A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Wim Laleman, Anita Omasta, Marc Van de Casteele, Marcel Zeegers, Ingrid Vander Elst, Lien Van Landeghem, Tamara Severi, Jos van Pelt, Tania Roskams, Johan Fevery, Frederik Nevens – 29 November 2005 – Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis.

Treating hepatitis C: Can you teach old dogs new tricks?

Charles M. Rice, Shihyun You – 29 November 2005 – Viruses depend on host‐derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl‐prolyl cis‐trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)‐mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication.

Prediction of significant fibrosis in HBeAg‐positive patients with chronic hepatitis B by a noninvasive model

Min‐De Zeng, Lun‐Gen Lu, Yi‐Min Mao, De‐Kai Qiu, Ji‐Qiang Li, Mo‐Bin Wan, Cheng‐Wei Chen, Ji‐Yao Wang, Xiong Cai, Chun‐Fang Gao, Xia‐Qiu Zhou – 29 November 2005 – A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2‐4 vs. stages 0‐1). Consecutive treatment‐naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172).

Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin–sensitive mechanism in murine and human hepatocytes

Paul Dent, Youwen Fang, Seema Gupta, Elaine Studer, Clint Mitchell, Sarah Spiegel, Philip B. Hylemon – 29 November 2005 – Several studies have argued that G‐protein–coupled receptors (GPCR) have the capacity to promote activation of receptor tyrosine kinases. The current studies were performed to examine the regulation of the extracellular regulated kinase (ERK)1/2 and AKT pathways by conjugated and unconjugated bile acids in primary hepatocytes.

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