S‐adenosylhomocysteine sensitizes to TNF‐α hepatotoxicity in mice and liver cells: A possible etiological factor in alcoholic liver disease

Zhenyuan Song, Zhanxiang Zhou, Silvia Uriarte, Lipeng Wang, Y. James Kang, Theresa Chen, Shirish Barve, Craig J. McClain – 7 March 2007 – In alcoholic liver disease, tumor necrosis factor‐α (TNFα) is a critical effector molecule, and abnormal methionine metabolism is a fundamental acquired metabolic abnormality. Although hepatocytes are resistant to TNFα‐induced killing under normal circumstances, previous studies have shown that primary hepatocytes from rats chronically fed alcohol have increased TNFα cytotoxicity.

Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOP

Giovanna M. Ledda‐Columbano, Monica Pibiri, Costanza Cossu, Francesca Molotzu, Joseph Locker, Amedeo Columbano – 7 March 2007 – It has been shown that the magnitude of DNA synthesis and the time at which maximal DNA synthesis occurs after two‐thirds partial hepatectomy (PH) is greatly reduced in the liver of aged rodents compared to young animals. This reduction could represent an intrinsic defect in proliferation or a more specialized change in the response to PH.

Ex Vivo transduced liver progenitor cells as a platform for gene therapy in mice

Sihong Song, Rafal P. Witek, Yuanqing Lu, Young‐Kook Choi, Donghang Zheng, Marda Jorgensen, Chengwen Li, Terence R. Flotte, Byron E. Petersen – 7 March 2007 – Allogeneic stem cell‐based transplants may be limited by allograft rejection, as is seen with conventional organ transplantation. One way to avert such a response is to use autologous stem cells, but that may carry the risk of recurrence of the original disease, particularly in the context of a genetic defect.

Identification of a Ribavirin‐resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy

Kung‐Chia Young, Karen L. Lindsay, Ki‐Jeong Lee, Wen‐Chun Liu, Jian‐Wen He, Susan L. Milstein, Michael M. C. Lai – 7 March 2007 – Ribavirin (RBV), a guanosine analogue, has been suggested to exert an antiviral action against hepatitis C virus (HCV) by causing lethal mutations and suppressing RNA polymerase in vitro, but the mechanism of its clinical therapeutic effects is currently unknown.

Long‐term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti‐inflammatory effect

David R. Nelson, Zhengkun Tu, Consuelo Soldevila‐Pico, Manal Abdelmalek, Haizhen Zhu, Yi Ling Xu, Roniel Cabrera, Chen Liu, Gary L. Davis – 7 March 2007 – An imbalance in Th1 and Th2 cytokine production is implicated in disease progression of HCV. Our aim was to determine the effect of IL‐10 administration in patients with HCV‐related liver disease. Thirty patients with advanced fibrosis who had failed antiviral therapy were enrolled in a 12‐month treatment regimen with SQ IL‐10 given daily or thrice weekly. Liver biopsies were performed before and after therapy.

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