interacts_with DB00472?
cDNA array analysis of cytokines , chemokines , and receptors involved in the development of TNBS-induced colitis : homeostatic role of P01282 . Crohn 's disease ( CD ) is a chronic inflammatory pathology of the intestine , characterized by diarrhea and weight loss . A healing effect of vasoactive intestinal peptide ( P01282 ) in the murine model of CD based on 2,4,6-trinitrobencene sulfonic acid ( TNBS ) administration has been previously shown . The aim of this work was to analyze the expression of several mediators related to the inflammatory cascade in colitic and P01282 -treated animals . With this aim , mice received either only TNBS or TNBS and P01282 treatment on alternate days . cDNA microarray analysis and real-time polymerase chain reaction were performed on total mRNA from colon to study the expression of a battery of proinflammatory molecules such as the enzyme P35354 , the chemokines P78423 , P48061 , O43927 , O95715 , P51681 , and P25025 , and the cytokines interleukin ( IL ) -1beta , IL-12 , Q14116 , P22301 , interferon-gamma , and P05112 . TNBS administration induced the expression of all the proinflammatory mediators studied , whereas P01282 treatment reduced their levels , increasing the anti-inflammatory P22301 and the TH2 cytokine P05112 , explaining its beneficial action through inhibition of the inflammatory/ Q8IXH7 response . These data describe not only the relation of several proinflammatory mediators to the development of TNBS colitis , reporting their time-course , but also show the beneficial action of P01282 in this model through complete blockage of the inflammatory cascade and recovery of the colon homeostasis , providing a potential new alternative for CD therapy . Inhibition of human steroid 5beta-reductase ( P51857 ) by finasteride and structure of the enzyme-inhibitor complex . The Delta(4)-3-ketosteroid functionality is present in nearly all steroid hormones apart from estrogens . The first step in functionalization of the A-ring is mediated in humans by steroid 5alpha- or 5beta-reductase . DB01216 is a mechanism-based inactivator of 5alpha-reductase type 2 with subnanomolar affinity and is widely used as a therapeutic for the treatment of benign prostatic hyperplasia . It is also used for androgen deprivation in hormone-dependent prostate carcinoma , and it has been examined as a chemopreventive agent in prostate cancer . The effect of finasteride on steroid 5beta-reductase ( P51857 ) has not been previously reported . We show that finasteride competitively inhibits P51857 with low micromolar affinity but does not act as a mechanism-based inactivator . The structure of the P51857 .NADP(+)*finasteride complex determined at 1.7 A resolution shows that it is not possible for NADPH to reduce the Delta(1-2)-ene of finasteride because the cofactor and steroid are not proximal to each other . The P01024 -ketone of finasteride accepts hydrogen bonds from the catalytic residues DB00135 -58 and DB00142 -120 in the active site of P51857 , providing an explanation for the competitive inhibition observed . This is the first reported structure of finasteride bound to an enzyme involved in steroid hormone metabolism . Specific Biomarkers Are Associated with Docetaxeland Gemcitabine-Resistant NSCLC Cell Lines . Five-year survival rate for lung cancer is limited to 10 % to 15 % . Therefore , the identification of novel therapeutic prognostic factors is an urgent requirement . The aim of this study is thus to highlight specific biomarkers in chemoresistant non-small cell lung cancer cell lines . Therefore , we checked-in the control condition as well as after short-term pharmacological treatment with either docetaxel or gemcitabine-the expression of genes such as tumor suppressor genes ( CDKN2A , P53355 , P49789 , P09211 , P16455 , RARβ2 , RASSF1A , and P35625 ) , genes associated with drug resistance ( P38398 , P35354 , P07992 , P17936 , P23921 , and Q13509 ) , and stemness-related genes ( CD133 , Q01860 , and O43623 ) in two cellular models of squamous carcinoma ( CAEP ) and adenocarcinoma ( RAL ) of the lung originally established . Their promoter methylation profile was also evaluated . Drug-related genes were upregulated . DB00515 resistance matched with high levels of P38398 and P07992 in both cell lines ; docetaxel sensitivity of CAEP cells was associated to levels of