Welgevonden hosts a number of large carnivores

such as lion, cheetah Acinonyx jubatus, and leopard as well as a large population of brown hyaena Hyaena brunnea. Research was conducted under the University of Pretoria Animal Use and Care Committee ethics clearance protocol A022-06 with all its amendments and the Limpopo province (South Africa) standing permit (No. S13631) for scientific research. During August 2010 to March 2011, we captured four leopards [two adult females (LF1 and LF2); one sub-adult female (LF3); one adult male (LM1)] using soft-hold foot snares (Frank, Simpson & Woodroffe, 2003). Each leopard was immobilized MG 132 using 4–5 mg kg−1 teletamine-zolazepam (Zoletil 100, Virbac RSA, Halfway House, South Africa) and fitted with a remote drop-off, Akt inhibitor ultra-high frequency GPS collar (Followit™ Tellus, Lindesberg, Sweden). Collars were programmed to record a GPS location every 2 h (06:00 h, 08:00 h, 10:00 h; apart from 12:00 h that consistently failed to fix) resulting in 11 GPS locations per day. Collars were released via a remote-controlled drop-off system on completion of the study. GPS data were imported into

ArcGIS v.9.2 (ERSI, Redlands, CA, USA). GPS clusters were classified by a set of decision rules: (1) consecutive GPS locations within 50 m of each other were merged into one cluster; (2) clusters within 100 m and 8 h (closest point to closest point) of other clusters were merged (Pitman et al., 2012). Therefore, the smallest GPS clusters possible were those that consisted of two GPS points (representing a site fidelity of 2 h). A GPS cluster site represents an activity performed by a

leopard in time and space; these activities are not automatically related to predation (other potential activities include resting, mating, territorial disputes, etc.). Clusters not damaged by fire or flood were systematically catalogued and investigated in the field for prey remains (e.g. carcass, hair, bone, blood) fitting the appropriate time frame. Prey remains were photographed and representative material taken for later identification conducted either macroscopically (e.g. carcass, horns, MCE skull) or microscopically (hair cuticle scale patterns and cross sections) using published references (Dreyer, 1966; Keogh, 1979, 1983; Buys & Keogh, 1984; Douglas, 1989), and a reference collection housed at the Centre for Wildlife Management, University of Pretoria, South Africa. Faeces were collected in two ways: (1) at GPS clusters; (2) opportunistically (i.e. independent of cluster investigations) while traversing the home ranges of collared leopards. Only samples with a diameter greater than 20 mm were collected for analysis to minimize the collection of non-leopard faecal samples (Norton, Henley & Avery, 1986). Accurately determining the age of a desiccated faecal sample was not possible.

We compared the Selleckchem MLN0128 sequence of a genomic fragment encoding the WT medaka raldh2 gene with the sequences of the corresponding fragments from four independent homozygous hio embryos. We found an A to G transversion in hio alleles that would cause the threonine 468 residue in the WT RALDH2 enzyme to be replaced

by alanine (Fig. 1B). A comparison of the predicted WT RALDH2 amino acid sequences among medaka, human, xenopus, and zebrafish revealed an overall amino acid sequence identity of 81% (between medaka and human or xenopus) and 84% (between medaka and zebrafish) (Fig. 1C). The threonine 468 residue was conserved among all species examined. Moreover, threonine 468 lies within the catalytic domain of WT RALDH2 (Fig. 1C). These results suggest that the mutant RALDH2 protein produced in hio mutants is

inactive. It has been well established that the defects of RA signaling lead to the impairment of fin development in zebrafish.7, 8, 10, 16 We showed that the injection of RALDH2-MO into WT embryos results in the BGB324 solubility dmso impairment of fin development, and the injection of raldh2 mRNA or exogenous RA rescued the defects of fin development of hio mutant (Supporting Fig. 1). These results indicate that RALDH2 and RA regulate fin development in medaka. In addition, hio embryos lacked tbx5 and wnt2ba expression, which acted downstream of RA during fin development (Supporting Fig. 2). Taken together, we concluded that RA signaling plays important roles in fin development in medaka. We have previously reported that the medaka hio mutation results in a small and malformed liver.3 To examine the role of raldh2-dependent signaling in liver formation in medaka, we employed three approaches. First, to investigate whether loss-of-function of raldh2 could account for this liver defect, we injected raldh2-MO into WT embryos and inspected the developing liver. We found that the raldh2 morphants had the same undersized livers as the hio

