by Chan, Ting Wah Victor. / Bibliography: leaves 131-149 / Thesis (M.Phil.) -- Chinese University of Hong Kong, 1983

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Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/HCO3 - co-transporter NBCn1 which regulates intracellular pH (pHi) in a range of tissues, including vascular smooth muscle and endothelium. Notably, the SLC4A7 knockout mouse has been shown to have an altered blood pressure phenotype. This thesis presents a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. There were genotype-dependent differences in DNA-nuclear protein interactions by formaldehyde-assisted isolation of regulatory elements, electrophoretic mobility shift assays and DNA pulldown assays. Subsequently, there were also genotypedependent differences in SLC4A7 expression level and NBCn1 availability at the plasma membrane. In turn, SLC4A7 genotype is associated with Na+/HCO3 --dependent steady-state pHi and recovery from intracellular acidosis. The genotypic effect on pHi regulation was independent of the calcineurin activity, or the amino acid substitution E326K resulting from a missense polymorphism. However, in the presence of Na+/H+ exchange activity, the SLC4A7 genotypic effect on net base uptake and steady-state pHi was detected only in vascular smooth muscle cells but not endothelial cells. The finding of a genotypic influence on SLC4A7 expression and pHi regulation in vascular smooth muscle cells provide an insight into the molecular mechanism underlying the association of variation at the SLC4A7 locus with blood pressure.

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Introduction: Hypertension is a complex disease that affects about 40% of adults worldwide, and is a major risk factor for cardiac hypertrophy and heart failure. Abnormal calcium handling plays a key role in hypertension and cardiovascular disease. In order to function normally cells of the cardiovascular system need to keep intracellular Ca2+ levels under tight control. This is achieved by a number of Ca2+ handling proteins including the plasma membrane Ca2+-ATPase (PMCA). Recent genome wide association studies have shown that single nucleotide polymorphisms in ATP2B1, the gene encoding PMCA1, are strongly linked with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: This thesis aims to examine whether there is a link between PMCA1 and blood pressure regulation, and the development of hypertension. It also aims to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1, a global PMCA1 heterozygous knockout mouse (PMCA1Ht) was used. Under basal conditions, 3 month old PMCA1Ht mice had about 50% reduction in PMCA1 protein expression compared to the wild type (WT) mice. PMCA1Ht and WT mice had similar blood pressure as measured by tail-cuff method. To study the mice under hypertensive stress conditions, 3 month old PMCA1Ht and WT mice were infused via minipump with angiotensin II. Upon angiotensin II treatment, PMCA1Ht mice showed a significantly greater increase in systolic and diastolic pressure compared to WT mice. Angiotensin II also induced vascular remodelling, with PMCA1Ht mice having greater media thickness and cross sectional area than WT mice. Moreover, PMCA1Ht mice showed a significantly greater cardiac hypertrophic response than WT mice. On the other hand, cardiac function and heart rate were similar in PMCA1Ht and WT mice. While angiotensin II had no effect on PMCA1 expression in the heart, it significantly increased PMCA1 expression in the aortas of both WT and PMCA1Ht mice. More importantly, WT mice had significantly higher PMCA1 expression level than the PMCA1Ht mice treated with the same dose of angiotensin II. This suggests that PMCA1 plays a pivotal role in Ca2+ extrusion in the vasculature and that under stressful conditions PMCA1Ht mice are less able to respond to stress through a compensatory increase in PMCA1 expression, leading to increased intracellular Ca2+ concentration, which in turn leads to increased vascular contractility and increased blood pressure. Conclusion: This work provides evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