Q13509 lower than RAL cells . Although CAEP cells were more sensitive to gemcitabine , both cell lines showed high levels of P23921 . Stemness-related genes were downregulated in the control condition but became upregulated in docetaxel-resistant cells , indicating the selection of a population with stemness features . We did not find an unequivocal correspondence between gene expression and respective DNA promoter methylation status , suggesting the involvement of additional mechanisms of gene expression regulation . These results highlight specific biomarkers consistent with the different responses of the two cell lines to standard pharmacological treatments and indicate specific molecular traits for their chemoresistance . Activating mutations of GNAS in canine cortisol-secreting adrenocortical tumors . BACKGROUND : Cushing 's syndrome or hypercortisolism is a common endocrinopathy in dogs . In approximately 15 % of cases , the disorder is caused by adrenocorticotropin ( DB01285 ) -independent hypersecretion of cortisol by an adrenocortical tumor ( AT ) . Without other explanation , the cortisol hypersecretion has been referred to as autonomous . OBJECTIVES : To investigate whether DB01285 -independent hypersecretion of cortisol may be associated with aberrant activation of the melanocortin 2 receptor ( Q01718 ) -cyclic AMP ( DB02527 ) -protein kinase A ( PKA ) pathway . ANIMALS : All analyses were performed on 44 cortisol-secreting ATs ( 14 adenomas and 30 carcinomas ) derived from dogs diagnosed with DB01285 -independent hypercortisolism . METHODS : Mutation analysis was performed of genes encoding the stimulatory G protein alpha subunit ( GNAS ) , Q01718 , and PKA regulatory subunit 1A ( P10644 ) in all ATs . RESULTS : Approximately one-third of all ATs harbored an activating mutation of GNAS . Missense mutations , known to result in constitutive activation , were present in codon 201 in 11 ATs , in codon 203 ( 1 AT ) , and in codon 227 ( 3 ATs ) . No functional mutations were found in Q01718 and P10644 . CONCLUSIONS AND CLINICAL IMPORTANCE : Activation of DB02527 signaling is a frequent event in canine cortisol-secreting ATs and may play a crucial role in both DB01285 -independent cortisol production and tumor formation . To the best of our knowledge , this is the first report of potentially causative mutations in canine cortisol-secreting ATs . GABA , glutamate , dopamine and serotonin transporters expression on forgetting . Notwithstanding several neurotransmission systems are frequently related to memory formation ; forgetting process and neurotransmission systems or their transporters ; the role of γ-aminobutyric acid ( P30531 ) , glutamate ( EACC1 ) , dopamine ( Q01959 ) and serotonin ( P31645 ) is poorly understood . Hence , in this paper western-blot analysis was used to evaluate expression of P30531 , P43005 , Q01959 and P31645 during forgetting in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine , the amnesic drug d-methamphetamine ( METH ) and fluoxetine plus METH . Transporters expression was determined in the hippocampus ( HIP ) , prefrontal cortex ( P27918 ) and striatum ( STR ) . Results indicated that forgetting of Pavlovian/instrumental autoshaping was associated to up-regulation of P30531 ( P27918 and HIP ) and Q01959 ( P27918 ) while P31645 ( HIP ) was down-regulated ; no-changes were observed in striatum . Methamphetamine administration did not affect forgetting at 216 h post-training but up-regulated hippocampal Q01959 and EACC , prefrontal cortex Q01959 and striatal P30531 or EACC1 . DB00472 alone prevented forgetting , which was associated to striatal P30531 and hippocampal Q01959 up-regulation , but prefrontal cortex P30531 down-regulation . DB00472 plus METH administration was also able to prevent forgetting , which was associated to hippocampal Q01959 , prefrontal cortex P31645 and striatal P30531 , Q01959 or P31645 up-regulation , but prefrontal cortex P30531 down-regulation . Together these data show that forgetting provokes primarily hippocampal and prefrontal cortex transporters changes ; forgetting represent a behavioral process hardly modifiable and its prevention could causes different transporters expression patterns . P35372 activation of P27361 /2 is P35626 and arrestin dependent in striatal neurons . In this study we investigated the mechanisms responsible for Q96HU1 