Sequential versus concomitant administration of ribavirin and interferon alfa‐n3 in patients with chronic hepatitis C not responding to interferon alone: Results of a randomized, controlled trial

Raffaello Sostegni, Valeria Ghisetti, Fabrizia Pittaluga, Giovanna Marchiaro, Giuseppe Rocca, Elisabetta Borghesio, Mario Rizzetto, Giorgio Saracco – 30 December 2003 – We conducted a three‐arm, randomized trial in 96 patients with chronic hepatitis C who did not respond to interferon alfa to compare treatments.

Cytokeratin expression is reduced in glycogenotic clear hepatocytes but increased in ground‐glass cells in chronic human and woodchuck hepadnaviral infection

Qin Su, Heide Zerban, Gerd Otto, Peter Bannasch – 30 December 2003 – Hepatocytes of normal adult liver express cytokeratins (CKs) 8/18, but bile duct cells additionally contain CK7/19. We have previously demonstrated the frequent occurrence of foci of altered hepatocytes in association with hepatic tumors in humans and provided evidence for a preneoplastic nature of the focal lesions. In this study, we investigated the CK expression in both the preneoplastic lesions and extrafocal parenchyma.

Endothelin 1 aggravates acute liver injury in perfused livers of rats after treatment with d ‐galactosamine

Masaru Iwai, Tadashige Yamauchi, Takashi Shimazu – 30 December 2003 – The effects of endothelin 1 (ET‐1) on hemodynamics and acute liver damage were studied using perfused livers of rats treated with d‐galactosamine. In control liver perfused in situ with constant pressure, infusion of ET‐1 into the portal vein at a concentration of 0.1 nmol/L decreased the flow rate without a significant leakage of lactate dehydrogenase (LDH) or aspartate transaminase (AST) into the effluent.

Beneficial hemodynamic effects of bosentan, a mixed ETA and ETB receptor antagonist, in portal hypertensive rats

Philippe Sogni, Richard Moreau, Alexandra Gomola, Adrian Gadano, Stephane Cailmail, Yvon Calmus, Martine Clozel, Didier Lebrec – 30 December 2003 – In patients with cirrhosis, the plasma level of endothelin, a potent vasoconstrictor peptide, is elevated, and endothelin plays a role in increased intrahepatic vascular resistance. Thus, the aim of this study was to evaluate the hemodynamic effects of bosentan, a mixed ETA and ETB endothelin receptor antagonist in three models of portal hypertension.

Neuropeptide Y stimulates bile secretion via Y1 receptor in the left dorsal vagal complex in rats

Masashi Yoneda, Kimihide Nakamura, Shiro Yokohama, Keisuke Tamori, Yoichi Sato, Kazunobu Aso, Masaru Aoshima, Toru Kono, Isao Makino – 30 December 2003 – Neuropeptide Y (NPY) injected into the cerebrospinal fluid and the left dorsal vagal complex enhances bile acid–independent and bicarbonate‐dependent bile secretion through vagal muscarinic pathways in animal models. NPY binds to and activates six different receptor subtypes, and NPY Y1 and Y2 receptors are distributed in the dorsal vagal complex.

Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography

Susanne Keiding, Søren B. Hansen, Henrik H Rasmussen, Antony Gee, Aksel Kruse, Klaus Roelsgaard, Ulrik Tage‐Jensen, Jens Frederik Dahlerup – 30 December 2003 – Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron‐emitting radiolabeled tracers.

Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia

Bettina Grasl‐Kraupp, Walter Rossmanith, Branislav Ruttkay‐Nedecky, Leonhard Müllauer, Bettina Kammerer, Wilfried Bursch, Rolf Schulte‐Hermann – 30 December 2003 – Transforming growth factor β1 (TGF‐β1) has been implicated as inhibitor of cell proliferation and a potent inducer of apoptosis in vitro and in vivo after the administration of high doses. To assess the role of endogenous TGF‐β1, we quantitated the cytokine and its receptors in rat liver during regenerative and hyperplastic growth, regression by apoptosis, and in hepatocellular carcinoma (HCC).

Retinoic acid treatment induces apoptosis or expression of a more differentiated phenotype on different fractions of cultured fetal rat hepatocytes

Laura Falasca, Anna Favale, Giampiero Gualandi, Gennaro Maietta, Laura Conti Devirgiliis – 30 December 2003 – The present study reports the effects of retinoic acid (RA) on cultured fetal rat hepatocytes. We show that RA treatment induces both differentiation and apoptosis. Hepatocytes cultured for 48 hours in the presence of 5 μmol/L RA form junctional complexes in the areas of contact between neighboring cells and develop bile canaliculi, typical features of mature and well‐differentiated cells.

Dissection of human humoral immune response against hepatitis C virus E2 glycoprotein by repertoire cloning and generation of recombinant fab fragments

Roberto Burioni, Paola Plaisant, Aldo Manzin, Domenico Rosa, Valeria Delli Carri, Francesca Bugli, Laura Solforosi, Sergio Abrignani, Pietro E. Varaldo, Giovanni Fadda, Massimo Clementi – 30 December 2003 – Demonstration of antibodies inhibiting key viral functions is the basis for the design of an effective vaccine. Dissection of the human antibody response by repertoire cloning may be a powerful means to address this issue. In this study, a panel of human monoclonal recombinant Fab fragments specific for hepatitis C virus (HCV) E2 envelope protein was generated.

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