4, 5 The role of β-catenin in hepatic progenitors has been recently identified. Significant colocalization of the oval cell and ductular marker A6 and β-catenin is observed after DDC feeding in mice.6 In β-catenin null liver, atypical ductular proliferation is significantly blunted, indicating a role of β-catenin in induction and proliferation of ductular cells after DDC injury. Likewise, another study reported expression of β-catenin and multiple

Wnt ligands in oval cells after DDC injury.7 Here we investigate the role of β-catenin in chronic hepatobiliary injury in mice in response to long-term DDC exposure, which resembles the primary sclerosing cholangitis (PSC) phenotype and leads to chronic atypical ductular proliferation and oval cell response.2, 8 Wildtype (WT) and β-catenin conditional liver knockout (KO) mice were exposed to the DDC diet for 80-150 days and examined histologically and biochemically Sorafenib mw for the ductular response and liver injury. Interestingly, we found that, in the absence of β-catenin, a sustained atypical ductular proliferation occurs in the long term, along with the development of significant hepatic fibrosis, which results in significant intrahepatic cholestasis. Further evaluation identified a small subset of hepatocytes Venetoclax research buy in baseline KO livers that escape albumin-cre-mediated β-catenin deletion that have a growth advantage after the DDC injury and eventually repopulate the KO livers

by β-catenin-positive hepatocytes, which results in modest but significant alleviation of hepatocyte injury. Although both WT and KO livers after chronic DDC exposure displayed enlargement of the livers, KO livers also showed nodular overgrowth due to increased hepatocyte proliferation, although there was no evidence of tumorigenesis. ALP, alkaline phosphatase; ALT, alanine amino transferase; AST, aspartate amino transferase; CEBPα, CCAAT enhancer binding protein-alpha; DAPI, 4,6-diamidino-2-phenylindole;

DDC, 3,5-diethoxycarbonyl-1,4-dihydrocollidine; GS, glutamine synthetase; HNF, hepatocyte nuclear factor; KO, IHC, immunohistochemistry; β-catenin conditional liver knockout mice; PCNA, proliferating cell nuclear antigen; RIPA buffer, radioimmunoprecipitation assay buffer; WT, wildtype littermate control mice. β-Catenin conditional knockout in liver was created as MCE公司 described.9 The genotype for these animals is Ctnnb1loxp/loxp; Alb-Cre+/− and are referred to as knockout (KO) mice throughout. As reported previously, all other genotypes were unequivocally devoid of any phenotype and referred henceforth as wildtype (WT) controls. Only male mice were used for all experiments. At the time of sacrifice, retro-orbital bleed was performed for serum biochemistry. Portions of lobes from excised liver were fixed in 10% neutral buffered formalin and processed for paraffin embedding. Part of liver was frozen in Tissue-Tek OTC compound for cryosections.

The colonoscopy found a large infiltrative and ulcerative mass at distal sigmoid colon which was proved to be a poorly differentiated adenocarcinoma. The other polyps were tubulovillous adenoma and inflammatory polyps. The thickening of gastric antrum and mucosal of terminal ileum were found on abdominal computed tomography and small intestinal study. Despite surgically removing

the colon cancer, the nutritional status got worse day by day. Results: A strong evidence of Cronkhite-Canada syndrome with malignant change of a polyp. Conclusion: Rare discussion on the progression of colonic cancer of the CCS has been literally reported, whether via the adenoma-carcinoma sequence or through another genetic mutation is still unknown. Further study should be YAP-TEAD Inhibitor 1 nmr done. Key Word(s): 1. Colon cancer; 2. Alopecia; 3. Nail dystrophy; 4. GI polyposis; Presenting Author: A YOUNG SEO Additional Authors: CHEOL MIN SHIN, YOUNG HOON CHOI, JONG PIL IM, DONG HO LEE, NAYOUNG KIM, YOUNGSOO PARK, HYUK YOON Corresponding Author: A YOUNG SEO Affiliations: selleck products Seoul National Univ. Bundang Hospital; Seoul National Univ. Hospital Objective: The objective is to evaluate the differences in clinical characteristics of CMV enterocolitis with or without inflammatory bowel disease (IBD). Methods: From 2003 to 2013 at Seoul National University

Bundang Hospital and Seoul National University Hospital, a total of 84 patients with symptoms including hematochezia or diarrhea or abdominal pain diagnosed as CMV enterocolitis based on the pathologic findings were reviewed retrospectively. Results: Among the 86 patients, 28 had IBD [23 with ulcerative colitis (UC), 4 with Crohn's disease and 1 with Behcet's colitis] treated with steroids or other immunosuppressive agents. CMV enterocolitis in patients without IBD (n = 58) was mainly associated with immunocompromised

or critically-ill non-immunosuppressed conditions. As for symptoms, hematochezia (78.6% and 34.5% in IBD and non-IBD groups, respectively) and weight loss (28.6% and 5.2%) were more common in IBD group than non-IBD group (P-values <0.01); fever was a common symptom in non-IBD group (10.7% and 50.0%, P < 0.001). Non-IBD group showed a higher positivity of CMV antigenemia MCE公司 testing, which was not statistically significant (58.3% and 82.4%, P = 0.094). Endoscopic findings were varied, but not different between the two groups. In patients with UC (n = 23), 17 patients (73.9%) were treated with antiviral agents, but 6 of them (35.3%) underwent total proctocolectomy despite antiviral therapy; spontaneous remission occurred in 5 out of 6 patients who were not given antiviral agents and 1 patient had undergone total proctocolectomy. Forty-seven patients (81.0%) in non-IBD group were treated with antiviral agents, but 19 patients (40.4%) died of underlying disease; 7 out of 11 patients (63.

Results: Completed surveys were collected from 106 endoscopists performing ERCP across all states in Australia (uptake rate 46.7%); majority are male (98%) and are predominantly gastroenterologists selleck (62.8%), age range between 31 to 72 years (median 53 years), with experience in performing ERCP ranging from 3 years to 38 years (median 18 years). 24.5% of respondents

are dual-trained with EUS; 61.6% completed a formal fellowship in ERCP; and 72.1% actively train registrars/fellows. The reported median weekly ERCP volume is 6 cases, median annual volume is 150 cases (range 10–500), and median institutional annual volume is 350 cases (range 50–1000). Audits were kept by 67.5% of respondents; and 75% of respondents performed greater than 100 cases per annum. The JQ1 concentration median estimated biliary cannulation rate of naïve papillae is 95% (range 80–99). The most common indications for ERCP are choledocholithiasis, malignant strictures and bile leak; over half of all cases are performed on inpatients with most referrals originating from surgeons. Anesthetists are utilized in 97.5% of ERCP cases. Over 90% of ERCPs are performed with sedation rather than general anaesthesia. The preferred ERCP position is swimmer’s/prone position (88%), although the left lateral (41%) and supine positions (24%) are also used. The method of bile duct cannulation

was overwhelmingly wire-guided cannulation (90.1%). In the event of difficult cannulation, bile duct access with precut sphincterotomy (33%) and double wire technique (30%) were the preferred methods.

In failed biliary cannulation, most endoscopists would reattempt ERCP themselves first (69%). 19% would refer to a colleague in the same institution whilst 6% resort to percutaneous drainage. Endoscopic papillary large balloon dilation is routinely performed by 54% of endoscopists for extraction of large CBD stones, with balloon sizes of 12–15 mm and 15–18 mm the preferred choice in 72.8%. For Post-ERCP pancreatitis prophylaxis, 76.5% use pancreatic duct (PD) stenting in high risk cases though only in a median of 10% of all cases performed; 18.5% of respondents never inserted MCE公司 PD stents. Prophylactic NSAIDs are now used by 60.5% of active ERCP practitioners with approximately 1 in 6 endoscopists using them routinely in all cases. Conclusion: The typical Australian ERCP practitioner is a 53 year old male gastroenterologist with 18 years of experience following a formal endoscopic fellowship, who performs 150 cases annually and is involved in training. The practice of ERCP continues to evolve in Australia with a high uptake of recent measures to prevent post ERCP pancreatitis as well as the management of difficult, large CBD stones. Recommendations to reserve ERCP for therapeutic indications appears to be followed, however only two thirds actively audit their practice to monitor their performance and 1 in 4 perform less than 100 cases per annum.

3B). UDCA treatment did not affect serum 4β-HC or 24S-HC concentrations but MAPK Inhibitor Library cost increased the 27-HC concentration significantly. Treatment with bezafibrate clearly increased serum 4β-HC levels, whereas it significantly reduced the 24S-HC and 27-HC levels. Differentiated HepaRG cells exhibit a gene expression pattern similar to primary human hepatocytes and human liver tissues and maintain significant levels of hepatic cell functions, including CYP and transporter activities.26 Rifampicin and carbamazepine are classical inducers of CYP3A4 by way of the activation of PXR,27 whereas GW4064 is one of the most potent agonists of FXR.28 As shown in Fig. 4A, bezafibrate, as well as rifampicin

and carbamazepine, induced both CYP3A4 mRNA expression

and activity in a dose-dependent manner. The DPX2 cell-based luciferase reporter gene assay demonstrated that in comparison with rifampicin, bezafibrate was a weak but significant activator of human PXR as well as carbamazepine (Fig. 4B). It is noteworthy that GW4064 activated human PXR at concentrations higher than 3 μM. Among the nuclear receptors and related coactivators (Fig. 5A), PXR expression was induced by bezafibrate to a greater degree than that by rifampicin, which suggests that PXR is a target gene of PPARs, as reported.29 In contrast, the small heterodimer partner (SHP; NR0B2), a target of FXR, and LXRα were down-regulated by bezafibrate, as well as rifampicin and carbamazepine. FXR and peroxisome proliferator-activated Panobinostat research buy receptor-γ coactivator-1α (PGC1α) expressions were significantly down-regulated by rifampicin and carbamazepine but not by bezafibrate. The MDR1 (ABCB1) and MRP2 (ABCC2) transporters (Fig. 5B) were up-regulated

by bezafibrate, similar to rifampicin, whereas MDR3, ABCG5, and ABCG8 were up-regulated by bezafibrate but not by rifampicin. In addition, Na+/taurocholate cotransporting polypeptide (NTCP) was down-regulated by Amino acid bezafibrate but did not change significantly by rifampicin. It is notable that significant messenger RNA (mRNA) expression of BSEP was observed in HepaRG cells treated with GW4064, whereas only a trace amount of BSEP expression was detected in control cells and those treated with other compounds. Enzymes involved in cholesterol, bile acid, and fatty acid syntheses and LDL receptor expression are summarized in Fig. 5C. CYP7A1, CYP7B1, and CYP27A1 were down-regulated and CYP8B1, fatty acid synthase (FAS), and LDL receptor (LDLR) were up-regulated by bezafibrate, which was the same as the effects of rifampicin. HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway, was down-regulated by rifampicin but was slightly up-regulated by bezafibrate. Our results clearly showed that the combination therapy of bezafibrate and UDCA significantly improved cholestasis in early-stage PBC patients who were refractory to UDCA monotherapy.