kinase P27361 /2 activation following agonist activation of endogenous mu opioid receptors ( MOR ) normally expressed in cultured striatal neurons . Treatment with the MOR agonist fentanyl caused significant activation of P27361 /2 in neurons derived from wild type mice . Fentanyl effects were blocked by the opioid antagonist naloxone and were not evident in neurons derived from MOR knock-out ( -/- ) mice . In contrast , P27361 /2 activation by fentanyl was not evident in neurons from P35626 -/- mice or neurons pretreated with small inhibitory RNA for arrestin3 . Consistent with this observation , treatment with the opiate morphine ( which is less able to activate arrestin ) did not elicit P27361 /2 activation in wild type neurons ; however , transfection of arrestin3-(R170E) ( a dominant positive form of arrestin that does not require receptor phosphorylation for activation ) enabled morphine activation of P27361 /2 . In addition , activation of P27361 /2 by fentanyl and morphine was rescued in P35626 -/- neurons following transfection with dominant positive arrestin3-(R170E) . The activation of P27361 /2 appeared to be selective as p38 Q96HU1 kinase activation was not increased by either fentanyl or morphine treatment in neurons from wild type , MOR-/- , or P35626 -/- mice . In addition , U0126 ( a selective inhibitor of MEK kinase responsible for P29323 phosphorylation ) blocked P27361 /2 activation by fentanyl . These results support the hypothesis that MOR activation of P27361 /2 requires opioid receptor phosphorylation by P35626 and association of arrestin3 to initiate the cascade resulting in P27361 /2 phosphorylation in striatal neurons . Dependence on phosphoinositide 3-kinase and DB01367 -RAF pathways drive the activity of RAF265 , a novel RAF/ P35968 inhibitor , and RAD001 ( DB01590 ) in combination . Activation of phosphatidylinositol-3-kinase ( PI3K ) -AKT and Kirsten rat sarcoma viral oncogene homologue ( P01116 ) can induce cellular immortalization , proliferation , and resistance to anticancer therapeutics such as epidermal growth factor receptor inhibitors or chemotherapy . This study assessed the consequences of inhibiting these two pathways in tumor cells with activation of P01116 , PI3K-AKT , or both . We investigated whether the combination of a novel RAF/vascular endothelial growth factor receptor inhibitor , RAF265 , with a mammalian target of rapamycin ( P42345 ) inhibitor , RAD001 ( everolimus ) , could lead to enhanced antitumoral effects in vitro and in vivo . To address this question , we used cell lines with different status regarding P01116 , P42336 , and P15056 mutations , using immunoblotting to evaluate the inhibitors , and MTT and clonogenic assays for effects on cell viability and proliferation . Subcutaneous xenografts were used to assess the activity of the combination in vivo . RAD001 inhibited P42345 downstream signaling in all cell lines , whereas RAF265 inhibited RAF downstream signaling only in P15056 mutant cells . In vitro , addition of RAF265 to RAD001 led to decreased AKT , S6 , and P06730 binding protein 1 phosphorylation in HCT116 cells . In vitro and in vivo , RAD001 addition enhanced the antitumoral effect of RAF265 in HCT116 and H460 cells ( both P01116 mut , P42336 mut ) ; in contrast , the combination of RAF265 and RAD001 yielded no additional activity in A549 and MDAMB231 cells . The combination of RAF and P42345 inhibitors is effective for enhancing antitumoral effects in cells with deregulation of both DB01367 -RAF and PI3K , possibly through the cross-inhibition of 4E binding protein 1 and S6 protein . Comparison of the novel antipsychotic ziprasidone with clozapine and olanzapine : inhibition of dorsal raphe cell firing and the role of P08908 receptor activation . Ziprasidone is a novel antipsychotic agent which binds with high affinity to P08908 receptors ( Ki = 3.4 nM ) , in addition to P28221 , 5-HT2 , and D2 sites . While it is an antagonist at these latter receptors , ziprasidone behaves as a P08908 agonist in vitro in adenylate cyclase measurements . The goal of the present study was to examine the P08908 properties of ziprasidone in vivo using as a marker of central P08908 activity the inhibition of firing of serotonin-containing neurons in the dorsal raphe nucleus . In anesthetized rats , ziprasidone dose-dependently slowed raphe unit activity ( ED50 = 