Subliminal Fas stimulation increases the hepatotoxicity of acetaminophen and bromobenzene in mice

Marina Tinel, Alain Berson, Nathalie Vadrot, Véronique Descatoire, Alain Grodet, Gérard Feldmann, Jean Paul Thénot, Dominique Pessayre – 27 February 2004 – The hepatotoxicity of several drugs is increased by mild viral infections. During such infections, death receptor ligands are expressed at low levels, and most parenchymal cells survive. We tested the hypothesis that subliminal death receptor stimulation may aggravate the hepatotoxicity of drugs, which are transformed by cytochrome P‐450 cytochrome P‐450 into glutathione‐depleting reactive metabolites.

TNF α‐induced ras activation due to ethanol promotes hepatocyte proliferation independently of liver injury in the mouse

Fuyumi Isayama, Matthias Froh, Ming Yin, Lars O. Conzelmann, Richard J. Milton, Stephen E. McKim, Michael D. Wheeler – 27 February 2004 – Tumor necrosis factor α (TNFα) has been shown to be both proapoptotic and mitogenic for hepatocytes and necessary for alcohol‐induced liver injury. Ras, a known proto‐oncogene, is very important in the regulation of cellular responses to TNFα. Therefore, the purpose of this study was to investigate the role of Ras in alcohol‐induced pathogenesis. Male C57Bl/6 mice were fed ethanol or high‐fat control diet via intragastric cannulation for 4 weeks.

Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti‐inflammatory cytokine expression in mice

Dan Takeuchi, Hiroyuki Yoshidome, Atsushi Kato, Hiroshi Ito, Fumio Kimura, Hiroaki Shimizu, Masayuki Ohtsuka, Yasuhiro Morita, Masaru Miyazaki – 27 February 2004 – Hepatic ischemia/reperfusion injury is a clinically important problem. While the mechanisms of the initial event and subsequent neutrophil‐dependent injury are somewhat understood, little is known about the regulation of endogenous hepatoprotective effects on this injury. Interleukin 12 (IL‐12) plays a role in the induction of this injury, but involvement of interleukin 18 (IL‐18) has not been clarified.

Minimal hepatic encephalopathy impairs fitness to drive

Christian Wein, Horst Koch, Birthe Popp, Gerd Oehler, Peter Schauder – 27 February 2004 – It has been suggested that the ability to drive a car is impaired in patients with cirrhosis of the liver and minimal hepatic encephalopathy (MHE). However, the only study using an on‐road driving test did not reveal such an impairment. In a prospective controlled study, we evaluated patients with cirrhosis of the liver for MHE and the ability to drive a car. MHE was diagnosed using three psychometric tests: Number Connection Test Part A, Digit Symbol Test, and a Complex Choice Reaction Test.

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