Defective endothelial nitric oxide synthase signaling is mediated by rho‐kinase activation in rats with secondary biliary cirrhosis

Go Anegawa, Hirofumi Kawanaka, Daisuke Yoshida, Kozo Konishi, Shohei Yamaguchi, Nao Kinjo, Akinobu Taketomi, Makoto Hashizume, Hiroaki Shimokawa, Yoshihiko Maehara – 26 February 2008 – In liver cirrhosis, down‐regulation of endothelial nitric oxide synthase (eNOS) has been implicated as a cause of increased intrahepatic resistance. We investigated whether Rho‐kinase activation is one of the molecular mechanisms involved in defective eNOS signaling in secondary biliary cirrhosis. Liver cirrhosis was induced by bile duct ligation (BDL).

Comprehensive and quantitative proteome profiling of the mouse liver and plasma

Keane K. Y. Lai, Deepak Kolippakkam, Laura Beretta – 26 February 2008 – We report a comprehensive and quantitative analysis of the mouse liver and plasma proteomes. The method used is based on extensive fractionation of intact proteins, further separation of proteins based on their abundance and size, and high‐accuracy mass spectrometry. This analysis reached a depth in proteomic profiling not reported to date for a mammalian tissue or a biological fluid, with 7099 and 4727 proteins identified with high confidence in the liver and in the corresponding plasma, respectively.

Liver disease in pregnancy

J. Eileen Hay – 26 February 2008 – Abnormal liver tests occur in 3%–5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. However, most liver dysfunction in pregnancy is pregnancy‐related and caused by 1 of the 5 liver diseases unique to the pregnant state: these fall into 2 main categories depending on their association with or without preeclampsia.

The cyclophilin inhibitor Debio‐025 shows potent anti–hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

Robert Flisiak, Andrzej Horban, Philippe Gallay, Michael Bobardt, Suganya Selvarajah, Alicja Wiercinska‐Drapalo, Ewa Siwak, Iwona Cielniak, Jozef Higersberger, Jarek Kierkus, Christian Aeschlimann, Pierre Grosgurin, Valérie Nicolas‐Métral, Jean‐Maurice Dumont, Hervé Porchet, Raf Crabbé, Pietro Scalfaro – 26 February 2008 – Debio‐025 is an oral cyclophilin (Cyp) inhibitor with potent anti–hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double‐blind, placebo‐controlled study.

S‐adenosylmethionine inhibits lipopolysaccharide‐induced gene expression via modulation of histone methylation

Ainhoa Iglesias Ara, Meng Xia, Komal Ramani, José M. Mato, Shelly C. Lu – 21 February 2008 – We previously showed that S‐adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) blocked lipopolysaccharide (LPS)‐induced tumor necrosis factor α (TNFα) expression in RAW (murine macrophage cell line) and Kupffer cells at the transcriptional level without affecting nuclear factor κ B nuclear binding. However, the exact molecular mechanism or mechanisms of the inhibitory effect were unclear. While SAMe is a methyl donor, MTA is an inhibitor of methylation.

Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease

Winston Dunn, Ronghui Xu, Jeffrey B. Schwimmer – 21 February 2008 – People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD.

Autophagy activation by rapamycin eliminates mouse Mallory‐Denk bodies and blocks their proteasome inhibitor‐mediated formation

Masaru Harada, Shinichiro Hanada, Diana M. Toivola, Nafisa Ghori, M. Bishr Omary – 21 February 2008 – The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory‐Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)‐overexpressing transgenic mice are predisposed to MDB formation.

Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration

Ghazaleh Aram, James J. Potter, Xiaopu Liu, Michael S. Torbenson, Esteban Mezey – 19 February 2008 – The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS−/−) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl4) administration. Wild‐type (WT) or iNOS−/− mice were subjected to biweekly CCl4 injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil.

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