Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice

Xiaodong Wang, Yongke Lu, Arthur I. Cederbaum – 15 July 2005 – Cytochrome P450 2E1 (CYP2E1) may be a central pathway in generating oxidative stress, reactive oxygen species, and causing hepatotoxic injury by alcohol and various hepatotoxins. This study evaluated the ability of CYP2E1 to potentiate or synergize the hepatotoxicity of Fas in vivo. C57BL/6 mice were injected intraperitoneally with pyrazole (Pyr) to induce CYP2E1. Then, 16‐hour fasted mice were administered agonistic Jo2 anti‐Fas antibody ip. Other mice were treated with Pyr or Jo2 alone.

Mesenteric Th1 polarization and monocyte TNF‐α production: First steps to systemic inflammation in rats with cirrhosis

Leticia Muñoz, Agustín Albillos, Mónica Nieto, Eduardo Reyes, Lourdes Lledó, Jorge Monserrat, Eva Sanz, Antonio de la Hera, Melchor Alvarez‐Mon – 15 July 2005 – A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF‐α) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis.

Corrections

Christophe Hézode, Françoise Roudot‐Thoraval, Son Nguyen, Pascale Grenard, Boris Julien, Elie‐Serge Zafrani, Jean‐Michel Pawlotsky, Daniel Dhumeaux, Sophie Lotersztajn, Ariane Mallat – 15 July 2005

rAAV‐mediated stable expression of heme oxygenase‐1 in stellate cells: A new approach to attenuate liver fibrosis in rats

Tung‐Yu Tsui, Chi‐Keung Lau, Jian Ma, Xiaobing Wu, Yan‐Qing Wang, Stefan Farkas, Ruian Xu, Hans J. Schlitt, Sheung‐Tat Fan – 15 July 2005 – Liver fibrosis is the consequence of activation of hepatic stellate cells mediated by persistent or recurrent liver injury, where oxidative stress or inflammatory response resulting from immune cells and cytokines are involved. Targeting of hepatic stellate cells could be an important strategy for the therapy of liver fibrosis.

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic

Dimitrios‐Petrou Bogdanos, Harold Baum, Manabu Okamoto, Paolo Montalto, Umesh C. Sharma, Eirini I. Rigopoulou, John Vlachogiannakos, Yun Ma, Andrew K. Burroughs, Diego Vergani – 15 July 2005 – The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC‐E2) antimitochondrial antibodies (AMAs). Anti–PDC‐E2 antibodies cross‐react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC‐E2212‐226 and hsp's is a cross‐reactive target.

Successful gene therapy of the Gunn rat by in vivo neonatal hepatic gene transfer using murine oncoretroviral vectors

Marta Bellodi‐Privato, Dominique Aubert, Virginie Pichard, Anne Myara, François Trivin, Nicolas Ferry – 15 July 2005 – Crigler‐Najjar type 1 disease (CN1) is a rare inherited metabolic disease characterized by complete absence of hepatic UDP‐glucuronosyl transferase (UGT1), resulting in high levels of unconjugated bilirubin. CN1 is an attractive candidate disease for gene therapy. Here we show that in vivo neonatal hepatocyte transduction using recombinant oncoretroviral vectors results in long‐term and complete phenotype correction in Gunn rats, a model for CN1.

Outcome and prognostic markers in severe drug‐induced liver disease

Einar Björnsson, Rolf Olsson – 15 July 2005 – The combination of high aminotransferases (hepatocellular injury) and jaundice has been reported to lead to a mortality rate of 10% to 50% for different drugs, a phenomenon known as “Hy's rule.” However, Hy's rule has never been validated, and limited data exist on predictors for outcome in hepatocellular and other forms of drug‐induced liver disease. All reports of suspected hepatic adverse drug reactions received by the Swedish Adverse Drug Reactions Advisory Committee (1970‐2004) were reviewed.

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