published_or_final_version / Paediatrics / Doctoral / Doctor of Philosophy

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

The C57 BL/KsJ db/db mouse is obese, hyperglycemic, hyperinsulinemic and serves as a model for noninsulin dependent diabetes mellitus (NIDDM). This study reports a dysfunction in the pituitary-thyroid axis and apparent peripheral resistence to thyroid hormones due to a reduction in T3 receptor binding. Diabetic mice have subnormal serum T4 concentrations and supranormal T3 concentrations which are most pronounced between 8 and 10 weeks of age. Thyroid glands of diabetic animals appear hypoactive histologically. Serum TSH concentrations approximate those found in normal mice. In vitro studies show that thryroid glands from diabetic animals are responsive to TSH. Pituitary glands from the same animals hypersecrete TSH and are responsive to TRH. Ultrastructural analysis of pituitary thyrotropes from diabetic mice indicate that these cells are hypersecretory and may be under chronic stimulation by TRH. Diet restriction maintains diabetic mice at a normal total body weight but these animals still possess abnormally large fat deposits. The thyroid hormone profile of these mice appears normal as does the histological appearance of the thyroid gland. Similarly, the blockade of peripheral deiodination by daily injection of iopanoic acid returns the thyroid hormone profile to normal.

Histamine is present in the central nervous system and is believed to be derived from neurons (50 percent) and mast cells (50 percent). This experiment was designed to analyze histologically the numbers and distribution of brain-associated mast cells in normal (+/+), mast cell deficient (W/W^v) and heterozygote (W/+, W^v/+) mice of the WBB6F_1 /J strain. Significant variations in the number and distribution of mast cells between the various genotypes were found. Based on the results, a hypothesis is proposed to account for the observed genotypical differences in mast cell numbers and distribution. Based on the total number of mast cells and the content of histamine in a typical mast cell, it is apparent that the mast cell is not a major source of brain histamine, suggesting that another non-neuronal pool of histamine must be present in the brain.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Pharmacology / Master / Master of Philosophy

Saccostomus campestris display sexual disparity in the use of summer daily torpor in response to energy stress. The hypothesis that males may compensate for a limited heterothermic capacity with lower normothermic body temperatures by maintaining lower resting metabolic rates relative to females was tested. Furthermore, the influence of testosterone on torpor incidence in males was investigated. Body temperature (T[b]) and oxygen consumption (VO₂) were measured at various ambient temperatures (Tₐ) and were compared between the sexes under food ad libitum and food restriction treatments. There were no significant differences in T[b] and VO₂ between sexes under food ad libitum treatment. Under food restriction there were pronounced sex differences in the employment of heterothermy. Females defended a lower setpoint T[b] for torpor (ca. 25°C), than males (ca. 29°C), and also employed torpor more frequently than males. Non-torpid males did, however show slight reductions in VO₂ under food restriction. The effect of testosterone on daily torpor was investigated by comparing minimum T[b]and torpor frequency of castrated mice implanted with testosterone-filled (experimental) and saline-filled (control) silastic capsules in response to food ad libitum and food restriction treatments. Testosterone inhibited torpor in males. The majority of control animals employed torpor under both food ad libitum and food restriction diets. It was concluded that although the animals were capable of shallow, summer torpor, it was confined to moderate ambient temperatures and was not used at low Tₐ's where several animals became pathologically hypothermic. Females derive energetic benefits from the use of torpor whereas males may partially compensate for their limited heterothennic capacity by a reduction in resting metabolic rates, accompanied by moderate reductions in body temperature during energetically stressful periods. The difference in the capacity for daily heterothenny between sexes was attributed to differences in their reproductive physiology. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2000.

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Natural killer (NK) cells are important in limiting tumor dissemination. The NK activity in C57B1/6 mice bearing Lewis lung carcinoma (LLC) was monitored during tumor development. During the initial period of tumor growth, NK activity was enhanced. As tumor growth progressed, NK activity became suppressed. Depletion of macrophages from the spleen cells of tumor-bearing mice restored the NK cytotoxic response. Plasma prostaglandin E2 (PGE2) concentrations were measured by a radioimmunoassay and found to become elevated during the course of tumor growth. To determine whether the suppressed NK activity might have been a result of the elevated levels of PGE2, mice were treated with a prostaglandin synthesis inhibitor, indomethacin. Indomethacin treatment prevented the rise in plasma PGE2 concentrations and the suppression in NK activity. These results support the hypothesis that the suppression of NK activity in tumor bearers is mediated by PGE2 which might be produced by the host's suppressor macro-phages.