Wound healing is a dynamic process that ultimately leads to restoration of tissue integrity and function. The pineal gland hormone melatonin is known for its anti-oncotic, anti- inflammatory and immuno-modulatory effects. However, its role in wound healing has not been established. Since melatonin is synthesised endogenously, we primarily sought to investigate whether the melatonin receptors played a role in the wound healing process. Using immunohistochemical methods and Western blot analysis we observed that MT₁ was normally absent in the rat skin but was strongly expressed on day 1 to day 3 post wounding in the epidermis adjacent to the wound edge. MT₁ expression was restricted to the stratum granulosum and stratum spinosum layers of the epidermis in the rat wounds. MT₁ expression declined thereafter and became nonexistent by day 21 when the wound had completely healed. In contrast, MT₂ was constitutively expressed in all the layers of the normal rat epidermis. MT₂ expression gradually decreased at the injury site following wounding but returned to the normal profile by day 21. Aged rat epidermis showed similar MT₁ and MT₂ expression as adult rats. The profile of tissue distribution of MT₁ and MT₂ in the human epidermis was comparable to the rat epidermis. In the CVUs MT₁ and MT₂ localisation profiles resembled that of a healing wound, akin to a day 1 or day 3 rat dermal wound, during the inflammatory phase. Surprisingly, in contrast to all the tissues investigated, MT₁ was also localised in the stratum basale layer of the keloid epidermis. MT₂ localisation in the same keloid tissues however resembled normal human skin profiles. Secondly, we determined the effects of exogenously administered melatonin, on scarring and wound healing, using a full thickness incisional model of wound healing in rats. Melatonin treatment significantly improved the quality of scarring by day 21. However, our findings would have been strengthened by a more explicit wound closure analysis, measurement of granulation tissue weight, tensile strength, hydroxyl proline content and immunohistochemical assessments of neutrophil infiltration, macrophages, fibroblasts, myofibroblasts and reepithelialization. The treatment also accelerated the angiogenic process and enhanced the VEGF protein profile. Arginase generates proline, the building block for collagen synthesis. Melatonin treatment increased arginase activity and consequently would increase collagen synthesis from day 1. An increase in NOS activity and therefore NO production is known to be detrimental during inflammation. However, various studies have also shown that the NO is essential for granulation tissue formation. Melatonin treatment significantly decreased iNOS activity during the acute inflammatory phase in this study, but significantly increased iNOS activity during the resolving phase. Other markers of inflammatory response and repair were also examined in this study. COX-2 has been shown to play an anti-inflammatory role and melatonin increased COX-2 activity and protein following wounding. SOD (the antioxidant enzyme) activity was also significantly increased during the chronic inflammatory phase on melatonin administration. HO-1 and HO-2 isoforms have also been previously demonstrated to participate in the repair process. Melatonin treatment increased up-regulation of both HO-1 and HO-2 protein expression in the wounded skin. A significant decrease in all the mitochondrial enzyme activities (except complex-II-III), was observed post wounding. Melatonin treatment restored the complex activities to near normal levels. Melatonin also protected mitochondrial membrane integrity and reduced oxidative stress as evidenced by the maintained level of aconitase and citrate synthase activities at near normal levels. In vitro experiments using macrophage and fibroblast cell lines illustrated that melatonin may decrease NOS activity and protein profiles indirectly by stimulating arginase activity and thereby depleting the availability of arginine. This study is the first to fully demonstrate the distribution of melatonin receptors in normal and abnormal wounds. Improvement in the quality of scarring in a rat model of wound healing on melatonin administration is promising but much more quantitative work and preclinical studies are required before melatonin advances into clinical assessment.

ix, 237 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1979) from the Dept. of Obstetrics and Gynaecology, University of Adelaide

[20] 172 [45] leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1974) from the Dept. of Medicine, University of Adelaide

Typescript (photocopy) / 1 v. (various paging) : ill., (part col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pharmacology, 1982

Includes bibliographical references (leaves 165-225) / xx, 298 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Molecular and Biological Sciences, Discipline of Physiology, 2004

No description available.

