The resistance of P. acnes–primed interferon γ–deficient mice to low‐dose lipopolysaccharide‐induced acute liver injury

Yoshiaki Shimizu, Julie A. Margenthaler, Keith Landeros, Naoki Otomo, Gerard Doherty, M. Wayne Flye – 30 December 2003 – Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure. Although interferon γ (IFN‐γ) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response.

Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa‐2b plus ribavirin

Maria Buti, Francisco Sanchez‐Avila, Yoav Lurie, Carlos Stalgis, Auristela Valdés, Maria Martell, Rafael Esteban – 30 December 2003 – Pegylated interferon (peginterferon) alfa‐2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa‐2b and ribavirin in 55 patients.

Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications

Sheng‐Chieh Hsu, Wan‐Jr Syu, I‐Jane Sheen, Hui‐Ting Liu, King‐Song Jeng, Jaw‐Ching Wu – 30 December 2003 – The mechanisms that link genotypes of hepatitis D virus (HDV) with clinical outcomes have not yet been elucidated. Genotypic variations are unevenly distributed along the sequences of hepatitis delta antigens (HDAgs). Of these variations, the packaging signal at the C‐terminus has a divergence of 74% between genotypes I and II.

A20 protects mice from D‐galactosamine/lipopolysaccharide acute toxic lethal hepatitis

Maria B. Arvelo, Jeffrey T. Cooper, Christopher Longo, Soizic Daniel, Shane T. Grey, Jerome Mahiou, Eva Czismadia, Graziella Abu‐Jawdeh, Christiane Ferran – 30 December 2003 – Apoptosis of hepatocytes is a seminal feature of fulminant hepatic failure. We show that the anti‐apoptotic protein A20 is upregulated in hepatocytes by pro‐inflammatory stimuli and functions to protect from apoptosis and limit inflammation by inhibiting NF‐κB.

Inhibition of rat liver fibrogenesis through noradrenergic antagonism

Liliane Dubuisson, Alexis Desmoulière, Boris Decourt, Laetitia Evadé, Christiane Bedin, Liliane Boussarie, Laurence Barrier, Michel Vidaud, Jean Rosenbaum – 30 December 2003 – The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)‐induced liver fibrosis in rats. Two weeks of CCl4 induced a ∼5‐fold increase in the area of fibrosis as compared with controls.

Absence of nuclear factor κB inhibition by NSAIDs in hepatocytes

Nuria A. Callejas, Marta Casado, Lisardo Boscá, Paloma Martín‐Sanz – 30 December 2003 – Stimulation of fetal hepatocytes with proinflammatory cytokines and lipopolysaccharide promotes the expression of cyclooxygenase‐2 (COX‐2) and nitric oxide synthase‐2 (NOS‐2), whereas the hepatoma cell line HepG2 exhibits a behavior similar to that described for adult hepatocytes and only expresses NOS‐2.

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF‐α via the PI 3‐kinase–Akt signaling pathway

Hirofumi Kawanaka, Michael K. Jones, Imre L. Szabo, Dolgor Baatar, Rama Pai, Kouji Tsugawa, Keizo Sugimachi, I. James Sarfeh, Andrzej S. Tarnawski – 30 December 2003 – Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF‐α in this signaling remain unknown.

Reply

Michael Fuchs, Boris Ivandic, Oliver Mueller, Carmen Schalla, Juergen Scheibner, Petra Bartsch, Eduard F. Stange – 30 December 2003

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