Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute cellular rejection

Marcelo Kugelmas, Michael J. Osgood, James F. Trotter, Thomas Bak, Michael Wachs, Lisa Forman, Igal Kam, Gregory T. Everson – 30 December 2003 – We recently reported on a series of patients who experienced acute cellular rejection (ACR) during the treatment of hepatitis C virus (HCV) infection in our posttransplantation cohort. Our hypothesis is that HCV clearance improves hepatic microsomal function, which in turn results in lower trough cyclosporine (CyA) and tacrolimus (TAC) levels, predisposing the patient to ACR.

Induction of hepatocyte growth factor activator messenger RNA in the liver following tissue injury and acute inflammation

A. Okajima, K. Miyazawa, Y. Naitoh, K. Inoue, N. Kitamura – 30 December 2003 – Hepatocyte growth factor activator (HGFA) is a serine protease that is responsible for localized activation of hepatocyte growth factor (HGF) in injured tissue. The activated HGF may be involved in regeneration of the injured tissue. HGFA is produced and secreted by the liver and circulates in the plasma as an inactive zymogen. In response to tissue injury, the HGFA zymogen is converted to the active form by limited proteolysis.

Cystic fibrosis transmembrane conductance regulator mediates the cyclic adenosine monophosphate‐induced fluid secretion but not the inhibition of resorption in mouse gallbladder epithelium

R H Peters, J H van Doorninck, P J French, R Ratcliff, M J Evans, W H Colledge, J Bijman, B J Scholte – 30 December 2003 – We have studied the physiological role of the cystic fibrosis (CF) gene product (cystic fibrosis transmembrane conductance regulator [CFTR]) in gallbladder epithelium using a knockout mouse model for CF. We found that normal mouse gallbladder epithelium expresses functional CFTR as shown by reverse‐transcription polymerase chain reaction (RT‐PCR) analysis and Ussing chamber experiments.

Improvement in cholestasis‐associated fatigue with a serotonin receptor agonist using a novel rat model of fatigue assessment

M G Swain, M Maric – 30 December 2003 – Fatigue is a common complaint in patients with liver disease; however, the etiology of fatigue is poorly understood and no therapeutic options are available to treat it. Altered central neurotransmission, especially serotonergic, appears to play a role in the genesis of fatigue. In this study, we describe a rat model of fatigue assessment using a swim tank, and we used this model to document the degree of fatigue in rat models of cholestasis caused by bile duct resection (BDR) and of hepatitis caused by carbon tetrachloride (CCl4) administration.

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