Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the rat

Julia H. Hayes, Carol J. Soroka, Laura Rios‐Velez, James L. Boyer – 30 December 2003 – In contrast to organic anions, substrates for the canalicular mdr1a and b are usually organic cations and are often sequestered in high concentrations in intracellular acidic compartments. Because many of these compounds are therapeutic agents, we investigated if their sequestration could be regulated. We used isolated perfused rat liver (IPRL), isolated rat hepatocyte couplets (IRHC), and WIF‐B cells to study the cellular localization and biliary excretion of the fluorescent cation, daunorubicin (DNR).

Recurrent familial intrahepatic cholestasis in the faeroe islands. phenotypic heterogeneity but genetic homogeneity

Niels Tygstrup, Bjarni Á. Steig, Jenneke A. Juijn, Laura N. Bull, Roderick H. Houwen – 30 December 2003 – Recurrent familial intrahepatic cholestasis is an autosomal recessive disorder characterized by episodes of severe pruritus and jaundice lasting for weeks to months without extrahepatic bile duct obstruction. Symptom‐free intervals may last for months to years, and chronic liver damage does not develop.

Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high‐volume plasmapheresis

Jens Otto Clemmesen, Alexander L. Gerbes, Veit Gülberg, Bent Adel Hansen, Fin Stolze Larsen, Claus Skak, Niels Tygstrup, Peter Ott – 30 December 2003 – Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2,sp ) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more.

Altered Gq/G11 guanine nucleotide regulatory protein expression in a rat model of hepatocellular carcinoma: Role in mitogenesis

Iain H. McKillop, C. Max Schmidt, Paul A. Cahill, James V. Sitzmann – 30 December 2003 – Guanine nucleotide regulatory proteins (G‐proteins) represent an important transmembrane pathway whereby extra‐cellular signals are transduced to intracellular signaling pathways. The mitogen‐activated protein kinase (MAPK) cascade has been identified as a key factor in transducing numerous mitogenic stimuli. MAPK activity is regulated via numerous receptor types, including those linked to Gq/G11‐proteins, which regulate phospholipase‐C activity.

Sorbitol as a test substance for measurement of liver plasma flow in humans

Susanne Keiding, Eva Engsted, Peter Ott – 30 December 2003 – The objective of this study was to evaluate whole‐body removal kinetics of sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma flow in humans, and to compare measurements of liver flow by Fick's principle using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg) was given intravenously to 6 controls for determination of sorbitol elimination capacity (SEC)and distribution volume, Vdsorb. Sorbitol infusion (287 μmol/min) was given to 17 liver patients and 11 controls.

Increased cerebrovascular resistance in cirrhotic patients with ascites

Mónica Guevara, Concepción Bru, Pere Ginès, Gloria Fernández‐Esparrach, Pau Sort, Ramón Bataller, Wladimiro Jiménez, Vicente Arroyo, Juan Rodés – 30 December 2003 – Studies assessing regional hemodynamics in patients with cirrhosis and ascites have shown vasodilation in the splanchnic circulation and vasoconstriction in the renal circulation and in the brachial and femoral artery vascular territories.The aim of this study was to assess the cerebral vascular resistance in cirrhotic patients with ascites.The resistive index in the middle cerebral artery (an index of the cerebral vascular resi

The diagnostic and predictive value of ascites nitric oxide levels in patients with spontaneous bacterial peritonitis

Guadalupe Garcia‐Tsao, Paul Angulo, Juan Carlos Garcia, Roberto J. Groszmann, Gregory W. Cadelina – 30 December 2003 – Nitric oxide (NO) is a messenger molecule involved in pathogen suppression. Cirrhosis is characterized by an increased risk for infections, including spontaneous bacterial peritonitis (SBP). The role of NO in the infections that develop in cirrhosis has not been clearly established. The aim of this study was to investigate the utility of measuring ascites NO in the diagnosis of SBP and/or in determining the predisposition of cirrhotic patients to develop this infection.

Hepatic bile versus gallbladder bile: A comparison of protein and lipid concentration and composition in cholesterol gallstone patients

Yolande C. Keulemans, Kam S. Mok, Laurens Th de Wit, Dirk J. Gouma, Albert K. Groen – 30 December 2003 – Many studies have demonstrated that gallbladder bile (but not hepatic bile) of animals or patients with cholesterol gallstones contains higher protein concentrations than does gallbladder bile of control patients without stones or with pigment stones. The underlying defect has not been elucidated.

Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen

Andrew L. Mason, Lizhe Xu, Linsheng Guo, Mary Kuhns, Robert P. Perrillo – 30 December 2003 – Hepatitis B virus (HBV) DNA has been detected by polymerase chain reaction (PCR) in the liver of patients with resolved chronic HBV infection and sustained clearance of hepatitis B surface antigen (HBsAg) from serum. However, it is unknown whether the virus is transcriptionally active at this time or if the covalently closed circular (CCC) replicative intermediate of HBV DNA can still be detected.

Emergence and takeover of YMDD motif mutant hepatitis B virus during long‐term lamivudine therapy and re‐takeover by wild type after cessation of therapy

Kazuaki Chayama, Yoshiyuki Suzuki, Masahiro Kobayashi, Mizuho Kobayashi, Akihito Tsubota, Michie Hashimoto, Yukiko Miyano, Hiromi Koike, Mariko Kobayashi, Isao Koida, Yasuji Arase, Satoshi Saitoh, Naoya Murashima, Kenji Ikeda, Hiromitsu Kumada – 30 December 2003 – Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine‐resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported.

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