Typewritten Bibiography: leaves 209-222.

Graduation date: 1968

The OSU global coupled atmosphere/ocean general circulation model (A/O GCM) has been used to simulate the present (lxCO₂) climate and to investigate a CO₂-induced (2xCO₂) climate change. Previous analysis of the lxCO₂ simulation showed distinct errors in the simulated sea surface temperature (SST) and sea ice which were attributed primarily to the atmospheric GM (AGCM). Analysis of the 2xCO₂ simulation showed that the CO₂-induced warming penetrated into the ocean; this caused a delay in the equilibration of the climate system with an estimated e-folding time of 50-75 years. The present study has two objectives. The principal objective is to answer the question: By what pathways and through which physical processes does the simulated ocean general circulation produce the penetration of the CO₂-induced warming into the ocean? The secondary objective is to evaluate the performance of the oceanic GCM (OGCM) in the lxCO₂ simulation. The comparison of the simulated lxCO₂ internal oceanic fields with the corresponding observations shows that although they are basically similar, there are distinct errors. Further analysis shows that these errors were generated by the OGCM during its spin-up integration prior to its coupling with the AGCM. This study thus shows that it is not sufficient to compare the simulated SST with the observed SST to evaluate the performance of the OGCM. It is also necessary to compare the simulated internal oceanic quantities with the corresponding observed quantities. The global mean analysis of the CO₂-induced climate changes shows that the ocean gains heat at a rate of 3 W/m² due to the CO₂ doubling. This heat penetrates downward into the ocean predominantly through the reduction in the convective overturning. The zonal mean analysis shows that the surface warming increased from the tropics toward the mid-latitudes of both hemispheres and penetrated gradually to the deeper ocean. The oceanic warming penetrated to a greater depth in the subtropics and mid-latitudes than in the equatorial region. A zonal mean heat budget analysis shows that the CO₂-induced warming of the ocean occurs predominantly through the downward transport of heat, with the meridional heat flux being only of secondary importance. In the tropics the penetration of the CO₂-induced heating is minimized by the upwelling of cold water. In the subtropics the heating is transported downward more readily by the downwelling existing there. In the high latitudes the suppressed convection plays the dominant role in the downward penetration of the CO₂-induced heating. / Graduation date: 1987

The miniaturization of Microtechnology-based Energy, Chemical and Biological Systems (MECS) is made possible by the use of high aspect ratio microchannel arrays to increase the surface-area-to-volume ratio of the flow conduits within the devices, resulting in an improvement in the heat and mass transfer performance of the devices. However, advantages of the MECS concept cannot be applied to high-temperature applications (above 650��C) due to lack of high-temperature MECS devices; therefore, the development of high-temperature MECS devices is necessary to overcome this bottleneck. This dissertation involves the development of high-temperature MECS devices from a high-temperature material, nickel aluminide (NiAl). NiAl foil was synthesized from elemental nickel (Ni) and aluminum (Al) foils through a two step process--tack bonding and reactive diffusion. The elemental foils were tack bonded at 500��C, 3.9 MPa for 15 minutes. The reactive diffusion process was then performed through a heat treatment at 1000��C for a period of time corresponding to the thickness of the composite foil. The synthesized NiAl foil showed an atomic ratio of Al to Ni up to 0.96. The foil also showed a decent flatness and surface roughness. This dissertation proposes a reactive diffusion bonding as a joining technique of nickel aluminides. An investigation of bonding parameter effects on the warpage of nickel aluminide fins in the reactive diffusion bonding process was performed. Results showed that bonding time and temperature had significant effects on warpage of the fin. The fin warpage increased with the increase of bonding time and bonding temperature. Results also suggested that the bonding pressure had an effect on the fin warpage. However, chemical compositions of the fin were not significant to the warpage. This research also proposes a new fabrication procedure for producing NiAl MECS devices. NiAl foils were used as the starting material, and the reactive diffusion bonding technique was employed as the joining technique. The research outcome indicated the viability of the proposed method in fabricating NiAl MECS devices. This method achieved leak-tight devices with a reasonable fin flatness. / Graduation date: 2003