65-fold ± 0.1) (Fig. 7B) and increased the sensitivity to Ca2+ (Fig. 7C), mimicking FA accumulation and steatotic condition. To demonstrate that GSK3 is the kinase or, at least, one of the kinases that contribute to VDAC phosphorylation in lean condition, we reduced its expression of 80% by small interfering RNA (siRNA) and observed a 46% decrease in P-Thr VDAC in HHL-5 cells (Fig. 7D). Finally, using recombinant (i.e., VDAC1, GSK3, Bcl-XL) and native purified proteins (i.e., VDAC), we observed in vitro that VDAC and Bcl-XL can be direct substrates for phosphorylation by GSK3β and suggest

that no other kinase is needed (Supporting Fig. 5). Unraveling the initial molecular mechanisms leading to fatty liver disease in humans is of major clinical importance. Because activation of signaling pathways may precede the clinical symptoms,1 a series BMS-354825 in vivo of models of liver steatosis were used to study the early stage of NAFLD. This led us to show, for the first time, that liver steatosis in humans is associated with a lack of VDAC phosphorylation. This modification was also observed both in a genetic model of obesity, the ob/ob mice, which is devoid of inflammation and fibrosis, at

least in young animals,13 and in the steatotic liver of HFD-fed mice. No change in other phosphorylable amino acids, such as tyrosine or serine, was observed (not shown). These observations suggest that VDAC lack of phosphorylation may represent a hallmark of steatosis in mammals. In addition Silmitasertib molecular weight to their impaired metabolic function,4 上海皓元医药股份有限公司 we show for the first time that mitochondria from ob/ob mice are more prone to Ca2+-induced PT, water and small molecules entry, and Cyt c release, suggesting a sensitization of the mitochondrial pathway of apoptosis. Indeed, tumor necrosis factor (TNF)-induced apoptosis and Ca2+ release by endoplasmic reticulum have been shown to be responsible for the massive hepatocyte loss observed in the late stages of NAFLD.20, 21 The absence of apoptosis and caspase activation in ob/ob mice might be explained by the earliness of the model.22 The cellular experiments revealed that intracellular FA accumulation

is rapidly followed by VDAC dephosphorylation and ΔΨm loss sensitization. Thus, our current data obtained in ob/ob mice and FA-treated cells offer novel insights into the early phases of NAFLD pathogenesis and early mitochondrial alterations. Importantly, we found differences in VDAC functions that were exacerbated by Ca2+. Thus, the level of VDAC phosphorylation proved to modulate the ionic channel permeability of VDAC in response to Ca2+, which may influence mitochondrial OM permeability.23, 24 Moreover, the overstimulation of oxidase function of VDAC purified from ob/ob mice by Ca2+ may affect the cellular metabolism by increasing NAD+ levels available either for redox processes, ADP-ribosylation reactions, or sirtuin-mediated deacetylations.

8%, 95% CI = 48.6%-80.4%). Moreover, basal urinary copper was directly correlated find more with the age at diagnosis (r = 0.58, P < 0.0001) in children with WD but not in the control group. The daily urinary copper level after PCT did not statistically differ between patients with WD (771.3 ± 103.3 μg/24 hours) and controls (585.5 ± 63.8 μg/24 hours, P = 0.69). Among WD patients, only 3 of 25 (12%) presented values

> 1575 μg/24 hours: all of them had fibrosis at liver biopsy and basal copper excretion > 100 μg/24 hours. Among controls, 3 of 58 (5.2%) had PCT cupriuria > 1575 μg/24 hours, and they presented with NASH, NRH, or AIH type 1. The ROC analysis (area under the curve = 0.61, P = 0.10) of 25 WD patients and 58 controls showed that at the cutoff value of 1575 μg/24 hours, the sensitivity was only 12% (95% CI = 2.5%-31.2%); it was raised to 64% (95% CI = 42.5%-82%) and 88% (95% CI = 68.8%-97.4%) only when the threshold was lowered to >500 μg/24 hours and >200 μg/24 hours, respectively. Liver

copper levels were measured in 30 WD patients and 24 control subjects and significantly differed between the two groups (813.6 ± 81.7 versus 38.4 ± 17 μg/g of dry weight, P < 0.0001). Only 2 of 30 WD patients (7%) had a liver copper level < 75 μg/g of dry weight, which has been proposed as a novel diagnostic threshold19; this website the remaining 28 had values > 250 μg/g of dry weight. Liver copper levels in WD patients did not directly correlate with the severity of the histological picture (data not shown) or the age at liver biopsy (r = 0.38, P = 0.03). Among controls, 4 of 24 (6%)

had liver copper levels > 50 μg/g of dry weight; 2 had CDG (318 and 250 μg/g of dry weight, respectively), 1 had NRH, and 1 had cryptogenic liver disease. The two patients affected by CDG also had low ceruloplasmin levels. The sensitivity and specificity of ceruloplasmin, basal 24-hour urinary copper, and 24-hour urinary copper after PCT at different thresholds are summarized in Table 3. MCE An evaluation of all items of the WD scoring system proposed by Ferenci et al.11 was possible in 30 patients with WD and in 24 control subjects. When the considered cutoff value for basal urinary copper was 40 μg/24 hours, only two patients with WD scored less than 4; when the cutoff value was 100 μg/24 hours, three patients did. Only two control subjects, both of whom had CDG, had a score of 4 regardless of the considered cutoff value (Fig. 3). When we considered 40 μg/24 hours instead of 100 μg/24 hours as the urinary copper ULN, the scoring system had the best diagnostic accuracy: a sensitivity of 93% versus 90%, a specificity of 91.6% versus 91.6%, a positive predictive value of 93% versus 93.1%, and a negative predictive value of 91.6% versus 88%. It is remarkable that all the patients with WD were positive for at least ceruloplasmin or basal urinary copper excretion.

The tk-Cyp3a11

report gene contains three copies of the Fulvestrant order DR-3 type PXRE (TGAACTataCGAACT) found in the mouse Cyp3a11 gene promoter. HepG2 cells were transfected on 48-well plates as previously described.29 When applicable, transfected cells were treated with drugs for 24 hours before harvesting for luciferase and β-gal assays. The transfection efficiency was normalized against the β-gal activity. Results are expressed as means ± standard deviation (SD). Statistical analysis was performed using the unpaired Student’s t test for the comparison between two groups. We have previously reported the creation of Tg mice that express the activated LXRα (FABP-VP-LXRα) in the liver (Fig. 1A).22 Created by fusing the VP activation domain of the herpes simplex virus to the aminoterminal of LXRα, VP-LXRα shares the same DNA-binding specificity as its Wt counterpart and constitutively activates LXR target gene expression.22 Gene-expression analysis revealed that activation of LXR in the liver regulated the expression of multiple drug-metabolizing enzymes and transporters,22 which prompted us to examine whether Tg mice had an altered sensitivity to APAP. In vehicle-treated mice, no significant alteration in liver histology was found in Tg mice,

when compared to Wt mice (Fig. 1B). After APAP INCB024360 chemical structure treatment, the Wt liver showed expected typical necrotic liver damage. In contrast, Tg mice showed little signs of liver damage (Fig. 1C), suggesting that this genetic activation of LXR conferred resistance to APAP hepatotoxicity. Consistent with their MCE reduced histological liver damage, APAP-treated Tg mice showed improved serum chemistry, compared to their Wt counterparts. These included lower serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, total bilirubin, and alkaline phosphatase (Fig. 1D). Vehicle-treated Tg mice showed little signs of hepatotoxicity, as judged by serum chemistry (Supporting Fig. 1). The hepatoprotective effect of the LXRα transgene prompted us to determine whether a pharmacological activation

of LXR would have a similar effect in preventing APAP toxicity. Indeed, the TO1317-treated Wt C57BL/6J mice showed less histological liver damage (Fig. 2A) and lower serum level of AST and ALT (Fig. 2B), compared to their vehicle-treated counterparts. We then used LXR DKO mice to determine whether the hepatoprotective effect of TO1317 was LXR dependent. The protective effect of TO1317 was abolished in LXR DKO mice, as indicated by the lack of relief in histological liver damage (Fig. 2C), as well as the serum levels of AST and ALT (Fig. 2D) in APAP- and TO1317-treated LXR DKO mice. These results demonstrated that the APAP protective effect of TO1317 required LXRs. Because TO1317 was also reported to activate PXR,30 we then used PXR−/− mice to determine whether the hepatoprotective effect of TO1317 required PXR.

40 We predict that alcohol-mediated increase in circulating endotoxin selleck screening library (i.e., LPS) induces MCP-1 in hepatocytes and macrophages to regulate fatty acid oxidation pathways in an autocrine or paracrine fashion in the liver. Future studies, using MCP-1-targeting strategies, will provide mechanistic insights into the pathophysiological mechanisms affected by MCP-1 in alcoholic liver injury. Overall, our studies show, for the first time, that MCP-1 in the liver regulates macrophage activation, proinflammatory responses, and hepatic steatosis in alcoholic liver disease.

These studies provide a link between inflammatory cell activation and pathways of fatty acid metabolism during alcoholic liver injury likely involved in the amplification and progression of disease. Therefore, it appears plausible that pharmacological approaches to block MCP-1 in the alcoholic liver may be beneficial to early alcoholic fatty liver injury and also abrogate

inflammatory pathways contributing to propagation in ALD. The authors thank Karen Kodys for labeling the oligonucleotides for the EMSA analysis. Additional Supporting Information may be found in the online version of this article. ”
“Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2/prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride Alectinib nmr (CCl4) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction),

上海皓元 and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4-cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4-cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (α-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway. Conclusion: Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis.

Five weeks postoperatively, the FVIII activity level was 2% and the factor VIII inhibitor was measured at 16 Bethesda units (BU). Twelve weeks later, the inhibitor titre had fallen

to 1 BU. He was taking rFVIIa for continued minor oozing from the prostate bed, but was not suffering from any spontaneous bleeds. Factor VIII gene sequencing revealed a missense mutation, Arg593Cys, in the A2 domain. EPZ-6438 research buy There are approximately 50 reported cases of the Arg593Cys mutation in the haemophilia A mutation database (http://hadb.org.uk) and it has been previously associated with inhibitors. Evaluation of this patient’s inhibitor showed a polyclonal response with the largest quantity of antibodies being directed against the A2 and C2 domains of FVIII (Fig. 1). selleck A 20-year-old man with moderate haemophilia A (FVIII activity 3%) had previously received factor infusions only for trauma-related bleeds. Approximately 18 months prior to presentation, a FVIII inhibitor of 10.2 Nijmegen-BU was detected on routine screening labs. The patient was not experiencing any change in the pattern of bleeding and on repeat evaluation 6 months later, the inhibitor was not detected. The patient presented with complaints of right-sided abdominal pain. CT scan was remarkable for a complex mass in the right lower quadrant and right hydronephrosis.

Preoperative PTT was 54.3 s and the patient received 100% FVIII correction prior to surgery. Intraoperative exploration revealed localized perforation and inflammation of the right colon with haemorrhage into the wall. He underwent emergent right hemicolectomy and ureteral stenting. There was no histologic evidence of acute appendicitis, thus a pseudotumor with erosion into the colon was suspected. Postoperatively, the MCE公司 patient received 50% FVIII dose every 12 h without correction of his PTT. A mixing study was consistent with an FVIII inhibitor

(Table 1), but titre was 0 by Bethesda assay. On postoperative day 5, the patient experienced oozing from the wound. Local pressure, rFVIIa and increased doses of FVIII were used and haemostasis was achieved. The patient was discharged, but returned 2 days later with a massive gastrointestinal haemorrhage from a vessel at the anastomotic site. Inhibitor titre was 32 BU. He was treated with endoscopically placed vascular clips, desmopressin (DDAVP) and activated prothrombin complex concentrate (aPCC) followed by rFVIIa. The bleeding resolved and the patient was discharged on prophylactic rFVIIa. Evaluation of the patient’s inhibitor 5 months later revealed a titre of 3.6 BU; in 13 months the inhibitor titre was 0 BU. Factor VIII gene sequencing revealed a missense mutation, Arg1941Gln, in the A3 domain. According to a recent search of the haemophilia A mutation database, there have been more than 10 previous reports of this mutation. The Arg1941Gln mutation has not been associated with inhibitor formation in previous reports.