300 micrograms/kg i.v. ) as did the atypical antipsychotics clozapine ( ED50 = 250 micrograms/kg i.v. ) and olanzapine ( ED50 = 1000 micrograms/kg i.v. ) . Pretreatment with the P08908 antagonist WAY-100,635 ( 10 micrograms/kg i.v. ) prevented the ziprasidone-induced inhibition ; the same dose of WAY-100,635 had little effect on the inhibition produced by clozapine and olanzapine . Because all three agents also bind to alpha 1 receptors , antagonists of which inhibit serotonin neuronal firing , this aspect of their pharmacology was assessed with desipramine ( DB01151 ) , a NE re-uptake blocker previously shown to reverse the effects of alpha 1 antagonists on raphe unit activity . DB01151 ( 5 mg/kg i.v. ) failed to reverse the inhibitory effect of ziprasidone but produced nearly complete reversal of that of clozapine and olanzapine . These profiles suggest a mechanism of action for each agent , P08908 agonism for ziprasidone and alpha 1 antagonism for clozapine and olanzapine . The P08908 agonist activity reported here clearly distinguishes ziprasidone from currently available antipsychotic agents and suggests that this property may play a significant role in its pharmacologic actions . P35372 phosphorylation , desensitization , and ligand efficacy . Mu opioid receptors are subject to phosphorylation and desensitization through actions of at least two distinct biochemical pathways : agonist-dependent mu receptor phosphorylation and desensitization induced by a biochemically distinct second pathway dependent on protein kinase C activation ( 1 ) . To better understand the nature of the agonist-induced mu receptor phosphorylation events , we have investigated the effects of a variety of opiate ligands of varying potencies and intrinsic activities on mu receptor phosphorylation and desensitization . Exposure to the potent full agonists sufentanil , dihydroetorphine , etorphine , etonitazine , and [ D-Ala2 , MePhe4 , Glyol5 ] enkephalin ( DAMGO ) led to strong receptor phosphorylation , while methadone , l-alpha-acetylmethadone ( DB01227 ) , morphine , meperidine , DADL , beta-endorphin(1-31) , enkephalins , and dynorphin A(1-17) produced intermediate effects . The partial agonist buprenorphine minimally enhanced receptor phosphorylation while antagonists failed to alter phosphorylation . DB00921 and full antagonists each antagonized the enhanced mu receptor phosphorylation induced by morphine or DAMGO . The rank order of opiate ligand efficacies in producing mu receptor-mediated functional desensitization generally paralleled their rank order of efficacies in producing receptor phosphorylation . Interestingly , the desensitization and phosphorylation mediated by methadone and DB01227 were disproportionate to their efficacies in two distinct test systems . This generally good fit between the efficacies of opiates in mu receptor activation , phosphorylation , and desensitization supports the idea that activated receptor/agonist/G-protein complexes and/or receptor conformational changes induced by agonists are required for agonist-induced mu receptor phosphorylation . Data for methadone and DB01227 suggest possible contribution from their enhanced desensitizing abilities to their therapeutic efficacies . Skeletal receptors for steroid-family regulating glycoprotein hormones : A multilevel , integrated physiological control system . Pituitary glycoprotein hormone receptors , including Q01718 , P16473 , and P23945 , occur in bone . Their skeletal expression reflects that central endocrine control is evolutionarily recent . DB01285 receptors , in osteoblasts or the adrenal cortex , drive P15692 synthesis . P15692 is essential to maintain vasculature . In bone , DB01285 suppression by glucocorticoids can cause osteonecrosis . DB00024 receptors occur on osteoblasts and osteoclasts , in both cases reducing activity . Thus , DB00024 directly reduces skeletal turnover , consistent with evolutionary adaptation to stress . DB00094 receptors accelerate bone resorption , whereas estrogen promotes bone formation , the forces usually balancing . With ovarian failure , low estrogen with high DB00094 causes rapid bone loss . The skeletal DB00094 effect in the menopause seems paradoxical , but it is a logical adaptation in lactation , where prolonged DB00094 elevation also occurs . In addition to receptors , there is some synthesis of pituitary