Hepatobiliary disposition of valproic acid and valproate glucuronide: Use of a pharmacokinetic model to examine the rate‐limiting steps and potential sites of drug interactions

C L Booth, G M Pollack, K L Brouwer – 1 April 1996 – Previous work in this laboratory has suggested that the nonlinear disposition of valproic acid (VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1‐2 mmol/L) was incubated with isolated rat hepatocytes in vitro. Uptake of [3H]‐VPA was linear from 10 to 50 seconds, with minimal (<7 percent) biotransformation.

Behavior of various cholesterol crystals in bile from patients with gallstones

P Portincasa, K J van Erpecum, A Jansen, W Renooij, M Gadellaa, G P van Berge‐Henegouwen – 1 April 1996 – Besides classical plate‐like cholesterol monohydrate crystals, a variety of crystal shapes have recently been described in model biles but their relevance for human gallstone formation is unknown. We therefore studied crystallization behavior in gallbladder bile from cholesterol stone patients (54 untreated, 13 ursodeoxycholate‐treated) and 6 pigment stone patients.

Nitric oxide is not involved in hepatocyte killing by neutrophils activated by N‐formyl‐methionyl‐leucyl‐phenylalanine or phorbol myristate acetate in vitro

J G Wagner, P E Ganey, R A Roth – 1 April 1996 – Polymorphonuclear leukocytes (PMNS) have been implicated as cellular mediators of hepatic injury in models of inflammation in vivo. In vitro, hepatocyte killing by activated PMNs is mediated in part by proteases, but the role of nitric oxide is unknown. NO is produced by PMNs and hepatocytes and can act either to damage or protect in various models of toxicity. Therefore, we tested the hypothesis that NO is important in PMN‐mediated hepatocyte killing in vitro.

Inhibition of hereditary hepatitis and liver tumor development in Long‐Evans cinnamon rats by the copper‐chelating agent trientine dihydrochloride

K Sone, M Maeda, K Wakabayashi, N Takeichi, M Mori, T Sugimura, M Nagao – 1 April 1996 – Trientine dihydrochloride (trientine) is an alternative medicinal copper chelating agent for patients with Wilson's disease of penicillamine intolerance. We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short‐ term and long‐term administration to Long‐Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease.

Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: A multicenter controlled trial

G V Gregorio, P Jara, L Hierro, C Diaz, A de la Vega, A Vegnente, R Iorio, F Bortolotti, C Crivellaro, L Zancan, H Daniels, B Portmann, G Mieli‐Vergani – 1 April 1996 – The comparative efficacy of prednisolone followed by interferon alfa (IFN‐α) versus IFN‐α alone in enhancing the rate of antibody to hepatitis B e antigen (anti‐HBe) seroconversion has not been evaluated in a large cohort of white children.

Intrahepatic hepatitis C RNA levels do not correlate with degree of liver injury in patients with chronic hepatitis C

P H McGuinness, G A Bishop, D M Painter, R Chan, G W McCaughan – 1 April 1996 – The balance between a direct cytopathic effect by hepatitis C virus (HCV) and immune‐mediated injury remains unclear. This report aims to test the following hypotheses: (1) that intrahepatic HCV load would correlate with the degree of liver injury; (2) that interferon alfa (IFN‐α) would decrease intrahepatic HCV‐RNA levels. Liver tissues (n = 56) were obtained from 47 patients with chronic HCV (9 before and after IFN‐α therapy).

Ultracentrifugation systematically overestimates vesicular cholesterol levels in bile

P K Yuet, D Blankschtein, J M Donovan – 1 April 1996 – To accurately determine the cholesterol (Ch) distribution between mixed micelles and vesicles in lithogenic bile, both ultracentrifugation and gel chromatography with the correct intermixed micellar/vesicular bile salt concentration (IMC) have been proposed. We have systematically compared both separation techniques with physiological model biles to ascertain their quantitative separation ability.

Interferon alfa for recurrent hepatitis B infection after liver transplantation

Norah A. Terrault, Connie Combs Holland, Linda Ferrell, Judith A. Hahn, John R. Lake, John P. Roberts, Nancy L. Ascher, Teresa L. Wright – 1 March 1996 – Reinfection with hepatitis B virus (HBV) after liver transplantation is nearly universal in patients not receiving immunoprophylaxis. Because reinfection reduces graft and patient survival, treatment of recurrent infection is important. Interferon alfa (IFN‐α) is an effective therapy for chronic hepatitis B infection in immunocompetent patients, but its efficacy in transplant recipients has not been established.

Effect of orthotopic liver transplantation on employment and health status

Christine M. Hunt, Julie S. Tart, Elaine Dowdy, Barbara Philips Bute, Diane M. Williams, Pierre‐Alain Clavien – 1 March 1996 – Employment, functional status, health status, and prevalence of anxiety and depression were assessed in patients who had undergone orthotopic liver transplantation at Duke University from 1984 to 1993 to identify social and economic factors that might influence return to work after liver transplantation. Patients were asked to complete mailed questionnaires. A transplant nurse coordinator assigned patients a Karnofsky score, unaware of the questionnaire responses.

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