A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high‐dose daily interferon alfa plus ribavirin and intravenous twice‐daily treatment with interferon beta

Yasuhiro Asahina, Namiki Izumi, Masakatsu Uchihara, Osamu Noguchi, Kaoru Tsuchiya, Kosei Hamano, Nobuhiko Kanazawa, Jun Itakura, Shozo Miyake, Takahiro Sakai – 30 December 2003 – Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of antiviral mechanisms by analyzing HCV dynamics in PBMC.

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas

Nathalie Théret, Orlando Musso, Bruno Turlin, Dominique Lotrian, Paulette Bioulac‐Sage, Jean‐Pierre Campion, Karim Boudjéma, Bruno Clément – 30 December 2003 – Matrix metalloproteinase‐2 (MMP2) is a key enzyme in the process of extracellular matrix remodeling involved in tumor invasion and metastasis. The activation of MMP2 involves interplay with the membrane type‐matrix metalloproteinase‐1 (MT1‐MMP) and the tissue inhibitor of metalloproteinase‐2 (TIMP2). In vitro, activated hepatic stellate cells are a main source of MMP2 and collagen I induces MMP2 activation.

Initial amplification of duck hepatitis B virus covalently closed circular DNA after in vitro infection of embryonic duck hepatocytes is increased by cell cycle progression

Christelle Borel, Olivier Schorr, Isabelle Durand, Fabien Zoulim, Alan Kay, Christian Trepo, Olivier Hantz – 30 December 2003 – The relationship between the cell cycle and early amplification of duck hepatitis B virus covalently closed circular (CCC) DNA was studied after in vitro infection of fetal hepatocytes. We first showed that embryonic hepatocytes proliferated for at least 6 days after plating and that complete viral replication including CCC DNA amplification occurred in these proliferating cells.

A randomized 4‐arm multicenter study of interferon alfa–2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone

Giorgio Saracco, Alessia Ciancio, Alda Olivero, Antonina Smedile, Luigi Roffi, Guido Croce, Cosimo Colletta, Giuseppe Cariti, Massimo Andreoni, Alberto Biglino, Guido Calleri, Giovanni Maggi, Gian Franco Tappero, Pier Giulio Orsi, Natalia Terreni, Antonio Macor, Angelo Di Napoli, Enrico Rinaldi, Giovannino Ciccone, Mario Rizzetto – 30 December 2003 – To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4‐arm randomized trial on patients with chronic hepatitis C not respondi

Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia

Rajiv Jalan, Steven W. M. Olde Damink, Nicolaas E. P. Deutz, Peter C. Hayes, Alistair Lee – 30 December 2003 – In patients with acute liver failure (ALF) and uncontrolled intracranial hypertension, moderate hypothermia (32°C) reduces intracranial pressure (ICP) and cerebral blood flow (CBF), and can be used as a bridge to liver transplantation. The purpose of this study was to test the hypothesis that moderate hypothermia reduced ICP by restoring CBF autoregulation. Nine patients with uncontrolled intracranial hypertension and ALF who fulfilled the criteria for poor prognosis were studied.

Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: Therapeutic implications

Anand Mehta, Sandra Carrouée, Bertha Conyers, Robert Jordan, Terry Butters, Raymond A. Dwek, Timothy M. Block – 30 December 2003 – Previously we have shown that the imino sugar inhibitor of N‐linked glycan processing, N‐nonyl‐deoxynojirimycin (N‐nonyl‐DNJ), had antiviral activity in the woodchuck model of chronic hepatitis B virus (HBV) infection. In studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit HBV secretion without inhibiting N‐linked glycoprocessing.

Prolonged, but not acute, glutathione depletion promotes Fas‐mediated mitochondrial permeability transition and apoptosis in mice

Delphine Haouzi, Mounia Lekehal, Marina Tinel, Nathalie Vadrot, Laure Caussanel, Philippe Lettéron, Alain Moreau, Gérard Feldmann, Daniel Fau, Dominique Pessayre – 30 December 2003 – Glutathione depletion either decreased or increased death‐receptor–mediated apoptosis in previous studies. Comparison of the durations of glutathione depletion before death‐receptor stimulation in these studies might suggest a different effect of prolonged versus acute thiol depletion.

Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma

Josep M. Llovet, Ramon Vilana, Concepció Brú, Lluís Bianchi, Joan Manuel Salmeron, Loreto Boix, Sergi Ganau, Margarita Sala, Mario Pagès, Carmen Ayuso, Manel Solé, Joan Rodés, Jordi Bruix – 30 December 2003 – Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used as adjuvant therapy before liver transplantation. This phase II study assesses the treatment‐related complications and response rate of RF for the treatment of single HCC ≤5 cm.

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