The Role of the Sympathetic Nervous System in the Hypothermic Effect of d-Fenfluramine

Experiments in this dissertation were conducted to characterize the effects of d-fenfluramine on body temperature and the mechanisms by which d-fenfluramine alter body temperature. The experiments were conducted in conscious male Sprague-Dawley rats. Body temperature was measured in all animals using telemetry. The results of the experiments indicated that d-fenfluramine altered body temperature in animals kept 28, 22, 16 and 4 degrees Centigrade. D-fenfluramine produced hyperthermia in animals kept at 28 degrees Centigrade and varying degrees hypothermia at normal and cooler ambient temperatures. Further experiments were conducted to explore the effects of d-fenfluramine on brown adipose tissue (BAT) thermogenesis, cutaneous vascular tone and whole body oxygen consumption. In animals kept at 22 and 4 degrees Centigrade, we found that d-fenfluramine activated BAT, as indicated by a decrease in BAT norepinephrine content, to the same magnitude. Thus, the hypothermia seen at normal and cooler ambient temperature was not due to lack of BAT activation. Also, activation of BAT by d-fenfluramine was mediated through the sympathetic nervous system and through release of central serotonin, since ganglionic blocker pentolinium and serotonin reuptake inhibitor fluoxetine blocked d-fenfluramine-mediated BAT activation. In animals kept at 16 degrees Centigrade, d-fenfluramine increased tail-skin temperature (Tsk), an index of cutaneous vascular tone, indicating that d-fenfluramine produced cutaneous vasodilation. d-fenfluramine-induced increase in Tsk was mediated through withdrawal of the sympathetic vasoconstrictor tone to the tail, since pentolinium blocks this effect. In animals kept at 28 degrees Centigrade, d-fenfluramine produced a decrease in Tsk, indicating vasoconstriction. The effects of d-fenfluramine on the Tsk were mediated through release of serotonin, since fluoxetine blocked these effects. D-fenfluramine increased whole body oxygen consumption, an index of metabolic activity and the increase was due to BAT activation, since pentolinium prevented the increase. Thus, although d-fenfluramine increased metabolic activity through BAT activation, the increase was insufficient to make up for the heat loss produced by cutaneous vasodilation and thus produces hypothermia. The hyperthermia seen at 28oC is due to activation of BAT and the subsequent inability of the animal to lose the excess heat due to cutaneous vasoconstriction produced by d-fenfluramine at 28 degrees Centigrade

The Use of Poly(vinyl alcohol)-based Hydrogels in Biomedical Applications

Polymers have found increasing favor in biomedical applications due to the greater control that researchers can exert over their properties. Researchers have focused on the development of therapies using biologically compatible polymers due to their ability to limit potentially harmful interactions with the body. This research has led to advances in tissue engineering, controlled and targeted drug delivery, and other biomedical fields, with the goal of improving both the effectiveness and accessibility of health care. Poly(vinyl alcohol) (PVA) hydrogels possess several chemical properties that make them well suited for biomedical applications. These include inertness and stability, biocompatibility, and pH-responsiveness. As a result, PVA based materials have been studied for potential applications in areas of biomedicine such as targeted drug delivery, tissue engineering, and wound healing. This thesis examines the properties of PVA and seeks to understand how the chemical and physical structure affects their properties. It then examines how these properties enhance their utility in potential biomedical applications. Finally, it reviews the research into development of PVA based materials for three different biomedical applications.Chemical Engineerin