56,76 This was followed by a flurry of reports on the ability of transplanted bone

marrow or cord blood progenitors to repopulate animal models of liver injury.77–80 The most notable of these used the mouse model of tyrosinemia,79 and demonstrated that the liver could be completely regenerated by bone marrow stem cells. This phenomenon was subsequently found to be predominantly due to fusion.81 While there continues to be controversy regarding whether bone marrow cells can transdifferentiate into hepatocyte-like cells under certain conditions,82 the weight of evidence suggests that the contribution of bone marrow to normal liver regeneration is insignificant.83,84 The observation that liver progenitor cells have mixed RXDX-106 datasheet epithelial and mesenchymal markers72,73,85 and the ease by which mesenchymal stem cells can be converted to hepatocyte-like cells86–88 raised the possibility that they may arise from the mesenchymal

lineage via mesenchymal to epithelial transition. Sicklick et al.89 further proposed that progenitor cells may be derived from hepatic stellate cells, and that the sonic hedgehog pathway regulated this process. In a follow up study, Yang et al.90 used cell fate mapping to show that stellate cells could became oval cells when activated GDC-0449 chemical structure in liver injury, and that these cells participate in ductular proliferation. The notion that there is a common schema within the stellate cell driving both fibrosis and regeneration by fluxing between epithelial however and mesenchymal phenotypes91,92 is an attractive one, but has not been borne out by other investigations. Careful fate mapping studies failed to show any evidence of mesenchymal to epithelial transition or vice versa during liver injury.93,94 In light of conflicting evidence, the role of epithelial-mesenchymal transition and vice versa in liver injury and repair remains highly controversial.95,96 Nevertheless, taken in context with current evidence,

it is likely that the majority of liver progenitor cells are in situ cells that are descendants of the fetal ductal plate.75 The main strategy in attempting to augment regeneration in the clinical setting thus lies in increasing the numbers of these progenitor cells following liver injury, either by stimulating the stem cell niche to proliferate, or simply by transplanting more progenitor cells into the injured liver. The role of progenitor cell regeneration in normal liver physiology is still debated. These cells likely have no significant role in day-to-day liver turnover.97 The progenitor compartment is activated only in severe liver injury, and the belief that it plays an important role in regenerating the injured liver comes from three lines of evidence.

2007) with raw data from an earlier study of macroalgal biomass levels in the same area (Amsler

et al. 1995), Amsler et al. (2008) estimated amphipod densities per unit area of the benthos in solid stands of the dominant brown macroalgae as over 300,000 amphipods · m−2 on D. menziesii and over 30,000 amphipods · m−2 on D. anceps. Richardson (1977) reported 11,253 amphipods from a single D. anceps individual at a more northerly location in the WAP, which is consistent with the estimate for our study area. Similarly, densities on the common, understory red alga Plocamium cartilagineum (Linnaeus) Dixon were estimated at over 26,000 amphipods · m−2 (Amsler et al. 2008). These estimated densities are one to three orders of magnitude higher than most reported amphipod densities in temperate and tropical waters (e.g., Nelson MK-2206 in vitro 1980, Wildish 1988, Brawley 1992, Reynolds et al. 2012, Myers and Heck 2013) and are particularly Alectinib cell line impressive because D. menziesii and especially D. anceps commonly cover very wide areas of the benthos, often with nearly 100% cover (Wiencke and Amsler 2012, Wiencke et al. in press, authors’ personal observations). Although the macroalgal-associated amphipod fauna (Huang et al. 2007)

includes suspension feeding taxa such as members of family Ischyroceridae and predators such as Bovallia gigantea, a majority of the species are currently members of family Pontogeneiidae and are primarily considered to be herbivores and omnivores (Thurston 1972, 1974, De Broyer et al. 2007). No analysis of associated amphipod