glycoproteins at distributed sites ; this is not well studied , but it may further modify the paradigm of central endocrine regulation . The Q7Z2W7 ion channel comprises direct Gq protein-activating capacity . The transient receptor potential ( TRP ) family of ion channels comprises receptors that are activated by a vast variety of physical as well as chemical stimuli . TRP channels interact in a complex manner with several intracellular signaling cascades , both up- and downstream of receptor activation . Investigating cascades stimulated downstream of the cold and menthol receptor Q7Z2W7 , we found evidence for both , functional and structural interaction of Q7Z2W7 with Gαq . We demonstrated menthol-evoked increase in intracellular Ca(2+) under extracellular Ca(2+)-free conditions , which was blocked by the P98160 inhibitors U73122 or edelfosine . This metabotropic Ca(2+) signal could be observed also in cells expressing a channel-dead ( i.e. non-conducting ) or a chloride-conducting Q7Z2W7 pore mutant . However , this intracellular metabotropic Ca(2+) signal could not be detected in Gαq deficient cells or in the presence of dominant-negative GαqX . Evidence for a close spatial proximity necessary for physical interaction of Q7Z2W7 and Gαq was provided by acceptor bleaching experiments demonstrating FRET between Q7Z2W7 - P27918 and Gαq-YFP . A Gαq-YFP mobility assay ( P42345 ) revealed a restricted diffusion of Gαq-YFP under conditions when Q7Z2W7 is immobilized in the plasma membrane . Moreover , a menthol-induced and Q7Z2W7 -mediated G protein activation could be demonstrated by FRET experiments monitoring the dissociation of Gαq-YFP from a Gβ/Gγ- P27918 complex , and by the exchange of radioactive [(35)S]GTPγS for GDP . Our observations lead to a view that extends the operational range of the Q7Z2W7 receptor from its function as a pure ion channel to a molecular switch with additional metabotropic capacity . Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals . In diabetic P01130 -/- mice , an ectopic P12643 -Msx2 gene regulatory program is upregulated in association with vascular calcification . We verified the procalcific actions of aortic Msx2 expression in vivo . CMV-Msx2 transgenic ( CMV-Msx2Tg(+) ) mice expressed 3-fold higher levels of aortic Msx2 than nontransgenic littermates . On high-fat diets , CMV-Msx2Tg(+) mice exhibited marked cardiovascular calcification involving aortic and coronary tunica media . This corresponded to regions of Msx2 immunoreactivity in adjacent adventitial myofibroblasts , suggesting a potential paracrine osteogenic signal . To better understand Msx2-regulated calcification , we studied actions in 10T1/2 cells . We found that conditioned media from Msx2-transduced 10T1/2 cells ( Msx2-CM ) is both pro-osteogenic and adipostatic ; these features are characteristic of Wnt signaling . Msx2-CM stimulated Wnt-dependent TCF/LEF transcription , and Msx2-transduced cells exhibited increased nuclear beta-catenin localization with concomitant alkaline phosphatase induction . Msx2 upregulated Wnt3a and Wnt7a but downregulated expression of the canonical inhibitor Dkk1 . Dkk1 treatment reversed osteogenic and adipostatic actions of Msx2 . DB06285 , a Q03431 agonist that inhibits murine vascular calcification , suppressed vascular P12643 -Msx2-Wnt signaling . Analyses of CMV-Msx2Tg(+) mice confirmed that Msx2 suppresses aortic Dkk1 and upregulates vascular Wnts ; moreover , TOPGAL(+) ( Wnt reporter ) ; CMV-Msx2Tg(+) mice exhibited augmented aortic LacZ expression . Thus , Msx2-expressing cells elaborated an osteogenic milieu that promotes vascular calcification in part via paracrine Wnt signals . Selective estrogen receptor modulation influences atherosclerotic plaque composition in a rabbit menopause model . OBJECTIVE : Osteoporosis trials suggest raloxifene decreased cardiovascular events in women with pre-existing atherosclerosis . We assessed the hypothesis that selective estrogen receptor modulation induces plaque stability in " menopausal " animals . METHODS AND RESULTS : Atherosclerosis was induced in 42 ovariectomized New Zealand white rabbits by cholesterol feeding and mechanical injury . Animals were imaged by magnetic resonance imaging ( Q9BWK5 ) for baseline atherosclerosis , and randomized to control ( OVX ( ovariectomized control group ) , n=12 ) , raloxifene 35-60 mg/kg/day