CYP2E1‐mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells

Natalia Nieto, Scott L. Friedman, Patricia Greenwel, Arthur I. Cederbaum – 30 December 2003 – Hepatic stellate cells (HSCs) are a major source of extracellular matrix, which, during fibrogenesis, undergo a process of “activation” characterized by increased proliferation and collagen synthesis. Oxidative stress can stimulate HSC proliferation and collagen synthesisin vitro. Cytochrome P4502E1 (CYP2E1) is an effective producer of reactive oxygen species.

Extracellular signal‐regulated kinase activation differentially regulates platelet‐derived growth factor's actions in hepatic stellate cells, and is induced by In Vivo liver injury in the rat

Fabio Marra, Maria Cristina Arrighi, Marilena Fazi, Alessandra Caligiuri, Massimo Pinzani, Roberto G. Romanelli, Eva Efsen, Giacomo Laffi, Paolo Gentilini – 30 December 2003 – Upon liver injury, hepatic stellate cells (HSC) show increased proliferation, motility, and extracellular matrix (ECM) production. The extracellular signal‐regulated kinases (ERK) control different functions in a cell‐specific manner. In this study, we evaluated the role of ERK activation in cultured HSC stimulated with platelet‐derived growth factor (PDGF) and after induction of liver injuryin vivo.

Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection

Takeshi Murakami, Nobuyuki Enomoto, Masayuki Kurosaki, Namiki Izumi, Fumiaki Marumo, Chifumi Sato – 30 December 2003 – An association has been reported between mutations in the amino acid residues 2209‐2248 of the nonstructural protein 5A (NS5A) gene (interferon‐sensitivity determining region [ISDR]) and interferon efficacy in hepatitis C virus (HCV)‐1b infection. This relationship was analyzed in chronic HCV‐2 infection. Forty patients with HCV‐2a and 35 with HCV‐2b were treated with interferon alfa for 6 months with a total dose of 468 to 860 million units.

Clinical manifestations of gallstone disease: Evidence from the multicenter Italian study on cholelithiasis (MICOL)

Davide Festi, Sandra Sottili, Antonio Colecchia, Adolfo Attili, Giuseppe Mazzella, Enrico Roda, Ferdinando Romano, MICOL Research Group – 30 December 2003 – Despite the many efforts to delineate the clinical manifestations of gallbladder disease, the precise symptom complex associated with gallstones is still a matter of debate, and even the existence of gallstone‐specific symptoms has been questioned. We carried out a large population‐based cross‐sectional study (MICOL) to identify symptoms significantly related to gallstones.

Persistent activation of nuclear factor‐κB in cultured rat hepatic stellate cells involves the induction of potentially novel rel‐like factors and prolonged changes in the expression of IκB family proteins

Ahmed M. Elsharkawy, Matthew C. Wright, Ron T. Hay, Michael J. Arthur, Timothy Hughes, Matthias J. Bahr, Klaus Degitz, Derek A. Mann – 30 December 2003 – Rat hepatic stellate cells (HSC) cultured in serum‐containing medium underwent a rapid (3‐hour) classical induction of p50:p65 and p65:p65 nuclear factor‐κB (NF‐κB) dimers. Subsequent culturing was associated with prolonged expression of active p50:p65 and persistent induction of a high‐mobility NF‐κB DNA binding complex consisting of potentially novel Rel‐like protein(s).

Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta‐analysis

George V. Papatheodoridis, John Goulis, Gioacchino Leandro, David Patch, Andrew K. Burroughs – 30 December 2003 – Endoscopic treatment (ET) is frequently used to prevent variceal rebleeding but this still occurs in about 50% of patients. Recently, transjugular intrahepatic portosystemic shunt (TIPS) has been compared with ET in several trials. Using a meta‐analysis, we evaluated randomized trials comparing TIPS to ET assessing prevention of rebleeding, survival, and the effects on resource use and the quality of patients' lives.

Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B

Rong‐Nan Chien, Yun‐Fan Liaw, Mark Atkins – 30 December 2003 – In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti‐HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV‐DNA levels, and alanine transaminase (ALT) levels.

Inhibition of system A amino acid transport and hepatocyte proliferation following partial hepatectomy in the rat

Thomas L. Freeman, Hao Q. Ngo, Mark E. Mailliard – 30 December 2003 – System A, the sodium‐dependent neutral amino acid transport activity, has a 3‐fold increase in its initial uptake velocity into hepatocytes following partial hepatectomy (PH) in the rat. The purpose of this study was to examine the effect of inhibition of System A–mediated amino acid transport on hepatocyte proliferation and liver regeneration. We describe thein vivocompetitive inhibition of System A activity following PH by the nonmetabolizable, System A–specific substrate, α‐(methylamino)isobutyric acid (MeAIB).

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