density is available for the much larger, blade-forming H. grandifolius that dominates in deeper waters because its size precludes the quantitative sampling methods employed by Huang et al. (2007). However, Huang et al. (2007) observed lower G protein-coupled receptor kinase amphipod densities on smaller blade-forming species compared to the highly branched Desmarestia spp. and P. cartilagineum and this is consistent with our personal observations of relatively lower amphipod densities on H. grandifolius. H. grandifolius does, however, appear to us to support relatively higher densities of gastropods, particularly of larger gastropod species, than the other dominant brown macroalgae. There are several reports of gastropod grazers being numerous in association with the larger macroalgae in the WAP (Richardson 1977, Picken 1979, 1980, Iken 1999). We have recently analyzed the gastropod fauna associated with the same individual macroalgae from which Huang et al. (2007) enumerated amphipods in our study area. Of the eight macroalgal species sampled, gastropod densities were generally an order of magnitude lower than amphipod densities, and were also somewhat lower than in previous reports from the region (Richardson 1977, Picken 1979, 1980). However, densities still ranged up to nearly one gastropod per gram wet algal biomass (M.O. Amsler, Y.M. Huang, unpublished).

2007) with raw data from an earlier study of macroalgal biomass levels in the same area (Amsler

et al. 1995), Amsler et al. (2008) estimated amphipod densities per unit area of the benthos in solid stands of the dominant brown macroalgae as over 300,000 amphipods · m−2 on D. menziesii and over 30,000 amphipods · m−2 on D. anceps. Richardson (1977) reported 11,253 amphipods from a single D. anceps individual at a more northerly location in the WAP, which is consistent with the estimate for our study area. Similarly, densities on the common, understory red alga Plocamium cartilagineum (Linnaeus) Dixon were estimated at over 26,000 amphipods · m−2 (Amsler et al. 2008). These estimated densities are one to three orders of magnitude higher than most reported amphipod densities in temperate and tropical waters (e.g., Nelson this website 1980, Wildish 1988, Brawley 1992, Reynolds et al. 2012, Myers and Heck 2013) and are particularly RO4929097 nmr impressive because D. menziesii and especially D. anceps commonly cover very wide areas of the benthos, often with nearly 100% cover (Wiencke and Amsler 2012, Wiencke et al. in press, authors’ personal observations). Although the macroalgal-associated amphipod fauna (Huang et al. 2007)

includes suspension feeding taxa such as members of family Ischyroceridae and predators such as Bovallia gigantea, a majority of the species are currently members of family Pontogeneiidae and are primarily considered to be herbivores and omnivores (Thurston 1972, 1974, De Broyer et al. 2007). No analysis of associated amphipod

density is available for the much larger, blade-forming H. grandifolius that dominates in deeper waters because its size precludes the quantitative sampling methods employed by Huang et al. (2007). However, Huang et al. (2007) observed lower PRKD3 amphipod densities on smaller blade-forming species compared to the highly branched Desmarestia spp. and P. cartilagineum and this is consistent with our personal observations of relatively lower amphipod densities on H. grandifolius. H. grandifolius does, however, appear to us to support relatively higher densities of gastropods, particularly of larger gastropod species, than the other dominant brown macroalgae. There are several reports of gastropod grazers being numerous in association with the larger macroalgae in the WAP (Richardson 1977, Picken 1979, 1980, Iken 1999). We have recently analyzed the gastropod fauna associated with the same individual macroalgae from which Huang et al. (2007) enumerated amphipods in our study area. Of the eight macroalgal species sampled, gastropod densities were generally an order of magnitude lower than amphipod densities, and were also somewhat lower than in previous reports from the region (Richardson 1977, Picken 1979, 1980). However, densities still ranged up to nearly one gastropod per gram wet algal biomass (M.O. Amsler, Y.M. Huang, unpublished).

Multiple factor scoring systems (Ranson’s criteria and APPACHE II classification system) and individual laboratory tests of pancreatitis injury and inflammatory response were compared using ANOVA one way test of variances for the degree of pancreatic damage. P value < 0.001 was considered statistically significant. Results: RESULTS: Fourty- six patients (67.6%) were males and twenty two (32.4%) females.

