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Includes bibliographical references (leaves 198-223) Examines the metabolism of plasma lipoprotein triacylglyceride in sheep (Ovis aries) under normal fed conditions, fasting and alloxan diabetes.

Includes bibliographical references (leaves 172-217). Examines the effects of estrogens and phytoestrogens on plasma lipoprotein levels and other risk factors for cardiovascular disease, including the oxidisability of low density lipoprotein

Includes bibliographical references (leaves 172-217). / viii, 217 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the effects of estrogens and phytoestrogens on plasma lipoprotein levels and other risk factors for cardiovascular disease, including the oxidisability of low density lipoprotein / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1999

Includes bibliographical references (leaves 198-223) / xxiv, 223 leaves, [13] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the metabolism of plasma lipoprotein triacylglyceride in sheep (Ovis aries) under normal fed conditions, fasting and alloxan diabetes. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, Waite Agricultural Research Institute, 1987

dsc-4(qm182), a mutation that suppresses the lengthened defecation cycle of clk-1 also suppresses the delay in germline development. dsc-4 encodes a putative orthologue of microsomal triglyceride transfer protein (MTP), a protein essential for the assembly and secretion of apo-B-containing low density lipoproteins (LDL). The effect of dsc-4 on clk-1(qm30), coupled to studies of apoB homologues in worms led to a model suggesting the possibility of using C. elegans in the study of LDL-like lipoprotein particles. The impact of the level of lipoproteins is particularly evident in the germline developmental rate of the worms. / We report here a further elucidation of clk-1 mutants in the study of the biology of LDL-like particles. In particular, we investigated the effect of targeting LDL receptor-like genes by RNA interference (RNAi) on the egg laying rate of clk-1(qm30). We find positive modulating effects by disruption of these putative LDL receptors. In confirmation of our model of lipoprotein metabolism in clk-1 mutants, we find that disruption of these putative LDL receptors produces strikingly different effects in wild-type, clk-1(qm30) or clk-1(qm30); dsc-4(qm182) animals. / In addition, we report unexpected effects of various clk-1 alleles on the phenotypes of animals in which lrp-1 and rme-2 are disrupted. Specifically, we observe an allele specific amelioration of the phenotypes associated with disruption of these genes (abnormal molting and sterility, respectively). We discuss the possible significance of these findings. (Abstract shortened by UMI.)

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Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons transport dietary alpha-tocopherol after intestinal absorption, LDL and HDL are the major carriers of alpha-tocopherol in fasting plasma and largely contribute to its delivery to cells and tissues. Exchanges of alpha-tocopherol occur between plasma lipoproteins. In addition, alpha-tocopherol transfers have also been observed, in both directions, between plasma lipoproteins and artificial chylomicrons such as intravenous lipid emulsion particles used in parenteral nutrition. In acute conditions, intravenous supply of vitamin E via lipid emulsions, which bypasses the intestinal tract, may offer some advantages over oral administration to rapidly increase alpha-tocopherol plasma concentration. However, many questions remain unanswered regarding kinetics and factors facilitating vitamin E exchanges between lipid emulsions and plasma lipoproteins. The first part of this work aimed at characterizing alpha-tocopherol transfers between alpha-tocopherol rich emulsion particles and plasma lipoproteins as well as the potential for plasma proteins to modulate such transfers. An in vitro model of incubation was used in which emulsion triglyceride concentration was relatively low and lipoprotein levels comparable to those commonly found in the circulation. Results indicate a high capacity for LDL and HDL to acquire extra-amounts of alpha-tocopherol by rapid mass transfers from alpha-tocopherol-rich emulsion particles. Data further shows that, at a fixed alpha-tocopherol concentration provided by emulsion particles, the limiting factor for alpha-tocopherol enrichment is not the capacity of plasma lipoproteins to accommodate extra-amounts of alpha-tocopherol but the facilitating effect of plasma proteins on alpha-tocopherol transfer, the duration of the incubation and possibly the competition between different acceptor particles. Two lipid transfer proteins, PLTP and CETP, appear to largely mediate facilitation of alpha-tocopherol transfer; however, other plasma proteins may be involved. Data further shows that alpha-tocopherol enriched LDL and HDL can readily transfer newly acquired alpha-tocopherol to cells, without any regulation by plasma proteins.<p>Short-term prophylactic vitamin E supplementation has been suggested to be beneficial in some patients in acute conditions who present reduced plasma vitamin E concentrations in association with important changes in plasma lipids and severe oxidative stress. However, it was not clear whether low plasma vitamin E concentration in critically ill patients is related to changes in the composition of plasma lipoproteins or to a decrease in the number of alpha-tocopherol carriers. In the second part of this work, two clinical studies were conducted to analyze changes of lipoprotein concentration and composition in relation to inflammatory reaction and oxidative stress in selected subgroups of critically ill patients, namely patients undergoing cardiac surgery with different procedures. Important changes in LDL and HDL lipid content were observed, some of which contrast with previous observations made in critically ill septic patients. The reduced plasma level of alpha-tocopherol measured after cardiac surgery is entirely due to a reduced number of circulating LDL and HDL particles. Data suggests that such reduced number in alpha-tocopherol carriers post-surgery may impede the delivery of alpha-tocopherol to cells in conditions of increased requirements due to oxidative stress. Avoidance of extracorporeal circulation during cardiac surgery does not reduce inflammation-related changes in plasma lipids but largely prevents oxidative stress. This data on changes occurring in plasma lipoproteins may help to better define strategies against pro-inflammatory changes or oxidative stress. If further studies would confirm a clinical benefit with evidence-based rationale, alpha-tocopherol enriched lipid emulsions may be used to guarantee a sufficient alpha-tocopherol supply in acute conditions associated with fewer alpha-tocopherol transporters and increased requirements due to high risk of oxidative tissue injury.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished