Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities

Ruud Dirkx, Ilse Vanhorebeek, Katrin Martens, Arno Schad, Markus Grabenbauer, Dariush Fahimi, Peter Declercq, Paul P. Van Veldhoven, Myriam Baes – 24 February 2005 – Peroxisome deficiency in men causes severe pathology in several organs, particularly in the brain and liver, but it is still unknown how metabolic abnormalities trigger these defects. In the present study, a mouse model with hepatocyte‐selective elimination of peroxisomes was generated by inbreeding Pex5‐loxP and albumin‐Cre mice to investigate the consequences of peroxisome deletion on the functioning of hepatocytes.

Antiviral efficacy of NS3‐serine protease inhibitor BILN‐2061 in patients with chronic genotype 2 and 3 hepatitis C

Markus Reiser, Holger Hinrichsen, Yves Benhamou, Henk W. Reesink, Heiner Wedemeyer, Cristina Avendano, Neus Riba, Chan‐Loi Yong, Gerhard Nehmiz, Gerhard G. Steinmann – 24 February 2005 – BILN‐2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)‐RNA levels in patients chronically infected with HCV genotype 1 in three 2‐day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN‐2061 in patients with genotypes 2 and 3 HCV infection.

SELDI‐TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma

E. Ellen Schwegler, Lisa Cazares, Laura F. Steel, Bao‐Ling Adam, David A. Johnson, O. John Semmes, Timothy M. Block, Jorge A. Marrero, Richard R. Drake – 22 February 2005 – Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC).

Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice

Simrat P. S. Saini, Ying Mu, Haibiao Gong, David Toma, Hirdesh Uppal, Songrong Ren, Song Li, Samuel M. Poloyac, Wen Xie – 22 February 2005 – The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are implicated in xenobiotic and endobiotic detoxification, including the clearance of toxic bilirubin. Previous studies have suggested both overlapping and preferential regulation of target genes by these receptors, but the mechanism of cross‐talk remains elusive.

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat

Turgay Çelik, M. Zafer Gören, Kubilay Çınar, Hakan Gürdal, F. Oğuz Önder, Akif Tan, Berna Terzioğlu, A. Mithat Bozdayı, Hakan Bozkaya, Özden Uzunalimoğlu, Cihan Yurdaydin – 22 February 2005 – Fatigue associated with cholestasis may impair health‐related quality of life. The pathogenesis of this symptom is largely unknown, but it has been suggested that central serotoninergic neurotransmission may be implicated and that serotonin 1A receptor agonists may yield improvement.

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C

Alan Lee Rothman, Chihiro Morishima, Herbert L. Bonkovsky, Stephen J. Polyak, Ranjit Ray, Adrian M. Di Bisceglie, Karen L. Lindsay, Peter F. Malet, Ming Chang, David R. Gretch, Daniel G. Sullivan, Atul K. Bhan, Elizabeth C. Wright, Margaret James Koziel – 22 February 2005 – The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients.

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