CXC chemokine signaling in the liver: Impact on repair and regeneration

Heather L. Van Sweringen, Nozomu Sakai, Amit D. Tevar, Justin M. Burns, Michael J. Edwards, Alex B. Lentsch – 29 May 2011 – The process of liver repair and regeneration following hepatic injury is complex and relies on a temporally coordinated integration of several key signaling pathways. Pathways activated by members of the CXC family of chemokines play important roles in the mechanisms of liver repair and regeneration through their effects on hepatocytes. However, little is known about the signaling pathways used by CXC chemokine receptors in hepatocytes.

Compromising mitochondrial function with the antiretroviral drug efavirenz induces cell survival‐promoting autophagy

Nadezda Apostolova, Leysa J. Gomez‐Sucerquia, Anna Gortat, Ana Blas‐Garcia, Juan V. Esplugues – 29 May 2011 – Hepatotoxicity is a very common side effect associated with the pharmacological treatment of human immunodeficiency virus (HIV) infection and its pathogenesis is poorly understood. Efavirenz (EFV) is the most widely used nonnucleoside reverse transcriptase inhibitor administered for the control of HIV and some of its toxic effects in hepatic cells have been recently shown to display features of mitochondrial dysfunction.

Impact of viral amino acid substitutions and host interleukin‐28b polymorphism on replication and susceptibility to interferon of hepatitis C virus

Nobuhiko Hiraga, Hiromi Abe, Michio Imamura, Masataka Tsuge, Shoichi Takahashi, C. Nelson Hayes, Hidenori Ochi, Chise Tateno, Katsutoshi Yoshizato, Yusuke Nakamura, Naoyuki Kamatani, Kazuaki Chayama – 26 May 2011 – Amino acid (aa) substitutions of core 70 and 91 and in the NS5A (nonstructural protein 5A) interferon sensitivity determining region (ISDR) as well as genetic polymorphisms in the host interleukin‐28B (IL28B) locus affect the outcome of interferon (IFN)‐based therapies for patients with chronic hepatitis C.

c‐Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma

Hanning You, Wei Ding, Hien Dang, Yixing Jiang, C. Bart Rountree – 26 May 2011 – c‐Met, a high‐affinity receptor for hepatocyte growth factor (HGF), plays a critical role in cancer growth, invasion, and metastasis. Hepatocellular carcinoma (HCC) patients with an active HGF/c‐Met signaling pathway have a significantly worse prognosis. Although targeting the HGF/c‐Met pathway has been proposed for the treatment of multiple cancers, the effect of c‐Met inhibition in HCC remains unclear.

Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus

Varun Garg, Rolf van Heeswijk, Jee Eun Lee, Katia Alves, Priya Nadkarni, Xia Luo – 26 May 2011 – The hepatitis C virus protease inhibitor telaprevir is an inhibitor of the enzyme cytochrome P450 3A, responsible for the metabolism of both cyclosporine and tacrolimus. This Phase I, open‐label, nonrandomized, single‐sequence study assessed the effect of telaprevir coadministration on the pharmacokinetics of a single dose of either cyclosporine or tacrolimus in two separate panels of 10 healthy volunteers each.

Safety of liver transplantation with chagas disease–seropositive donors for seronegative recipients

Fernando Salvador, Oscar Len, Israel Molina, Elena Sulleiro, Silvia Sauleda, Itxarone Bilbao, Lluis Castells, Teresa Pont, Joan Gavaldà, Albert Pahissa – 26 May 2011 – The shortage of organs for transplantation has prompted the investigation of extended criteria donors, such as donors with transmissible infectious diseases. Here we report our recent experience with liver transplantation using organs from donors who were serologically positive for Chagas disease. We also provide a review of the literature and emphasize donor screening and preventive measures.

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