AP was associated with gallstone disease in 33 patients (48.5%), due to alcohol abuse in 29 (42.6%), and due to other causes of unknown origin in 6 (8.9%). M ± SD value of age, white cells and the number of positive Ranson and APACHE II variables were significantly higher in patients AG-014699 concentration included in the group III compared with this website those of group I, 58.89 ± 16.93 years vs 42.21 ± 16.55 years (p < 0.001), 17800 ± 7000 vs 11143 ± 5692 (p < 0.001), 3.63 ± 1.26 vs 1.79 ± 1.25 (p < 0.001) and 14.47 ± 4.3 vs 8.07 ± 1.14 (p < 0.001), respectively. There were futhermore significant differences in Ranson's criteria and APACHE II classification system between the patients of the group II and III.

Although without significant difference, M ± SD of hematocrit and fasting blood sugar were higher in the patients of the group III compared to those of the group I, 35.12 ± 10.71 vs 32.69 ± 14.65 and 157.82 ± 48.42 vs 153.90 ± 108.90, respectively. Conclusion: CONCLUSION: The early detection of pancreatic necrosis signifies severe disease and is being used as a grave prognostic indicator in the initial evaluation of these patients. Balthazar grade score plus necrosis score in combination with age, white blood cells and multiple factor score systems may be largely used to asses the severity of AP. Key Word(s): 1. acute pancreatitis; 2. Balthazar score;

3. pancreatic necrosis; 4. severity of AP; Presenting Author: ANILA KRISTO Additional Authors: BASHKIM RESULI, JOVAN BASHO, ADRIANA BABAMETO, JONILA ÇELA, ELIZANA PETRELA, IRGEN TAFAJ, KLERIDA SHEHU Sitaxentan Corresponding Author: ANILA KRISTO Affiliations: Service of Gastrohepatology; Department of Statistics Objective: The clinical spectrum of acute pancreatitis (AP) depends on whether or not pancreatic necrosis is present and to what extent. There is controversy in the literature as to whether the extent of necrosis on contrast- enhanced computed tomography (CT) predict organ failure. Methods: To asses the association between morphologic changes and clinical-biochemical markers in patients with AP. A consecutive series of 68 patients with AP, with mean age of 54.2 ± 15.9 y/old, admitted to our service of gastroenterology between Jannuary 1, of 2009 and December 31, 2011 were included in this study. Blood biochemical data were obtained at the time of admission while CT within 72 h after the onset of disease.

Children attending to the rehabilitation centre of Buzias in Romania were sampled consecutively. Construct validity of the PedHAL was evaluated by concurrent testing with objective and subjective measures of physical function and functional ability. Reproducibility was tested by a 3-day test–retest by intraclass

correlation coefficient (ICC) and limits of agreement (LOA). Responsiveness to rehabilitation was assessed by Haemophilia Joint Health Score (HJHS) and PedHAL. Twenty-nine children with severe (n = 25) or moderate (n = 4) haemophilia participated. Mean age was 13.2 years (SD 4.0). Median score of the PedHAL was 83.5 (IQR 47.9–90.5). The PedHAL correlated moderately with HJHS (rho = −0.59), Functional Independence Score in& Haemophilia (rho = 0.65) and Child Health Questionnaire-physical function (rho = 0.40) and not selleck inhibitor with Child Health Questionnaire-mental health, Child Health Questionnaire-behaviour and 6MWT. Test-retest reliability was good (ICC = 0.95). LOA was 17.4 points for the sum score. HJHS scores improved slightly after rehabilitation, whereas PedHAL

scores did not change. In general, construct validity and test–retest reliability were good, test–retest agreement showed some variability. Therefore, currently the PedHAL may be more appropriate for research purposes than for individual patient monitoring www.selleckchem.com/products/PD-0325901.html in clinical practice. “
“An increasing Sucrase number of individuals with haemophilia and other severe bleeding disorders who are ≥40 years of age are entering