Antibody targeting of SR-BI turns out to be superior to anti-CD81 therapy for several reasons. The expression pattern of SR-BI is more restricted than the ubiquitously expressed CD81,49 which may allow for a reduction of the treatment dose and potential side effects. In fact, a 2-week treatment of chimeric mice with mAb16-71 induced no significant changes in hepatic serum markers as compared

with untreated mice. Although our limited data suggest that mAb16-71 therapy might be safe in humans, more extensive preclinical toxicity studies must be performed in different animal species, as well as safety and pharmacokinetic studies in healthy volunteers and, ultimately, in liver transplant patients. It needs to be emphasized that mice represent a very stringent model for safety testing of anti-SR-BI mAb therapy

because these animals do not express cholesteryl Proteasome inhibitor ester transfer protein (CETP), which facilitates cholesterol transport and triglyceride exchange in humans, thus potentially providing an alternative route of lipid metabolism in case of reduced SR-BI function upon mAb16-71 treatment.50 In addition, mAb16-71 remains effective in blocking HCV dissemination, even if administered several days after viral inoculation. This suggests that SR-BI may be a molecule involved in direct cell-to-cell transmission of HCV in vivo and represents an important advantage over anti-CD81 blockade which did not prevent virus spread even when administered therapeutically soon after viral challenge.31 In fact, our antibody seems more effective in vivo than what could be anticipated from cell culture experiments. This implies see more still unknown discrepancies between the currently used cell MCE culture systems and the in vivo reality, thereby further emphasizing the value of experiments in animal models. Viruses with mutations or deletions in their envelope proteins have been described to become independent for SR-BI.51-53 However, it remains to be determined whether these mutated viruses are also not reliant on SR-BI in vivo. We could not identify

any adaptive mutations in the envelope region of the virus that was recovered from two mAb16-71-treated mice that became HCV-positive 9 days and 29 days after cessation of the 2-week antibody treatment. Furthermore, it is doubtful that such variants would arise and expand in an infected patient, because they are sensitive to neutralizing antibodies that are ubiquitously present in the plasma of all chronically infected patients.13, 51-54 A viral mutant losing its SR-BI dependence would most likely be immediately neutralized by the host’s preexisting adaptive immune response. Besides SR-BI, claudin-1 and occludin may be very attractive targets for antiviral therapy. These tight junction proteins are essential for viral entry and direct cell-to-cell transmission.29, 30, 34, 55 In a recent publication, Lupberger et al.

, 2010). Aggression by adult mares towards unrelated foals has often been recorded in mountain zebra (Penzhorn, 1984; Lloyd & Rasa, 1989), but is very rare in plains zebra (Pluháček, Bartošová & Bartoš, 2010c). Female Grévy’s zebras form only loose associations without any hierarchy (Klingel, 1974; Rubenstein, 1989; Sundaresan et al., 2007) and exhibit a lower level of aggression than the two other zebra species (Klingel, 1974; Penzhorn, 1984; Andersen, 1992; Pluháček, Bartoš & Čulík, 2006). Therefore, http://www.selleckchem.com/products/CP-673451.html zebras form an optimal model for investigating the relationship between social organization and maternal

behaviour. Although an evolutionary approach has been suggested to understand the dynamics of parent–offspring relationships in mammals (Bateson, 1994), only few studies have compared the suckling behaviour in different species (e.g. Trillmich, 1990; Lavigueur & Barrette, 1992; Maestripieri, 1994a; McGuire, Vermeylen & Bemis, 2011). The only interspecific comparison of equid suckling behaviour was published from wild Grévy’s and plains zebra (Becker & Ginsberg, 1990), comparing also data from the literature on feral horses (Tyler, 1972; Crowell-Davis, 1985). Becker & Ginsberg (1990) concluded that Grévy’s zebra foals spent selleck screening library the least amount of time suckling and had the longest intervals between suckling

bouts compared with other equids. They proposed that the shorter time spent by suckling found in Grévy’s zebra compared with other equids would be an adaptation to arid environment 上海皓元 (Becker & Ginsberg, 1990). Recently, we re-evaluate their suggestions using rejection and termination of suckling bouts (as indicators of conflict over energy intake) in three captive zebra species

