Thesis--Gothenburg. / Summary in English. Includes bibliographical references (p. 222-227).

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2009. / Title from first page of PDF file (viewed July 14, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 64-86).

Thesis (M.A.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on August 12, 2009) Includes bibliographical references.

Thesis (M. Ed.)--Acadia University, 2001. / Includes bibliographical references (leaves 95-96). Also available on the Internet via the World Wide Web.

Thesis--PlanB (M.S.)--University of Wisconsin--Stout, 1999. / Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 84-95). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 84-95). Also available on the Internet.

Thesis (M.S.)--State University of New York at Binghamton, Department of Psychology, 2008. / Includes bibliographical references.

Chronic non-healing wounds commonly present in patients with diabetes. These wounds are characterised by elevated numbers of immature leukocytes and M1 macrophages and reduced numbers of endothelial cells and M2 macrophages, impairing wound healing resolution. Topical treatment of murine diabetic wounds with a Hoxa3 gene expression vector redresses the balance of inflammatory and pro-healing cells within the lesion, reducing excessive inflammation and rescuing the wound healing phenotype. In this thesis I present experiments to further understanding of how diabetes alters the macrophage phenotype and how this may cause the decreased endothelial cell and M2 macrophage numbers in the diabetic wound. In vitro culture was used to characterize the intrinsic changes of diabetic macrophages isolated from the environmental effects of the diabetic wound milieu. These same systems were used to develop a cell culture system for the promotion of monocytic to endothelial transdifferentiation. Finally the in vitro macrophage culture system was used to assess the effects of Hoxa3 treatment upon diabetic macrophages and how Hoxa3 transcriptional activity in macrophages may contribute to the restoration of wound healing. In vitro cultured diabetic macrophages were observed to raise an increased response to classical and alternative activation signals that may contribute to the excessive inflammatory state of diabetic cutaneous wounds. Treatment of these macrophages for four days with a Hoxa3 conditioned medium protein transduction system upregulated the expression of the plasminogen activator urokinase receptor gene Plaur and enhanced the expression of macrophage maturation markers. These macrophages also exhibit an enhanced response to classical activation stimuli, a reduced alternative activation response. In an in vitro neovascularisation assay Hoxa3 treated macrophages inhibit vessel growth. These effects of Hoxa3 treatment of diabetic macrophages are unexpected based on the rescue of the inflammatory phenotype with Hoxa3 treatment of diabetic wounds. Non-diabetic macrophages were also treated for four days with a Hoxa3 conditioned medium and exhibited upregulation of macrophage maturation markers. These macrophages showed no difference in activation state polarisation compared to macrophages grown in a control conditioned medium but did upregulate activation markers in unstimulated cells. This may be indicative of a priming for response to low levels of activation stimuli. The Hoxa3 treated non-diabetic cells also promoted the formation of vessel networks in a neovascularisation co-culture assay, possibly through the promotion of angiogenesis. These results suggest that diabetes directly effects the maturation and inflammatory phenotype of macrophages and that Hoxa3 treatment rescues the impaired maturation phenotype and may stimulate macrophage populations to a pro-angiogenic state.

Skeletal muscle is a highly metabolically active tissue, both in the adult and the fetus. Mitochondria are essential in providing energy in the form of ATP from the oxidative metabolism of carbohydrates, fats and amino acids. Mitochondrial function is influenced by the abundance and activity of the complexes comprising the electron transfer system (ETS) and the balance between mitochondrial fusion and fission. Any factors which affect the development of skeletal muscle, and mitochondria in particular, may have an impact not only on neonatal health but also on the metabolic health of the adult offspring. However, the normal developmental profile of skeletal muscle mitochondrial function as the fetus prepares for the increased metabolic challenges associated with extrauterine life, is not well characterised. The hormones, cortisol and triiodothyronine (T3) are known to be crucial in the maturation of several physiological processes during late gestation. Further, their role in regulating adult metabolism is well-documented. However, whether they play a role in regulating fetal mitochondrial function is unknown. Using fetal sheep, the aims of this project were twofold: 1) to determine any changes in skeletal muscle mitochondrial function which occur over the last third of gestation and in the first two days of neonatal life and 2) to determine any regulatory roles of cortisol and T3 in these developmental changes. Mixed fibre-type skeletal muscle was collected from fetuses at 3 time points over late gestation and from newborn lambs. In addition, skeletal muscle samples were taken from fetuses which had been thyroidectomised (TX) and fetuses infused with either T3 or cortisol. Respirometry, enzyme assays, qRT-PCR and western blotting were carried out on the skeletal muscle samples in order to assess mitochondrial parameters. Mitochondrial activity, as measured by carbohydrate- and fat- stimulated ADP-coupled oxygen uptake, increased with age in a thyroid hormone dependent manner, rising predominantly postnatally. Mitochondrial density, abundance of ETS complexes I-IV and ATP-synthase and expression of the adenine nucleotide transferase 1 and mitofusin 2 were all positively influenced by age, with the natural prepartum rise being prevented in the thyroidectomised fetuses. However, T3 infusion alone was insufficient to raise any of these factors prematurely. Cortisol infusion resulted in an increase in some aspects of mitochondrial oxidative capacity in a muscle-specific manner. Overall, the data presented shows that there are developmental changes in skeletal muscle mitochondria during the perinatal period. They also suggest that these changes are regulated by both cortisol and thyroid hormones in preparation for birth, although neither hormone alone was sufficient to induce all the functional changes.