Bile acids inhibit interleukin‐6 signaling via gp130 receptor‐dependent and ‐independent pathways in rat liver

Dirk Graf, Caroline Kohlmann, Katrin Haselow, Thor Gehrmann, Johannes G. Bode, Dieter Häussinger – 20 October 2006 – Interleukin‐6 (IL‐6) is a major regulator of the acute phase reaction in the liver and is thought to mediate protective effects in response to hepatotoxins. In this study, the influence of bile acids on IL‐6 signal transduction was analyzed. It was shown that hydrophobic bile acids such as glycochenodeoxycholate (GCDC) inhibited IL‐6–induced tyrosine phosphorylation of signal transducer and activator of transcription (STAT) 3 in hepatocytes and in perfused rat liver.

Gilbert's disease and atazanavir: From phenotype to UDP‐glucuronosyltransferase haplotype

Tim O. Lankisch, Ulrike Moebius, Michael Wehmeier, Georg Behrens, Michael P. Manns, Reinhold E. Schmidt, Christian P. Strassburg – 20 October 2006 – Gilbert's disease leads to intermittent non‐hemolytic hyperbilirubinemia by a reduction of hepatic bilirubin glucuronidation associated with the presence of the UDP‐glucuronosyltransferase (UGT) 1A1*28 polymorphism. It is considered benign because it does not result in hepatocellular damage. However, pharmacogenetic analyses have linked UGT1A1*28 to drug toxicity and cancer predisposition.

The role of trans‐oesophageal echocardiography for perioperative cardiovascular monitoring during orthotopic liver transplantation

Andrew J. Burtenshaw, John L. Isaac – 20 October 2006 – Patients undergoing orthotopic liver transplantation frequently display considerable physiological changes during the procedure as a result of both the disease process and the surgery. Anaesthesia is often challenging and relies upon advanced monitoring techniques to provide data pertinent to peri‐operative management. Traditionally the pulmonary artery flotation catheter has been regarded as the gold standard for cardiac output and right heart monitoring.

Gabapentin in patients with the pruritus of cholestasis: A double‐blind, randomized, placebo‐controlled trial

Nora V. Bergasa, Monnie McGee, Iona H. Ginsburg, Danielle Engler – 20 October 2006 – Pruritus is defined as the second order of nociception, the first being pain; thus, there is a rationale to study gabapentin, a drug that increases the threshold to experience nociception. The aim of this double‐blind, randomized, placebo‐controlled trial was to study the effect of gabapentin on the perception of pruritus and its behavioral manifestation, scratching, in cholestasis. The participants were 16 women with chronic liver disease and chronic pruritus.

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia

Cara L. Mack, Rebecca M. Tucker, Brandy R. Lu, Ronald J. Sokol, Andrew P. Fontenot, Yoshiyuki Ueno, Ronald G. Gill – 20 October 2006 – Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus‐induced, subsequent autoimmune‐mediated injury of bile ducts.

Aiming at minimal invasiveness as a therapeutic strategy for Budd‐Chiari syndrome

Aurélie Plessier, Annie Sibert, Yann Consigny, Antoine Hakime, Magaly Zappa, Marie‐Hélène Denninger, Bertrand Condat, Olivier Farges, Carine Chagneau, Victor de Ledinghen, Claire Francoz, Alain Sauvanet, Valérie Vilgrain, Jacques Belghiti, François Durand, Dominique Valla – 20 October 2006 – The 1‐year spontaneous mortality rate in patients with Budd‐Chiari syndrome (BCS) approaches 70%. No prospective assessment of indications and impact on survival of current therapeutic procedures has been performed.

Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C

Masao Honda, Taro Yamashita, Teruyuki Ueda, Hajime Takatori, Ryuhei Nishino, Shuichi Kaneko – 20 October 2006 – The clinical manifestations of chronic hepatitis B (CH‐B) and chronic hepatitis C (CH‐C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH‐B or CH‐C; however, the signaling pathways underlying each condition have yet to be clarified.

Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice

Steve S. Choi, Jason K. Sicklick, Qi Ma, Liu Yang, Jiawen Huang, Yi Qi, Wei Chen, Yin‐Xiong Li, Pascal J. Goldschmidt‐Clermont, Anna Mae Diehl – 20 October 2006 – Rac, a small, GTP‐binding protein in the Rho family, regulates several cellular functions, including the activation of NADPH oxidase, a major intracellular producer of reactive oxygen species (ROS). Hepatic stellate cells (HSCs) isolated from mice that are genetically deficient in NADPH oxidase produce less ROS, and their activation during chronic liver injury is abrogated, resulting in decreased liver fibrosis.

Spatiotemporal expression of heme oxygenase‐1 detected by in vivo bioluminescence after hepatic ischemia in HO‐1/luc mice

Huawei Su, Gooitzen M. van Dam, Carlijn I. Buis, Dorien S. Visser, Jan Willem Hesselink, Theo A. Schuurs, Henri G.D. Leuvenink, Christopher H. Contag, Robert J. Porte – 20 October 2006 – Upregulation of heme oxygenase‐1 (HO‐1) has been proposed as a critical mechanism protecting against cellular stress during liver transplantation, providing a potential target for new therapeutic interventions. We investigated the feasibility of in vivo bioluminescence imaging (BLI) to noninvasively quantify the spatiotemporal expression of HO‐1 after warm hepatic ischemia in living animals.

Mediators of rat ischemic hepatic preconditioning after cold preservation identified by microarray analysis

Àurea Navarro‐Sabaté, Carmen Peralta, Maria Nieves Calvo, Anna Manzano, Marta Massip‐Salcedo, Joan Roselló‐Catafau, Ramon Bartrons – 20 October 2006 – Hepatic ischemia‐reperfusion injury associated with liver transplantation is an as yet unresolved problem in clinical practice. Preconditioning protects the liver against the deleterious effects of ischemia, although the mechanism underlying this preconditioning is still unclear.

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