Diabetic cardiomyopathy (DCM), a disorder of the heart muscle, is one of the major and most rampant culprits claiming thousands and thousands of lives around the globe every year by interfering with the blood circulation and causing the development of heart failure eventually. The progression of the disease is asymptomatic and having a long latent period, and it is characterized functionally by ventricular dilation, diastolic dysfunction, interstitial fibrosis and cardiomyocytes hypertrophy. It was suggested the pathogenesis of the disease and the related complications are related to the effects of hyperglycemia on cardiomyocytes. So understanding the physiology of both the normal and pathological conditions, and the underlying mechanisms involved are of paramount importance to derive therapies to cope with this disease. However, it is difficult, if not impossible, to study the physiology in vivo using a live sample or to build a cellular model with adult cardiomyocytes due to the insufficient number of the cells harvested. This is not until the emergence of Embryonic Stem Cells (ESCs) that a cellular model with clinical sufficient number of cardiomyocytes could be built for investigation and drug screening. With a view to mimicking the situation of the Diabetic cardiomyopathy of the Type II Diabetes mellitus (DM) patients, mouse ESCs are used to differentiate into cardiomyocytes using the traditional hanging drop method to produce Embryoid body (EB). The cardiomyocytes were then enriched and plated so that different testing conditions could be applied. The effect of high glucose (HG), Insulin and the combination of high glucose and insulin were then analyzed. This was to show the significance of hyperglycemia, hyperinsulinemia due to insulin resistance and the role of insulin in hyperglycemia on cardiomyocytes respectively. The results agreed with previous findings that high glucose and insulin alone do induce cells apoptosis while the combination of insulin and glucose did decrease the number of apoptosis and while the co-culture of insulin with High dosage of glucose has shown to reduce the effect of hypertrophy. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Despite major advances in diagnosis and prevention of coronary artery disease (CAD), the development of therapies to regenerate functional cardiomyocytes after myocardial infarction (MI) is very challenging. Studies have demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) secrete a panel of growth factors and anti-inflammatory cytokines to activate resident cardiomyocytes and cardiac stem cells in myocardial repair after MI. However, the mechanisms of modulating BM-MSC secretions are not well understood. Recently, molecular candidates in regulating BM-MSCs paracrine secretion to improve cardiac protection have been explored. Amongst the molecular candidates, Nuclear casein kinase and cyclin-dependent kinase substrate 1 (Nucks1) is suggested as a regulatory protein in nuclear factor-kappa B (NF-κB) signaling pathway by interacting with TANK-binding kinase 1 (TBK1). TBK1 is a non-canonical I kappa B (IκB) kinase that can activate the NF-κB transcription factor and its transcriptional response. NF-κB signaling pathway controls many cellular responses such as cell survival, proliferation and cytokine productions. We hypothesizes Nucks1 may have potential roles in regulating mouse BM-MSCs secretion of growth factors and cytokine profiles in heart repairs after MI. To test our hypothesis, the cardiac protection efficacy of acute infarcted mouse myocardium was measured after the transplantation of WT versus Nucks1 KO BM-MSCs. To this end, we developed a mouse model of acute myocardial infarction (AMI) induced by ligation of left descendant coronary artery. Acute infarcted mouse myocardium receiving WT or Nuck1 KO BM-MSCs transplantation, demonstrated a significant improvement of left ventricular ejection fraction (LVEF), ESP, +dP/dt, ESPVR and vessel density, and reduced infarction size in comparison with PBS control group post-4 weeks of transplantation. Furthermore, acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs transplantation provided better cardioprotective effects than those receiving WT BM-MSCs transplantation. Immunostaining disclosed CD31 and smooth muscle actin (SMA) expression in acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs were relatively higher than those receiving WT BM-MSCs transplantation. Additionally, a distinct secretion profile of growth factors and cytokines between Nucks1 KO BM-MSCs versus WT BM-MSCs under in vitro ischemia was studied. Expression of vascular endothelial growth factor alpha (VEGFα) in Nucks1 KO BM-MSCs under hypoxia/ serum deprivation was significantly higher than that of WT BMMSCs. Taken together, our data suggested BM-MSCs provide cardiac protection in acute infarcted myocardium. Transplantation of Nucks1 KO BMMSCs may further enhance the cardiac repair of the acute infracted myocardium through an induction of VEGFα. / published_or_final_version / Medicine / Master / Master of Philosophy

Objective: The review aims to evaluate associations of occasional and moderate drinking with cardiovascular diseases (CVD), specifically to compare results for occasional and moderate drinking, as moderate drinking is widely investigated while occasional drinking is relatively understudied and can potentially inform whether alcohol is causally related to CVD. Methods: A systematic review was conducted by searching for observational and interventional studies from three databases (ScienceDirect, Ebscohost, and PubMed) for alcohol consumption and its association with cardiovascular health. Online internet sources were also used for more supplementary research in this literature review. Patient-oriented outcomes, primarily on heart diseases, including cardiovascular heart disease, myocardial infarction, and coronary heart disease, were extracted from all study groups. Results: Fifteen studies were included, most of which were conducted in the United States of America (9 studies). Generally, moderate alcohol consumption is associated with a reduction in CVD risks, including extensive coronary calcification, sudden cardiac death, congestive heart failure, acute coronary syndrome, ischemic heart disease. Studies also suggests that alcohol may be associated with better endothelial function and lower systolic blood pressure Current occasional alcohol use is found to be associated lower IHD mortality in men, but is not related to IHD mortality in women. Conclusion: We found consistent evidence of protective association of moderate alcohol consumption against cardio-mortality and CVD, while occasional alcohol consumption has relatively less protection against CHD deaths. Such associations were only found in studies with living controls. Only a small number of studies have studied occasional drinking, in relation to cardiovascular health. Further studies that specifically examine occasional drinking, are needed. If the biological effects of occasional drinking towards CVD are limited, then occasional drinking may indicate the magnitude of residual and unobserved confounding in the association with cardiovascular health. This will in turn inform alcohol-related policies such as alcohol duties and minimum alcohol pricing. / published_or_final_version / Public Health / Master / Master of Public Health

M. Tech. Biomedical Sciences. / Aims to assess the prevalence rates of hyperlipidaemia, hyperglycaemia, elevated homocysteine levels, elevated FVII levels and high blood pressure, as risk parameters of arterial thrombosis, in a rural black community in the Limpopo Province South Africa.

Not available / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Doctor of Medicine

No description available.

No description available.