Systematic Review.
Sorensen, Jesper Roed; Winther, Kristian Hillert; Bonnema, Steen Joop; Godballe, Christian; Hegedüs, Laszlo
Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. A systematic review was conducted to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. PubMed and EMBASE databases were searched for relevant literature from January 1950 through January 2015 with the following study eligibility criteria: English-language publications; adult subclinical or overt hypothyroid patients; intervention, observational, or retrospective studies; and respiratory manifestations. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed, and Cochrane's risk of bias tool was used. A total of 1699 papers were screened by two independent authors for relevant titles. Of 109 relevant abstracts, 28 papers underwent full-text analyses, of which 22 were included in the review. Possible mechanisms explaining respiratory problems at multiple physiological levels were identified, such as the ventilator control system, diaphragmatic muscle function, pulmonary gas exchange, goiter caused upper airway obstruction, decreased capacity for energy transduction, and reduced glycolytic activity. Obstructive sleep apnea syndrome was found among 30% of newly diagnosed patients with overt hypothyroidism, and demonstrated reversibility following treatment. The evidence for or against a direct effect on pulmonary function was ambiguous. However, each of the above-mentioned areas was only dealt with in a limited number of studies. Therefore, it is not possible to draw any strong conclusions on any of these themes. Moreover, most studies were hampered by considerable risk of bias due for example to small numbers of patients, lack of control groups, randomization and blinding, and differences in body mass index, sex, and age between subjects and controls. Mechanistic data linking hypothyroidism and respiratory function are at best limited. This area of research is therefore
Recent advances in paediatric respiratory medicine.
Turnbull, Andrew; Balfour-Lynn, Ian M
This review highlights important advances in paediatric respiratory medicine since 2014, excluding cystic fibrosis. It focuses mainly on the more common conditions, bronchopulmonary dysplasia, bronchiolitis and preschool wheezing, asthma, pneumonia and sleep, and highlights some of the rarer conditions such as primary ciliary dyskinesia and interstitial lung disease (ILD). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Respiratory carcinogenicity assessment of soluble nickel compounds.
Oller, Adriana R
The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.
Respiratory carcinogenicity assessment of soluble nickel compounds.
Oller, Adriana R
The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...
Acute kidney injury with hypoxic respiratory failure
Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David
A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diag...
Acute respiratory tract obstruction in children
Ahmad, Zahoor
35 cases of acute respiratory tract obstruction in paediatric age group who needed surgical intervention in the form of bronchoscopy, tracheostomy or both are reviewed here. All these patients were seen and managed at National Iranian Oil company Hospital Ummeidiya Khouzestan Iran, from April 1985 to April 1988. The results obtained with a review of use of instruments is described. Most of the patients presented with foreign body inhalations, some due to allergic oedema and one case had laryn...
Acute respiratory failure following ovarian hyperstimulation syndrome
Antonello Nicolini
Full Text Available Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6 ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non
Assessing the impact of a respiratory diagnosis on smoking cessation.
Jones, Alexandra
The aim of this study was to assess the impact of respiratory diagnoses on smoking cessation. A total of 229 current and former smokers, with and without respiratory diagnoses completed an anonymous online questionnaire assessing how their smoking habit changed when diagnosed with various respiratory conditions. Among all participants the most common reason for quitting smoking was to reduce the risk of health problems in general. In those with a chronic respiratory diagnosis, this was their most common reason for quitting. Motivation to quit smoking, scored by participants on a scale of 0-10, increased at the time of diagnosis then further increased after diagnosis of a chronic respiratory condition but declined after diagnosis of an acute respiratory condition. The research had a small sample size so further research is required. However, important themes are highlighted with the potential to influence clinical practice. All clinicians should receive training to promote cessation at the time of diagnosing respiratory conditions.
Practical approach to management of respiratory complications in neurological disorders
Mangera Z
Full Text Available Zaheer Mangera, Kirat Panesar, Himender MakkerRespiratory Medicine, North Middlesex University Hospital, London, UKAbstract: Patients with certain neurological diseases are at increased risk of developing chest infections as well as respiratory failure due to muscular weakness. In particular, patients with certain neuromuscular disorders are at higher risk. These conditions are often associated with sleep disordered breathing. It is important to identify patients at risk of respiratory complications early in the course of their disease, although patients with neuromuscular disorders often present in the acute setting with respiratory involvement. This review of the respiratory complications of neurological disorders, with a particular focus on neuromuscular disorders, explores why this happens and looks at how to recognize, investigate, and manage these patients effectively.Keywords: respiratory failure, respiratory muscle weakness
Air pollution and respiratory infection in children
Douglas, J W.B.; Waller, R E
Air pollution, as estimated by domestic coal consumption was categorized into 4 groups; very low, low, moderate, and high. The predicted pollution categories were later compared with measured smoke and SO/sub 2/ concentrations and found to be as expected. The smoke concentration was found to be 67, 138, 217, and 281 ..mu..g/m/sup 3/ while the SO/sub 2/ concentration was 90, 130, 191, and 257 ..mu..g/m/sup 3/ in the very low, low, moderate, and high pollution groups respectively. These values excluded the greater London area which had somewhat lower smoke but similar SO/sub 2/ concentrations. The air pollution had no effect on upper-respiratory illness in British children but had a highly significant effect on lower-respiratory illness. The percent of children experiencing the first lower-respiratory tract infection during the first 9 months of life in the 4 pollution groups were 7.2 in the very low, 11.4 in the low, 16.5 in the moderate and 17.1 in the high.
Respiratory symptoms and functions in barn workers
Ege Gulec Balbay
Full Text Available Introduction and aim. The presented study was undertaken to investigate the respiratory health problems in family barns with one or more cows and at least one family member working in the barn. Methods. 150 workers (128 female, 22 male from 4 villages of Yığılca district near the city of Düzce in north-west Turkey were enrolled in this study between October – December 2011. An Occupational and Environmental Chest Diseases questionnaire developed by the American Thoracic Society, pulmonary function test, physical examination and investigation for nasal eosinophil were performed in all subjects. Results. The mean age of workers was 47.7 ± 14.2 years. Cough was present in 24% of subjects. The rates of phlegm, wheezing, chest tightness and dyspnea were 13.3%, 6%, 6% and 27.3%, respectively. Obstructive ventilatory pattern was observed in 37 workers (24.6%. 43 workers (28.6% showed restrictive ventilatory pattern. Nasal eosinophilia was detected in 47.3% (71/150 of the subjects. Pulmonary functions of workers with nasal eosinophilia did not differ from the other workers. There were statistically significant negative correlations between the duration of working in barns and respiratory functions. Conclusions. Pulmonary functions of barn workers have been found to be decreased related to the duration of barn working. Furthermore, respiratory symptoms increased in relation with both barn working and biomass consumption. Precautions should therefore be taken to ventilate both barns and houses.
Does respiratory muscle training increase physical performance?
Sperlich, Billy; Fricke, Hannes; de Marées, Markus; Linville, John W; Mester, Joachim
Special force units and military personnel undergo demanding physical exercise and might benefit from high-intensity respiratory muscle training (RMT) by increasing their endurance performance. This study examined the effects of a 6-week high-intensity RMT on running performance and oxygen uptake (VO2max) in a group of German Special Force Squad members. 17 participants were randomly assigned to a training or control group. Baseline and post-testing included a ramp test, as well as an incremental test on a treadmill, performed to physical exhaustion. VO2, respiratory exchange ratio, and heart rate were measured breath by breath. Furthermore, maximum running speed (V(max)), 4 mmol x 1(-1) lactate threshold (V4) and perception of respiratory effort were determined. During pulmonary testing, sustained maximum inspiratory and expiratory pressure (PI(max) and PE(max)) were obtained. RMT was performed daily at approximately 90% PI(max) for 6 weeks with 2 x 30 breath cycles using an Ultrabreathe lung trainer. No statistical differences were detected between the groups for any parameter after RMT. High-intensity RMT did not show any benefits on VO2max and endurance performance and are unlikely to be of benefit to military or paramilitary training programs for an increase in endurance performance.
Respiratory diagnostic possibilities during closed circuit anesthesia.
Verkaaik, A P; Erdmann, W
An automatic feed back controlled totally closed circuit system (Physioflex) has been developed for quantitative practice of inhalation anesthesia and ventilation. In the circuit system the gas is moved unidirectionally around by a blower at 70 l/min. In the system four membrane chambers are integrated for ventilation. Besides end-expiratory feed back control of inhalation anesthetics, and inspiratory closed loop control of oxygen, the system offers on-line registration of flow, volume and respiratory pressures as well as a capnogram and oxygen consumption. Alveolar ventilation and static compliance can easily be derived. On-line registration of oxygen consumption has proven to be of value for determination of any impairment of tissue oxygen supply when the oxygen delivery has dropped to critical values. Obstruction of the upper or lower airways are immediately detected and differentiated. Disregulations of metabolism, e.g. in malignant hyperthermia, are seen in a pre-crisis phase (increase of oxygen consumption and of CO2 production), and therapy can be started extremely early and before a disastrous condition has developed. Registration of compliance is only one of the continuously available parameters that guarantee a better and adequate control of lung function (e.g. atalectasis is early detected). The newly developed sophisticated anesthesia device enlarges tremendously the monitoring and respiratory diagnostic possibilities of artificial ventilation, gives new insights in the (patho)physiology and detects disturbances of respiratory parameters and metabolism in an early stage.
Respiratory gated beam delivery cannot facilitate margin reduction, unless combined with respiratory correlated image guidance
Korreman, Stine S.; Juhler-Nottrup, Trine; Boyer, Arthur L.
Purpose/objective: In radiotherapy of targets moving with respiration, beam gating is offered as a means of reducing the target motion. The purpose of this study is to evaluate the safe magnitude of margin reduction for respiratory gated beam delivery. Materials/methods: The study is based on data for 17 lung cancer patients in separate protocols at Rigshospitalet and Stanford Cancer Center. Respiratory curves for external optical markers and implanted fiducials were collected using equipment based on the RPM system (Varian Medical Systems). A total of 861 respiratory curves represented external measurements over 30 fraction treatment courses for 10 patients, and synchronous external/internal measurements in single sessions for seven patients. Variations in respiratory amplitude (simulated coaching) and external/internal phase shifts were simulated by perturbation with realistic values. Variations were described by medians and standard deviations (SDs) of position distributions of the markers. Gating windows (35% duty cycle) were retrospectively applied to the respiratory data for each session, mimicking the use of commercially available gating systems. Medians and SDs of gated data were compared to those of ungated data, to assess potential margin reductions. Results: External respiratory data collected over entire treatment courses showed SDs from 1.6 to 8.1 mm, the major part arising from baseline variations. The gated data had SDs from 1.5 to 7.7 mm, with a mean reduction of 0.3 mm (6%). Gated distributions were more skewed than ungated, and in a few cases a marginal miss of gated respiration would be found even if no margin reduction was applied. Regularization of breathing amplitude to simulate coaching did not alter these results significantly. Simulation of varying phase shifts between internal and external respiratory signals showed that the SDs of gated distributions were the same as for the ungated or smaller, but the median values were markedly shifted
Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.
Dominelli, Paolo B; Archiza, Bruno; Ramsook, Andrew H; Mitchell, Reid A; Peters, Carli M; Molgat-Seon, Yannick; Henderson, William R; Koehle, Michael S; Boushel, Robert; Sheel, A William
What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the
[Respiratory infections caused by respiratory syncytial virus in the adult population: description of 16 cases].
Reina, Jordi; López, Carla
Respiratory infections of viral etiology are frequent in the adult population. Those caused by respiratory syncytial virus (RSV) are a little known entity. The aim of this study was to determine the clinical and epidemiological characteristics of adult patients with respiratory infection due to RSV. We performed a prospective study from October 2012 to March 2013 on respiratory infections caused by RSV. Viral detection was performed using a technique of reverse transcription polymerase chain reaction genomic amplification in real time. We diagnosed 16 patients, 12 (75%) requiring hospitalization. Patients were grouped into immunocompromised (7 [43.7%]) and immunocompetent cases (9 cases 56.3%]). The first group included 3 patients with HIV infection (42.8%) and 4 hematologic patients (57.2%). The second group included those who had a baseline disease, 5 cases (55.5%), and those who lacked it, 4 cases (44.4%), and did not require hospitalization. The main clinical manifestations of patients prompting them to attend the Emergency Department were cough (50%), dyspnea (43.5%), fever (25%), expectoration (25%) and flu symptoms (25%). The most frequent diagnoses at discharge were pneumonia (37.5%) and flu syndrome (31.2%). Respiratory infections caused by RSV represent a rare condition that mainly affects immunocompromised patients. The underlying pathology determines the evolution of the process, which is favorable except in cases of severe immunosuppression. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Seasonal variations of respiratory viruses detected from children with respiratory tract infections in Riyadh, Saudi Arabia
Saad S. Albogami
Full Text Available ARTIs have a huge impact in health systems in which 20–30% of all hospital admissions and 30–60% of practitioner visits are related to respiratory tract infections. The aim of this study is to determine the prevalence, age distribution, and seasonal variation of respiratory viruses. This study was descriptive retrospective study in which all patients 14 years of age and below who presented with signs and symptoms of ARTIs between January 2013 and December 2014 and had respiratory specimen tested by direct immunofluorescence assays for viruses identification were included in the study. During that period, a total of 4611 patients who presented with ARTIs from January 2013 to December 2014 were investigated, viruses were detected in 1115 (24%. RSV was associated with 97.4% of the total viral pathogens. Viruses were detected throughout all the two years with a peak in winter; Dec (n: 265, Jan (n: 418, Feb (n: 218, and Mar (n: 109. Viral pathogens are very important cause of ARTIs in our region. RSV was the most common virus detected with the highest detection rate in children who are two years old and below. A multi-center surveillance with more sensitive detection methods like PCR may help to provide a comprehensive understanding of virus distribution in our area, which may contribute implant an effective prevention approach for each virus. Keywords: Pediatrics, Infectious diseases, Respiratory infections, Respiratory syncytial virus, Saudi Arabia
Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus
Malemud Charles J
Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal
Oral Probiotics Alter Healthy Feline Respiratory Microbiota.
Vientós-Plotts, Aida I; Ericsson, Aaron C; Rindt, Hansjorg; Reinero, Carol R
Probiotics have been advocated as a novel therapeutic approach to respiratory disease, but knowledge of how oral administration of probiotics influences the respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial DNA our objective was to determine whether oral probiotics changed the composition of the upper and lower airway, rectal, and blood microbiota. We hypothesized that oral probiotics would modulate the respiratory microbiota in healthy cats, demonstrated by the detection and/or increased relative abundance of the probiotic bacterial species and altered composition of the microbial population in the respiratory tract. Six healthy young research cats had oropharyngeal (OP), bronchoalveolar lavage fluid (BALF), rectal, and blood samples collected at baseline and 4 weeks after receiving oral probiotics. 16S rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative abundance of representative operational taxonomic units (OTUs) were determined. Hierarchical and principal component analyses (PCA) demonstrated relatedness of samples. Mean microbial richness significantly increased only in the upper and lower airways. The number of probiotic OTUs (out of 5 total) that significantly increased in relative abundance vs. baseline was 5 in OP, 3 in BAL and 2 in feces. Using hierarchical clustering, BALF and blood samples grouped together after probiotic administration, and PERMANOVA supported that these two sites underwent significant changes in microbial composition. PERMANOVA revealed that OP and rectal samples had microbial population compositions that did not significantly change. These findings were visualized via PCA, which revealed distinct microbiomes in each site; samples clustered more tightly at baseline and had more variation after probiotic administration. This is the first study describing the effect of oral probiotics on the respiratory microbiota via detection of probiotic species in the airways. Finding
Oral Probiotics Alter Healthy Feline Respiratory Microbiota
Aida I. Vientós-Plotts
Full Text Available Probiotics have been advocated as a novel therapeutic approach to respiratory disease, but knowledge of how oral administration of probiotics influences the respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial DNA our objective was to determine whether oral probiotics changed the composition of the upper and lower airway, rectal, and blood microbiota. We hypothesized that oral probiotics would modulate the respiratory microbiota in healthy cats, demonstrated by the detection and/or increased relative abundance of the probiotic bacterial species and altered composition of the microbial population in the respiratory tract. Six healthy young research cats had oropharyngeal (OP, bronchoalveolar lavage fluid (BALF, rectal, and blood samples collected at baseline and 4 weeks after receiving oral probiotics. 16S rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative abundance of representative operational taxonomic units (OTUs were determined. Hierarchical and principal component analyses (PCA demonstrated relatedness of samples. Mean microbial richness significantly increased only in the upper and lower airways. The number of probiotic OTUs (out of 5 total that significantly increased in relative abundance vs. baseline was 5 in OP, 3 in BAL and 2 in feces. Using hierarchical clustering, BALF and blood samples grouped together after probiotic administration, and PERMANOVA supported that these two sites underwent significant changes in microbial composition. PERMANOVA revealed that OP and rectal samples had microbial population compositions that did not significantly change. These findings were visualized via PCA, which revealed distinct microbiomes in each site; samples clustered more tightly at baseline and had more variation after probiotic administration. This is the first study describing the effect of oral probiotics on the respiratory microbiota via detection of probiotic species in the
Respiratory alkalosis in children with febrile seizures.
