Genetic factors influence ethanol‐induced uroporphyria in Hfe (—/—) mice

Nadia Gorman, Heidi W. Trask, William J. Bement, Juliana G. Szakacs, George H. Elder, Dominic Balestra, Nicholas J. Jacobs, Judith M. Jacobs, Jacqueline F. Sinclair, Glenn S. Gerhard, Peter R. Sinclair Ph.D. – 7 March 2007 – Two major risk factors for porphyria cutanea tarda (PCT) are alcohol consumption and homozygosity for the C282Y mutation in the hereditary hemochromatosis gene (HFE). We recently described an animal model for alcohol‐induced uroporphyria, using Hfe(–/–) mice. In the present study we show that this effect is dependent on genetic background and ethanol dose.

Peroxisome proliferator‐activated receptor α protects against alcohol‐induced liver damage

Tamie Nakajima, Yuji Kamijo, Naoki Tanaka, Eiko Sugiyama, Eiji Tanaka, Kendo Kiyosawa, Yoshimitsu Fukushima, Jeffrey M. Peters, Frank J. Gonzalez, Toshifumi Aoyama – 7 March 2007 – The mechanisms underlying alcoholic liver disease are not completely understood, but lipid accumulation seems to be central to the cause of this disease. The peroxisome proliferatoractivated receptor α (PPARα) plays an important role in the control of lipid homeostasis, metabolism of bioactive molecules, and modulation of inflammatory responses.

HBV genotype B is associated with better response to interferon therapy in HBeAg( + ) chronic hepatitis than genotype C

Chun Tao Wai, Chi‐Jen Chu, Munira Hussain, Anna S. F. Lok – 7 March 2007 – Hepatitis B virus (HBV) genotype and precore/core promoter mutations have been implicated in spontaneous and interferon alfa (IFN‐α)—related hepatitis B e antigen (HBeAg) seroconversion. We performed a retrospective analysis of a previously reported randomized controlled trial to determine the effects of HBV genotype and precore/core promoter mutations on IFN‐α response in patients with HBeAg‐positive chronic hepatitis. Clinical data and stored sera from 109 (95%) patients in the original trial were analyzed.

p38 MAPK mediates fibrogenic signal through smad3 phosphorylation in rat myofibroblasts

Fukiko Furukawa, Koichi Matsuzaki, Shigeo Mori, Yoshiya Tahashi, Katsunori Yoshida, Yasushi Sugano, Hideo Yamagata, Masanori Matsushita, Toshihito Seki, Yutaka Inagaki, Mikio Nishizawa, Junichi Fujisawa, Kyoichi Inoue – 7 March 2007 – Hepatic stellate cells (HSCs) spontaneously transdifferentiate into myofibroblast (MFB)‐phenotype on plastic dishes. This response recapitulates the features of activation in vivo. Transforming growth factor β (TGF‐β) plays a prominent role in stimulating liver fibrogenesis by MFBs.

Interferon alfa down‐regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice

Yutaka Inagaki, Tomoyuki Nemoto, Miwa Kushida, Yin Sheng, Kiyoshi Higashi, Kazuo Ikeda, Norifumi Kawada, Fumiaki Shirasaki, Kazuhiko Takehara, Kota Sugiyama, Mitsukiyo Fujii, Hiroshi Yamauchi, Atsuhito Nakao, Benoit de Crombrugghe, Tetsu Watanabe, Isao Okazaki – 7 March 2007 – The equilibrium between the production and degradation of collagen is rigorously controlled by a number of growth factors and cytokines.

Heme oxygenase‐1 and its reaction product, carbon monoxide, prevent inflammation‐related apoptotic liver damage in mice

Gabriele Sass, Miguel Che Parreira Soares, Kenichiro Yamashita, Stefan Seyfried, Wolfram‐Hubertus Zimmermann, Thomas Eschenhagen, Elzbieta Kaczmarek, Thomas Ritter, Hans‐Dieter Volk, Gisa Tiegs – 7 March 2007 – Heme oxygenase‐1 (HO‐1), a stress‐responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin, and iron, has previously been shown to protect grafts from ischemia/reperfusion injury and rejection. Here we investigated the protective potential of HO‐1 in 5 models of immune‐mediated liver injury.

Bile acids induce mitochondrial ROS, which promote activation of receptor tyrosine kinases and signaling pathways in rat hepatocytes

Youwen Fang, Song Iy Han, Clint Mitchell, Seema Gupta, Elaine Studer, Steven Grant, Phillip B. Hylemon, Paul Dent – 7 March 2007 – Previous studies have demonstrated in hepatocytes that deoxycholic acid (DCA) promotes inactivation of protein tyrosine phosphatases (PTPases) and activation of ERBB1 and the extracellular‐regulated kinase (ERK) 1/2 pathway. The present studies have determined the biochemical mechanism(s) through which these events occur.

Isoleucine infusion during “simulated” upper gastrointestinal bleeding improves liver and muscle protein synthesis in cirrhotic patients

Steven W. M. Olde Damink, Rajiv Jalan, Nicolaas E. P. Deutz, Cornelis H. C. Dejong, Doris N. Redhead, Paula Hynd, Peter C. Hayes, Peter B. Soeters – 26 February 2007 – Upper gastrointestinal (GI) bleeding in cirrhotic patients has a high incidence of mortality and morbidity. Postbleeding catabolism has been hypothesized to be partly due to the low biological value of hemoglobin, which lacks the essential amino acid isoleucine.

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