Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1997. / Copy of author's previously published article. Bibliography: leaves 189-219.

Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Food Science." Includes bibliographical references (p. 96-102).

Thesis (Ph. D.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 148-191).

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Karen L. Rascati. Vita. Includes bibliographical references.

Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on Dec. 1, 2009). Includes bibliographical references.

Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

A dissertation presented in compliance with the requirements for the Master's Degree in Technology: Chiropractic, Technikon Natal, 2001. / Low back pain is a major health problem worldwide, and considerable amounts of money are spent on a variety of practitioners including medical practitioners, chiropractors, osteopaths, physiotherapists and others. There is a lack of consensus among these groups regarding the most appropriate therapy or management for low back pain. This disparity leads to the meritable conclusion that more research is required to accurately identify solutions for the management of low back pain (Walker, 1997:95-96). / M

Previous studies in the sheep, rabbit, cat and rat have demonstrated the ability of the neuropeptide, arginine vasopressin (AVP), to suppress endotoxin-induced fever when perfused into a discrete brain locus. Fever can also be suppressed if AVP is microinjected into the cerebral ventricles of the rat. The mechanisms by which AVP mediates antipyresis are unknown. Experiments were conducted, therefore, to examine the effect of intracerebroventricular (icv) AVP on an established fever and to assess the mechanism of action using a specific, V₁-receptor antagonist (M-AVP). Studies were also conducted to elucidate the effector mechanisms utilized to accomplish antipyresis induced by icv AVP. Finally, cerebrospinal fluid (CSF) AVP concentrations were measured in febrile and non-febrile rats to determine the role of endogenously released AVP in the CSF during fever. AVP administered icv was shown to have marked antipyretic effects at very low doses. This antipyresis was elicited in rats with an established fever but the peptide had no effect on the temperature of non-febrile rats. Thus AVP both prevented and reversed endotoxin-induced fever. Furthermore, this AVP-induced antipyresis was abolished by pretreatment with the the V₁-antagonist, M-AVP. The antipyretic effects of AVP were, therefore, receptor mediated and likely to be of physiological importance. Efforts to manipulate the endogenous AVP system by icv M-AVP were also attempted. When M-AVP was injected icv, the fever height of endotoxin-treated rats was not different from endotoxin-treated controls. In addition, M-AVP did not influence the magnitude of the antipyresis induced by indomethacin. It has become clear, however, that this method of administering the antagonist is inappropriate to block endogenous AVP effects occurring within the neuropil. Subsequent experiments in another laboratory have shown that M-AVP must be microinjected into the AVP-sensitive brain locus to effectively block endogenous activity. The antipyretic response to icv AVP was further investigated at three ambient temperatures in an attempt to identify the effector mechanisms involved. Responses of non-febrile and febrile rats to icv injections of AVP and sc injections of indomethacin were observed at cold (4°C), neutral (25°C) and warm (32°C) ambient temperatures. As in the previous experiments, AVP at 25°C decreased brain temperatures of febrile but not non-febrile rats. This antipyretic effect was also observed at the warm ambient temperature and during cold exposure. Responses to sc indomethacin were qualitatively similar to icv AVP at neutral and warm temperatures. In the cold, however, indomethacin decreased the brain temperature of both non-febrile and febrile animals, although unlike AVP, brain temperature of non-febrile animals decreased somewhat more than that of febrile animals. These data showed that AVP decreased brain temperature of febrile more so than non-febrile rats at all ambient temperatures and may therefore have been acting partially on febrile set-point. It was possible that AVP affected specific effector mechanisms since antipyretic effects were of different magnitudes at different ambient temperatures. The observation that AVP and indomethacin had qualitatively similar effects on fever at three ambient temperatures suggested that they may act via a common neural pathway. Further analysis of the mechanism of icv AVP-induced antipyresis was conducted at the three ambient temperatures while measuring specific effectors: heat loss and heat production. At 25°C, AVP-induced antipyresis was mediated by tail skin vasodilation while metabolic rate was unaffected. At 4°C, the antipyresis produced by AVP was mediated exclusively by inhibition of heat production since the metabolic rate decreased markedly following AVP. This antipyresis at 4°C was accompanied by cutaneous vasoconstriction. At 32°C, neither vasomotor tone, metabolic rate nor evaporative heat loss could be shown to contribute to the small antipyretic effect elicited by AVP. These data strongly suggest that icv AVP produced antipyresis by affecting the febrile body temperature set-point mechanism since the thermoregulatory strategy to lose heat varied at different ambient temperatures and the decrease in body temperature could not be shown to be due to changes in a single effector mechanism. As an index of endogenous AVP activity, cerebrospinal fluid (CSF) concentrations of AVP were measured in febrile and non-febrile rats in order to determine the role of CSF AVP in fever and antipyresis. The results demonstrated that the AVP release pattern was not altered in endotoxin-treated febrile compared to non-febrile rats. It was concluded that CSF AVP had no role in the febrile process. In summary, icv AVP appears to induce antipyresis by its action on febrile set-point rather than on a specific effector system. This action of AVP is mediated by a V₁-like receptor mechanism which is not affected by endogenous CSF AVP. The neural/neurochemical basis for the thermoregulatory set-point has not been clearly established so the mechanism of action by which AVP affects set-point remains to be determined. These data contribute, however, to the growing body of evidence that AVP is acting centrally as a neurotransmitter or neuromodulator to regulate body temperature during the febrile process. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Inflammation appears to be an attempt by the organism to re-establish homeostasis as a response to local reactive change in tissues following injury or irritation. This injury or irritation (whether caused by micro-organisms, toxins, antigens, etc.) first leads to an increased passage of fluid through the walls of the microvasculature, followed by stasis of circulation within the affected area. This, in turn, is followed by migration of leukocytes into the area and finally concluded by connective tissue proliferation leading to the deposition of granulation tissue. There are many experimental models employed for the evaluation of drugs with possible anti-inflammatory activity. Since many of these systems employ whole animals, it seems rational that various hematological parameters could be applied. Our purpose was to test such parameters in two selected systems (i.e., adjuvant-induced arthritis and cotton pellet granuloma formation) during drug evaluation. The parameters under investigation included: total white blood cell count, differential leukocyte count, sedimentation rate and serum protein patterns.

It has become apparent in recent years that many centrally active agents possess potential anti-inflammatory capabilities. The central or peripheral mechanisms of action for these agents have not been delineated nor has their clinical efficacy baan established or refuted. The centrally active drugs, cryogenine and tetrabenazine (a benzoquinolizine derivative), previously have been shown in this laboratory to inhibit certain models of induced inflammation. The present study in rats verifies the anti-inflammatory properties of cryogenic and established that a structurally related series of benzoquinolizine derivatives possessed the capability of inhibiting both exudative (carrageenan-induced pedal edema) and proliferative (cotton pellet granuloma) models of inflammation when administered orally.