Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2

Toshinori Kamisako, Inka Leier, Yunhai Cui, Jörg König, Ulrike Buchholz, Johanna Hummel‐Eisenbeiss, Dietrich Keppler – 30 December 2003 – The secretion of bilirubin conjugates from hepatocytes into bile represents a decisive step in the prevention of hyperbilirubinemia.

Breakdown of tolerance to pyruvate dehydrogenase complex in experimental autoimmune cholangitis: A mouse model of primary biliary cirrhosis

David E. Jones, Jeremy M. Palmer, Stephen J. Yeaman, John A. Kirby, Margaret F. Bassendine – 30 December 2003 – The autoimmune liver disease primary biliary cirrhosis (PBC) is characterized by autoreactive responses to a highly conserved self‐antigen, pyruvate dehydrogenase complex (PDC). We recently reported the development of PBC‐like lesions in SJL mice sensitized with PDC and have named this model disease experimental autoimmune cholangitis (EAC). In the present study, the breakdown of tolerance to PDC has been investigated in animals sensitized for EAC.

Intracellular single‐chain antibody against hepatitis B virus core protein inhibits the replication of hepatitis B virus in cultured cells

Masato Yamamoto, Norio Hayashi, Tetsuo Takehara, Keiji Ueda, Eiji Mita, Tomohide Tatsumi, Yutaka Sasaki, Akinori Kasahara, Masatsugu Hori – 30 December 2003 – Hepatitis B virus (HBV) is one of the major causes of chronic liver diseases and hepatocellular carcinoma. In this study, we used a single chain antibody (sFv), which is a man‐made antibody with a strong affinity of immunoglobulin, to inhibit HBV replication.

Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species

Sherryll L. Michael, Neil R. Pumford, Philip R. Mayeux, Michael R. Niesman, Jack A. Hinson – 30 December 2003 – Hepatotoxic doses of acetaminophen to mice produce not only acetaminophen‐protein adducts in the centrilobular cells of the liver, but nitrotyrosine‐protein adducts in the same cells, the site of the necrosis. Nitration of tyrosine occurs with peroxynitrite, a species formed by reaction of nitric oxide (NO·) with superoxide (O2·−).

Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy

Manuel Tsiang, James F. Rooney, John J. Toole, Craig S. Gibbs – 30 December 2003 – In a recent phase II clinical study, 13 chronic hepatitis B–infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1‐log10 decrease in plasma hepatitis B virus (HBV)‐DNA levels. The decline of viral load during therapy displayed a biphasic kinetic profile that was modeled to determine the efficacy of inhibition of viral production, as well as kinetic constants for the clearance of free virus and the loss of infected cells.

Role of transforming growth factor β type II receptor in hepatic fibrosis: Studies of human chronic hepatitis C and experimental fibrosis in rats

Dominique Roulot, Ann‐Marie Sevcsik, Thierry Coste, A. Donny Strosberg, Stefano Marullo – 30 December 2003 – Transforming growth factor β (TGF‐β) is an antiproliferative and profibrogenic cytokine that signals through a receptor consisting of type I and type II (TβRII) components. We have examined changes in the expression of TβRII during liver injury, correlating this with the antiproliferative and profibrogenic effects of TGF‐β1 .

Bile acids modulate the interferon signalling pathway

Philippe Podevin, Olivier Rosmorduc, Filomena Conti, Yvon Calmus, Peter J. Meier, Raoul Poupon – 30 December 2003 – We have previously shown that cholestasis and bile acids inhibit 2′,5′ oligoadenylate synthetase (OAS) activity in the liver and in primary hepatocyte cultures. Here, we assessed the influence of bile acids on interferon (IFN) pathway activation in three hepatoma cell lines. In HepG2 cells, bile acids (100‐200 μmol/L) inhibited IFN‐induced 2′,5′ OAS activity to an extent depending on their surface activity index.

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