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

Thesis (MSc. Medical Science (Chemical Pathology)) -- University of Limpopo, 2017 / Obesity has been associated with dyslipidaemia (increased levels of triglycerides, total cholesterol and low levels of HDL-C together with small dense lipoprotein particles) in the absence of metabolic disorders such as, type 2 diabetes mellitus and inflammation. Since community based studies in South Africa reported that obesity is more common in women, and rural Africans have a more favourable lipid profile compared to their White counterparts, the current study investigated the association of obesity in women without metabolic disorders with lipid levels and changes in proportions of small and large LDL and HDL particles. Methods The present study was part of the project “Prevention, Control and Integrated Management of Chronic Disease in a rural area, South Africa”. A total of 521 women participated in the above project. After excluding people with diabetes mellitus, insulin resistance and inflammation, 308 women were left and of these 67 were obese. Sixty seven ages matched, randomly selected non-obese women served as controls. Anthropometry variables as well as systolic and diastolic blood pressures were measured and the WHO steps questionnaire was administered to collect information on medication, lifestyle and diseases. Fasting blood levels of total cholesterol, HDL C, triglyceride, adiponectin, CRP, glucose and insulin were measured. Proportions of small and large HDL and LDL particles were determined. Results There was no significant difference in TC, TG and LDL-C levels (p=0.558, 0.087 and 0.948) between obese and non-obese women or between women with increased waist circumference (WC) and those with normal WC. The HDL-C concentration was significantly lower in obese women compared to women with non- obese (p=0.001). The lipid ratios TC/HDL-C and Apo B-100/Apo A-I were significantly higher in obese women than those with non- obese (p=0.013 and p=0.006) respectively. The same phenomenon was observed in women with xv increased waist circumference (p=0.001** and p=0.025* respectively). Adiponectin levels were significantly lower in obese women compared to non-obese women (p=0.004**) and in women with increased waist circumference compared to those with normal waist circumference (p=0.016*). The proportions of small dense HDL and LDL lipoprotein particles were similar in obese and non-obese women. Both obese and abdominally obese women had significantly higher odds ratios of low levels of HDL-C and elevated Apo B-100/Apo A-I. Adiponectin was a significant predictor of elevated TC and TG in both obese and abdominally obese women while BMI was a significant predictor of low HDL-C in obese women. Waist circumference was a significant predictor of low HDL-C in abdominally obese women. Conclusion In the current study, obesity in women was significantly associated with lipid abnormalities such as low HDL-C levels, raised lipid ratios (TC/HDL-C and Apo B 100/Apo A-I) and low levels of adiponectin, after excluding metabolic disorders / VLIR

Huian plasma high-density lipoprotein (HDL) were isolated by a procedure employing polyanion precipitation and column chromatography. Lipid and protein composition of the HDL isolated by this method was found to be similar to another HDL preparation isolated by ultracentrifugation. However, minor differences were noted, including a higher phospholipid and apoproteinE content and lower triglyceride content of the HDL isolated by column chromatography. Four subfraction of HDL were obtained following chromatography on an anion exchange column. The subfraction four had the highest esterified to free cholesterol ratio, the second highest phospholipid to unesterified cholesterol, and the lowest molecular weight. In addition it was consistently coincided with lecithin: cholesterol acyltransferase (LCAT) activity and found to be the best substrate for the enzyme.

Introduction: Cardiovascular disease affects a greater proportion of females than it does males, and is responsible for an estimated 52 percent of female deaths per annum, globally. Due to the loss of oestrogen associated with the menopause, post-menopausal females are at elevated risk for hypercholesterolaemia which is a primary risk factor for cardiovascular disease. It has not yet been conclusively established whether resistance training can be used to ameliorate hypercholesterolaemia. Aim: This randomized controlled trial investigated what effect 12 weeks of progressive resistance training would have on plasma lipoproteins in a sample of post-menopausal females. Methods: Caucasian women (n=30 intervention and n=18 control) between the ages of 55 and 65 years who were not taking hormone replacement therapy were recruited. Participants did not smoke, were sedentary, were not taking any form of cholesterol-lowering medication, had at least one cholesterol abnormality at baseline but were otherwise healthy and able to participate in a strength training programme. Following extensive medical pre-screening, information dissemination and voluntary consent, the sample was divided into two groups. The exercise sample undertook 12 weeks of resistance training on five days of the week. The control group received no intervention. Measurements were obtained at baseline and every four weeks thereafter and included measures of strength, biochemistry (oestradiol, testosterone, full blood lipid profile, glycated haemoglobin and sex hormone binding globulin), anthropometry, morphology and self-reports (dietary intake, energy expenditure and the profile of mood states questionnaire). Results: There was no change to low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride content or total cholesterol as a result of the intervention. Back, chest and leg strength increased significantly (p<0.01) (increases of 51 percent, 35 percent and 43 percent respectively from baseline); waist circumference dropped (p<0.01) by 5 percent overall and diastolic blood pressure decreased significantly (-9 percent, p<0.01) in the exercise cohort but no change was noted in the matched control. Dietary intake, energy expenditure and body mass remained unchanged in both samples. Morphology (sum of skinfolds, estimated body fat content and girth measures) did not change and nor did other biochemical measures (HbA1c and sex hormone binding globulin) or hormone levels (oestradiol and testosterone). Despite the lack of overall change, an important finding was noted in individual results where a clear indication of ‘responders’ and ‘non-responders’ emerged. Conclusion: Overall mean results suggest that 12 weeks resistance training undertaken five days of the week was ineffective in reducing hypercholesterolaemia in this sample. Despite there being no identifying characteristics determined in this sample, evidence of responders and non-responders to the intervention indicates that reliance on mean data may not be sufficient when analysing data from exercise interventions. Therefore, while progressive resistance training had a positive effect on strength, waist circumference and diastolic blood pressure, it did not positively influence the plasma lipoproteins in this cohort of post-menopausal women. / Maiden name: Kelly, Janet Erica

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