Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Preface - Biotechnology is generally considered to be the wave of the future. To facilitate accurate and rapid development of medication and treatments, it is critical that we are able to simulate the human body. One section of this complex model would be the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding general simulation of cellular structures, protein structures and bodily processes. Their aim is to develop treatments and medication for major diseases. Some of these diseases are epidemics like cancer, cardiovascular diseases, stress, obesity, etc. One of the most important causes of these diseases is poor blood glucose control. Current management methods for insulin dependent diabetes are limited to trial and error systems: clearly ineffective and prone to errors. It is critical that better management systems be developed, to ease the diabetic epidemic. The blood glucose control system is one of the major systems in the body, as we are in constant need of energy to facilitate the optimum functioning of the human body. This study makes use of a developed simulation model for the human energy system to ease the management of Diabetes mellitus, which is a malfunction of the human energy system. This dissertation is presented in two parts: The first part discusses the human energy simulation model, and the verification thereof, while the second presents possible applications of this model to ease the management of Diabetes. The human energy system simulation model - This section discusses the development and verification of the model. It also touches on the causes, and current methods, of managing diabetes, as well as the functioning of the human energy system. The human energy model is approached with the conservation of energy in mind. A top down model is developed, using data from independent studies to verify the model. Application of human energy simulation model - The human energy simulation model is of little use if the intended audience cannot use it: people suffering from malfunctioning energy systems. These include people having trouble with obesity, diabetes, cardiovascular disease, etc. To facilitate this, we need to provide a variety of products useable by this group of people. We propose a variety of ways in which the model can be used: Cellular phone applications, Personal digital assistants (PDAs) applications, as well as computer software. By making use of current technology, we generate a basic proof-of-concept application to demonstrate the intended functionality. / MIng (Mechanical Engineering) North-West University, Potchefstroom Campus, 2004

Preface - Biotechnology is generally considered to be the wave of the future. To facilitate accurate and rapid development of medication and treatments, it is critical that we are able to simulate the human body. One section of this complex model would be the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding general simulation of cellular structures, protein structures and bodily processes. Their aim is to develop treatments and medication for major diseases. Some of these diseases are epidemics like cancer, cardiovascular diseases, stress, obesity, etc. One of the most important causes of these diseases is poor blood glucose control. Current management methods for insulin dependent diabetes are limited to trial and error systems: clearly ineffective and prone to errors. It is critical that better management systems be developed, to ease the diabetic epidemic. The blood glucose control system is one of the major systems in the body, as we are in constant need of energy to facilitate the optimum functioning of the human body. This study makes use of a developed simulation model for the human energy system to ease the management of Diabetes mellitus, which is a malfunction of the human energy system. This dissertation is presented in two parts: The first part discusses the human energy simulation model, and the verification thereof, while the second presents possible applications of this model to ease the management of Diabetes. The human energy system simulation model - This section discusses the development and verification of the model. It also touches on the causes, and current methods, of managing diabetes, as well as the functioning of the human energy system. The human energy model is approached with the conservation of energy in mind. A top down model is developed, using data from independent studies to verify the model. Application of human energy simulation model - The human energy simulation model is of little use if the intended audience cannot use it: people suffering from malfunctioning energy systems. These include people having trouble with obesity, diabetes, cardiovascular disease, etc. To facilitate this, we need to provide a variety of products useable by this group of people. We propose a variety of ways in which the model can be used: Cellular phone applications, Personal digital assistants (PDAs) applications, as well as computer software. By making use of current technology, we generate a basic proof-of-concept application to demonstrate the intended functionality. / MIng (Mechanical Engineering) North-West University, Potchefstroom Campus, 2004