mutants (Fig. 2A). Estimation of liver size via in situ hybridization using a gata6 probe confirmed the reduced liver size in the raldh2 morphants (Fig. 2B). Second, to determine whether the hio/raldh2 mutation was responsible for the small livers of these mutants, we 上海皓元 injected in vitro transcribed raldh2 mRNA into the cytoplasm of one-cell stage embryos that were the progeny of intercrossed hio heterozygotes and used gata6 in situ hybridization to assay these embryos for rescue of liver size. As expected, 25% of the progeny of intercrossed hio heterozygotes (uninjected controls) had small livers. In contrast, the percentage of progeny with decreased liver size was reduced to 14% after injection of raldh2 mRNA (Fig. 2C). Finally, we investigated whether treatment with exogenous RA, the bulk of which is synthesized by RALDH2, could rescue the liver defects caused by the hio mutation.

After filtering against existing SNP databases and picking out variants on exonic and splicing, 44 variants were reserved. The largest overlapping autozygous regions were at chromosome 16. We focused on two non-synonymous variants from HSD3B7 gene. Follow-up Sanger sequencing

identified selleck chemicals HSD3B7 mutations in the proband and his families. Conclusion: We make a genetic diagnosis of HSD3B7 deficiency using exome sequencing and homozygosity mapping. HSD3B7 deficiency is an automatic recessive disease and early diagnosis and primary bile acid treatment lead to progressive normalization of liver function and avoidance of liver transplantation. Key Word(s): 1. Exome sequencing; 2. Cholestasis; 3. HSD3B7 deficiency; Presenting Author: QINGHUA HU Additional Authors: ZHONGWEI LIU, HAITAO ZHU, KUNLUN CHEN, CHUAN QIU, KAIFA TANG Corresponding Author: QINGHUA HU Affiliations: Department of Medicine, 323 Hospital of PLA; School of Medicine, Xi’an Jiaotong University; School

of Public Health & Tropical Medicine, Tulane University; Affiliated Hospital of Guiyang Medical College Objective: Excessive endoplasmic reticulum (ER) stress plays an important role in inducing hepatocytes apoptosis in alcoholic liver disease (ALD). Curcumin has been proved to have a broad spectrum of biological activities including anti-inflammation, anti- neoplasm, antioxidation and anti- apoptosis. Previous studies have demonstrated the protective effect of curcumin medchemexpress against ethanol- induced hepatocyte apoptosis, but the mechanism is not completely clarified. In this study, we investigated whether curcumin’s hepatoprotecive effect acts via attenuating Stem Cell Compound Library order ER stress. Methods: Liver slice culture was used in this study. Isolated hepatocyte cultures were incubated whether by ethanol or curcumin or both of them. Ethanol cytotoxicity was evaluated by trypan blue exclusion test and released lactate dehydrogenase (LDH) activity. Hepatocyte apoptosis was assessed by flow cytometry. Real- time PCR and western blotting were utilized to qualify the expression

levels of GRP78 which is the hall marker of ER stress and Casepase 12 which reflexes ER stress- induced apoptosis specifically at transcriptional and translational levels. Results: Ethanol’s cytotoxicity to hepatocytes was evidenced by trypan blue exclusion test and released LDH activity. The apoptosis rate increases significantly after ethanol incubation but attenuated by co- administration of curcumin. Expectedly, expressions of GRP78 and cleaved Caspase12 increased significantly after ethanol incubation, indicating that ethanol evoked ER stress. However, after co- administration of curcumin, expression levels of GRP78 and cleaved Caspase12 were impaired dramatically. Conclusion: These results indicated that curcumin exerts its hepatoprotective effects by attenuating ER stress- induced apoptosis in hypatocytes incubated by ethanol. Key Word(s): 1. Curcumin; 2. Apoptosis; 3. Ethanol; 4.

