Galactosamine‐induced fulminant hepatic necrosis in unanesthetized canines

J A Diaz‐Buxo, S Blumenthal, D Hayes, P Gores, B Gordon – 30 December 2003 – A large animal model of fulminant hepatic necrosis is necessary to test the efficacy of artificial liver support systems. A recent model was developed using D‐galactosamine in anesthetized dogs. Because of the difficulties encountered with prolonged anesthesia, a similar protocol was used in 10 unanesthetized dogs. Intravenous infusions of D‐galactosamine (1.0 to 1.5 gm/kg) did not result in uniform death of all animals at 72 hours or development of hypoglycemia.

Hepatoprotective effect of the endothelin receptor antagonist TAK‐044 against ischemia‐reperfusion injury in the canine liver

Y Kitayama, N Yamanaka, E Kawamura, N Kuroda, E Okamoto – 30 December 2003 – The present study was designed to investigate if TAK‐044, a novel endothelin (ET) ETA/ETB receptor antagonist, inhibits ischemia‐ reperfusion liver injury. The initial study showed the presence of both ETA and ETB receptors in canine hepatic membrane fractions using the specific binding assay of labeled ET‐1 with ET isomers and TAK‐044. The nonselective ETA/ETB receptor antagonist TAK‐044 inhibited the specific binding of ET‐1 to the receptors in a concentration‐dependent manner.

Hepatic venous outflow block caused by short‐length hepatic vein stenoses

D Valla, A Hadengue, M el Younsi, N Azar, G Zeitoun, M Boudet, G Molas, J Belghiti, S Erlinger, J Hay, J Benhamou – 30 December 2003 – In contrast with the well‐recognized membranous obstruction of the inferior vena cava, short‐length hepatic vein stenoses are not well‐ recognized causes of hepatic venous outflow block. The aim of this study was to ascertain the prevalence, causes, manifestations, and outcome of short‐length hepatic vein stenoses.

Ironic insult added to copper injury

M L Schilsky – 30 December 2003 – Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron‐induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long‐Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer.

B7/BB‐1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C

K Mochizuki, N Hayashi, K Katayama, N Hiramatsu, T Kanto, E Mita, T Tatsumi, N Kuzushita, A Kasahara, H Fusamoto, T Yokochi, T Kamada – 30 December 2003 – Cytotoxic T lymphocytes (CTL) are closely related to the mechanism of liver injury in chronic viral hepatitis. Recently, it has been suggested that antigen‐specific T cell activation requires both presentation of antigen by major histocompatibility complex (MHC) molecules and the delivery of costimulatory signals.

Adenovirus‐mediated expression of cytokine‐induced neutrophil chemoattractant in rat liver induces a neutrophilic hepatitis

J J Maher, M K Scott, J M Saito, M C Burton – 30 December 2003 – C‐X‐C chemokines are potent chemoattractants that are believed to mediate neutrophilic inflammation in several organs. Recent studies suggest a role for C‐X‐C chemokines in the pathogenesis of neutrophilic hepatitis but do not prove causation. We investigated the biological consequences of hepatic chemokine production in vivo by transiently overexpressing cytokine‐induced neutrophil chemoattractant (CINC), a member of the C‐X‐C chemokine family, in intact rats.

Protective effect of L‐carnitine in ammonia‐precipitated encephalopathy in the portacaval shunted rat

G Therrien, C Rose, J Butterworth, R F Butterworth – 30 December 2003 – L‐carnitine administration prevents the neurological symptoms of acute ammonia toxicity. To further evaluate its efficacy in the prevention of hepatic encephalopathy in hyperammonemic conditions, L‐carnitine (16 mmol/kg, intraperitoneally [i.p.) was administered 1 hour before ammonium acetate (NH4OAc) (8.5 mmol/kg, subcutaneously) to portacaval shunted (PCS) rats. Cerebrospinal fluid (CSF) ammonia, lactate, and amino acid levels were measured in relation to deteriorating neurological status in these animals.

Nitric oxide does not reverse pulmonary hypertension associated with end‐stage liver disease: A preliminary report

M A Ramsay, A Schmidt, H A Hein, A T Nguyen, K Lynch, C A East, K J Ramsay, G B Klintmalm – 30 December 2003 – Pulmonary hypertension is a well known, though uncommon complication of end‐stage liver disease (ESLD). Patients with severe pulmonary hypertension and ESLD undergoing orthotopic liver transplantation (OLT) may develop right ventricular failure and death. This study investigates the reversibility of pulmonary hypertension by the inhalation of nitric oxide in patients under evaluation for OLT.

Detection of type 2‐like T‐helper cells in hepatitis C virus infection: Implications for hepatitis C virus chronicity

S Tsai, Y Liaw, M Chen, C Huang, G C Kuo – 30 December 2003 – One striking clinical feature of hepatitis C virus (HCV) infection is that more than 50% of patients with acute hepatitis C will develop chronic infection. To investigate its possible mechanisms, we examined the activation of type 2‐like T‐helper (Th2‐like) cells relating to the development of chronicity.

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