South african society of pathologists: Abstracts of papers

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Factors affecting haem degradation in rat brain

[No abstract available]Articl

Lack of effect of phenobarbitone treatment on metabolism and brain uptake of delta aminolaevulinic acid in rats

Rats were treated daily with phenobarbitone and delta aminolaevulinic acid (ALA) for 5 days. Phenobarbitone treatment had no significant effect on ALA metabolism and excretion or on ALA uptake into brain tissue. No significant behavioral effects other than those attributable to phenobarbitone alone were observed. These results do not support the suggestion that porphyrinogenic drugs may precipitate acute neuropathic effects in the hereditary hepatic porphyrias through altering porphyrin precursor metabolism or uptake of these compounds by neural tissue.Articl

Effect of iron and hexachlorobenzene on liver haem biosynthesis

The original publication is available at http://www.samj.org.za[No abstract available]Publisher’s versio

Catecholamine-cAMP-Ca2+ induces arrhythmias in the healthy pig heart

[No abstract available

Plasticity of brain muscarinic receptors in aging rats: The adaptative response to scopolamine and ethanol treatment

Young and aged rats were treated chronically with ethanol or scopolamine. Muscarinic receptors were measured in cerebral cortex, hippocampus and striatum. Following scopolamine treatment muscarinic receptor density in cerebral cortex, hippocampus and striatum of young rats increased by 34, 57 and 27%, respectively; in brains of aged rats the increase was 41% in cerebral cortex, 43% in hippocampus and nil in striatum. Affinity of muscarinic receptors was not changed by scopolamine treatment. Following chronic ethanol administration there was a 48% increase in cortical muscarinic receptor density in young, but not aged rats. The density of muscarinic receptors in hippocampus and striatum of both young and aged rats was not affected by ethanol treatment. Affinity of receptors in hippocampus of aged, ethanol-treated rats was increased compared to age-matched controls. Adaptative responses of the muscarinic receptor/transducer system to neurotransmitter availability are present in both young and aged rats, buth the ethanol-induced response is present only in young animals. This suggests differences in the mechanism of action of ethanol and receptor agonists and antagonists in modulating receptor plasticity

Increased sensitivity of the hippocampus in ethanol-dependent rats to toxic effect of N-methyl-D-aspartic acid in vivo

Chronic administration of ethanol in animals leads to CNS tolerance and physical dependence. Subsequent withdrawal of ethanol causes hyperexcitability which is thought to be related to increased sensitivity of N-methyl-d-aspartic acid (NMDA) receptors. The purpose of this study was to investigate sensitivity to NMDA in ethanol-treated animals by detecting damage after intrahippocampal injection of NMDA. Choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) specific activity was used as markers of cholinergic and γ-aminobutyric acid neurons, respectively. Ethanol-dependent animals were more liable to die following intrahippocampal injection of either 120 or 240 nmol of NMDA. There was a significantly greater decrease in hippocampal GAD but not ChAT specific activity in the surviving animals. These data support the hypothesis that ethanol dependence is associated with increased sensitivity to NMDA which may be responsible for excitotoxic brain damage and death

Ethanol and protein kinase C in rat brain

The effect of chronic ethanol consumption on the catalytic activity of protein kinase C isolated from rat brain was studied in two different ways. Enzyme activity was first measured by phosphorylation of Histone IIIS in vitro. There was no change in the activity of the cytosolic enzyme. Membrane-associated enzyme activity was reduced in the ethanol-treated animal. This difference was not evident if the enzyme was stimulated by arachidonate. The reduction in enzyme activity was confirmed by analysis of the phosphorylation of endogenous substrates in intact synaptosomes. When the binding of the ligand [3H]phorbol dibutyrate was measured by quantitative autoradiography, increased binding to membrane-associated protein kinase C was observed in the CA1 region of the hippocampus but not in other brain regions. These results indicate that ethanol treatment results in a general reduction in membrane-associated protein kinase C activity as measured in vitro but the effect may not be consistent in all brain regions. The differential effect in the CA1 region of the hippocampus may be a reflection of a disruption in the normal regulation of protein kinase C activity in this area and may indicate that this region is a sensitive target for the action of ethanol

The effect of chronic ethanol consumption on muscarinic receptors in rat brain

Ethanol (15% v/v) was administered in the drinking water to male Wistar rats over period of 3 months. Binding properties of muscarinic receptors were studied in synaptosomes from selected brain areas using [3H]quinuclidinyl benzilate and its displacement by the selective antagonist, pirenzepine and the agonist, carbachol. Dissociation constants (Kd) of all three ligands in the cerebral cortex, hippocampus and striatum of ethanol-treated groups did not differ from those in controls. Density of [3H]quinuclidinyl benzilate binding sites in the cortex of ethanol-treated animals was approx. 50% higher than in controls (2.06 ± 0.2 and 1.32 ± 0.2 pmol/mg of protein respectively, mean ± SD, n = 6, P < 0.001). This was largely attributable to an increase in M1 binding sites as shown by pirenzepine displacement studies. In the hippocampus and striatum binding capacity of muscarinic receptors was not affected by ethanol treatment. Synthesis of acetylcholine in cerebral cortex prisms from ethanol-treated animals was not inhibited under resting conditions, but stimulation of synthesis by high K+ concentration was significantly altenuated by comparison with controls. These results suggest that chronic ethanol consumption induces changes in cholinergic neurotransmission in selected brain areas

Interaction of chronic ethanol consumption and aging on brain muscarinic cholinergic receptors

It has been proposed that ethanol and aging may interact synergistically to impair brain function through effects on central muscarinic receptors. Previous studies have investigated the effect of either chronic ethanol treatment or aging, but not both factors simultaneously, on brain muscarinic receptors. We have studied brain muscarinic receptors in animals treated with ethanol for up to 25 months. Ethanol consumption for 3 and 9 months resulted in increased density of quinuclidinyl benzilate (QNB) binding sites in cortex, coinciding with an increase in high-affinity pirenzepine binding sites and low-affinity carbachol binding sites. Upregulation of QNB binding sites in striatum and hippocampus became obvious after further ethanol treatment (15 and 21 months, respectively). Affinity of QNB binding sites and carbachol binding sites was not altered by ethanol treatment. However, there was an ethanol-related decrease in affinity of low-affinity pirenzepine binding sites in cerebral cortex. Density of QNB binding sites and low-affinity pirenzepine binding sites decreased with age in three brain areas investigated. There were age-related changes in receptor affinity in hippocampus and striatum, but not in cortex. Ethanol-related upregulation of muscarinic receptors was superimposed on age-related loss of receptors. We conclude that acceleration of the aging process associated with ethanol abuse is unlikely to be explained on the basis of alterations in receptor density or affinity