Schuchmann, Sebastian; Hauck, Sarah; Henning, Stephan; Grüters-Kieslich, Annette; Vanhatalo, Sampsa; Schmitz, Dietmar; Kaila, Kai
Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco(2) were measured immediately on admission to the hospital. Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco(2) 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco(2) 37.7 ± 4.3 mmHg; p respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the
Photodynamic therapy for recurrent respiratory papillomatosis.
Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M
Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment. We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23
[Effects of intermittent hypoxic exposure on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha and erythropoietin levels].
Zhang, Cheng-yan; Zhang, Ji-xin; Lü, Xiao-tao; Li, Bao-yu
To investigate the effects of intermittent hypoxic exposure and normoxic convalescence on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) levels. Rat models of intermittent hypoxic exposure were established, combined with the clinical research on volunteers experiencing the intermittent plateau work. Blood samples for red blood cell (RBC) counts, hemoglobin (Hb) and hematocrit (HCT) were collected, serum HIF-1alpha and EPO levels were measured using enzyme linked immunosorbent assay. RBC counts, Hb concentration and HCT were significantly higher than the normoxic group (P hypoxic exposure can enhance serum hypoxia inducible factor-1 alpha and erythropointin levels and the generation of red blood cells, which leads to an increase in hemoglobin concentration and hematocrit. The results have changed with the hypoxic exposure period prolonged. Normoxic convalescence after intermittent hypoxic exposure can make the related indexes reduced, and contribute to the organism recovery.
A flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of Dictyostelium differentiation-inducing factor 1
Neumann, Christopher S.; Walsh, Christopher T.; Kay, Robert R.
Differentiation-inducing factor 1 (DIF-1) is a polyketide-derived morphogen which drives stalk cell formation in the developmental cycle of Dictyostelium discoideum. Previous experiments demonstrated that the biosynthetic pathway proceeds via dichlorination of the precursor molecule THPH, but the enzyme responsible for this transformation has eluded characterization. Our recent studies on prokaryotic flavin-dependent halogenases and insights from the sequenced Dd genome led us to a candidate ...
Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country.
Rodríguez-Martínez, Carlos E; Rodríguez, Diego Andrés; Nino, Gustavo
There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV-adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2-year period 2009-2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3-month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre-existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05-2.89; P = 0.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01-100.9; P = 0.049) were independent predictors of mixed RSV-adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV-adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country. © 2015 Wiley Periodicals, Inc.
Role of hippocampal dentate gyrus neurons in the protective effects of heat shock factor 1 on working memory
Min Peng; Xiongzhao Zhu; Ming Cheng; Xiangyi Chen; Shuqiao Yao
Increasing evidence suggests that heat shock factor 1 exerts endogenous protective effects on working memory under conditions of chronic psychological stress. However, the precise underlying mechanisms remain poorly understood. This study examined the protective factors affecting working memory in heat shock transcription factor 1 gene knockout mice. The results indicated that the number of correct T maze alternations decreased following mild chronic psychological stress in knockout mice. This change was accompanied by a decrease in neurogenesis and an increase in neuronal apoptosis in the hippocampal dentate gyrus. The number of correct T maze alternations was positively correlated with neurogenesis in hippocampal dentate gyrus, and negatively correlated with neuronal apoptosis. In wild type mice, no significant difference was detected in the number of correct T maze alternations or neuronal apoptosis in hippocampal dentate gyrus. These results indicate that the heat shock factor 1 gene has an endogenous protective role in working memory during mild chronic psychological stress associated with dentate gyrus neuronal apoptosis.Moreover, dentate gyrus neurogenesis appears to participate in the protective mechanism.
Determinants of Chronic Respiratory Symptoms among Pharmaceutical Factory Workers
Sahle Asfaw
Full Text Available Background. Chronic respiratory symptoms including chronic cough, chronic phlegm, wheezing, shortness of breath, and chest pain are manifestations of respiratory problems which are mainly evolved as a result of occupational exposures. This study aims to assess determinants of chronic respiratory symptoms among pharmaceutical factory workers. Methods. A case control study was carried out among 453 pharmaceutical factory workers with 151 cases and 302 controls. Data was collected using pretested and structured questionnaire. The data was analyzed using descriptive statistics and bivariate and multivariate analysis. Result. Previous history of chronic respiratory diseases (AOR = 3.36, 95% CI = 1.85–6.12, family history of chronic respiratory diseases (AOR = 2.55, 95% CI = 1.51–4.32, previous dusty working environment (AOR = 2.26, 95% CI = 1.07–4.78, ever smoking (AOR = 3.66, 95% CI = 1.05–12.72, and service years (AOR = 1.86, 95% CI = 1.16–2.99 showed statistically significant association with chronic respiratory symptoms. Conclusion. Previous history of respiratory diseases, family history of chronic respiratory diseases, previous dusty working environment, smoking, and service years were determinants of chronic respiratory symptoms. Public health endeavors to prevent the burden of chronic respiratory symptoms among pharmaceutical factory workers should target the reduction of adverse workplace exposures and discouragement of smoking.
A speculated cause of respiratory inhibition in infants.
Minowa, Hideki; Arai, Ikuyo; Yasuhara, Hajime; Ebisu, Reiko; Ohgitani, Ayako
In our previous studies, we documented that threatened premature labor and asymmetrical intrauterine growth restriction were risk factors for respiratory inhibition. The goal of this study was to determine the cause of respiratory inhibition by considering perinatal risk factors. We examined 1497 infants with a gestational age of 36 weeks or greater. All infants were monitored using pulse oximetry and examined via cranial sonography. Respiratory inhibition was defined as severe hypoxemia caused by respiratory inhibition immediately after crying or gastroesophageal reflux or as a respiratory pause during feeding. We examined the relationships between respiratory inhibition and perinatal factors and speculated on the cause of respiratory inhibition. The median gestational age, birth weight, Apgar score at 1 min, and Apgar score at 5 min of the subjects were 38.9 weeks, 2930 g, 8.0 points, and 9.0 points, respectively. Respiratory inhibition was observed in 422 infants. Lateral ventricle enlargement and increased echogenicity in the ganglionic eminence were observed in 417 and 516 infants, respectively. Respiratory inhibition was significantly correlated with shorter gestational periods, twin pregnancies, lateral ventricle enlargement, and increased echogenicity in the ganglionic eminence. We speculate that umbilical cord compression is a major cause of respiratory inhibition.
The association between gender and pediatric respiratory morbidity.
Ben-Shmuel, Atar; Sheiner, Eyal; Wainstock, Tamar; Landau, Daniella; Vaknin, Flear; Walfisch, Asnat
To evaluate the association between newborn gender and the risk for later pediatric respiratory morbidity. A population based cohort analysis was performed by comparing the risk of long-term respiratory morbidity (until 18 years of age) according to gender. Respiratory morbidity included hospitalizations involving pneumonia, asthma, bronchitis, bronchiolitis, upper respiratory tract infection (URTI), influenza, and bronchiectasis. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were constructed to compare cumulative respiratory morbidity. A Cox proportional hazards model controlled for confounders. During the study period 240 953 newborns met the inclusion criteria. Among them, 118 113 were females (49.0%) and 122 840 were males (51.0%). During the 18 years of follow-up, 13 719 (5.7%) different newborns were hospitalized with respiratory related morbidity. Males had significantly higher rates of respiratory morbidity as compared with females (6.4% vs 4.9% respectively, P respiratory morbidity (log rank P respiratory morbidity while adjusting for gestational age, birthweight, and other confounders (HR 1.29, 95% CI 1.25-1.34, P respiratory morbidity, independent of obstetrical characteristics such as gestational age and birthweight. © 2018 Wiley Periodicals, Inc.
Biological agents and respiratory infections: Causative mechanisms and practice management.
Takayanagi, Noboru
Biological agents are increasingly being used to treat patients with immune-mediated inflammatory disease. In Japan, currently approved biological agents for patients with rheumatoid arthritis (RA) include tumor necrosis factor inhibitors, interleukin-6 receptor-blocking monoclonal antibody, and T-cell costimulation inhibitor. Rheumatologists have recognized that safety issues are critical aspects of treatment decisions in RA. Therefore, a wealth of safety data has been gathered from a number of sources, including randomized clinical trials and postmarketing data from large national registries. These data revealed that the most serious adverse events from these drugs are respiratory infections, especially pneumonia, tuberculosis, nontuberculous mycobacteriosis, and Pneumocystis jirovecii pneumonia, and that the most common risk factors associated with these respiratory infections are older age, concomitant corticosteroid use, and underlying respiratory comorbidities. Because of this background, in 2014, the Japanese Respiratory Society published their consensus statement of biological agents and respiratory disorders. This review summarizes this statement and adds recent evidence, especially concerning respiratory infections in RA patients, biological agents and respiratory infections, and practice management of respiratory infections in patients treated with biological agents. To decrease the incidence of infections and reduce mortality, we should know the epidemiology, risk factors, management, and methods of prevention of respiratory infections in patients receiving biological agents. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications.
Sardinha, Aline; Freire, Rafael Christophe da Rocha; Zin, Walter Araújo; Nardi, Antonio Egidio
Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.
Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples.
Arvia, Rosaria; Corcioli, Fabiana; Ciccone, Nunziata; Della Malva, Nunzia; Azzi, Alberta
Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 10(3) copies/ml to 10(4) copies/ml. For parainfluenza virus 2 only it was 10(5) copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be
Retrospective respiratory triggering renal perfusion MRI
Attenberger, Ulrike I.; Michaely, Henrik J.; Schoenberg, Stefan O. (Dept. of Clinical Radiology and Nuclear Medicine, Univ. Hospital Mannheim, Univ. of Heidelberg, Mannheim (Germany)), e-mail: firstname.lastname@example.com; Sourbron, Steven P. (Div. of Medical Physics, Univ. of Leeds, Leeds (United Kingdom)); Reiser, Maximilian F. (Dept. of Clinical Radiology, Univ. Hospitals Munich, Grosshadern, Ludwig-Maximilians-Univ., Munich (Germany))
Background: Artifacts of respiratory motion are one of the well-known limitations of dynamic contrast-enhanced MRI (DCE-MRI) of the kidney. Purpose: To propose and evaluate a retrospective triggering approach to minimize the effect of respiratory motion in DCE-MRI of the kidney. Material and Methods: Nine consecutive patients underwent renal perfusion measurements. Data were acquired with a 2D saturation-recovery TurboFLASH sequence. In order to test the dependence of the results on size and location of the manually drawn triggering regions of interest (ROIs), three widely differing triggering regions were defined by one observer. Mean value, standard deviation, and variability of the renal function parameters plasma flow (FP), plasma volume (VP), plasma transit time (TP), tubular flow (FT), tubular volume (VT), and tubular transit time (TT) were calculated on a per-patient basis. Results: The results show that triggered data have adequate temporal resolution to measure blood flow. The overall average values of the function parameters were: 152.77 (FP), 15.18 (VP), 6,73 (TP), 18.50 (FT), 35.36 (VT), and 117.67 (TT). The variability (calculated in % SD from the mean value) for three different respiratory triggering regions defined on a per-patient basis was between 0.81% and 9.87% for FP, 1.45% and 8.19% for VP, 0% and 9.63% for TP, 2.15% and 12.23% for TF, 0.8% and 17.28% for VT, and 1.97% and 12.87% for TT. Conclusion: Triggering reduces the oscillations in the signal curves and produces sharper parametric maps. In contrast to numerically challenging approaches like registration and segmentation it can be applied in clinical routine, but a (semi)-automatic approach to select the triggering ROI is desirable to reduce user dependence.
Propagation of respiratory aerosols by the vuvuzela.
Ka-Man Lai
Full Text Available Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658 × 10(3 per litre for the vuvuzela and 3.7 × 10(3 per litre for shouting, representing a mean log(10 difference of 2.20 (95% CI: 2.03,2.36; p 97% of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others.
Respiratory muscle decline in Duchenne muscular dystrophy.
Khirani, Sonia; Ramirez, Adriana; Aubertin, Guillaume; Boulé, Michèle; Chemouny, Chrystelle; Forin, Véronique; Fauroux, Brigitte
Duchenne muscular dystrophy (DMD) causes progressive respiratory muscle weakness. The aim of the study was to analyze the trend of a large number of respiratory parameters to gain further information on the course of the disease. Retrospective study. 48 boys with DMD, age range between 6 and 19 year old, who were followed in our multidisciplinary neuromuscular clinic between 2001 and 2011. Lung function, blood gases, respiratory mechanics, and muscle strength were measured during routine follow-up over a 10-year period. Only data from patients with at least two measurements were retained. The data of 28 patients were considered for analysis. Four parameters showed an important decline with age. Gastric pressure during cough (Pgas cough) was below normal in all patients with a mean decline of 5.7 ± 3.8 cmH2 O/year. Sniff nasal inspiratory pressure (SNIP) tended to increase first followed by a rapid decline (mean decrease 4.8 ± 4.9 cmH2 O; 5.2 ± 4.4% predicted/year). Absolute forced vital capacity (FVC) values peaked around the age of 13-14 years and remained mainly over 1 L but predicted values showed a mean 4.1 ± 4.4% decline/year. Diaphragmatic tension-time index (TTdi) increased above normal values after the age of 14 years with a mean increase of 0.04 ± 0.04 point/year. This study confirms the previous findings that FVC and SNIP are among the most important parameters to monitor the evolution of DMD. Expiratory muscle strength, assessed by Pgas cough, and the endurance index, TTdi, which are reported for the first time in a large cohort, appeared to be informative too, even though measured through an invasive method. © 2013 Wiley Periodicals, Inc.
Adenovirus respiratory tract infections in Peru.
Julia S Ampuero
Full Text Available BACKGROUND: Currently, there is a paucity of data regarding human adenovirus (HAdv circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. METHODS/PRINCIPAL FINDINGS: Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI or severe acute respiratory infection (SARI were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. CONCLUSIONS/SIGNIFICANCE: HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness.
Adenovirus respiratory tract infections in Peru.
Ampuero, Julia S; Ocaña, Víctor; Gómez, Jorge; Gamero, María E; Garcia, Josefina; Halsey, Eric S; Laguna-Torres, V Alberto
Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness.
Perinatal respiratory infections and long term consequences
Luciana Indinnimeo
Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the
Fractal ventilation enhances respiratory sinus arrhythmia
Girling Linda G
Full Text Available Abstract Background Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA – a mechanism known to improve ventilation/perfusion matching. Methods Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV or in fractal mode (FV at baseline and then following infusion of oleic acid to result in lung injury. Results Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043; post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028; at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047; post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026. Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively. Conclusion These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.
Adenovirus Respiratory Tract Infections in Peru
Ampuero, Julia S.; Ocaña, Víctor; Gómez, Jorge; Gamero, María E.; Garcia, Josefina; Halsey, Eric S.; Laguna-Torres, V. Alberto
Background Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. Methods/Principal Findings Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. Conclusions/Significance HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness. PMID:23056519
Correlation between the respiratory waveform measured using a respiratory sensor and 3D tumor motion in gated radiotherapy
Tsunashima, Yoshikazu; Sakae, Takeji; Shioyama, Yoshiyuki; Kagei, Kenji; Terunuma, Toshiyuki; Nohtomi, Akihiro; Akine, Yasuyuki
Purpose: The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion. Methods and materials: A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function. Results: The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy. Conclusion: Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use
Upper respiratory tract infections in athletes.
Page, Clifton L; Diehl, Jason J
Upper respiratory tract infections (URTIs) represent the most common acute illnesses in the general population and account for the leading acute diagnoses in the outpatient setting. Given the athlete's expectation to return to activity as soon as possible, the sports medicine physician should be able to accurately diagnose and aggressively treat these illnesses. This article discusses the common pathogens, diagnosis, treatment options, and return-to-play decisions for URTIs, with a focus on the common cold, sinusitis, pharyngitis, and infectious mononucleosis in the athlete.
Asthma disease management and the respiratory therapist.
Kallstrom, Thomas J; Myers, Timothy R
The role of the respiratory therapist (RT) is expanding with the growing acceptance and use of the disease-management paradigm for managing chronic diseases. RTs are key members of the asthma disease-management team, in acute-care settings, patients' homes, out-patient clinics, emergency departments, and in the community. Utilizing RTs as disease managers allows patients to be treated faster and more appropriately, discharged to home sooner, and decreases hospital admissions. RT are leaders in the emerging field of asthma disease management.
Intrathoracic lipoblastoma presenting with severe respiratory distress
Joseph Motshedi Sekgololo; Risenga Frank Chauke; Peter Shere Ramoroko; Khondker Mofazzal Hossain
Lipoblastoma is a rare benign tumour which originates from an adipose tissue. In this study we report the case of a three year old boy who presented with a large intrathoracic tumour occupying the whole of the left hemithorax. He presented in severe respiratory distress. A chest X-ray showed total opacity of the left hemithorax, and CT-scan showed a low attenuation mass inkeeping with fat in the left hemithorax. A complete resection of a tumour was undertaken, with histopathology report confi...
I. V. Babachenko
Full Text Available The link between heart disease and infectious pathogens is well known. Despite the high frequency of cardiac pathology in infectious diseases, it is rarely diagnosed because of lack of specific clinical and laboratory symptoms. It is especially difficult to diagnose in children. Airborne infections in the structure of infectious morbidity of children occupy a leading place.The aim of this work was to study the nature of the lesions of the heart in children suffering from acute infection of the respiratory tract.Materials and methods: 341 children with acute respiratory infection of moderate severity were surveyed by a method of ECG dispersion mapping. Cardiac pathology has not previously been determined in these children. Signs of disease of the heart was identified in 76 children (22%. Further study included instrumental (ECG, ECHO-KG, daily monitoring of ECG, biochemical and etiological (ELISA, PCR, immunocytochemical research methods for determining the nature of the damage to the heart and the etiology of the disease.Results. Myocarditis was diagnosed in 2% of children, a violation of repolarization – in 21%, heart rhythm disorders – in 35% (AV – blockade in 4%. Most often signs of heart disease were detected in children with Epstein-Barr virus (32%, streptococcal (28%, cytomegalovirus (25%, herpesvirus type 6 infection (24%. Pathogens from the group of acute respiratory virus infections were identified in 28%, enterovirus – in 10%, Haemophilus influenzae – in 10%, Mycoplasma pneumonia – in 10%, Pneumococcus – in 9%, Chlamydia – in 9%, Parvovirus B19 – in 6%.Conclusion. Sensitive screening test to detect cardiac pathology is the method of ECG dispersion mapping. Heart damage in children with respiratory diseases in 60% of cases is associated with mixed infections. Timely diagnosis of lesions of the heart in infectious diseases in children allows to adjust the
Respiratory Management in the Patient with Spinal Cord Injury
Rita Galeiras Vázquez
Full Text Available Spinal cord injuries (SCIs often lead to impairment of the respiratory system and, consequently, restrictive respiratory changes. Paresis or paralysis of the respiratory muscles can lead to respiratory insufficiency, which is dependent on the level and completeness of the injury. Respiratory complications include hypoventilation, a reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Vital capacity (VC is an indicator of overall pulmonary function; patients with severely impaired VC may require assisted ventilation. It is best to proceed with intubation under controlled circumstances rather than waiting until the condition becomes an emergency. Mechanical ventilation can adversely affect the structure and function of the diaphragm. Early tracheostomy following short orotracheal intubation is probably beneficial in selected patients. Weaning should start as soon as possible, and the best modality is progressive ventilator-free breathing (PVFB. Appropriate candidates can sometimes be freed from mechanical ventilation by electrical stimulation. Respiratory muscle training regimens may improve patients' inspiratory function following a SCI.
[Neuromuscular disease: respiratory clinical assessment and follow-up].
Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J
Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
The respiratory local lymph node assay as a tool to study respiratory sensitizers
Arts, J.H.E.; Jong, W.H. de; Triel, J.J. van; Schijf, M.A.; Klerk, A. de; Loveren, H. van; Kuper, C.F.
The local lymph node assay (LLNA) is used to test the potential of low molecular weight (LMW) compounds to induce sensitization via the skin. In the present study, a respiratory LLNA was developed. Male BALB/c mice were exposed head/nose-only during three consecutive days for 45, 90, 180, or 360
Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.
Nichols, Nicole L; Vinit, Stéphane; Bauernschmidt, Lorene; Mitchell, Gordon S
Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB-SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3-28days after intrapleural injections of: 1) CTB-SAP (25 and 50μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB+SAP). CTB-SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7days post-25μg CTB-SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36±7%; intercostal: 56±10% of controls; n=9; pneuron death and provides an opportunity to study compensation for respiratory motor neuron loss. Copyright © 2014 Elsevier Inc. All rights reserved.
Static respiratory muscle work during immersion with positive and negative respiratory loading.
Taylor, N A; Morrison, J B
Upright immersion imposes a pressure imbalance across the thorax. This study examined the effects of air-delivery pressure on inspiratory muscle work during upright immersion. Eight subjects performed respiratory pressure-volume relaxation maneuvers while seated in air (control) and during immersion. Hydrostatic, respiratory elastic (lung and chest wall), and resultant static respiratory muscle work components were computed. During immersion, the effects of four air-delivery pressures were evaluated: mouth pressure (uncompensated); the pressure at the lung centroid (PL,c); and at PL,c +/-0.98 kPa. When breathing at pressures less than the PL,c, subjects generally defended an expiratory reserve volume (ERV) greater than the immersed relaxation volume, minus residual volume, resulting in additional inspiratory muscle work. The resultant static inspiratory muscle work, computed over a 1-liter tidal volume above the ERV, increased from 0.23 J. l(-1), when subjects were breathing at PL,c, to 0.83 J. l(-1) at PL,c -0.98 kPa (P work was minimal. When breathing at PL,c +0.98 kPa, subjects adopted an ERV less than the immersed relaxation volume, minus residual volume, resulting in 0.36 J. l(-1) of expiratory muscle work. Thus static inspiratory muscle work varied with respiratory loading, whereas PL,c air supply minimized this work during upright immersion, restoring lung-tissue, chest-wall, and static muscle work to levels obtained in the control state.
Effect of physiotherapy in respiratory diseases during healing stays
Schneebergerová, Jana
Title: Effect of physiotherapy in respiratory diseases during healing stays Objective: The main objective of this work is to analyze the importance of physiotherapy as one of the treatments used in the care of pediatric patients with bronchial asthma. Method: In the theoretic part of the dissertation anatomy and physiology of the respiratory tract, respiratory biomechanics, problems of asthma bronchiale, possibilities of asthma treatment, prevention and improvement of quality of life in child...
I.V. Davidova
Full Text Available Mucolytics are widely used in pediatric respiratory pathology treatment. This review contains information about main groups of mucolytics. Special attention is given to acetylcystein. It also includes substantiation report of mucolytics in complex treatment of acute and chronic bronchopulmonary disorders in children.Key words: acetylcystein, mucocillary clearence, acute respiratory viral infection, bronchoobstructive syndrome, respiratory function. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 62–66
Predicting respiratory hospital admissions in young people with cerebral palsy.
Blackmore, Amanda Marie; Bear, Natasha; Blair, Eve; Langdon, Katherine; Moshovis, Lisa; Steer, Kellie; Wilson, Andrew C
To determine the early predictors of respiratory hospital admissions in young people with cerebral palsy (CP). A 3-year prospective cohort study using linked data. Children and young people with CP, aged 1 to 26 years. Self-reported and carer-reported respiratory symptoms were linked to respiratory hospital admissions (as defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes) during the following 3 years. 482 participants (including 289 males) were recruited. They were aged 1 to 26 years (mean 10 years, 10 months; SD 5 years, 11 months) at the commencement of the study, and represented all Gross Motor Function Classification Scale (GMFCS) levels. During the 3-year period, 55 (11.4%) participants had a total of 186 respiratory hospital admissions, and spent a total of 1475 days in hospital. Statistically significant risk factors for subsequent respiratory hospital admissions over 3 years in univariate analyses were GMFCS level V, at least one respiratory hospital admission in the year preceding the survey, oropharyngeal dysphagia, seizures, frequent respiratory symptoms, gastro-oesophageal reflux disease, at least two courses of antibiotics in the year preceding the survey, mealtime respiratory symptoms and nightly snoring. Most risk factors for respiratory hospital admissions are potentially modifiable. Early identification of oropharyngeal dysphagia and the management of seizures may help prevent serious respiratory illness. One respiratory hospital admission should trigger further evaluation and management to prevent subsequent respiratory illness. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Enhancement of Immune Memory Responses to Respiratory Infection
AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD...5a. CONTRACT NUMBER Enhancement of Immune Memory Responses to Respiratory Infection 5b. GRANT NUMBER W81XWH-16-1-0360 5c. PROGRAM ELEMENT NUMBER...entitled "ENHANCEMENT OF IMMUNE MEMORY RESPONSES TO RESPIRATORY INFECTION: AUTOPHAGY IN MEMORY B-CELLS RESPONSE TO INFLUENZA VACCINE (AMBRIV