Effects of tilting on central hemodynamics and homeostatic mechanisms in cirrhosis

Søren Møller, Annette Nørgaard, Jens H. Henriksen, Erik Frandsen, Flemming Bendtsen – 7 March 2007 – Patients with cirrhosis have a hyperdynamic circulation and an abnormal blood volume distribution with central hypovolemia, an activated sympathetic nervous system (SNS) as well as the renin‐angiotensin‐aldosterone system (RAAS). As the hyperdynamic circulation in cirrhosis may be present only in the supine patient, we studied the humoral and central hemodynamic responses to changes with posture.

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.

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