Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure

A Michalak, C Rose, J Butterworth, R F Butterworth – 1 October 1996 – It has been proposed that alterations of excitatory and inhibitory amino acids play a role in the pathogenesis of hepatic encephalopathy in acute liver failure. To evaluate this possibility, in vivo cerebral microdialysis was used to sample extracellular concentrations of amino acids in the frontal cortex of unanesthetized rats at various times during the progression of encephalopathy resulting from acute liver failure.

Role of sinusoidal endothelial cells of the liver in concanavalin A‐induced hepatic injury in mice

P A Knolle, G Gerken, E Löser, H P Dienes, F Gantner, G Tiegs, K Meyer zum Büschenfelde, A W Lohse – 1 October 1996 – CD4+ T lymphocytes have been identified as being responsible for organ damage in the murine model of experimental liver injury induced by intravenous injection of concanavalin A (Con A). Liver sinusoidal endothelial cells (SEC) and Kupffer's cells (KC) are among the first cells that come into contact with lymphocytes in the liver sinusoid.

Cellular target of cyclophosphamide toxicity in the murine liver: Role of glutathione and site of metabolic activation

L D DeLeve – 1 October 1996 – Hepatic venoocclusive disease (HVOD) is caused by the disruption of the microcirculation by an as‐yet unknown mechanism. Previous in vitro studies with azathioprine, monocrotaline, and dacarbazine suggested that toxins that cause HVOD initially causing HVOD target sinusoidal endothelial cells (SEC) perhaps via profound glutathione (GSH) depletion. The current study examines cyclophosphamide toxicity in SEC and hepatocytes, as well as the interplay between the two cell types.

The course of galactose elimination capacity in patients with alcoholic cirrhosis: Possible use as a surrogate marker for death

C Merkel, G Marchesini, A Fabbri, S Bianco, G Bianchi, E Enzo, D Sacerdoti, M Zoli, A Gatta – 1 October 1996 – There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow‐up, and to validate changes in galactose elimination as a surrogate end point for death from liver‐related causes.

Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection

A Pauwels, N Mostefa‐Kara, B Debenes, E Degoutte, V Levy – 1 October 1996 – In cirrhotic patients with gastrointestinal hemorrhage, bacterial infections are frequent and play a significant role in mortality. We have previously found that patients with a Child‐Pugh's class C or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection. The aims of the study were (1) to validate these indicators and (2) to assess the effectiveness of a systemic antibiotic treatment in preventing bacterial infections in bleeding cirrhotics with a high risk of infection.

T‐ and B‐cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti‐ hepatitis C virus—positive blood donors without viremi

M Lechmann, H G Ihlenfeldt, I Braunschweiger, G Giers, G Jung, B Matz, R Kaiser, T Sauerbruch, U Spengler – 1 October 1996 – As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV‐related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core‐ and E1‐related 25‐mer peptides were examined in 10 healthy anti‐HCV‐seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B).

Spermidine acetyltransferase in rat hepatocytes cultured at different oxygen tensions

C Vargiu, S Colombatto, G Giribaldi, M A Grillo – 1 October 1996 – To understand the mechanism involved in the liver zonation of polyamines, we have studied the possible role of oxygen tension. When hepatocytes were cultured at 21% and at 5% oxygen in atmosphere to mimic periportal and perivenous conditions, polyamine content was modified. The observed modifications suggested an effect on the interconversion pathway. Spermidine acetyltransferase (SAT) activity and N1‐acetylspermidine were therefore measured in the same conditions.

Portacaval anastomosis induces region‐selective alterations of the endogenous opioid system in the rat brain

J de Waele, R M Audet, D K Leong, R F Butterworth – 1 October 1996 – Portacaval anastomosis (PCA) in the rat results in a broad spectrum of neurological and neurobehavioral changes, including alterations of circadian rhythms, impaired locomotor activity, and reflexes, as well as decreased threshold to noxious stimuli. In addition, following portacaval shunting, rats drink significantly more ethanol in a free‐ choice drinking paradigm. Available evidence suggests that many of these behavioral changes may be modulated by the endogenous opioid system of the brain.

Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole

I R Wanless, J Belgiorno, P Huet – 1 October 1996 – This study documents the hepatic morphology and the ultrastructure of a model of hepatic fibrosis in rabbits. Rabbits were given a cholesterol‐ supplemented diet (1%), a stilbestrol diet (10 mg subcutaneously twice a week), or both treatments simultaneously for 7 weeks. Rabbits given the combined treatment developed sinusoidal and portal fibrosis with only a mild disturbance of acinar vascular relationships.

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