kept in the same facility (thus under same living conditions; Pluháček et al., 2012). On the other hand, we revealed higher incidence of allonursing in Grévy’s zebra than in plains and mountain zebra, where allonursing was associated with adoption (Olléová, Pluháček & King, 2012). We suggested that higher tolerance towards non-filial offspring, including the occurrence of allosuckling in Grévy’s zebras, could be affected by different social systems of zebra species as reported in several species of ungulates, rodents and primates (McGuire & Novak, 1984; Maestripieri, 1994b; Ekvall, 1998; Das, Redbo & Wiktorsson, 2000; Landete-Castillejos et al., 2000; McGuire et al., 2011). Previous studies on suckling behaviour of various equid species (E. caballus, E. hemoinus, E. quagga, E. zebra) reported that suckling bout duration and frequency could be affected highly by the age and the sex of the foal, the animal terminating the bout, parity of the mare and mother’s pregnancy (Joubert, 1972b; Tyler, 1972; Rogalski, 1973; Rashek, 1976; Duncan et al.

(HEPATOLOGY 2011;) See Editorial on Page 1430 Two models of cirrhosis formation have developed. One hypothesis indicates that cirrhosis develops as a consequence of a progressive deposition

of collagen and scar tissue Regorafenib induced by chronic inflammation and necrosis. Another, not mutually exclusive, hypothesis indicates that telomere shortening represents an underlying cause of cirrhosis.8 Telomeres form the ends of human chromosomes. The main function of telomeres is the maintenance of chromosomal stability. However, telomeres shorten as a consequence of cell division due to the “end replication problem” of DNA polymerase, processing of telomeres during S-phase of cell cycle, and the absence of telomerase expression in most somatic tissues.9 Telomere shortening limits the proliferative life span of human cells to 50-70 cell doublings by induction

of a permanent cell GW-572016 concentration cycle arrest (replicative senescence) in response to telomere dysfunction.10, 11 Previous studies have shown that telomere shortening also limits the life span of primary human hepatocytes.12 Studies of human cirrhosis have demonstrated that telomere shortening is a general marker of cirrhosis formation correlating with an accumulation of senescent hepatocytes.13, 14 In addition, studies on telomerase-deficient mice have provided the first experimental evidence that telomere shortening limits the regenerative response to acute and chronic liver injury, accelerating the formation of liver fibrosis and steatosis.15, 16 Together, these studies have led to the telomere model of cirrhosis formation, indicating that chronic liver diseases increase the rate of cell turnover, thus leading to accelerated telomere shortening and regenerative exhaustion.8, 17 In agreement with this hypothesis, it has been recognized that proliferative activity declines after long latencies of chronic liver disease and this decline was associated with the progressive formation of disease.18

Genetic studies have proven that mutations in telomerase are the underlying cause of accelerated telomere shortening and organ failure in some rare human diseases, including some forms of dyskeratosis congenita (DKC)19 and aplastic anemia.20 MCE In addition, 10% of the cases of familial idiopathic lung fibrosis are associated with telomerase mutations.21, 22 In most of these cases heterozygous mutations were found in either the RNA (TERC) or protein component (TERT) of telomerase. Interestingly, familial cases of idiopathic lung fibrosis and bone marrow failure also showed an increased frequency of unexplained liver pathologies, including fibrosis, inflammation, macrovesicular steatosis, and hepatic nodular regeneration.23-25 Some of these patients carried mutations in telomerase genes.

Thus, loss of p-catenin limits cholestatic injury by modulating BA biosynthesis through regulation of FXR. These findings support an important role of Wnt/p-catenin signaling in bile duct homeostasis and repair and provide novel therapeutic opportunity of modulating p-catenin signaling for alleviating BA-associated hepatic injury during cholestasis. Disclosures: Satdarshan

(Paul) S. Monga – Consulting: Bristol Myers Squibb, Phase Rx, Merck The following people have nothing to disclose: Kari Nejak-Bowen, Michael Thompson During DMXAA concentration cholestasis the balance between biliary growth/loss is regulated by neuroendocrine peptides and neurotransmitters by autocrine/paracrine and endocrine pathways. Gonadotropin-releasing hormone (GnRH) is a trophic peptide hormone (released from the hypothalamus) regulating reproductive functions in mammals. GnRH also alters the function of extra-pituitary non-reproductive organs such as the kidneys and pancreas. Since no data exists regarding the role of GnRH in regulating biliary homeostasis, we aimed to evaluate if GnRH regulates biliary growth in normal and bile duct ligated (BDL) rats by interacting with GnRH receptor (GnRHR). Methods: The studies were performed in: (i) normal rats treated with saline or GnRH (1 μg/day); BIBW2992 and (ii) BDL rats that, immediately after surgery, were treated with non-immune serum or anti-GnRH antibody (300μg/day) for

1 wk. Then, we measured: (i) intrahepatic bile duct mass (IBDM) in liver sections; and CK-19 and PCNA expression in total liver and cholangiocytes; and (ii) serum levels of GnRH by EIA kits. We measured the expression of: (i) GnRH and GnRHR in liver sections and cholangiocytes from normal and BDL rats and biliary lines by immunofluorescence, qPCR or immunoblots; and (ii) the levels of GnRH in the medium 上海皓元医药股份有限公司 of short-term (12 hr) cultures of cholangiocytes from normal and BDL rats and

biliary lines by EIA kits. In vitro, the: (i) dose- (10, 50 and 100 nM) and time- (24 to 72 hr) dependent effects of GnRH (in the absence/presence of the GnRHR antagonist, Cetrorelix acetate, 5-10 μM); and (ii) effect of Cetrorelix acetate (5-10 μM) on the proliferation of biliary lines was measured by MTS assays. GnRH expression was transiently knocked-down in biliary lines using siRNA and cell proliferation was assessed by MTS assays. Results: GnRH and GnRHR are expressed by normal bile ducts, cholangiocytes and biliary cell lines. GnRH biliary expression increased after BDL. Cholangiocytes secrete GnRH and, after BDL, GnRH secretion increased. Administration of GnRH to normal rats increased GnRH serum levels, biliary proliferation and IBDM, whereas administration of anti-GnRH antibody to BDL rats reduced biliary proliferation and IBDM. GnRH induced a dosedependent increase in biliary proliferation that was reduced by Cetrorelix acetate. Silencing of GnRH decreased the proliferation of biliary lines.

, MD (AASLD Postgraduate Course, Early Morning Workshops, Parallel Session) Consulting: GlaxoSmithKline, tibotec Grant/Research Support: Gilead, vertex, Ocera Forcione,

David G., MD (AASLD/ASGE Endoscopy Course) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Forns, Xavier, MD (Early Morning Workshops) Consulting: Tibotec/Jansen, MSD, Boheringher Ingelheim Grant/Research Support: Roche, MSD, Gilead Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Fox, Ira J., MD (AASLD/NASPGHAN Pediatric Symposium) Advisory Committees or Review Panels: Regenerative Ensartinib clinical trial Medical Solutions Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Franco, Jose, MD (Meet-the-Professor Luncheon) Nothing to disclose Content of the presentation

does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s)

Frenette, NVP-BGJ398 cost Catherine T., MD (Meet-the-Professor Luncheon) Speaking and Teaching: Onyx, Salix, Gilead Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Fried, Michael W. MCE公司 (Parallel Session) Consulting: Genentech, Merck, Abbvie, Vertex, Janssen, Bristol Myers Squibb, Gilead Grant/Research Support: Genentech, Merck, AbbVie, Vertex, Janssen, Bristol Myers Squibb, Gilead Patent Held/Filed: HCCPlex Fried, Michael W., MD (AASLD Postgraduate Course, HCV Symposium) Advisory Committees or Review Panels: GlaxoSmithKline Consulting: Roche/Genentech, Janssen, Vertex, Merck, Bristol Myers Squibb, Abbott, Merck, Gilead, Novartis Grant/Research Support: Roche/Genentech, Janssen, Vertex, Merck, Bristol Myers Squibb, Abbott, Merck, Gilead Friedland, Shai, MD (AASLD/ASGE Endoscopy Course) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Friedman, Joshua, MD, PhD (Early Morning Workshops, Parallel Session) Nothing to disclose Friedman, Lawrence S.