34 Thus, JNK1 and JNK2 have a wide range and redundant

or distinct functions, and upstream molecules, such as MAP3Ks, must regulate the complex functions of JNK. We consider that ASK1 plays major roles in tumor-suppressing CAL-101 part of JNK in hepatocarcinogenesis. However, knockdown of ASK1 in HCC cell lines slightly decreased cell proliferation. This finding suggests that ASK1 may weakly promote the proliferation of some HCC cells, which could explain why the WT and ASK1−/− mice did not exhibit significant differences in tumor size. On the other hand, mice with liver-specific p38 deficiency exhibit increased HCC development similar to ASK1−/− mice.4, 6 The accelerated hepatocarcinogenesis in p38-deficient mice is reportedly attributable to compensatory

JNK activation and cancer cell proliferation. Although p38 activation was attenuated in ASK1−/− mice, JNK activation was also attenuated, unlike the liver-specific p38-deficient mice. Thus, the mechanisms of accelerated hepatocarcinogenesis in ASK1−/− mice and liver- specific p38-deficient mice appear to differ. p38 has also been reported to play IWR-1 solubility dmso an important role in DNA damage responses, such as cellular senescence, by inducing cyclin-dependent kinase inhibitors.30 In this study, we showed that ASK1 is involved in DNA damage-induced p21 up-regulation through p38 activation. Furthermore, the ASK1-p38 pathway has been reported to have an inhibitory effect on malignant transformation of fibroblasts by triggering apoptosis in response to oncogene-induced reactive oxygen species (ROS).35 Thus, the ASK1-p38 pathway may play a key role in the inhibition of tumor initiation in hepatocarcinogenesis. Defective death-receptor signaling is considered a cause of tumor immune escape, so understanding its apoptotic mechanism is very important not only from the point of view of carcinogenesis, but also

for cancer therapeutics.21 Several in vitro studies have demonstrated that ASK1 is implicated in the TNF-α- and Fas-mediated apoptotic pathways,11, 上海皓元医药股份有限公司 36 but the in vivo role of ASK1 has not been determined. Our current findings provide the first evidence that ASK1 plays an important role in TNF-α- and Fas-mediated hepatocyte apoptosis in vivo and suggest that the JNK- Bim-mediated mitochondrial apoptotic pathway is an important downstream target of ASK1. JNK-mediated Bim phosphorylation triggers the proapoptotic activity of Bim by causing its release from sequestration to the microtubular dynein motor complex.25 Bim initiates the mitochondrial apoptotic pathway by activating Bax and Bak directly and indirectly blocking prosurvival Bcl-2 family members.37 Recent reports have shown that Bim plays an important role in Fas- and TNF-α-induced hepatocyte apoptosis.

Thus, data from high-quality observational or quasi-experimental studies become critical in the assessment of the overall effectiveness of therapeutic or diagnostic modalities in large patient populations. The recently passed Healthcare Reform Law of 2010 places further emphasis on CER. For example, the law authorizes the establishment of a nonprofit corporation known as the Patient-Centered Outcome Research Institute (PCORI), which is expected to oversee the conduct of CER and dissemination of the research findings.16 The extent to which CER will be supported and used while the reform is implemented

in the coming years selleck kinase inhibitor remains to be seen. It is certain, however, that interest will remain high on promoting research to determine the effectiveness of new (and existing) therapies in the context of usual medical

practice settings within the United States in the foreseeable future. “
“Previous studies have indicated that lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion may not be durable in the Asian population. We investigated the useful predictors of post-treatment hepatitis B virus (HBV) relapse in patients with nucleos(t)ide analogue (NA)-induced HBeAg loss/seroconversion. A total of 157 non-cirrhotic patients with NA-induced HBeAg loss/seroconversion (78, lamivudine; 68, entecavir; 11, telbivudine) were retrospectively analyzed. All patients had at least 12 months of post-treatment follow-up and consolidation therapy duration. The cumulative rate of post-treatment HBV relapse at 5 years was 57.1%. Multivariate analysis revealed that age and baseline XL765 clinical trial hepatitis B surface antigen (HBsAg) levels MCE independently predicted post-treatment HBV relapse. The post-treatment HBV relapse rate was significantly higher in patients aged >40 years than in those <40 years (p< 0.001). A baseline HBsAg level of 2,000 IU/mL was the optimal cut-off value for predicting post-treatment HBV relapse (p=0.002). The post-treatment HBV relapse risk further increased with the presence of both risk factors (age ≥ 40 years and baseline HBsAg level ≥ 2,000 IU/mL; p< 0.001). A prolonged consolidation therapy period of ≥ 18 or 24 months

had no positive effect on sustained viral suppression. There was no significant difference in post-treatment HBV relapse rates between patients with lamivudine- and entecavir-induced HBeAg loss/seroconverion during the off-treatment follow-up (p = 0.31). The combination of an age of 40 years and a baseline HBsAg level of 2,000 IU/mL was a useful marker for predicting post-treatment HBV relapse in patients with NA-induced HBeAg loss/seroconversion. “
“Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE.

In this respect, noninvasive evaluation of the liver with FibroScan is a promising option.[46] We were able to reach a high participation rate. Altogether, 73% of the patients participated and the participants and nonparticipants were comparable in terms of demographic variables and disease characteristics, making significant selection bias unlikely (Table 1). Specifically, starting age of PN,

duration of PN, length of the remaining small intestine, and number of septic episodes were comparable. A challenge in our study design is the Sunitinib supplier wide age range of the patients, whereas treatment of IF patients has significantly developed over time. Composition of parenteral lipids has changed from soy-based to olive-oil– and fish-oil–based lipids, amount of PN fat is limited, and early initiation of enteral nutrition and cyclic PN infusions are persuaded.[5, 35, 47] Although the changes in clinical practice may have modulated our results and may hamper their applicability for newly treated

children with IF, this study provides reliable population-based information regarding the current long-term outcomes. The authors thank pediatric radiologists K. Lauerma, R. Kivisaari, and R. Seuri from the Medical Imaging Center, Helsinki University Central Hospital (Helsinki, Finland), for carrying out the abdominal US exams and US-guided liver needle biopsies. “
“Patients with cirrhosis receiving norfloxacin show

a restored inflammatory balance that likely prevents clinical complications this website derived from an excessive proinflammatory response to bacterial product challenges. This study sought to investigate associated inflammatory MCE公司 control mechanisms established in patients with cirrhosis receiving norfloxacin. A total of 62 patients with cirrhosis and ascites in different clinical conditions were considered. Blood samples were collected and intracellular and serum norfloxacin were measured. Inflammatory mediators were evaluated at messenger RNA and protein levels. Neutrophils from all patients were cultured with lipopolysaccharide (LPS) and anti–interleukin-10 (anti–IL-10) monoclonal antibody in different conditions. IL-10 and heme oxygenase-1 (HO-1) were up-regulated in patients receiving norfloxacin and correlated with norfloxacin in a concentration-dependent manner, whereas proinflammatory inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-κB behaved inversely. Higher IL-10 levels correlated with lower white blood cell count and higher mean arterial pressure. No correlations were found between IL-10 and disease clinical scores or liver function markers in blood. Neutrophilic in vitro assays showed that the effect of LPS on proinflammatory mediator levels in the presence of norfloxacin was abrogated by significantly increasing IL-10 and HO-1 expression.

Cellular kinase responsible for NS5A hyperphosphorylation thus might be an alternative antiviral target next to enzymatic

GS-1101 cell line viral proteins e. g. NS3 and NS5B. We have previously identified an NS5A phosphorylation site responsible for NS5A hyperphosphorylation. Phosphorylation level of this site increased upon viral infection; In addition, abrogation of its phosphorylation by mutation completely abolished viral replication, indicating its roles in HCV replication. In the present study, we sought to identify kinases responsible for NS5A phosphorylation at this site. Our bioinformatic analysis and the existing chemical proteomics data suggested a role of calmodulin-dependent kinase (CaMKII) in NS5A phosphorylation at this site. Calmodulin inhibitor (W7) inhibited NS5A phosphorylation at this site and reduced HCV RNA levels in infected Huh7.5.1 cells

in a dosedependent manner. Similarly, CaMKII specific inhibitor (KN93) reduced NS5A phosphorylation and reduced HCV RNA levels in infected Huh7.5.1 cells in a dose- and time-dependent manner. Reverse transcription plus polymerase chain reaction analysis indicated expression of CaMKII gamma and delta in the Huh7.5.1 cells. Small hairpin RNA based gene knockdown of CaMKII EX 527 nmr delta not gamma reduced HCV RNA levels in infected Huh7.5.1 cells. We conclude that CaMKII delta may be responsible for NS5A hyperphosphorylation at the identified site and that inhibition of CaMKII reduces NS5A phosphorylation and reduces HCV RNA levels in infected Huh7.5.1 cells. (This work is supported MCE公司 by NSC 101-2324-B-002-022 and NHRI EX10210213-BI, TAIWAN) Disclosures: The following people have nothing to disclose: Yi-Hung Chen, Ming-Jiun Yu BACKGROUND: Hepatitis

C virus (HCV) causes persistent infection in the majority of infected individuals. However, the mechanisms of persistence and clearance are only partially understood. CD81-CLDN1 co-receptor complex plays a pivotal role in initiation and maintenance of infection. A monoclonal antibody targeting the co-receptor complex has been shown to confer protection against HCV infection. AIM: We aimed to study the presence of anti-receptor autoantibodies in HCV infected patients and its correlation to persistence and spontaneous viral clearance. METHODS: Because of the central role of CD81-CLDN1 co-receptor complexes in HCV infection, we used a recombinant soluble CD81/CLDN1 protein to develop a novel sensitive ELISA that could detect low nanomolar concentrations of anti-CD81/CLDN1 antibodies. Using 50 serum samples from healthy individuals as control and a well defined cohort of single-source outbreak of HCV (Pestka, Zeisel et al. Proc. Natl. Acad. Sci.

