Effect of intraduodenal bile salt on pancreaticobiliary responses to bombesin and to cholecystokinin in humans

Paul W. Thimister, Wim P. Hopman, Albert Tangerman, Gerd Rosenbusch, Hans L. Willems, Jan B. Jansen – 30 December 2003 – Bile salts modulate postprandial gallbladder emptying and pancreatic enzyme secretion, possibly by interfering with plasma cholecystokinin (CCK) responses. The regulatory role of bile salts in the absence of nutrients from the gut is poorly understood.

Vascular endothelial growth factor tightly regulates in vivo development of murine hepatocellular carcinoma cells

Hitoshi Yoshiji, Shigeki Kuriyama, Junichi Yoshii, Masaharu Yamazaki, Masaji Kikukawa, Hirohisa Tsujinoue, Toshiya Nakatani, Hiroshi Fukui – 30 December 2003 – Angiogenesis is essential for the development of a solid tumor, including hepatocellular carcinoma (HCC). HCC is a well‐known hypervascular tumor. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. Its role has not been clarified in vivo in HCC development.

Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats

Joël Fort, Frédéric Oberti, Christophe Pilette, Nary Veal, Yves Gallois, Olivier Douay, Marie Christine Rousselet, Jean Rosenbaum, Paul Calès – 30 December 2003 – The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 μg/kg twice daily, subcutaneously).

Augmented interleukin‐1β–induced depression of locomotor activity in cholestatic rats

Mark G. Swain, Paul Beck, Kevin Rioux, Tai Le – 30 December 2003 – “Sickness behaviors” such as lethargy, fatigue, and malaise occur commonly in patients with cholestatic liver diseases and contribute significantly to the morbidity associated with these diseases. However, the cause of these symptoms is unknown. Interleukin‐1β (IL‐1β) released within the brain has been implicated in the genesis of a number of “sickness behaviors,” including malaise and lethargy.

Mutations in NS5A region of hepatitis C virus genome correlate with presence of NS5A antibodies and response to interferon therapy for most common european hepatitis C virus genotypes

Lionel Frangeul, Pascale Cresta, Michele Perrin, Françoise Lunel, Pierre Opolon, Henri Agut, Jean‐Marie Huraux – 30 December 2003 – A part of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) amino acid sequence, designated as an interferon (IFN)‐sensitive determining region (ISDR), has been shown to be correlated with a response to IFN in Japanese patients. We have shown previously that the presence of NS5A antibodies (Abs) detected by the INNOLIA test (IL‐NS5A Ab) is also correlated with a response to IFN.

Mice deficient in the urea‐cycle enzyme, carbamoyl phosphate synthetase i, die during the early neonatal period from hyperammonemia

J. Paul Schofield, J. Paul Schofield, Timothy M. Cox, C. Thomas Caskey, Maki Wakamiya – 30 December 2003 – Ammonia liberated during amino acid catabolism in mammals is highly neurotoxic and is detoxified by the five enzymes of the urea cycle that are expressed within the liver. Inborn errors of each of the urea cycle enzymes occur in humans. Carbamoyl phosphate synthetase I (CPSase I; EC 6.3.4.16) is located within the inner mitochondrial matrix and catalyzes the initial rate‐limiting step of the urea cycle.

Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis

Takumi Kawaguchi, Shotaro Sakisaka, Michio Sata, Michio Mori, Kyuichi Tanikawa – 30 December 2003 – Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze‐fracture electron microscopy have produced limited information. Recently, several TJ‐associated proteins like ZO‐1 and 7H6 have been identified and characterized.

Hepatitis C virus RNA profiles in chronically infected individuals: Do they relate to disease activity?

Patrizia Pontisso, Giorgio Bellati, Maurizia Brunetto, Liliana Chemello, Guido Colloredo, Rosellina Di Stefano, Massimo Nicoletti, Maria Grazia Rumi, Maria Grazia Ruvoletto, Roberta Soffredini, Lilli Mario Valenza, Giuseppe Colucci – 30 December 2003 – Fluctuations of hepatitis C virus (HCV)‐RNA serum levels were monitored in a multicenter study in 76 chronic HCV carriers who had been followed longitudinally without receiving antiviral therapy to assess their relation with the course of liver disease activity.

Efficacy of lamivudine in patients with hepatitis B e antigen–negative/hepatitis B virus DNA–positive (precore mutant) chronic hepatitis befficacy of lamivudine in patients with hepatitis B e antigen–negative/hepatitis B virus DNA–positive (precore mutant

Nicolaos C. Tassopoulos, Riccardo Volpes, Giuseppe Pastore, Jenny Heathcote, Maria Buti, Robert D. Goldin, Sasha Hawley, Judy Barber, Lynn Condreay, D. Fraser Gray – 30 December 2003 – This placebo controlled, double‐blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)‐negative/hepatitis B virus (HBV) DNA–positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26.

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