Browsing by Author "Neethling, A. C."

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    Isovaleric acidaemia in two South African children
    (Health & Medical Publishing Group, 1977) Malan, C.; Neethling, A. C.; Shanley, B. C.
    Two siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacks. However, both out patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.
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    Katesjolestrogene
    (Health & Medical Publishing Group, 1980) Neethling, A. C.; Taljaard, J. J. F.
    Hydroxylation of oestrogens in the 2 or 4 positions leads to the formation of catechol oestrogens. These compounds are physiologically active in animals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an oestrogenic action or interaction with the catecholaminergic systems. These compounds are also formed in human subjects. Surprisingly high levels are found in the urine. The peri-ovulatory peak in urinary catechol oestrogen excretion is compatible with a role for these compounds in the control of gonadotropin secretion.
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    Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta aminolaevulinic acid
    (Health and Medical Publishing Group (HMPG), 1975) Shanley, B. C.; Neethling, A. C.; Percy, V. A.; Carstens, M.
    It has been proposed that delta aminolaevulinic acid (ALA), which is overproduced in the inherited hepatic porphyrias, may be responsible for the neurological manifestations of the acute attacks seen in these disorders. Studies were conducted in rats to test the neurotoxicity of ALA. It was found that, after intraperitoneal or subcutaneous injections, ALA is rapidly eliminated via the kidneys. In nephrectomised animals sustained elevation of blood ALA concentration was demonstrated, but despite this, brain uptake was extremely low. Experiments on incorporation of [4 14C] ALA into brain haem yielded similar information. After intraventricular injection of [4 14C] ALA, significant uptake by brain tissue occurred. The subsequent disappearance of ALA was moderately rapid and was virtually complete within 24 hours. Uptake of [4 14C] ALA was apparently significantly greater in the hypothalamus than in other brain areas. The subcellular distribution of radioactivity did not reveal any preferential uptake by nerve endings. Intraventricular injection of unlabelled ALA revealed definite but transitory neurotoxic effects in doses of 3 micromoles and greater. These include involuntary movements and ataxia. No effect of ALA administration on brain protein synthesis could be demonstrated. It is concluded that ALA does have effects on the nervous system in vivo, but the significance of these effects in relation to the pathogenesis of the neurological manifestations of acute porphyria is questionable.
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    Pathogenesis of neural manifestations in acute porphyria
    (Health & Medical Publishing Group, 1977) Shanley, B. C.; Percy, V. A.; Neethling, A. C.
    At least 4 possible mechanisms may be postulated to explain the neural manifestations of acute porphyria in the hereditary hepatic porphyrias. These are: (i) excessive amounts of porphyrins or porphyrin precursors produced in the liver during acute attacks are transported to the central and peripheral nervous system, where they exert neurotoxic effect; (ii) unidentified metabolites of the aforementioned compounds may be responsible; (iii) in patients with these diseases there may be a metabolic defect in neural haem biosynthesis which is aggravated by precipitating factors, thereby leading to acute neural manifestations; and (iv) the hepatic and nervous system lesions may be metabolically quite unrelated. Each of these possibilities is considered, and evidence is adduced that a genetic defect in haem biosynthesis in the nervous system is the most plausible hypothesis.
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    Sex-dependent differences in phenobarbitone-induced oestradiol-2-hydroxylase activity in rat liver
    (Health & Medical Publishing Group, 1981) Theron, C. N.; Neethling, A. C.; Taljaard, J. J. F.
    Oestradiol-2-hydroxylase (E2-OH) activity was measured in liver and brain microsomes of 6-8-week-old Wistar rats. Phenobarbitone (75 mg/kg daily for 3 days) significantly increased enzyme activity in the liver of males and females, but there were striking differences between the two sexes. In males the enzyme activity was increased by 37% over control values and in females by 200%. The total microsomal cytochrome P-450 content was increased by 75% in males and by 82% in females. The apparent Michaelis constant (Km) of E2-OH for 17β-oestradiol in untreated males (9.8 μM) and females (9.2 μM) did not differ significantly. Phenobarbitone treatment, however, tended to reduce the apparent Km in males (8.2 μM) and to increase it in females (18.7 μM). E2-OH activity was also detected in brain tissue of both sexes, but it was 50-200-fold lower than in the liver and was not increased by phenobarbitone.