“
“Nonalcoholic fatty liver disease (NAFLD) has been consistently found to be associated with features of the metabolic syndrome (MS), a condition carrying a high risk of cardiovascular events. The present study aimed to determine whether, in children and adolescents, NAFLD is atherogenic beyond its association

with MS and its components. We assessed both flow-mediated learn more dilation of the brachial artery (FMD) and carotid intima-media thickness (cIMT), along with lipid profile, glucose, insulin, insulin resistance, and high-sensitivity C-reactive protein (CRPHS), in 250 obese children, 100 with and 150 without NAFLD, and 150 healthy normal-weight children. NAFLD was diagnosed by ultrasound examination and persistently elevated alanine aminotransferase, after exclusion of infectious and metabolic disorders. Compared to controls and children without liver

involvement, those with ultrasound-diagnosed NAFLD (and elevated alanine aminotransferase) demonstrated significantly impaired FMD and increased cIMT. Patients with NAFLD had more features of MS and elevated CRPHS levels. In addition, percent FMD was remarkably reduced, whereas cIMT was increased in obese children with MS compared to those without MS. Using logistic regression analysis, the presence of NAFLD was found to be an independent predictor of low percent FMD (odds ratio, 2.25 [95% confidence interval, 1.29 to 3.92]; P = 0.004) as well as of increased cIMT (1.98 [1.16 to 3.36]; P = 0.031), after adjustment for age, gender, Tanner stage, and presence of MS. When we analyzed the relations between cIMT and measures Erlotinib supplier of FMD in patients with NAFLD, the

disease was associated with increased cIMT in children with impaired FMD status. Conclusion: The presence of liver disease entails more severe functional and anatomic changes in the arterial wall. Its detection may help identify individuals with increased cardiometabolic risk. (HEPATOLOGY 2010.) Over the last two decades medchemexpress the rise in the prevalence rates of overweight and obesity may explain the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of liver disease in pediatric populations worldwide.1 NAFLD comprises a disease spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), progressive to cirrhosis. NAFLD is presently considered a hepatic manifestation of the metabolic syndrome (MS),1 with insulin resistance (IR) as the main pathogenetic mechanism.2 Because of the underlying metabolic disorder, NAFLD patients are expected to have a higher risk of vascular and coronary heart disease as well.3 Indeed, it has been reported that subjects with fatty liver have elevated levels of plasma biomarkers of inflammation, impaired endothelial function, and early carotid changes.3, 4 Carotid intima-media thickness (cIMT) and brachial flow-mediated dilation (FMD) as assessed noninvasively by ultrasound are preclinical markers of vascular health.

These results suggested that the PI3K/Akt inhibitor LY294002 can enhance chemosensitivity of human gastric cancer to vincristine. This preclinical evaluation of a rational Belnacasan in vitro combination of LY294002 and vincristine may provide a new strategy to resolve the multidrug resistance of gastric cancer. Key Word(s): 1. PI3K/Akt; 2. chemosensitivity; 3. gastric cancer; 4. vincristine; Presenting Author: GUODONG CHEN Additional Authors: YULAN LIU Corresponding Author: GUODONG CHEN Affiliations: Department of Gastroenterology, Peking University

