A.T., V.C., and P.M.M. received speaker fees on the occasion of scientific educational meetings organized by Instrumentation Laboratory. While processing this paper the following article addressing the same issue has been published: Lisman T, Bakhtiari K, Pereboom ITA, Hendriks HGD, Meijers JCM, Porte RJ. Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged

conventional coagulation tests. J Hepatol 2010;52:355–61. “
“The increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve Napabucasin gallstones. In investigating novel therapeutics for CG, we assessed the preventive effects of

n-3 polyunsaturated fatty acids (n-3PUFA) on the formation of CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice. Mice were divided into the following six groups: (A) regular diet (RD); (B) RD+n-3PUFA; (C) LD; (D) LD+n-3PUFA; (E) LD+UDCA; (F) LD+n-3PUFA+UDCA. After Cetuximab in vivo RD/LD feeding for 2 weeks, n-3PUFA or UDCA was administered orally and the diet maintained for 8 weeks. The levels of phospholipids and cholesterol in bile, CG formation, gallbladder wall thickness, MUC gene expression in gallbladder were analyzed. No stone or sludge was evident in the RD groups (Groups A, B). Mice in the n-3PUFA treatment (Groups D, F) showed significantly lower stone formation than the other LD groups (Groups C, E). The combination treatment of n-3PUFA and UDCA suppressed stone formation more than mono-therapy with n-3PUFA or UDCA. Bile phospholipid levels were significantly elevated in the Group F. Hypertrophy of the gallbladder wall was evident in mice fed LD. MUC 2, 5AC, 5B and 6 mRNA expression levels were significantly elevated in the LD-fed group, and this was suppressed by n-3PUFA with or without UDCA. N-3PUFA attenuated gallstone

formation in mouse, through increasing the levels of bile phospholipids and suppressing bile mucin formation. “
“p130Cas, Crk-associated substrate (Cas), is an adaptor/scaffold protein that plays a central role in actin cytoskeletal reorganization. We previously showed that mice in which Cas was deleted (Cas−/−) died in utero because of early cardiovascular maldevelopment. To further Tideglusib investigate the in vivo roles of Cas, we generated mice with a hypomorphic Cas allele lacking the exon 2–derived region (CasΔex2/Δex2), which encodes Src homology domain 3 (SH3) of Cas. CasΔex2/Δex2 mice again died as embryos, but they particularly showed progressive liver degeneration with hepatocyte apoptosis. Because Cas expression in the liver is preferentially detected in sinusoidal endothelial cells (SECs), the observed hepatocyte apoptosis was most likely ascribable to impaired function of SECs. To address this possibility, we stably introduced a Cas mutant lacking the SH3 domain (Cas ΔSH3) into an SEC line (NP31).