Fan Boli. / "January 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 219-248). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Public Health. Johannesburg, April 2012 / Introduction: Sub-Saharan Africa has a high burden of HIV and other blood borne pathogens. Botswana’s estimated prevalence of HIV and HBV are between 17-40%, and 14 % respectively. Ninety percent of the three million health care workers exposed annually to blood borne pathogens through injury are in developing countries. Previous studies in Botswana indicate 24%-26% health workers sustain needle stick and other sharps injuries annually, posing a threat to them. Dentistry requires work with sharp objects in a confined space; thus oral health workers (OHWs) are at high risk of infection from occupational blood exposures (OBEs). Universal (Standard) Precautions were first recommended by the Center for Disease Control in the United States of America and were adopted in several countries, including Botswana, to minimize the risk of exposure to, and infection from, blood. However, studies in different health care settings, mainly in developed countries, have shown that these guidelines are not always adhered to. Few studies have been done to evaluate their utilization in developing countries. Aim: To quantify the occupational blood exposure experience of OHWs in Botswana’s public service and determine the infection control practices through self reporting and observation. The Objectives were: 1) To determine the demographic profile of the OHWs in Botswana, 2) To determine self reported blood exposure experience of oral health workers within the 12 months prior to the study, 3) To determine self reported infection control practice of oral health workers within the 12 months prior to the study, 4) To determine the knowledge of risks associated with blood borne pathogens amongst oral health workers at the time of the study, 5) To determine, by observation, which v precautions were practiced by oral health workers to prevent exposure at the time of the study, 6) To assess whether there was a written policy available in the dental facility on the prevention and management of occupational blood exposures. Methodology: A cross sectional descriptive survey was carried out using a combination of self reporting and observation. A total of 85 OHWs in 5 of the 6 main oral health facilities were invited to participate. Knowledge of risks pertaining to blood borne pathogens, frequency of blood exposures and practice of universal precautions were assessed. Documents and posters were also reviewed. Results: Sixty eight (80%) OHWs returned the questionnaires and 51 (60%) observations were carried out. At least 80% of respondents had correct knowledge of occurrences that can contribute to the spread of blood borne pathogens in the dental environment. Over 60% were aware of universal precautions and 75% knew that post exposure prophylaxis (PEP) was available at their facilities. Almost 43% of the respondents had experienced blood splashes in the last year and 35.3% experienced needlestick injuries. Half of these reported the injury and 16.2% took PEP. Predictors of needlestick injuries during the previous year were perception of risk, knowledge of and compliance with, Universal Precautions Personal protective equipment was poorly utilised; only 17.6% were observed to use protective eye wear. Two thirds of the respondents were observed to use double-handed recapping. None of the facilities visited had a written protocol displayed. Conclusion and recommendations: The prevalence and reporting of OBEs amongst vi OHWs were comparable with findings of other studies. Self protection through compliance with universal precautions, immunization and post exposure prophylaxis was not fully utilised. The high burden of disease in the country warrants that further efforts be made to protect oral health workers. Appropriate guidelines should be made available at all dental facilities and staff needs to be retrained regarding standard precautions. Monitoring of exposures and vaccination status should be carried out. Further research should be undertaken regarding the poor uptake of prophylaxis.

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Thesis (M Med (Family Medicine))--University of Limpopo, 2010. / Background: The state of Hypertension disease is universally under diagnosed and/or inadequately treated resulting in extensive target-organ damage and premature deaths. Therefore, sustainable and aggressive population-based programs for hypertension awareness, prevention, treatment, and control are keys of success in limiting this epidemic. The study aims to determine the Kang Adult population’s hypertension prevalence and the relationship between high blood pressure, anthropometric measures and their life style factors such as diet, use of tobacco products and alcohol consuming habits. Methodology: The study, a population based cross-sectional trial, was conducted on adult residents of Kang (18 year-old and above) from November to December 2008. Data was collected using the questionnaire, through physical measurements of weight, height and BP using a modified protocol based on World Health Organization (WHO) STEP wise instruments on chronic disease (Bonita, 2001). The sample consisted of 161 participants between 20 and 82 years of age. Results: Hypertension was observed in 31.6% of participants (95% CI: 24.6%-39.5%). With regard to the hypertension prevalence rate, no significant differences were observed between males and females (males 28.3% versus females 33.6%, p = 0.59). An elevated blood pressure was seen with significantly higher frequency in overweight group compared with the normal weight group (p = 0.029), in obese group compared x with the normal weight group (p = 0.002), and in obese group compared with the overweight group (p = 0.045). The study found no significant association between hypertension and use of tobacco products (p=0.46) or alcohol consumption (p=0.73), went in vigorous-intensity activity (p=0.22) and moderate-intensity activity that causes large increases in breathing, or heart rate for at least 10 minutes continuously (p=0.70). Conclusions: It is concluded that hypertension is a common problem in adult Kang population, with a prevalence of 31.6%. Hypertension prevalence was found to be associated with anthropometric measurements such as overweight and obesity. No significant association between hypertension and use of tobacco products, alcohol consumption, vigorous-intensity and moderate-intensity activities that cause increases in breathing or heart rate for at least 10 minutes continuously. However, the present study had the limitation of a small sample size. Further studies are needed to clarify the hypertension magnitude throughout the country, with large samples.