Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene

José E. Manautou, Dirk R. de Waart, Cindy Kunne, Noam Zelcer, Michael Goedken, Piet Borst, Ronald Oude Elferink – 25 October 2005 – MRP3 is an ABC transporter localized in the basolateral membrane of epithelial cells such as hepatocytes and enterocytes. In this study, the role of Mrp3 in drug disposition was investigated. Because Mrp3 preferentially transports glucuronide conjugates, we investigated the in vivo disposition of acetaminophen (APAP) and its metabolites. Mrp3+/+ and Mrp3−/− knockout mice received APAP (150 mg/kg), and bile was collected.

Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma

Meta W. Djojosubroto, Allison C. Chin, Ning Go, Sonja Schaetzlein, Michael P. Manns, Sergei Gryaznov, Calvin B. Harley, K. Lenhard Rudolph – 25 October 2005 – Most cancer cells have an immortal growth capacity as a consequence of telomerase reactivation. Inhibition of this enzyme leads to increased telomere dysfunction, which limits the proliferative capacity of tumor cells; thus, telomerase inhibition represents a potentially safe and universal target for cancer treatment.

Interferon alfa‐2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

Regino P. González‐Peralta, Deirdre A. Kelly, Barbara Haber, Jean Molleston, Karen F. Murray, Maureen M. Jonas, Mark Shelton, Giorgina Mieli‐Vergani, Yoav Lurie, Steven Martin, Thomas Lang, Andrew Baczkowski, Michael Geffner, Samir Gupta, Mark Laughlin, for the International Pediatric Hepatitis C Therapy Group – 25 October 2005 – Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa‐2b and ribavirin in children with chronic HCV.

Mannose‐binding lectin in chronic hepatitis B virus infection

Wai Po Chong, Yuk Fai To, Wai Kee Ip, Man Fung Yuen, Tung Ping Poon, Wilfred H.S. Wong, Ching Lung Lai, Yu Lung Lau – 25 October 2005 – Mannose binding lectin (MBL) is a pattern‐recognition molecule of the innate immune system. The roles of MBL and its gene (mbl2) polymorphisms, −221X/Y and codon 54A/B, in hepatitis B virus (HBV) infection were investigated in this study.

Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview‐based study of 1032 patients

M. Eric Gershwin, Carlo Selmi, Howard J. Worman, Ellen B. Gold, Mitchell Watnik, Jessica Utts, Keith D. Lindor, Marshall M. Kaplan, John M. Vierling, USA PBC Epidemiology Group – 25 October 2005 – Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC.

Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients

Erwin Geuken, Dorien S. Visser, Henri G.D. Leuvenink, Koert P. de Jong, Paul M.J.G. Peeters, Maarten J.H. Slooff, Folkert Kuipers, Robert J. Porte – 25 October 2005 – The adenosine triphosphate (ATP)‐binding cassette (ABC)‐transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content.

Lamivudine plus interleukin‐12 combination therapy in chronic hepatitis B: Antiviral and immunological activity

Eirini I. Rigopoulou, Deepak Suri, Shilpa Chokshi, Ivana Mullerova, Steven Rice, Richard S. Tedder, Roger Williams, Nikolai V. Naoumov – 25 October 2005 – Interleukin‐12 (IL‐12) is an immunomodulatory cytokine that promotes cellular immunity. Pre‐clinical data suggest that IL‐12 inhibits hepatitis B virus (HBV) replication by stimulating interferon‐gamma (IFN‐γ) production.

Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease

Giovanni Musso, Roberto Gambino, Marilena Durazzo, Giampaolo Biroli, Monica Carello, Emanuela Fagà, Giovanni Pacini, Franco De Michieli, Laura Rabbione, Alberto Premoli, Maurizio Cassader, Gianfranco Pagano – 25 October 2005 – Circulating levels of four adipokines (adiponectin, TNF‐α, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non‐obese, non‐diabetic patients with biopsy‐proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology.

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