interacts_with DB00784?
Genetic markers in the EET metabolic pathway are associated with outcomes in patients with aneurysmal subarachnoid hemorrhage . Preclinical studies show that epoxyeicosatrienoic acids ( EETs ) regulate cerebrovascular tone and protect against cerebral ischemia . We investigated the relationship between polymorphic genes involved in EET biosynthesis/metabolism , cytochrome P450 ( CYP ) eicosanoid levels , and outcomes in 363 patients with aneurysmal subarachnoid hemorrhage ( aSAH ) . Epoxyeicosatrienoic acids and dihydroxyeicosatetraenoic acid ( DHET ) cerebrospinal fluid ( P04141 ) levels , as well as acute outcomes defined by delayed cerebral ischemia ( P42126 ) or clinical neurologic deterioration ( CND ) , were assessed over 14 days . Long-term outcomes were defined by Modified Rankin Scale ( P59665 ) at 3 and 12 months . P10632 *4 allele carriers had 44 % and 36 % lower mean EET and DHET P04141 levels ( P=0.003 and P=0.007 ) and were 2.2- and 2.5-fold more likely to develop P42126 and CND ( P=0.039 and P=0.041 ) , respectively . P34913 55Arg , P51589 *7 , P10632 *1B , and P10632 g.36785A allele carriers had lower EET and DHET P04141 levels . P10632 g.25369T and P10632 g.36755A allele carriers had higher EET levels . Patients with P10632 *2C and P34913 404del variants had worse long-term outcomes while those with P34913 287Gln , P51589 *7 , and P11712 g.816G variants had favorable outcomes . Epoxyeicosatrienoic acid levels were associated with Fisher grade and unfavorable 3-month outcomes . Dihydroxyeicosatetraenoic acids were not associated with outcomes . No associations passed Bonferroni multiple testing correction . These are the first clinical data demonstrating the association between the EET biosynthesis/metabolic pathway and the pathophysiology of aSAH . Q13224 subunit selective DB01221 antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat cortical neurones . N-Methyl-D-aspartate ( DB01221 ) receptor-mediated glutamatergic neurotransmission is thought to play a central role in the development of alcohol dependence and this alteration is supposed to be due to a differential up-regulation of the Q13224 type of subunits . In this work , we examined the effect of some known ( CP-101,606 ; CI-1041 and Co-101,244 ) and novel indole-2-carboxamide derivative Q13224 subunit selective DB01221 receptor antagonists ( SSNAs ) ( RG-13579 and RG-1103 ) on the neurotoxic effect of withdrawal in ethanol pre-treated cultures of rat cortical neurones . The extent of neurotoxicity was estimated by measuring the activity of lactate dehydrogenase ( LDH ) that was released into the culture medium during the 24h withdrawal period . Here , we demonstrate that Q13224 SSNAs given in the course of the withdrawal potently reduced the LDH release in ethanol pre-treated cultures . One of our novel compound , RG-1103 , proved to be more potent than the reference Q13224 SSNAs tested in this work having similar potency as the most potent but non-subunit selective DB01221 receptor antagonist dizocilpine ( MK-801 ) . DB00659 , a currently used therapeutic drug for the treatment of alcoholism was also effective although only in high micromolar concentrations . According to these observations , Q13224 SSNAs are potent inhibitors of ethanol-withdrawal-induced neurotoxicity and considering that these agents have acceptable side effect profiles , they could be promising therapeutic candidates in the pharmacotherapy for physical signs of acute alcohol-withdrawal and associated neuronal damage . Expression of renin-angiotensin system components in the early bovine embryo . The renin-angiotensin system ( DB01367 ) , mainly associated with the regulation of blood pressure , has been recently investigated in female reproductive organs and the developing foetus . Angiotensin II ( Ang II ) influences oviductal gamete movements and foetal development , but there is no information about DB01367 in the early embryo . The aim of this study was to determine whether DB01367 components are present in the pre-implantation embryo , to determine how early they are expressed and to investigate their putative role at this stage of development . Bovine embryos produced in vitro were used for analysis of DB01367 transcripts ( RT-PCR ) and localisation of the receptors P30556 and P50052 ( immunofluorescent labelling ) . We also investigated the effects of Ang II , DB00275 ( P30556 antagonist ) and PD123319 ( P50052 antagonist ) on oocyte cleavage , embryo expansion and hatching . Pre-implanted embryos possessed P30556 and P50052 but not the other DB01367 components . Both receptors were present in the trophectoderm and in the inner cell mass of the blastocyst . P30556 was mainly localised in granular-like structures in the cytoplasm , suggesting its internalisation into clathrin-coated vesicles , and P50052 was found mainly in the nuclear membrane and in the mitotic spindle of dividing trophoblastic cells . Treating embryos with PD123319 increased the proportion of hatched embryos compared with the control . These results , the first on DB01367 in the early embryo , suggest that the pre-implanted embryo responds to Ang II from the mother rather than from the embryo itself . This may be a route by which the maternal DB01367 influences blastocyst hatching and early embryonic development . Growth factors expression in patients with erosive esophagitis . Although the pathogenesis and treatment of erosive esophagitis ( EE ) is well recognized , little is known about the cellular and molecular mechanisms of mucosal healing in EE patients . In this pilot study , we enrolled typical EE patients to evaluate what kinds of growth factors and their receptors were activated in their injured esophageal mucosa . Forty endoscopically proved EE patients were consecutively enrolled . Messenger RNA expressions , which includes keratinocyte growth factor ( KGF ) and its receptor ( P21802 ) , epidermal growth factor ( P01133 ) and its receptor ( P00533 ) , hepatocyte growth factor ( P14210 ) and its receptor ( HGFR ) , basic fibroblast growth factor ( P09038 ) , vascular endothelial growth factor ( P15692 ) , and cyclooxygenase ( P36551 ) -1 and P35354 , were measured using real-time polymerase chain reaction ( PCR ) . Data were compared between the injured EE mucosa and their normal esophageal mucosa above EE . The mRNA expressions of P14210 , HGFR , P01133 , P15692 , and P35354 , but not P00533 , KGF , P21802 , P09038 , and P23219 , were significantly increased in the injured mucosa of EE patients compared with those of normal mucosa ( P < 0.05 ) . The study found that P14210 , HGFR , P01133 , P15692 , and , P35354 are activated in the injured mucosa of EE patients ; their activation might be involved in mucosal repair and ulcer healing of EE . P10828 mutants : Dominant negative regulators of peroxisome proliferator-activated receptor gamma action . Thyroid hormone ( DB00279 ) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis . Their actions are mediated by their respective receptors : thyroid hormone receptors ( TR ) and peroxisome proliferator-activated receptors ( Q07869 ) . We recently found that a dominantly negative TRbeta mutant ( PV ) that causes a genetic disease , resistance to thyroid hormone , acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPARgamma in cultured thyroid cells . This finding suggests that TRbeta mutants could crosstalk with PPARgamma-signaling pathways . The present study explored the molecular mechanisms by which PV represses the PPARgamma transcriptional activity . Gel-shift assays show that the PV , similar to wild-type TRbeta , bound to the peroxisome proliferator response element ( PPRE ) as homodimers and heterodimers with PPARgamma or the retinoid X receptor ( RXR ) , thereby competing with PPARgamma for binding to PPRE and for sequestering RXR . Association of PPRE-bound PV with corepressors [ e.g. , nuclear receptor corepressor ( NCoR ) ] that led to transcriptional repression was independent of DB00279 and troglitazone . Chromatin immunoprecipitation assay further demonstrated that , despite the presence of ligands , NCoR was recruited to PPRE-bound PV on a PPARgamma-target gene , the lipoprotein lipase , in vivo , suggesting the dominant action of PV on PPARgamma-mediated transcriptional activity . Thus , the dominant negative action of PV is not limited on the wild-type TRs . The findings that TRbeta mutants affect PPARgamma functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPARgamma-target genes involved in metabolic pathways , lipid homeostasis , and carcinogenesis . Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid . DB00784 ingestion , usually in excess and over prolonged period is known to produce interstitial nephritis , or less commonly papillary necrosis , with acute renal failure . However , it is not dose-dependent for the induction of tubulointerstitial damage . Excess iodine ingestion is known to produce toxicity and possible death , but acute renal failure is rare . There is evidence from clinical and experimental data that iodine has toxic effect on tubular epithelial cells . Iodine has not been documented to produce red cell hemolysis and hemoglobinuria . We present a unique case of acute renal failure from hemoglobinuric and acute interstitial nephritis secondary to suicidal ingestion of potassium iodide solution and also ingestion of a few mefenamic acid tablets . These agents led to potentiation of the renal injury from hemoglobinuric tubulopathy , probably from the iodine , and renal dysfunction from alteration of renal perfusion by selective P23219 inhibition of prostaglandin production , and induction of acute interstitial nephritis from mefenamic acid , leading to acute renal failure which was reversible by hemodialysis and supportive therapy . Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis . Renal cell carcinoma ( RCC ) is more frequently observed in patients on dialysis than in patients with normal renal function . However , the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear . We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms , and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients . We evaluated the immunohistochemical expression of oxidative stress markers , such as P35228 , 8-OHdG , and P35354 in 42 cases on dialysis and 51 cases with normal renal function as a control . The methylation status of p16INK4a , Q8N726 , P40337 , and RASSF1A was analysed together with clinicopathological factors . Histologically , the papillary type was observed more frequently in dialysis RCC than in sporadic RCC . Immunohistochemically , overexpression of P35228 ( p < 0.0001 ) and P35354 ( p = 0.0002 ) was more frequently observed in dialysis RCC . Furthermore , the 8-OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC . Hypermethylation of p16INK4a was more frequently found in dialysis RCC ( p < 0.05 ) . However , no significant correlations between oxidative stress markers and DNA hypermethylation status were observed . The overexpression of P35228 , P35354 , and 8-OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC . Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha ( P01375 alpha ) release in the course of pretransplant conditioning : role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human P01375 alpha ( DB04956 ) . Contribution of host-related cytokine release in the course of pretransplant conditioning to early tissue damage and induction of acute graft-versus-host disease ( GVHD ) after allogeneic bone marrow transplantation ( BMT ) has been shown in experimental models . We performed a clinical phase I/II trial applying a monoclonal antibody neutralizing human tumor necrosis alpha ( P01375 alpha ) during pretransplant conditioning as additional prophylaxis in high-risk patients admitted to allogeneic BMT ; P01375 alpha serum levels and clinical courses in 21 patients receiving anti- P01375 alpha prophylaxis were compared with data from 22 historical controls . Absence of significant release of P01375 alpha in the period of busulphan ( BUS ) treatment , but significant induction of P01375 alpha by total body irradiation ( TBI ) and cyclophosphamide ( CY ) conditioning were correlated with significantly earlier onset of acute GVHD in patients receiving TBI/CY regimens as compared with BUS/CY-treated patients . Prophylactic application of monoclonal anti- P01375 alpha seemed to postpone onset of acute GVHD from day 15 to day 25 ( P < .05 ) after TBI/CY and from day 33 to day 53 after BUS/CY ( P < .10 ) conditioning . Application of monoclonal anti- P01375 alpha in low and intermediate doses was safe and not associated with an increased incidence of infectious or hematologic complications . Thus , our data provide indirect and direct evidence for involvement of conditioning-related cytokine release in induction of early acute GVHD in the clinical setting and support further investigation of this novel approach in randomized trials . A new algorithm for weekly phenprocoumon dose variation in a southern Brazilian population : role for P11712 , P08684 /5 and Q9BQB6 genes polymorphisms . DB00946 is widely used in prophylaxis and treatment of thromboembolic disorders . However , its pharmacokinetics and pharmacodynamics vary according to several genetic and non-genetic factors . DB00946 metabolism is mediated by P11712 and CYP3A enzymes . Moreover , Q9BQB6 is phenprocoumon target of action . Therefore , the aim