Doctoral Degrees (Chemical Pathology)

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Browsing Doctoral Degrees (Chemical Pathology) by Subject "Dissertations -- Medicine"

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    Interactions between the noradrenergic and dopaminergic neurotransmitter systems in the rat brain
    (Stellenbosch : Stellenbosch University, 1990) Allin, Rosemary; Taljaard, J. J. F.; Russel, V. A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Department of Pathology.
    ENGLISH ABSTRACT: The development of a dissection technique enabled the nucleus accumbens to be dissected into six and the striatum into eighteen discrete areas. The concentration of monoamines in these areas was analysed by high performance liquid chromatography (HPLCl with electrochemical detection. The distribution of the different monoamines in the nucleus accumbens was not identical. In general, concentrations were found to be low in the rostral area of the nucleus accumbens. Marked differences were observed in the medial area. Dopamine (DA) levels were significantly lower in the ventrorostral than in the dorsorostral nucleus accumbens and high in both medial and caudal areas. Noradrenaline (NA) and serotonin (5-HT) levels were considerably lower than those of DA. The NA concentration was highest in the caudal area of the nucleus accumbens and the 5-HT concentration was highest in the ventrocaudal area There was evidence for a rostrocaudal decrease in DA and 5-UT turnover in the nucleus accumbens. In the striatum, DA levels were higher rostrally than caudally, the lowest levels being found in the globus pallidus. NA levels were low throughout the striatum but significantly higher in the globus pallidus 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels were higher ventrally than dorsally and ancreased along the rostrocaudal axis. Selective lesioning of the locus coeruleus (LC) noradrenergic neurons by the administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) or by direct infusion of 6-hydroxydopamine (6-OHDA) resulted in a decrease in NA concentration in the rostral area or the nucleus accumbens. DA and 5-HT levels were not affected by those lesions. DSP4 lesions caused increased 3,4-dihydroxyphenyl acetic (DOPAC) turnover in the ventromedial and ventrocaudal areas, indicating increased catechol-O-methyitransferase (COMT) activity in these areas, 6-OHDA lesions of the medial forebrain bundle (MFB) resulted in decreased NA and DA levels in all areas of the nucleus accumbens. DA turnover was increased, indicating increased monoamine oxidase (MAO) activity in the medial and caudal areas after MFB lesions. lncreased 5-HIAA/5-HT ratios were also found in the medial and caudal areas. The distribution or DA DI and D2 receptors in the nucleus accumbens was determined by means of radioligand binding assays [3H|SCH23390 was used to label DA D1 receptors and [3H]spiperone was used for DA D2 receptors. The distribution of DA D1 and D2 receptors was not superimposable although there was considerable overlap. DA D1 receptor density roughly followed the DA innervation, being low rostrally and high medially and caudally. There were no dorsoventral differences. In the ventrorostral area it appears that relatively few, more active neurons can activate a similar number or postsynaptic DA D1 receptors. DA D2 receptor density was lowest in the ventrorostral area, highest in the dorsomedial area and similar in the remaining areas of the nucleus accumbens. Chronic treatment with desipramine resulted in no significant changes in DA D1 or D2 receptor number or affinity in the nucleus accumbens, therefore increased dopaminergic transmission occurring after chronic antidepressant treatment would appear not to be due to direct changes in DA receptor binding.
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    Mutational analysis of the solute carrier family 11 member 1 gene (SLC11A1) implicated in iron transport
    (Stellenbosch : Stellenbosch University, 2003-12) Zaahl, Monique G. (Monique Glenda); Kotze, Maritha J.; Warnich, L.; Winter, T. A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences.
    ENGLISH ABSTRACT: The solute carrier family 11 member 1 gene (SLC11A 1) is a divalent metal ion transporter with various pleiotropic effects on macrophage function. This gene that regulates iron, and is also regulated by cellular iron levels, has previously been linked to many infectious and autoimmune diseases. In this analysis, in vitro studies using the luciferase reporter system as well as case-control association studies were applied to investigate the significance of SLC11 A1 allelic variation in patients with diverse disease phenotypes. For in vitro studies, five different SLC11A 1 promoter constructs were generated, followed by transfection into U937 and THP-1 cells. The inserted fragments included two previously described alleles (alleles 2 and 3), two novel alleles identified in this study (alleles 8 and 9) and a C to T point mutation at nucleotide position -237 in the presence of allele 3. The most striking finding was the opposite effect observed for allele 3 in the presence of the -237C~ T polymorphism, similar to that of allele 2. Although the SLC11A 1 gene has previously been implicated in iron transport, we have demonstrated, for the first time, that the various alleles investigated cause differential expression of the gene upon iron loading. Association studies were performed by investigating diseases including oesophageal cancer (DC), inflammatory bowel disease (lBO) and hereditary haemochromatosis (HH) (or primary iron overload). Significant associations (P