The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production

Oscar Gonzalez, Vanessa Fontanes, Santanu Raychaudhuri, Rachel Loo, Joseph Loo, Vaithilingaraja Arumugaswami, Ren Sun, Asim Dasgupta, Samuel W. French – 20 November 2009 – The hepatitis C viral (HCV) genome is translated through an internal ribosome entry site (IRES) as a single polyprotein precursor that is subsequently cleaved into individual mature viral proteins. Nonstructural protein 5A (NS5A) is one of these proteins that has been implicated in regulation of viral genome replication, translation from the viral IRES and viral packaging.

Epithelial‐to‐mesenchymal transitions in the liver

Steve S. Choi, Anna Mae Diehl – 20 November 2009 – The outcome of liver injury is dictated by the effectiveness of repair. Successful repair (i.e., regeneration) results in replacement of dead epithelial cells with healthy epithelial cells, and reconstructs normal hepatic structure and function. Liver regeneration is known to involve replication of surviving mature hepatocytes and bile duct cells. This review discusses recent evidence for other mechanisms that might also replace dead hepatic epithelial cells and repair liver damage, particularly during chronic injury.

Betaine for nonalcoholic fatty liver disease: Results of a randomized placebo‐controlled trial

Manal F. Abdelmalek, Schuyler O. Sanderson, Paul Angulo, Consuelo Soldevila‐Pico, Chen Liu, Joy Peter, Jill Keach, Matt Cave, Theresa Chen, Craig J. McClain, Keith D. Lindor – 20 November 2009 – Based on animal studies and pilot studies in humans, betaine, a methyl donor for the remethylation of homocysteine, may be a therapeutic agent for nonalcoholic steatohepatitis (NASH). We evaluated the safety and efficacy of betaine for patients with NASH and whether betaine positively modified factors postulated to be “second hits” and underlying mechanisms of NASH.

Epidemiology and natural history of primary biliary cirrhosis in a Canadian health region: A population‐based study

Robert P. Myers, Abdel Aziz M. Shaheen, Andrew Fong, Kelly W. Burak, Alex Wan, Mark G. Swain, Robert J. Hilsden, Lloyd Sutherland, Hude Quan – 20 November 2009 – The recent epidemiology and outcomes of primary biliary cirrhosis (PBC) in North America are incompletely described, partly due to difficulties in case ascertainment. In light of their availability, broad coverage, and limited expense, administrative databases may facilitate such investigations.

Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders

Vinod K. Rustgi, William M. Lee, Eric Lawitz, Stuart C. Gordon, Nezam Afdhal, Fred Poordad, Herbert L. Bonkovsky, Leif Bengtsson, Gurudatt Chandorkar, Matthew Harding, Lindsay McNair, Molly Aalyson, John Alam, Robert Kauffman, Shahin Gharakhanian, John G.

Disruptions of occludin and claudin‐5 in brain endothelial cells in vitro and in brains of mice with acute liver failure

Feng Chen, Norifumi Ohashi, Wensheng Li, Christopher Eckman, Justin H. Nguyen – 20 November 2009 – Brain edema in acute liver failure (ALF) remains lethal. The role of vasogenic mechanisms of brain edema has not been explored. We previously demonstrated that matrix metalloproteinase‐9 (MMP‐9) contributes to the pathogenesis of brain edema. Here, we show that MMP‐9 mediates disruptions in tight junction (TJ) proteins in vitro and in brains of mice with ALF.

Role of β3‐adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis

Jonel Trebicka, Martin Hennenberg, Andrea Schulze Pröbsting, Wim Laleman, Sabine Klein, Michaela Granzow, Frederik Nevens, Johan Zaagsma, Jörg Heller, Tilman Sauerbruch – 20 November 2009 – Increased intrahepatic resistance and splanchnic blood flow cause portal hypertension in liver cirrhosis. Nonselective β‐adrenoceptor (β‐AR) antagonists have beneficial effects on hyperdynamic circulation and are in clinical use. In this context, the role of the β3‐AR is undefined. Here we investigated their expression and role in portal hypertension in patients and rats with liver cirrhosis.

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