Therapy of hepatitis C: Other options

H L Bonkovsky – 30 December 2003 – Because current standard therapy of chronic hepatitis C with α interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to α interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virological improvement.

Cytotoxic effect of 7α‐hydroxy‐4‐cholesten‐3‐one on HepG2 cells: Hypothetical role of acetaldehyde‐modified Δ4‐3‐ketosteroid‐5β‐reductase (the 37‐kd‐liver protein) in the pathogenesis of alcoholic liver injury in the rat

Renee C. Lin, Michael J. Fillenwarth, Xiangnan Du – 30 December 2003 – We recently identified ▵4‐3‐ketosteroid‐5β‐reductase as the 37 kd liver protein which is highly susceptible to acetaldehyde modification in rats continuously fed alcohol. The 5β‐reductase is a key enzyme involved in bile acid synthesis. We report here that the ability to degrade 7α‐hydroxy‐4‐cholesten‐3‐one (HCO) was lower in the liver cytosol of alcohol‐fed rats than in control animals, suggesting an inhibition of the 5β‐reductase enzyme activity by acetaldehyde modification.

Effects of l‐arginine on the systemic, mesenteric, and Hepatic circulation in patients with cirrhosis

Shigeru Kakumitsu, Hiroshi Shijo, Masanori Yokoyama, Tetsuhiro Kim, Nobuo Akiyoshi, Kazuhiro Ota, Katsuhiko Kubara, Makoto Okumura, Kazuhide Inoue – 30 December 2003 – Nitric oxide (NO) is known to play an important role in modulating both the hepatic and mesenteric circulation under physiological and pathological conditions. We investigated how l‐arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirrhosis. The study design was a single‐blind controlled study.

Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol‐induced cholestasis in the rat

Nynke R. Koopen, Henk Wolters, Rick Havinga, Roel J. Vonk, Peter L. Jansen, Michael Müller, Folkert Kuipers – 30 December 2003 – To test the hypothesis that impaired activity of the bile canalicular organic anion transporting system mrp2 (cmoat) is a key event in the etiology of 17α‐ethinylestradiol (EE)‐induced intrahepatic cholestasis in rats, EE (5 mg/kg subcutaneously daily) was administered to male normal Wistar (NW) and mrp2‐deficient Groningen Yellow/Transport‐deficient Wistar (GY/TR−) rats.

Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: The influence of virus C infection

Maria Jose Moran, Antonio Fontanellas, Eric Brudieux, Isabelle Hombrados, Victor de Ledinghen, Patrice Couzigou, Hubert de Verneuil, Rafael Enriquez De Salamanca – 30 December 2003 – Porphyria cutanea tarda (PCT) is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO‐D). This deficiency causes overproduction, hepatic deposition, and increased excretion of uroporphyrin. Iron overload and hepatic viral infections are considered aggravating factors of the disease.

Pancreastatin receptor is coupled to a guanosine triphosphate–binding protein of the Gg/11α family in rat liver membranes

José Santos‐Álvarez, Carmen González‐Yanes, Víctor Sánchez‐Margalet – 30 December 2003 – Pancreastatin (PST), a recently discovered regulatory peptide derived from chromogranin A, has been shown to have a glycogenolytic effect in the hepatocyte that is mediated by increasing intracellular calcium. Our previous studies on pancreastatin signaling suggested that PST receptor is coupled to some G proteins in the plasma membrane of the hepatocyte. The nature of this interaction was investigated using antisera against Gq/11α by different approaches.

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