by diet admixture ( RLX ( raloxifene therapy group ) , n=24 ) , or immediate sacrifice ( n=6 ) for immunohistopathologic correlation of Q9BWK5 . Six months later , rabbits underwent repeat Q9BWK5 then sacrifice for micro-computed tomography ( microCT ) and molecular analysis . Unlike OVX , RLX reduced atheroma volume . Analysis for lesion inflammation revealed reductions in P35354 ( cyclooxygenase-2 ) , P03956 ( matrix metalloproteinase-1 ) , P13500 ( monocyte chemoattractant protein-1 ) expression and macrophage infiltration in RLX versus OVX with concomitant upregulation of estrogen receptor alpha (ERalpha). microCT showed similar total vascular calcification between groups , but calcifications in RLX were less nodular with better radial organization ( mean calcific arc angle 63+/-7 degrees versus 33+/-6 degrees in OVX ) , the predicted result of a 53 % increase in P12643 ( bone-morphogenetic protein-2 ) . CONCLUSIONS : Raloxifene treatment results in reduced lesion volume , enhanced mechanical stability of vascular calcification , and less inflamed lesions characterized by less macrophage infiltration and reduced P35354 , P03956 and P13500 expression . Inhibitory effects of botulinum toxin on P28335 receptor-induced Cl- current in Xenopus oocytes . Several low molecular weight G proteins have been identified , but their functional roles remain unclear . To clarify the involvement of low molecular weight G protein in receptor-stimulated turnover of polyphosphoinositide ( PI ) turnover , influences of botulinum toxins on serotonin ( 5-HT ) -stimulated Cl- current mediated by PI turnover were investigated using Xenopus oocytes injected with rat brain mRNA . Treatment with botulinum toxin C , D or purified ADP-ribosyltransferase of botulinum toxin ( botulinum toxin P01024 enzyme ) inhibited the 5-HT-induced Cl- current in oocytes , and ADP-ribosylated 23 kDa proteins . Both botulinum toxin P01024 enzyme-induced inhibition of the current and ADP-ribosylation were suppressed by pretreatment with antibotulinum toxin P01024 enzyme antibody . Botulinum toxin D treatment of oocytes was ineffective in the response of Cl- current induced by injection of 50 pmol inositol 1,4,5-trisphosphate and 50 pmol Ca2+ . It is suggested that low molecular weight G proteins ADP-ribosylated by botulinum toxin P01024 enzyme are involved in phospholipase C activation in Xenopus oocytes . Serum levels of DB01277 and P17936 during adjuvant chemotherapy for primary breast cancer . High serum concentrations of insulin-like growth factor-1 ( DB01277 ) are associated with an increased risk of breast , prostate , colorectal , and lung cancer whereas IGF binding protein-3 ( P17936 ) seems to exert a protective effect . Therefore , patients may benefit from low DB01277 levels and high P17936 levels . This study evaluated whether adjuvant anthracycline-containing chemotherapy modulates DB01277 and/or P17936 serum levels in breast cancer patients . In 18 patients undergoing adjuvant treatment for primary breast cancer , DB01277 and P17936 serum levels were measured with immunoassays during chemotherapy regimens of either 5-fluorouracil , epirubicin and cyclophosphamide ( FEC ) or epirubicin and cyclophosphamide ( EC ) . Mean pre-treatment values of DB01277 and P17936 were 124+/-13 and 3698+/-186 ng/ml , respectively . No significant changes in DB01277 and P17936 serum concentrations were observed during adjuvant anthracycline-containing chemotherapy . DB01277 levels significantly correlated with P17936 levels before and during chemotherapy . In conclusion , these chemotherapy regimens do not seem to modulate DB01277 or P17936 levels in a favourable or unfavourable way . Whole blood lead concentration and erythrocyte delta-aminolevulinic acid dehydratase ( P13716 ) activity in selected canine populations in Greece . In a total number of 275 dogs of various ages , sex and breed , blood lead concentrations ( O43927 ) and erythrocyte P13716 activity were measured . Sixty-six of the dogs were living in lead mining areas ( Group A ) , 157 in urban areas ( Group B ) and 52 in rural areas ( Group C ) of Greece . Mean O43927 differed significantly ( P < 0.05 ) between locations and were 326,97 and 68 micrograms/L , respectively . Mean P13716 activity was significantly different ( P < 0.05 ) only between Groups A and B as between groups A and C . A significant ( P < 0.05 ) negative correlation existed between O43927 and P13716 activity . A normal range of erythrocyte P13716 activity of 807-992 mumol/ DB02272 /LRBC/h was established for dogs . None of the 33 Group A dogs and 2 of the Group B dogs that had a O43927 of 350 micrograms/L presented clinical signs indicating acute or chronic lead intoxication . No erythrocyte basophilic stippling or large number of nucleated red blood cells were seen in the 30 dogs of Group A with O43927 > 350 micrograms/L . DB00472 induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats . DB00472 ( FLX ) is a drug commonly used as antidepressant . However , its effects on tumorigenesis remain controversial . Aiming to evaluate the effects of FLX treatment on early malignant changes , we analyzed serotonin ( 5-HT ) metabolism and recognition , aberrant crypt foci ( Q9NQ94 ) , proliferative process , microvessels , vascular endothelial growth factor ( P15692 ) , and cyclooxygenase-2 ( P35354 ) expression in colon tissue . Male Wistar rats received a daily FLX-gavage ( 30mgkg(-1) ) and , a single dose of 1,2 dimethylhydrazine ( Q03001 ; i.p. , 125mgkg(-1) ) . After 6 weeks of FLX-treatment , our results revealed that FLX and nor-fluoxetine ( N-FLX ) are present in colon tissue , which was related to significant increase in serotonin ( 5-HT ) levels ( P < 0.05 ) possibly through a blockade in P31645 mRNA ( serotonin reuptake transporter ; P < 0.05 ) resulting in lower 5-hydroxyindoleacetic acid ( 5-HIAA ) levels ( P < 0.01 ) and , P28335 receptor mRNA expressions . FLX-treatment decreased dysplastic Q9NQ94 development ( P < 0.01 ) and proliferative process ( P < 0.001 ) in epithelia . We observed a significant decrease in the development of malignant microvessels ( P < 0.05 ) , P15692 ( P < 0.001 ) , and P35354 expression ( P < 0.01 ) . These findings suggest that FLX may have oncostatic effects on carcinogenic colon tissue , probably due to its modulatory activity on 5-HT metabolism and/or its ability to reduce colonic malignant events . Can P35354 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids ? Selective P35354 inhibitors increase the risk of myocardial infarction and stroke . This has been attributed to their ability to inhibit endothelial P35354 derived prostacyclin ( DB01240 ) but not platelet P23219 derived thromboxane A2 ( TXA2 ) . On the other hand , aspirin blocks both P23219 and P35354 enzymes without decreasing DB01240 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease ( Q8NE62 ) . The inhibitory action of aspirin on P23219 and P35354 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid ( DB00154 ) , arachidonic acid , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DB01708 ) . These fatty acids form precursors to PGE1 , DB01240 , PGI3 , lipoxins ( LXs ) , and resolvins that have anti-inflammatory actions . In contrast , increase in the concentrations of DB00154 , AA , EPA , and DB01708 is much less with specific P35354 inhibitors since they do not block the formation of eicosanoids through P23219 pathway . P35354 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions . EPA and DB01240 have anti-arrhythmic action . EPA , DB01708 , and AA augment eNO formation that prevents atherosclerosis . This suggests that P35354 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO , DB01240 , LXs , and resolvins and implies that combining EFAs with P35354 inhibitors could prevent these complications . Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells . The selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine is widely used in the treatment of depression in children and fertile women , but its effect on developing tissues has been sparsely investigated . The aim of this study was to investigate if enamel organs and ameloblast-derived cells express serotonin receptors that are affected by peripherally circulating serotonin or fluoxetine . Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old mice and ameloblast-like cells ( LS8 cells ) express functional serotonin receptors , the rate-limiting enzyme in serotonin synthesis ( Thp1 ) , as well as the serotonin transporter ( P31645 ) , indicating that enamel organs and ameloblasts are able to respond to serotonin and regulate serotonin availability . DB00472 and serotonin enhanced the alkaline phosphatase activity in the cell culture medium from cultured LS8 cells , whereas the expression of enamelin ( Enam ) , amelogenin ( Amel ) , and matrix metalloproteinase-20 ( O60882 ) were all significantly down-regulated . The secretion of vascular endothelial growth factor ( P15692 ) , monocyte chemotactic protein 1 ( P13500 ) , and interferon-inducible protein 10 ( P02778 ) was also reduced compared with controls . In conclusion , enamel organs and ameloblast-like cells express functional serotonin receptors . Reduced transcription of enamel proteins and secretion of vascular factors may indicate possible adverse effects of fluoxetine on amelogenesis . Paraplegic mice are leading to new advances in spinal cord injury research . STUDY DESIGN : Experimental laboratory investigations with paraplegic mouse models . OBJECTIVES : To review the most recent advances in the field of spinal cord injury research ; immune system response , regeneration , and functional recovery . SETTINGS : Laval University and Laval University Medical Center , Quebec , Canada . METHODS : Assessment of regenerative processes and locomotor function recovery induced by a variety of treatments and approaches in wild-type and genetically engineered mice with complete or incomplete lesions of the spinal cord . RESULTS : Recent studies have reported a number of significant observations providing additional insight into the role and mechanism of regeneration , immune system response , and functional recovery after spinal cord injury ( SCI ) using incomplete paraplegic mice with Nogo-A , Q9BZR6 , EphA4 , P14136 /vimentime , P15018 , or Fas gene knock-out . A novel antibody called P02778 was also recently found to increase tissue sparing and angiogenesis after SCI . In an attempt to explore the possibilities of reactivating spared neurons below the injury level , researchers have found that pharmacological activation of specific subtypes of serotonin receptors ( eg , P08908 /2A/7 ) can sustain the production of basic locomotor-like movements in complete paraplegic mice . CONCLUSION : The growing availability of genetically engineered and mutant mouse strains along with molecular biology tools has led scientists to increasingly use murine models in SCI research . These new tools and models may assist scientists in understanding further the complex pathological consequences of SCI . DB00472 -induced proliferation and differentiation of neural progenitor cells isolated from rat postnatal cerebellum . Previous studies have shown that the serotonin-reuptake inhibitor ( SSRI ) fluoxetine affects neural progenitors derived from postnatal cerebellum or adult hippocampus and stimulates their proliferation . In the human cerebellum , the proliferation of cerebellar granule cells ( CGC ) continues until the 11th postnatal month and could be influenced in infants by breastfeeding-delivered SSRIs . Current information about fluoxetine effects on postnatal cerebellar neural progenitors is limited . Here we report the characterization of fluoxetine actions on rat postnatal cerebellar neural progenitors . RT-PCR and immunostaining revealed the expression of serotonin transporter ( P31645 ) , 5HT(1A) receptors , tryptophan hydroxylase ( P17752 ) , and serotonin ( 5HT ) . Protracted in vitro fluoxetine treatment increased cell proliferation and differentiation . The proliferative effects of fluoxetine , 5HT , and the selective agonist of 5HT(1A) receptors trans-8-hydroxy-2-(N-n-propyl-N-3'-iodo-2'-propenyl)aminotetralin ( 8-OH-PIPAT ) were abolished by the selective antagonist of 5HT(1A) receptors , N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride ( WAY-100635 ) . Furthermore , fluoxetine-induced activation of both the DB02527 -response element-binding ( CREB ) protein and extracellular signal-regulated protein kinases ( P27361 /2 ) , which was abolished by the selective inhibitor of Q96HU1 kinase kinase ( MEK ) 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene ( U0126 ) , and increased cyclin D1 expression . All these effects were prevented by WAY-100635 . Collectively , our results demonstrate that rat postnatal cerebellum contains neural progenitors capable of proliferating and differentiating in response to fluoxetine exposure , possibly through the activation of 5HT(1A) receptors . The relevance of these findings for possible SSRI effects on the developing postnatal/infant human cerebellum should be explored .