пятница, 13 июня 2008 г.

Enhanced actions of insulin-like growth factor-i and interferon-α co-administration in experimental cirrhosis

Abstract BASIC STUDIES ENHANCED ACTIONS OF INSULIN-LIKE GROWTH FACTOR-I AND INTERFERON- CO-ADMINISTRATION IN EXPERIMENTAL CIRRHOSIS Federico Tutau, Carlos Rodrguez-Ortigosa, Juan Enrique Puche, Nerea Juanarena, Iigo Monreal, Mara Garca Fernndez, Encarna Clavijo, Alberto Castilla and Inma Castilla - Cortzar 1 Department of Physiology, School of Medicine, University of Mlaga, Mlaga, Spain 2 Department of Medical Physiology, School of Medicine, University USP-CEU, Madrid, Spain 3 Department of Internal Medicine, Liver Unit, CIMA, University of Navarra, Pamplona, Spain 4 Department of Internal Medicine, Hospital Sierrallana, Torrelavega, Spain 5 School of Medicine, Cantabria, Spain CORRESPONDENCE Inma Castilla de Cortzar Larrea, Department of Medical Physiology.Medicine, University USP-CEU, Campus Monteprncipe, 28660, Boadilla del Monte, Madrid, Spain Tel: +34 686 652 710 Fax: +34 91 359 44 79 e-mails: , Abbreviations: AU, arbitrary units of fluorescence; HGF, hepatocyte growth factor; IFN-, interferon-; IGF-I, insulin-like growth factor-I; PXR, pregnane X receptor; -SMA, -smooth muscle actin; TGF-, transforming growth factor-; TIMPs, tissular inhibitor of metalloproteinases.ABSTRACT Background: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation.Liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis.Supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects.Other hand, interferon- (IFN-) therapy seems to suppress the progression of hepatic fibrosis.Aims: The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN- to _Wistar_ rats with CCl4-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology.The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors involved in fibrogenesis, fibrolysis and/or hepatoprotection.Results: Both IGF-I and IFN- exerted significant effects on fibrogenesis.Significantly increased serum albumin and HGF whereas IFNtherapy did not.Of TGF- expression was only observed by the effect of IFNtherapy.Addition, only the co-administration of IGF-I and IFN- was able to increase the PXR.With both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture.
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