uncharted territory with respect to the identification and management of medical, physical and social issues relevant to ageing with a bleeding disorder. This is because the population experienced considerable mortality during the HIV/AIDs and hepatitis C epidemic due to exposure to tainted blood products for treatment of bleeding. As a result, few older individuals with this disorder survive today. To provide insight for how the comprehensive care team can adapt to the changing needs of the adult haemophiliac we evaluated the patient perspective. The objective of this study was to identify key themes of importance in the ageing population with haemophilia and other inherited bleeding disorders. For this study all subjects with a diagnosis of haemophilia A or B, von Willebrand disease or rare bleeding disorders 40 years or older from a single clinic were invited to participate. Audio-recordings of groups of six to eight participants were conducted by an independent investigator without content expertise. Transcripts were analysed using N*vivo (v. 8) software using thematic content analysis. Overall, 32 subjects, 18 men/14 women, with a mean age of 57.5 years (median 56.0 years) and range of 40–77 years, participated. Three major themes emerged: (i) reflection on living an active life, (ii) ‘normal’ ageing vs.

Likewise, UDCA is anti-apoptotic in a number of cell lines, but this effect has not been investigated in bone cells. Therefore, the consequences of bilirubin and LCA on apoptosis, and if UDCA has antiapoptotic effects have been assessed on osteoblastic cells. Material and Methods: The

experiments were performed in primary human osteoblasts (hOB) and human osteosarcoma cell selleck chemicals line (Saos-2). Cells were treated at different times and concentrations of camptothecin as proapoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, caspase-3 activity, flow cytometry (annexin V-FITC labeling), and gene expression of Bcl-2-associated X protein (BAX) as antiapoptotic, and BCL2 and BCL2-like 1 protein (BCL2L) as proapoptotic genes, respectively. Results: Both LCA (10 μM) and bilirubin (50 μM) significantly induced cell apoptosis as indicated by DNA fragmentation (4.7 and

3.7 fold vs control, respectively, p<0.001), with parallel results by caspase-3 activity and flow cytometry. UDCA (100 μM) alone had no consequences on DNA fragmentation. However, UDCA (10 μM) reduced significantly the apoptotic effects of camptothecin (0.5 μM) by 61%, (p<0.001), and counteracted the apoptotic effects of LCA and bilirubin, as observed by DNA fragmentation (56% and 60%, respectively, p<0.001), caspase-3 activity and flow cytometry. Moreover, both bilirubin 50 μM and LCA 10 μM up-regulated BAX in Saos-2 cells, at levels as high as those observed with CAM 0.5 μM. UDCA (10 μM) down-regulated BAX Dabrafenib by 67 %, and it diminished or completely abolished the up-regulation of BAX induced by CAM, bilirubin and LCA, in a dose-dependent manner, in both Saos-2 and hOB cultures. Opposite effects of CAM, bilirubin and LCA were found regarding the expression of BCL2 and BCL2L1, the two genes linked to apoptosis repression. The addition of UDCA in the experiments, partially

PAK5 or totally counteracted the decreased expression of these two genes induced by bilirubin or LCA in a dose-dependent manner. Conclusions: Bilirubin and lithocholic acid induce apoptosis in osteoblastic cells. Ursodeoxycholic acid has clear antiapoptotic effects counteracting the consequences of these two substances increased in cholestasis. These results suggest that ursodeoxycholic acid may have further benefitial effects on neutralizing the decreased bone formation in patients with cholestasis. Disclosures: The following people have nothing to disclose: Silvia Ruiz-Gaspa, Marta Dubreuil, Nuria Guañabens, Andres Combalia, Pilar Peris, Ana Monegal, Albert Pares Background: Pruritus of acute viral hepatitis (AVH) is often the most troublesome symptom to treat. The exact pathogenesis of pruritus is unknown, but therapeutic options such as cholestyramine, ursodeoxycholic acid (UDCA), rifampicin, 5-HT receptor antagonists (Ondansetron), being used with variable outcomes. In one study Opioid antagonists (Naltrexone) has been tried clinically with good success in relieving pruritus.