People’s Hospital Objective: Primary gastric lymphoma (PGL) is the most common extranodal lymphoma while diffuse large B-cell lymphoma (DLBCL) is the main histological subtype. The therapeutic efficacy and outcome of DLBCL have not been well defined. This study aimed to analyze the therapeutic efficacy of surgery, chemotherapy and the combination of chemotherapy with surgery for DLBCL. Methods: All the cases satisfied the PGL diagnosis criteria defined by Dawson. The stage of the disease was determined according to the Ann Arbor criteria proposed for gastrointestinal lymphoma. Clinical features of 30 Chinese patients (stage I and II) with newly diagnosed gastrointestinal DLBCL were retrospectively analyzed. Therapeutic outcomes were compared

between different treatment groups. Survival curves selleck products and the univariate analysis were analyzed by the Kaplan-Meier method. Results: Of the 30 patients recruited into the study, 20 were male and 10 were female with a median age of 65 years (range 29–80 years). 13 patients (43 %) received chemotherapy, 5 years survival rate was 53.8%, 6 patients (20 %) received surgery, 5 years survival rate was 65.9%, 11 patients (37 %) received the combination of chemotherapy with surgery, this treatment attain 63.6% 5 year survival rate. There was no significant difference in survival curves among chemotherapy only, surgery only and the combination of chemotherapy 上海皓元 with surgery (p > 0.1). Surgery and the combination of chemotherapy did not provide a significant

survival benefit for patients. Conclusion: Chemotherapy should be the first-line therapy procedure for DLBCL. As the traditional treatment, surgery will not be classic therapy for DLBCL. Key Word(s): 1. DLBCL; 2. Therapeutic Efficacy; Presenting Author: XIAOMEI ZHANG Additional Authors: CHAO YANG, HAIXU CHEN, BENYAN WU Corresponding Author: CHAO YANG, BENYAN WU Affiliations: General Hospital of Chinese PLA; Institute of Gerontology and Geriatrics; Department of Gastroenterology & Hepatology; Department of Gerontal Gastroenterology Objective: Radiation-induced gastrointestinal syndrome (RIGS) is a common complication in radiotherapy for solid organ malignancies in abdomen or pelvis. However, currently there are no approved medical countermeasures for RIGS. We aimed to study the therapy effect of cytokines treated Flk-1+MSCs on RIGS.

Key Word(s): 1. cancer stem cells; 2. Lgr5 and CD44; 3. colon polyps; 4. colorectal cancer; Presenting Author: HONG WEI Additional Authors: XIN-PU MIAO Corresponding Author: HONG WEI Affiliations: Department of GastroenterologyHai Nan Provincial People’s Hospital Objective: To study the detection and clinical ABT-199 significance of blood

platelets count and Coagulation in patients with ulcerative colitis (UC). Methods: The levels of peripheral blood platelets count (BPC) and coagulation in patients with UC (n = 57) and normal control group (n = 26) were detected and the effects on disease severity were analyzed subsequently. Results: The levels of peripheral BPC and FIB in active phase group were significantly higher than those in control group (P < 0.01), PT in active phase group were significantly lower than those in control group (P < 0.01);

the levels of peripheral blood platelets count (BPC) and FIB in severe stage were significantly higher than those in patients medium and mild stage, PT in severe stage were significantly lower than those patients in medium and mild stage (P < 0.01). Blood platelets Selleckchem MDV3100 count (BPC) were correlated with FIB in patients with UC, and were negative correlated with PT. Conclusion: I t is proposal that blood platelets count and Coagulation would provide useful marker of active of UC, They had important value to judge active phase and severity of UC. Key Word(s): 1. Ulcerative colitis; 2. Blood platelets; 3. Coagulation; Presenting Author: FEIXUEFEI CHEN Additional Authors: YANBOYAN BO, XIULI ZUO, YANQING LI Corresponding Author: XIULI ZUO Affiliations: no Objective: As a member of the nerve growth factor family, brain-derived neurotrophic factor (BDNF), widely distributed in the central central, peripheral and enteric

nervous system, plays fundamental roles in the differentiation, survival and maintenance of neurons. Besides these roles, BDNF has been implicated to enhance gastrointestinal motility. There are growing evidences to support this view. Patients with a variety of neurologic disorders or ALS who were MCE treated with r-metHuBDNF appeared to have a dose-related “diarrhea.” A 2-week treatment with recombinant BDNF dose-dependently accelerated colonic emptying and increased stool frequency. In rats, BDNF has an excitatory effect on myoelectric activities of the colon. Endogenous BDNF enhances the peristaltic reflex by augmenting the release of serotonin and calcitonin gene-related peptide induced by mucosal stimulation. All these suggest that BDNF plays an important role in gut motor functions. However, there are no researches about the acute and direct effects of BDNF on the contractile activity in the isolated intestinal tracts of mice. In central, Binding of BDNF to TrkB dimers activates the phospholipase C (PLC) pathway, which results in the formation of the second messengers DAG and IP3 and calcium release from intracellular stores.