of this study was to evaluate the association of single nucleotide polymorphisms ( SNPs ) in Q9BQB6 , P11712 , P08684 and P20815 genes with the variance of weekly phenprocoumon dose as well as to develop an algorithm for dose prediction based on genetic and environmental factors . A total of 198 patients with stable phenprocoumon dose , 81 % of European ancestry , were investigated . Genotypes were determined by allelic discrimination with TaqMan assays . Polymorphisms -1639G > A and 1173C > T in Q9BQB6 and the presence of P11712 *2 and/or P11712 *3 are associated with lower doses . On the other hand , 3730G > A in Q9BQB6 gene is associated with higher doses . No association was found between P08684 *1B , P20815 *3 and P20815 *6 polymorphisms . Among non-genetic factors , gender , height , age and use of captopril , omeprazole , simvastatin and β-blockers are associated with dose . Two algorithms were derived : one for the whole sample explained 42 % of dose variation and one for patients of European ancestry only which explained 46 % of phenprocoumon dose . The mean absolute difference between observed and predicted dose was low in both models ( 3.92 mg/week and 3.54 mg/week , for models 1 and 2 , respectively ) . However , more studies with other genes and environmental factors are needed to test and to improve the algorithm . Targeted therapies for adrenocortical carcinoma : IGF and beyond . Standard chemotherapy for adrenocortical cancer currently is under evaluation in the context of the recently completed FIRM-ACT evaluating the combination of mitotane with either streptozocin or etoposide , cisplatin , and doxorubicin . New agents are eagerly sought by the ACC community that hopes to make progress against this deadly disease . Investigators have begun to dissect the molecular and genomic context of ACC with a goal of identifying potential novel therapeutic agents . One gene consistently overexpressed in ACC is insulin growth factor type 2 . Targeting its receptor P08069 has shown encouraging results in ACC cell lines and against murine xenografts . As a result , clinical trials to evaluate agents targeting the P08069 have been done including mitotane and DB05759 ( a monoclonal antibody ) and the GALACCTIC trial that has just completed accrual to evaluate OSI-906 , a small molecule P08069 antagonist . On the horizon are other agents targeting other tyrosine kinases , including P01133 and FGF , and novel strategies such as individualized tumor analysis to select treatment . Microglial activation , increased P01375 and P31645 expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia . A chronic stress paradigm comprising exposure to predation , tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some , but not all , animals . Here , we sought to extend our behavioural studies to investigate how susceptibility ( sucrose preference < 65 % ) or resilience ( sucrose preference > 65 % ) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes . All chronically stressed animals , displayed increased level of anxiety , but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions . These changes were not present in resilient or acutely stressed animals . Compared to resilient animals , susceptible mice showed elevated expression of tumour necrosis factor alpha ( P01375 ) and the 5-HT transporter ( P31645 ) in the pre-frontal area . Enhanced expression of 5HT(2A) and P23219 in the pre-frontal area was observed in all stressed animals . In turn , indoleamine-2,3-dioxygenase ( P14902 ) was significantly unregulated in the raphe of susceptible animals . At the cellular level , increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals . Consequently , the susceptible animals display a unique molecular profile when compared to resilient , but anxious , animals . Unexpectedly , this altered profile provides a rationale for exploring anti-inflammatory , and possibly , P01375 -targeted therapy for major depression . Expression of P35354 and DB01221 receptor genes at the cochlea and midbrain in salicylate-induced tinnitus . OBJECTIVE/HYPOTHESIS : The expression of the genes for cyclooxygenase ( P36551 ) and DB01221 receptor ( NR ) has seldom been reported in tinnitus . We hypothesized that expression of P35354 and NR was altered in the cochlea and midbrain in salicylate-induced tinnitus . STUDY DESIGN : Experimental study on mice . METHODS : We evaluated the tinnitus score and mRNA expression levels of P35354 and NR subtype 2B ( Q13224 ) in the cochlea and midbrain in response to intraperitoneal injections of salicylate for 4 days . RESULTS : At day 4 of tinnitus induction , the mean weights of the whole body and midbrain did not change greatly in both control and salicylate groups . The tinnitus score was not elevated from day 1 to day 4 in the control group , but increased day by day in the salicylate group . The mRNA expression level of P35354 decreased slightly in the salicylate group in the cochlea ( 1.1 ± 0.33 vs. 1.3 ± 0.49 , P = .0752 ) and in the midbrain ( 0.9 ± 0.10 versus 1.0 ± 0.35 , P = .0489 ) . Inversely , the expression levels of the Q13224 gene increased moderately in the salicylate group in the cochlea ( 3.7 ± 0.47 versus 2.3 ± 1.13 , P < 0.0001 ) and in the midbrain ( 1.6 ± 0.64 versus 1.0 ± 0.44 , P = .0007 ) . CONCLUSIONS : Salicylate induced tinnitus and altered the expression of the P35354 and Q13224 genes in the cochlea and midbrain of mice . These findings might contribute to further understanding of pathophysiology and therapy of tinnitus . Receptor kinase inhibitors target NSCLC : two antibodies and a small-molecule MET inhibitor . Joining cetuximab , sorafenib , afatinib , intedanib , and crizotinib in phase III development for non-small cell lung cancer ( NSCLC ) are ramucirumab ( developed by ImClone , a subsidiary of Lilly ) , necitumumab ( developed by ImClone and Bristol-Myers Squibb ) , and tivantinib ( ARQ 197 , developed by ArQule and Daiichi Sankyo ) . DB09559 is a second-generation anti- P00533 monoclonal antibody ( mAb ) similar to cetuximab . Enrollment has been stopped in one of two necitumumab phase III trials because of safety concerns . DB05578 is an anti- P35968 mAb targeting the same pathway as bevacizumab . Although the phase II safety data for ramucirumab appear better than the data for necitumumab , fewer phase III data are available . Tivantinib is a highly selective , orally available MET tyrosine kinase inhibitor . MET is overexpressed in 61 % of NSCLC cases . Although tivantinib is the last of the three agents discussed here to enter phase III , its phase II results are the most robust . Inhibition of human brain and RBC acetylcholinesterase ( P22303 ) by heptylphysostigmine ( HPTL ) . Heptylphysostigmine ( HPTL ) , a derivative of the P22303 inhibitor physostigmine ( PHY ) , is under investigation as a therapeutic agent in Alzheimer 's disease . HPTL is active against human RBC P22303 both in vitro and in vivo . Activity of HPTL against human brain has not been documented . We have developed an in vitro assay system using particulate membrane fractions which permits comparison of inhibition and recovery kinetics of human RBC ( primarily globular dimer ) and brain ( primarily globular tetramer ) membrane-bound forms . Under these conditions the HPTLIC50 is similar for the two forms . RBC P22303 inhibition spontaneously reverses in 24 h , as occurs in vivo . In striking contrast , activity of inhibited brain enzyme does not recover on overnight incubation . DDVP-induced inhibition , but not HPTL inhibition , can be reversed by the oxime DB00733 . Some recovery of HPTL inhibition , but not to the level seen with RBC P22303 , occurs on addition of heat-stable fractions from serum or P04141 . Brain enzyme recovers rapidly from PHY in this system . Responses of brain and RBC P22303 to HPTL indicate that these forms are functionally as well as structurally distinct . Since brain inhibition apparently does not spontaneously reverse like RBC inhibition , peripheral measurements of patient responses should be assessed with caution during treatment with HPTL . Investigation of the binding of isoform-selective inhibitors to prostaglandin endoperoxide synthases using fluorescence spectroscopy . Prostaglandin endoperoxide synthase ( PGHS ) is a heme protein that catalyzes the committed step in prostaglandin and thromboxane biosynthesis . Two isoforms of PGHS exist , a constitutive form termed P23219 and an inducible form termed P35354 . We report here fluorescence resonance energy transfer analysis of isoform-selective inhibitors interacting with P23219 and P35354 . By measuring fluorescence quenching due to the energy transfer of the inhibitor fluorescence to the heme prosthetic group of PGHS , we determined these inhibitors bind in the arachidonic acid substrate access channel with an R0 of 35 A for P23219 with the P23219 inhibitor and an R0 of 21 A for P35354 with the P35354 inhibitor . The observed fluorescence quenching is completely dynamic and dominated by quenching by the heme . Time-resolved results combined with molecular modeling determine the distance from the inhibitor to the heme moiety to be 20 A in P23219 and 18 A in P35354 . Preliminary stopped-flow kinetic studies reveal that the rate of quenching is limited by a first-order protein transition , which is slow , and that bound inhibitor undergoes rapid exchange . Germline mutations and genotype-phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea . The aim of our study was to assess the frequency of germline mutations and develop the genetic testing strategy in patients with apparently sporadic pheochromocytoma/paraganglioma ( PPGL ) in Korea . We included 53 patients diagnosed with non-syndromic PPGL without a family history of PPGLs in three referral centers from 2004 to 2011 . DB00139 dehydrogenase complex B ( P21912 ) , O14521 , Von Hippel-Lindau ( P40337 ) , and rearranged during transfection ( P07949 ) genes were examined by direct sequencing and multiple ligation-dependent probe amplification . The study patients were composed of 26 men and 27 women , and mean age was 50.1 ± 13.5 years . The frequency of germline mutations was 13.2 % ( 7/53 ) : P07949 ( n = 2 ) , P40337 ( n = 1 ) , P21912 ( n = 2 ) , and O14521 ( n = 2 ) . Six of seven mutation carriers were diagnosed before the age of 50 . One of two patients harboring an P21912 mutation had malignant PPGLs . One patient with multifocal head and neck paraganglioma ( PGL ) and pheochromocytoma ( PHEO ) carried a O14521 mutation . The carriers of germline mutations in patients with apparently sporadic PPGL were 13.2 % in our study . We recommend genetic testing in patients below 50 years and O14521 genetic testing in patients with multifocal PPGLs . In malignant PPGLs , P21912 genetic testing may be performed . Peroxisome proliferator-activated receptor-gamma is a target of nonsteroidal anti-inflammatory drugs mediating cyclooxygenase-independent inhibition of lung cancer cell growth . Nonsteroidal anti-inflammatory drugs ( NSAIDs ) inhibit the growth of different cancer cell types , suggesting a broad role for their cyclooxygenase ( P36551 ) targets and eicosanoid products in tumor cell growth . Sulindac sulfide , a P36551 inhibitor , inhibited the growth of non-small-cell lung cancers ( NSCLC ) both in soft agar and as xenografts in nude mice . Importantly , the concentration of sulindac sulfide required to inhibit NSCLC cell growth greatly exceeded the concentration required to inhibit prostaglandin ( PG ) E(2) synthesis in NSCLC cells , suggesting that NSAID inhibition of cell growth is mediated by additional targets distinct from P36551 . Both sulindac sulfide and ciglitazone , a defined peroxisome proliferator-activated receptor-gamma ( PPARgamma ) agonist , stimulated a promoter construct containing a Q07869 response element linked to luciferase and potently inhibited NSCLC cell growth at similar concentrations , indicating a role for PPARgamma as a target of NSAID action in these cells . Overexpression of PPARgamma in NSCLC cells strongly inhibited the transformed growth properties of the cells , providing a molecular confirmation of the results obtained with the PPARgamma agonists . Increased expression of PPARgamma , as well as ciglitazone and sulindac sulfide induced expression of P12830 , which has been linked to increased differentiation of NSCLC . Despite the fact that SCLC cell lines expressed little or no cytosolic phospholipase A(2) , P23219 , or P35354 , sulindac sulfide and PPARgamma agonists also inhibited the transformed growth of these lung cancer cells . We propose that PPARgamma serves as a target for NSAIDs that accounts for P36551 -independent inhibition of lung cancer cell growth . Prostaglandin receptors ( EP2 and EP4 ) and angiotensin receptor ( P50052 ) mRNA expression increases in the oviducts of Nelore cows submitted to ovarian superstimulation . Many peptides are responsible for the coordination of muscle contraction , secretion and ciliary beating of the oviduct epithelium to allow the transport of gametes and embryos , including vascular endothelial growth factors ( P15692 ) , prostaglandins ( PGs ) , endotelin-1 ( ET-1 ) and angiotensin II ( Ang II ) . The effect of reproductive biotechnologies used to improve embryo yield on oviduct gene expression is poorly understood . Thus , the aim of the present study was to evaluate the effect of ovarian superstimulation on the mRNA expression of the genes encoding the major peptides involved in oviduct contraction in bovine . Therefore , Nelore cows were submitted to P-36 ( n=5 ) or P-36/eCG ( n=5 ) ovarian superstimulatory protocols and a control group of cows was not submitted to any superstimulatory protocol ( n=5 ) . The relative expression of P15692 ( P15692 , Flk1 , Flt1 ) , Ang II ( P50052 , ACE1 ) , ET1 ( ET1 , P42892 ) and PG pathway members ( O14684 , EP2 , EP4 , P23219 , P35354 ) was analyzed using real time RT-PCR in each of oviduct segment ( infundibulum , ampulla and isthmus ) . All target genes were expressed in the three segments of the bovine oviduct ; however , specific genes were regulated by ovarian superstimulation : EP2 and EP4 receptors mRNA was affected by P-36/eCG protocol , in the ampulla and infundibulum , respectively ; and P50052 mRNA was up-regulated by both the P-36/eCG and P-36 protocols in the isthmus . The upregulation of EP2 , EP4 and P50052 expression in the superstimulated cows suggests a suitable effect of DB00094 and eCG on bovine oviduct physiology , coordinating the contraction in Nelore cows . Cytokine responses of intestinal epithelial-like Caco-2 cells to non-pathogenic and opportunistic pathogenic yeasts in the presence of butyric acid . Candida albicans , Saccharomyces cerevisiae and their cell wall components , zymosan and glucan , have been shown to stimulate interleukin-8 ( P10145 /CXCL-8 ) production by intestinal epithelial cell-like Caco-2 cells pre-cultured with 10 mM butyric acid . We examined in this study whether these yeasts also altered the production of other cytokines and cyclooxygenases ( COXs ) by Caco-2 cells . Culturing Caco-2 cells with 10 mM butyric acid and 15 % FBS for 4 days enhanced the basal levels of mRNA encoding P05231 , P10145 , Q14116 , monocyte chemoattractant protein ( MCP ) -1 , stem cell factor , transforming growth factor ( TGF ) -beta1 , TGF-beta3 , tumor necrosis factor ( P01375 ) -alpha , P23219 , and P35354 , but not of granulocyte-macrophage colony-stimulating factor ( GM- P04141 ) and TGF-beta2 . The inclusion of live S. cerevisiae or C. albicans further enhanced the production of P10145 , but not of the other cytokines and COXs . The non-pathogenic yeasts , C. kefyr , C. utilis , C. versatilis , Kluyveromyces lactis , K. marxianus , Schizosaccharomyces pombe and Zygosaccharomyces rouxii , used for the production of fermented foods and probiotics , and the opportunistic pathogens , C. glabrata , C. krusei , C. parapsilosis and C. tropicalis , isolated from human tissue samples also enhanced P10145 secretion by Caco-2 cells . Cyclo-oxygenases and prostaglandins in acute inflammatory demyelination of the peripheral nerve . OBJECTIVE : To investigate the expression of cyclo-oxygenases ( P36551 ) , key enzymes in propagating inflammatory responses by converting arachidonic acid to prostaglandins , in inflammatory demyelinating disorders of the peripheral nervous system ( PNS ) . METHODS : Expression and distribution of P36551 messenger RNA ( mRNA ) and protein were studied in sural nerve biopsies , serum , and P04141 samples from patients with Guillain-Barré syndrome ( GBS ) , chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP ) , or , for comparison , with vasculitic neuropathy ( VN ) , which is a inflammatory nondemyelinating disorder , and noninflammatory neuropathies ( Q8N4C6 ) using RT-PCR , immunohistochemistry , and immunoblotting . To confirm functional P35354 activity , the expression of prostaglandin E(2) ( PGE(2) ) and prostaglandin F(2alpha) ( P49763 (2alpha) ) was evaluated by ELISA ex vivo and in vitro . RESULTS : Whereas P23219 expression was unaltered in all investigated groups , a significant upregulation of P35354 mRNA was detected in sural nerves from patients with GBS , CIDP , or VN but not in control subjects with noninflammatory disorders . Macrophages were identified as its primary cellular source . Increased P35354 protein levels were detectable in serum and P04141 from all patients with GBS and , in smaller numbers only , in samples from patients with CIDP or VN but not from the Q8N4C6 group studied . Moreover , increased levels of PGE(2) and P49763 (2alpha) were measurable in sera from patients with GBS , CIDP , or VN and in cell culture supernatants from in vitro stimulated macrophages , indicative of P35354 activity . CONCLUSIONS : Cyclo-oxygenase-2 , expressed by macrophages , may generate prostaglandins during acute inflammatory demyelination of the peripheral nerve .