Biomedical subjects

W Hilgier

Publications and source records attributed to W Hilgier.

47 records · Page 3Linked to original sources

PubMedDate not supplied

Effects of thioacetamide-induced hepatic failure on the N-methyl-D-aspartate receptor complex in the rat cerebral cortex, striatum, and hippocampus. Binding of different ligands and expression of receptor subunit mRNAs.

Hepatic encephalopathy (HE) is characterized by symptoms pointing at disturbances in glutamatergic neurotransmission in the brain, particularly in the striatum. The binding parameters of ligands specific for different recognition sites in the N-methyl-D-aspartate (NMDA) receptor complex and the distribution of the receptor subunit mRNAs (NR1, NR2A-D) were assessed in rats with acute HE induced with a hepatotoxin, thioacetamide (TAA). The binding of: 1. L-[3H]glutamate (NMDA-displaceable); 2. [3H]dizocilpine and N-(1-[2-thienyl]-cyclohexyl) [3H]piperidine ([3H]TCP); and 3. The coactivator site agonist [3H]glycine was assayed in purified membranes of the cerebral cortex, hippocampus, and striatum. In HE rats, Bmax of NMDA-displaceable glutamate binding was increased in the cerebral cortex and hippocampus, but slightly decreased in the striatum. In this region, the binding affinity was also slightly increased. In HE, Bmax of [3H]dizocilpine binding was unchanged in the striatum and cerebral cortex, but substantially decreased in the hippocampus. Pretreatment with phorbol ester enhanced the binding of dizocilpine more in HE than in control rats. Bmax of [3H]TCP binding was decreased in the cerebral cortex and striatum, but increased in the hippocampus. The different responses of these two phencyclidine site antagonists to HE may be indicative of a conformational change within the ion channel and/or the presence of microdomains reacting differently to extrinsic factors. HE did not affect glycine binding, but potentiated the maximal stimulation of [3H]dizocilpine binding by glycine in the cerebral cortex. The results emphasize the brain region and domain specificity of the responses of the NMDA receptor complex to HE.

Animals↗

PubMedDate not supplied

The effect of acute and repeated hyperammonemia on gamma-glutamyl transpeptidase in homogenates and capillaries of various rat brain regions.

The effect of hyperammonemia of varying degree and duration on the gamma-glutamyl-transpeptidase (GGT) activity was studied in the homogenates and capillaries of different brain regions of the rat. "Acute" hyperammonemia (750 and 600 mg of ammonium acetate per kg b.w. were injected i.p. at 30 min interval, and the animals were decapitated immediately), in which blood ammonia was increased 14-fold, and brain ammonia six-fold above the control level, produced a 20% increase of the enzyme activity in cerebellum, and a 17% decrease in gyrus dentatus, but had no effect in the frontal cortex and the CA1 and CA3 regions of hippocampus. "Subchronic" hyperammonemia (two injections of 600 mg ammonium acetate/kg were given at 24 h intervals, and tissue samples were removed 24 h later), that was accompanied by only a 60% increase of blood or brain ammonia, increased the activity in cerebellum to 38% above control, but produced no effect in the other brain regions. "Chronic" hyperammonemia (three injections of 600 mg ammonium acetate/kg at 24 h intervals and excision of tissue samples 30 min after the last injection), in which blood and brain ammonia were, respectively, 60 and 100% higher than in control animals, elevated the GGT activity in the cerebellum by 57%, in CA1 by 15%, and in CA3 by 21%, but produced no effect in the frontal cortex or gyrus dentatus. By contrast, "chronic" hyperammonemia produced a 30% increase of GGT activity in cerebral cortical capillaries, but only a 10% increase in hippocampal capillaries, and no change in cerebellar capillaries. The results suggest that, hyperammonemia of relatively long duration may contribute to the enhancement of brain GGT activity observed in chronic forms of hepatic encephalopathy. However, ammonia does not appear to activate the enzyme directly.

Ammonia↗

PubMedDate not supplied

Effects of ammonia and hepatic failure on the net efflux of endogenous glutamate, aspartate and taurine from rat cerebrocortical slices: modulation by elevated K+ concentrations.

Cerebrocortical minislices derived from control rats ("control slices") and from rats with thioacetamide (TAA)-induced hepatic failure showing moderate hyperammonemia and symptoms of hepatic encephalopathy (HE) ("HE slices"), were incubated with physiological saline in the absence or presence of 5 mM ammonium acetate ("ammonia"), at potassium ion (K+) concentrations ranging from 5 to 15 mM. The efflux of endogenous aspartate (Asp), glutamate (Glu) and taurine (Tau) to the incubation medium was assayed by HPLC. At 5 mM K+, perfusion of control slices with ammonia did not affect Glu and slightly depressed Asp efflux. Raising K+ concentrations in the incubation medium to 7.5 led to inhibition of Glu and Asp efflux by ammonia and the inhibitory effect was further potentiated at 10 mM K+. The inhibition was also significant at 15 mM K+. This suggests that, depression of excitatory neurotransmission associated with acute hyperammonemia is more pronounced under conditions of intense neuronal activity than in the resting state. HE moderately increased the efflux of Glu and Asp, and the stimulatory effect of HE on Glu and Asp efflux showed virtually no variation upon changing K+ concentration up to 15 mM. Ammonia strongly, and HE moderately, increased Tau efflux at 5 mM K+. However, both the ammonia- and HE-dependent Tau efflux decreased with increasing K+ concentration in the medium and was no longer significant at 10 mM concentration, indicating that intense neuronal activity obliterates the neuroprotective functions of this amino acid triggered by hyperammonemia.

Ammonia↗

PubMedDate not supplied

[Plasmapheresis and amino acid mixtures of "Aminosteril-Hepa" type preparations in treating hepatic encephalopathy].

An effect of Aminosteril-Hepa intravenous infusions or plasmapheresis on selected amino acids, ammonia, alpha-aminonitrogen serum levels and serum GGTP activity was analysed in 28 patients with liver cirrhosis with and without hepatic encephalopathy. The patients were given protein controlled dietary treatment. It was found, that plasmapheresis exerted more potent effect on previously elevated ammonia and serum alpha-aminonitrogen levels as well as serum GGTP activity than intravenous infusions of Aminosteril-Hepa. It was clearly seen in patients with liver cirrhosis without hepatic encephalopathy. Aminosteril-Hepa intravenous infusions decreased serum glutamine levels to higher degree than plasmapheresis. Both types of therapy have had no significant effect on serum phenylalanine, tyrosine, and tryptophan levels in all patients.

Amino Acids↗

PubMedDate not supplied