Includes bibliographical references (34 leaves). / xxi, 204 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the in vitro antioxidant properties of red wine containing polphends and the isoflavone genistein. Subsequently the effect of red wine on low density lipoprotein oxidation and fatty streak lesion development in cholesterol-fed rabbits was examined. / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 1998

Any lipoproteins and cells present in the inflammatory environment of atherosclerotic plaques are likely to be exposed to high levels of oxidative stress. As 7,8-dihydroneopterin (7,8-NP) is synthesized by interferon-γ (IFN-γ)-activated macrophages, this pteridine is also thought to exist at sites of inflammation. 7,8-NP s in vivo role remains controversial, but numerous in vitro studies have identified a radical scavenging activity. The possibility of 7,8-NP protecting against oxidative damage in inflammatory environments like plaque was investigated in this thesis. Both human monocyte-derived macrophages (HMDMs) and low density lipoprotein (LDL) were used as substrates. The extent of protein hydroperoxide formation in each model, and 7,8-NP s effect on this process, were specifically studied since most previous research has focussed on lipid rather than protein peroxidation. For the first time, neopterin (including oxidized 7,8-NP) was also directly detected by high performance liquid chromatography in the inflammatory environments of 19 pus and two atherosclerotic plaque samples. Peak concentrations even reached the low micromolar range. The positive correlation identified in the pus between neopterin and a well known antioxidant, vitamin E, further hinted at a potential antioxidant function. However, no significant association was noted between neopterin and markers of protein or lipid oxidation. Exposure of HMDMs to the AAPH peroxyl radical generator resulted in significant quantities of lipid hydroperoxides but not protein hydroperoxides, as detected by the FOX assays. This is likely due to the large accumulation of polyunsaturated fatty acidrich lipid in the primary HMDMs during differentiation in 10% human serum and is of relevance to atherosclerotic plaque, where macrophages also become lipid-loaded. The addition of up to 200μM 7,8-NP failed to prevent AAPH-induced lipid peroxidation and was also unable to inhibit a loss of cellular thiols or viability. This lack of effect suggests the damaging peroxyl radicals are not being scavenged by 7,8-NP. The high lipid content of HMDM cells appears to cause the AAPH and/or 7,8-NP to localize to a cellular site, where they are unable to interact. Macrophage-mediated oxidation of LDL in iron(II)-supplemented Hams F10 was associated with the formation of 30-40 moles of protein hydroperoxides per mole of LDL. The close parallel between protein and lipid peroxidation supports the theory that lipid-derived radicals are involved in protein hydroperoxide formation on LDL and indicates that protein hydroperoxides are an early product of LDL oxidation. Their detection during exposure of LDL to both the THP-1 macrophage cell line and primary HMDM cells confirms that protein hydroperoxides are also a normal consequence of macrophage-mediated LDL oxidation. Incubation of LDL with micromolar 7,8-NP prevented macrophage-mediated protein hydroperoxide formation in a concentration-dependent manner. Lipid oxidation and vitamin E loss were similarly inhibited by 7,8-NP during the cell-mediated attack of LDL. Kinetic analysis revealed protection due to extension of the lag phase, with 7,8-NP depletion and initiation of the propagation phase coinciding. This supports a radical scavenging activity for 7,8-NP, resulting in protection of the entire LDL particle. By contrast, the release of nanomolar quantities of 7,8-NP by IFN-γ-stimulated THP-1 macrophages failed to prevent LDL oxidation. HMDMs activated by IFN-γ did significantly inhibit LDL oxidation, including protein hydroperoxide formation, for up to 48 hours but this antioxidant effect was not due to the de novo synthesis of 7,8-NP. These results indicate that both the prevalence of protein hydroperoxides, and the ability of 7,8-NP to act as an antioxidant, depend on the system under investigation. Neopterin exists in inflammatory environments but, considering the lack of protection against AAPH-mediated HMDM oxidation and the 7,8-NP concentration required to inhibit macrophage-mediated LDL oxidation, strong evidence for an antioxidant activity of 7,8-NP in atherosclerotic plaque is currently lacking.

Proefschrift Maastricht. / Lit. opg. - Met een samenvatting in het Nederlands.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim Dalı, 2006. / Bibliyografya var.

Thesis (Ph.D.)--University of Western Australia, 2006.

Diss. (sammanfattning) Örebro : Örebro universitet, 2006. / Härtill 4 uppsatser.

Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 2 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2008. / Härtill 4 uppsatser.

Thesis (Ph. D.)--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 June 17, 2009) Vita. Includes bibliographical references.

Thèse (Med.Exp.) -- Université du Québec à Chicoutimi, programme en extension de l'Université Laval, 2006. / La p. de t. porte en outre: Mémoire présenté à la faculté des études supérieures de l'Université Laval comme exigence partielle du programme de maîtrise en médecine expérimentale - génétique des populations humaines offert à l'Université du Québec à Chicoutimi en vertu d'un protocole d'entente avec l'Université Laval pour l'obtention du grade de maître ès sciences (M.Sc.). CaQCU Bibliogr.: f. 63-101. Document électronique également accessible en format PDF. CaQCU