Endothelin‐1 modulates intrahepatic resistance in a rat model of noncirrhotic portal hypertension

Patrick S. Kamath, Gertrude M. Tyce, Virginia M. Miller, Brooks S. Edwards, Duane K. Rorie – 30 December 2003 – Factors that increase resistance to blood flow through the hepatic sinusoids when portal hypertension occurs in the absence of significant hepatic fibrosis are not completely understood. Experiments were designed to test the hypothesis that endothelin‐1 (ET‐1) is one of the humoral factors that increases sinusoidal vascular resistance in a bile duct– ligated noncirrhotic portal hypertensive (BDL) rat.

MMP2 activation by collagen I and concanavalin A in cultured human hepatic stellate cells

Nathalie Théret, Kaisa Lehti, Orlando Musso, Bruno Clément – 30 December 2003 – Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix components. In fibrotic livers, there is a markedly increased activity of matrix metalloproteinase 2 (MMP2), a major enzyme involved in extracellular matrix remodeling. We have previously shown that hepatic stellate cells secrete latent MMP2 and that MMP2 activation occurs in coculture of hepatic stellate cells and hepatocytes concomitantly with matrix deposition.

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

Michael J. Krowka, Robert P. Frantz, Michael D. McGoon, Cathy Severson, David J. Plevak, Russell H. Wiesner – 30 December 2003 – Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as “portopulmonary hypertension.” Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension.

Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes

Ran Oren, Mariana D. Dabeva, Anthony N. Karnezis, Petko M. Petkov, Richard Rosencrantz, Jaswinder P. Sandhu, Steven F. Moss, Shaobai Wang, Ethel Hurston, Ezio Laconi, Peter R. Holt, Swan N. Thung, Liang Zhu, David A. Shafritz – 30 December 2003 – Recently, we reported near‐complete repopulation of the rat liver by transplanted hepatocytes using retrorsine (RS), a pyrrolizidine alkaloid that alkylates cellular DNA and blocks proliferation of resident hepatocytes, followed by transplantation of normal hepatocytes in conjunction with two‐thirds partial hepatectomy (PH).

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

Abdelmajid Sabile, Gabriel Perlemuter, Fulvia Bono, Kyoko Kohara, France Demaugre, Michinori Kohara, Yoshiharu Matsuura, Tatsuo Miyamura, Christian Bréchot, Giovanna Barba – 30 December 2003 – Several lines of evidence suggest that hepatitis C virus (HCV) core protein may modulate cellular transduction signals and alter lipid metabolism. We have investigated the binding of HCV core protein to cellular proteins by combining 2 yeast hybrid, confocal, and surface plasmon resonance assays.

Chronic ethanol consumption causes alterations in the structural integrity of mitochondrial DNA in aged rats

Alan Cahill, Gabriel J. Stabley, Xiaolan Wang, Jan B. Hoek – 30 December 2003 – Chronic ethanol consumption adversely affects the respiratory activity of rat liver mitochondria. It causes increased cellular production of oxygen radical species and selectively decreases mitochondrial glutathione (GSH) levels. Here we show, using Southern hybridization techniques on total rat genomic DNA, that long‐term (11‐13 months) ethanol feeding, using the Lieber‐DeCarli diet, results in a 36% (P < .05; n = 4) decrease in hepatic mitochondrial DNA (mtDNA) levels when compared with paired controls.

Cost effectiveness of interferon α2b combined with ribavirin for the treatment of chronic hepatitis C

Zobair M. Younossi, Mendel E. Singer, John G. McHutchison, Kenneth M. Shermock – 30 December 2003 – Treatment of chronic hepatitis C with Interferon (IFN) α2b monotherapy results in 10% to 15% sustained virological response (SVR). Combining IFN with ribavirin increases this response. In this analysis, using the Markov model, 6 treatment strategies for chronic hepatitis C (previously untreated) were compared on the basis of incremental cost per additional quality‐adjusted life years ($/QALY).

Requirement for interleukin‐12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in mice

Alex B. Lentsch, Hiroyuki Yoshidome, Atsushi Kato, Roscoe L. Warner, William G. Cheadle, Peter A. Ward, Michael J. Edwards – 30 December 2003 – Hepatic ischemia and reperfusion causes neutrophil‐dependent liver injury. Although the mechanisms of ischemia/reperfusion‐induced liver neutrophil recruitment are somewhat understood, less is known regarding the early events that initiate the inflammatory injury. Using a murine model of partial hepatic ischemia and reperfusion, we evaluated the role of endogenous interleukin (IL)‐12 in this inflammatory response.

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