Tauroursodeoxycholic acid protects rat hepatocytes from bile acid‐induced apoptosis via activation of survival pathways

Marieke H. Schoemaker, Laura Conde de la Rosa, Manon Buist‐Homan, Titia E. Vrenken, Rick Havinga, Klaas Poelstra, Hidde J. Haisma, Peter L. M. Jansen, Han Moshage – 27 May 2004 – Ursodeoxycholic acid (UDCA) is used in the treatment of cholestatic liver diseases, but its mechanism of action is not yet well defined. The aim of this study was to explore the protective mechanisms of the taurine‐conjugate of UDCA (tauroursodeoxycholic acid [TUDCA]) against glycochenodeoxycholic acid (GCDCA)‐induced apoptosis in primary cultures of rat hepatocytes.

The role of endothelin‐1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat

Yiqun Ling, Junlan Zhang, Bao Luo, Daisheng Song, Lichuan Liu, Liping Tang, Cecil R. Stockard, William E. Grizzle, David D. Ku, Michael B. Fallon – 27 May 2004 – Endothelin‐1 (ET‐1) stimulation of endothelial nitric oxide synthase (eNOS) via pulmonary endothelial endothelin B (ETB) receptors and pulmonary intravascular macrophage accumulation with expression of inducible nitric oxide synthase (iNOS) and heme oxygenase‐1 (HO‐1) are implicated in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL).

Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma

Christoph Jüngst, Bin Cheng, Ralph Gehrke, Volker Schmitz, Hans Dieter Nischalke, Jan Ramakers, Peter Schramel, Peter Schirmacher, Tilman Sauerbruch, Wolfgang Helmut Caselmann – 27 May 2004 – Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8‐oxo‐2′‐deoxyguanosine (8‐oxo‐dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C → T:A transversions.

Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees

Marian E. Major, Harel Dahari, Kathleen Mihalik, Montserrat Puig, Charles M. Rice, Avidan U. Neumann, Stephen M. Feinstone – 27 May 2004 – To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion.

Susceptibility of murine periportal hepatocytes to hypoxia‐reoxygenation: Role for NO and Kupffer cell–derived oxidants

Hisashi Taniai, Ian N. Hines, Sulaiman Bharwani, Ronald E. Maloney, Yuji Nimura, Bifeng Gao, Sonia C. Flores, Joe M. McCord, Matthew B. Grisham, Tak Yee Aw – 27 May 2004 – Ischemia/reperfusion (I/R) is an important problem in liver resection and transplantation that is associated with hepatocellular dysfunction and injury. This study was designed to investigate whether a difference in hepatocyte susceptibility occurs in the periportal (PP) and/or perivenous (PV) zones in response to hypoxia/reoxygenation (H/R), and to delineate the mechanisms underlying this susceptibility.

Plasticity in the adult rat pancreas: Transdifferentiation of exocrine to hepatocyte‐like cells in primary culture

Jessy Lardon, Saskia De Breuck, Ilse Rooman, Leentje Van Lommel, Mogens Kruhøffer, Torben Orntoft, Frans Schuit, Luc Bouwens – 27 May 2004 – Under certain experimental conditions, hepatocytes can arise in the pancreas. It has been suggested that the pancreas retains a source of hepatocyte progenitor cells. However, such cells have not been yet identified in the adult pancreas. We describe here the transdifferentiation of primary rat pancreatic exocrine cells into hepatocyte‐like cells during 5 days of tissue culture in the presence of dexamethasone (DX).

Prediction of liver fibrosis in patients with features of the metabolic syndrome regardless of alcohol consumption

Fabrice Lainé, Claude Bendavid, Romain Moirand, Sabrina Tessier, Michèle Perrin, Anne Guillygomarc'h, Dominique Guyader, Emmanuelle Calon, Alain Renault, Pierre Brissot, Bruno Turlin, Yves Deugnier – 27 May 2004 – The aim of this study was to determine noninvasive predictive factors of significant liver fibrosis in patients with increased serum aminotransferases associated with features of metabolic syndrome (abdominal obesity, systemic hypertension, fasting hyperglycemia, and dyslipidemia). One hundred seventy‐three patients were prospectively examined, regardless of alcohol consumption.

Improvement of rat liver graft quality by pifithrin‐α–mediated inhibition of hepatocyte necrapoptosis

Amr M. El‐Gibaly, Claudia Scheuer, Michael D. Menger, Brigitte Vollmar – 27 May 2004 – Early graft dysfunction due to ischemia reperfusion injury remains a major clinical challenge in liver transplantation. Because apoptosis may contribute to graft dysfunction, we studied whether transient inhibition of p53 is capable of improving graft quality by reducing apoptotic cell death. Rat livers were harvested and stored for 24 hours or 48 hours in a 4°C solution containing either pifithrin‐α (PFT‐α), a specific p53‐inhibitor, or the vehicle dimethyl‐sulfoxide.

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