It has been hypothesised that endogenous testosterone and AAS may predispose humans to premature CHD. However, there is no direct evidence to link these hormones with a greater prevalence of premature CHD. The aim of this thesis was to better describe atherosclerotic risk associated with these hormones by clarifying their effect on additional risk factors for premature atherosclerosis. Little is known about the effect of testosterone and AAS on 'atherogenic dyslipidaemia', a phenotype characterised by elevated postprandial triglyceridaemia, small dense LDL and a low HDLC concentration, which confers a high risk of CHD. Accordingly, the magnitude of postprandial triglyceridaemia, LDL and HDL particle size, and LDLC, HDLC and Lp(a) concentration were compared in male (n=9) and female (n=3) bodybuilders after self administration of AAS for 5-6 weeks (ON cycle) and again after a 4-6 week 'washout' period (OFF cycle), and in normal males (T) (n=10) before and during a reversible suppression of endogenous testosterone, induced using a GnRH agonist (triptorelin), and in a control group (C) (n=8). Lipoprotein size was assessed by gradient gel electrophoresis (GGE), lipoprotein concentrations by immuno and enzymatic assay, and postprandial triglyceridaemia by a standardised oral fat tolerance test (65g/m² ). HDLC decreased in male bodybuilders (0.94±0.30 vs 0.70±0.27 mmol/L, p=0.004; x ± SD) and female bodybuilders (1.3±0.5 vs 0.8±0.2 mmol/L) ON cycle. GGE studies suggested that mostly HDL₂ was reduced. There were no significant reductions in LDL particle size ON cycle. Two males had larger LDL species ON cycle. Lp(a) decreased in male bodybuilders (124.7±128.0 to 69.3±73.3 U/L, p=0.008). ON cycle postprandial triglyceride excursion was unchanged in female bodybuilders and reduced (11.6±10.0 vs 7.5±5.4 mmol/L.hr; p=0.027) in male bodybuilders. In the triptorelin study, HDLC was increased in T (1.07±0.18 vs 1.41±0.28 mmol/L, p=0.002) and not in C. GGE studies indicated an increase of HDL₂ in five T subjects and no increase in C. Total cholesterol increased in T (4.77±0.80 vs 5.24±1.04 mmol/L, p=0.039) but not in C. LDL size increased in four T subjects, and not in C. Lp(a) increased in T (277.9±149.l vs 376.5±222.2 U/L, p=0.004), but not in C. Postprandial triglyceridaemia was unchanged in both T and C. The results of these studies did not show any additional atherogenic effects of endogenous testosterone or AAS in humans. Rather, a suppression of Lp(a) may be an antiatherogenic effect of these hormones. A reduced postprandial triglyceridaemia and increased LDL size in individuals who are predisposed to 'atherogenic dyslipidaemia', may be further antiatherogenic effects of AAS use.

Thesis (Ph. D.)--University of Washington. / Bibliography: l. [101]-112.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 82-86).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 186-198).

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

Digitized by Kansas Correctional Industries

Abstract not available

Recent advances in technology permitted the first simultaneous digital recording of intranarial pressure and on-axis acoustic data from bottlenose dolphins during a biosonar target recognition task. Analysis of pressurization events in the intranarial space quantifies and supports earlier work, confirming that intranarial pressure is increased when whistle vocalizations are emitted. The results show complex relationships between various properties of the biosonar click to the intranarial pressure difference at the time it was generated. The intranarial pressure that drives the production of clicks is not the primary determinant of many of the acoustic properties of those clicks. A simple piston-cylinder physical model coupled with a sound production model of clicks produced at the monkey-lips/dorsal bursae complex yields an estimate of mechanical work for individual pressurization events. Individual pressurization events are typically associated with a single click train. Mechanical work for an average pressurization event is estimated at 10 Joules.

Thesis (Ph. D.)--University of Hong Kong, 1989.

Obesity features increased accumulation of fat in the body and results in adverse health consequences, including type II diabetes mellitus and cardiovascular diseases. The global epidemic of obesity and lack of effective treatments call for the search of new anti-obesity medication. Activation of prostaglandin receptor subtype 4 (EP4) had been shown to produce potent anti-inflammatory effect and possibly induce brite adipocytes to increase energy expenditure, both of which can potentially ameliorate obesity. The purpose of this dissertation is to characterize the metabolic phenotypes of EP4 receptor in mice and to elucidate whether administration of CAY10580, a selective EP4 agonist, could protect against obesity and its related complications. The experiments were carried out on diet-induced obese mice and EP4 knockout mice. Anthropometric measurement, glucose and insulin tolerance test, indirect calorimetry, quantitative real-time PCR, plasma analytes measurement and histological studies were performed. The findings revealed that EP4 activation by CAY10580 prevented high-fat diet fed mice from becoming obese, but it did not exhibit a curative effect in reversing obesity in mice. Activation of EP4 by CAY10580 suppressed body weight gain and adiposity in high-fat diet fed mice by reducing the weight of epididymal, subcutaneous and peri-renal white adipose tissues, inter-scapular brown adipose tissue and liver. The lower adiposity resulted in improved glucose and insulin sensitivity and lower plasma leptin level. The cause of reduced adiposity by EP4 activation is not due to changes in energy intake, obligatory energy expenditure, locomotor activities, adaptive thermogenesis and lipolysis. EP4- mediated reduction in adiposity was characterized by smaller adipocyte size and greater proportion of small adipocytes in subcutaneous white adipose tissue. Furthermore, mice deficient in EP4 also showed reduced adiposity at epididymal, subcutaneous and peri-renal white adipose tissues, and inter-scapular brown adipose tissue. The reduced adiposity in EP4 deficient mice was associated with impaired cold intolerance. Taken together, EP4 activation is effective in preventing obesity and relieving obesity-associated glucose and insulin tolerance, and EP4 might play an essential role in adiposity maintenance through the modulation on adipocyte development. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences