Each year approximately 600 000 infants, most of them in Sub-Saharan Africa are born with HIV infection as a result of mother to child transmission of HIV. Whereas significant progress has been made in reduction of mother to child transmission of HIV in developed countries, the situation remains desperate in developing countries. Progress has been hampered by shortage of staff, facilities, limited access to voluntary counselling and testing and lack of support for women by their partners and communities. The challenge is to increase voluntary counselling and testing uptake during antenatal care. Onandjokwe district in Northern Namibia is currently introducing the Prevention of Mother to Child Transmission Program (PMTCT). It has been found the previous PMTCT programs have failed because they adopted a top down approach where there was no community consultation. This study was conducted to explore the community perceptions, knowledge and attitudes regarding mother to child transmission of HIV through focus group discussions and in-depth interviews of key community members.

Orientador: José Eduardo Tanus dos Santos / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-07T16:45:40Z (GMT). No. of bitstreams: 1 Gomes_ValeriaAguiar_D.pdf: 9967733 bytes, checksum: 0f5a9488cc56b0e1272b80bd9cb6ea0b (MD5) Previous issue date: 2012 / Resumo: A síndrome do ovário policístico (SOP) é a endocrinopatia mais comum em mulheres na idade reprodutiva e está frequentemente associada a alguns fatores de risco cardiovascular. A grande maioria das doenças cardiovasculares (DCV) ocorre inicialmente com o remodelamento vascular, em que as metaloproteinases de matriz (MMPs) são os principais mediadores. Sendo assim, o objetivo do presente estudo foi comparar os níveis plasmáticos da MMP-2 e da MMP-9 e dos inibidores teciduais de MMPs (TIMPs) das pacientes com SOP com as controles saudáveis e examinar se os níveis desses biomarcadores estão associados com às características clínicas e bioquímicas da SOP. Além disso, avaliar o efeito do anticoncepcional oral sobre os níveis plasmáticos de MMPs e respectivos inibidores endógenos nas mulheres com SOP. Para isso, na primeira parte do estudo, avaliamos 65 controles ovulatórias e 80 pacientes com SOP. As concentrações plasmáticas de MMP-8, MMP-9, TIMP-1, TIMP-2 foram medidas por Elisa e, as de MMP-2, por zimografia. Os níveis de MMP-2, MMP-8, MMP-9 e TIMP-1 não foram significativamente diferentes entre os grupos (p? 0,05). Pacientes com SOP apresentaram menores níveis plasmáticos de TIMP-2 do que as controles saudáveis (182,30 ± 5,60 vs. 204,20 ± 7,28 ng/ml; p ?0,05). Além disso, a testosterona foi preditor independente dos níveis de TIMP-2 (estimativa = -0,35, p = 0,04) e da razão MMP-9/TIMP-1 (estimativa = 0,01, p = 0,04). Para avaliar se a redução do hiperandrogenismo iria promover alguma alteração no perfil das MMPs, foram analisadas 20 mulheres com SOP que queriam contracepção hormonal (grupo SOP- ACO), 20 mulheres ovulatórias que desejavam contracepção hormonal (grupo controle- ACO) e 15 mulheres ovulatórias que desejavam contracepção não-hormonal (grupo controle). O tratamento com ACO contendo 30 mcg de etinilestradiol/2mg de acetato de clormadinona durante 6 meses reduziu significativamente as concentrações plasmáticas de MMP-2 no grupo controle ( de 1,44 ± 0,11 unidades arbitrárias no tempo basal para 1,22 ± 0,07 unidades arbitrárias após 6 meses; p = 0,01), e no grupo SOP ( de 1,43 ± 0,08 unidades arbitrárias no tempo basal para 1,25 ± 0,09 unidades arbitrárias após 6 meses; p = 0,007). O ACO reduziu as concentrações de TIMP-2 e TIMP-1 no grupo controle (todos p ?0,05), mas não teve efeitos na MMP-9 plasmática e nas razões MMP-2/TIMP-2 e MMP-9/TIMP-1 (todos p? 0,05) nos grupos avaliados. Os achados do presente estudo indicam que as mulheres com SOP possuem um desequilíbrio nas razões MMP-2/TIMP-2 e MMP-9/TIMP-1, bem como níveis reduzidos de TIMP-2. Parte desses achados estão relacionados ao hiperandrogenismo presente nessas mulheres. Na segunda parte do estudo, observamos que a redução do hiperandrogenismo, promovido pelo tratamento em longo prazo com o ACO, reduziu as concentrações plasmáticas de MMP-2. Considerando o desequilíbrio no perfil das MMPs apresentado pelas mulheres com SOP e, as possíveis consequências decorrentes desse cenário, o tratamento com ACO se mostra benéfico nessas pacientes, podendo reduzir os riscos de futuras complicações cardiovasculares / Abstract: The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and it is often associated with some cardiovascular risk factors. The majority of cardiovascular disease (CVD) occurs initially with vascular remodeling in which matrix metalloproteinases (MMPs) are key mediators. Therefore, the aim of this study was to compare plasma levels of MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMPs) of PCOS patients with healthy controls and to examine whether the levels of these biomarkers are associated with clinical and biochemical characteristics of PCOS. In addition to it, our goal was to evaluate the effect of oral contraceptives on plasma levels of MMPs and their endogenous inhibitors in women with PCOS. In order to prove it, in the first part of the study we evaluated 65 controls and 80 patients with ovulatory PCOS. The plasma concentration of MMP-8, MMP-9, TIMP-1 and TIMP-2 were measured by Elisa, and MMP-2 by zymography. The levels of MMP-2, MMP-8, MMP-9 and TIMP-1 were not significantly different between groups (p? 0.05). PCOS patients had lower their plasma levels of TIMP-2 than healthy controls ones (182,30 ± 5,60 vs. 204,20 ± 7,28 ng/ml; p = 0,02). Furthermore, testosterone was an independent predictor of the levels of TIMP-2 (estimate = -0.35, p = 0.04) and the MMP-9/TIMP- 1 ratio (estimate = 0.01, p = 0.04). To assess whether the reduction of hyperandrogenism would promote a change in the profile of MMPs, we analyzed 20 women with PCOS who wanted to hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 15 ovulatory women who wanted non-hormonal contraception wanted a nonhormonal contraception (non-OC control group). Treatment with OC containing 2 mg chlormadinone acetate/30 ?g ethinylestradiol for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control (from 1.44 ± 0.11 arbitrary units at baseline to 1.22 ± 0.07 arbitrary units after 6 months; p = 0.01) and the PCOS groups (from 1.43 ± 0.08 arbitrary units at baseline to 1.25 ± 0.09 arbitrary units after 6 months; p = 0.007) and TIMP-2 and TIMP-1 levels (448.0 ± 66.3 ng/mL versus 349.0 ± 40.9 ng/mL; p = 0.009) in the OC-control group (all p ?0.05) but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP- 1 ratios (all p? 0.05) in any group. The results of this study indicate that women with PCOS have an imbalance in the MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios and reduced levels of TIMP-2. Parts of these findings are also related to hyperandrogenism presence in these women. In the second part of the study, we observed that the reduction of hyperandrogenism promoted by long-term treatment with the OC reduced plasma concentrations of MMP-2. Given the imbalance in the profile of MMPs presented by women with PCOS and the possible consequences of this scenario, treatment with OC shows beneficial in these patients may reduce the risk of future cardiovascular complications / Doutorado / Farmacologia / Doutora em Farmacologia

Background: Vietnam, like other low-income countries, is facing an epidemic burden of cardiovascular disease risk factors (CVDRFs). The magnitude and directions of CVDRF progression are matters of uncertainty. Objectives: To describe the epidemiological progression of CVDRFs and the preventive effects of community lifestyle interventions, with reference to the differences in progression of CVDRF patterns between men and women. Methods: The study was conducted during 2001-2009 in nationally representative samples and in a local setting of rural areas of Ba-Vi district, Ha-Tay province. Both epidemiological and interventional approaches were applied: (i) a population-based cross-sectional survey of 2,130 people aged ≥25 years in Thai-Binh and Hanoi; (ii) an individual participant-level meta analysis of 23,563 people aged 24-74 years from multiple similar surveys in 9 provinces around Vietnam; (iii) a 17-month cohort study of 497 patients in a hypertension management programme; (iv) a quasi-experimental trial on community lifestyle promotion integrated with a hypertension management programme, evaluated by surveys of 4,645 people in both intervention and reference communes before and after a 3-year intervention. Main findings: (i) in the general adult population ≥25 years, CVDRFs were common, often clustered within individuals, and increased with age; (ii) the Vietnamese population is facing a growing epidemic of CVDRFs, which are generally not well managed; (iii) it is possible to launch a community intervention in low-resource settings within the scope of a commune-based patient-targeted programme on hypertension management; (iv) community health intervention with comprehensive healthy lifestyle promotion improves blood pressure and some behavioural CVDRFs. Conclusion: Alarming increases in CVDRFs in the general population need comprehensive multi-level prevention strategies, which combine both individual high-risk and population health approaches. The commune-based hypertension-centred management programmes integrated with community health promotion are the initial but essential steps towards comprehensive and effective management of CVDRFs and should be part of an integrated and co-ordinated national program on the prevention and control of chronic diseases in low-resource settings like Vietnam.

Background: The global burden of cardiovascular diseases (CVDs) is escalating as part of the rapid health transition that developing countries are experiencing. This increase is associated with shifts in demographics and economics, two of the major factors that affect diet and activity. The term social drift phenomenon (SDP) is used to describe the observations that: in the early stages of the epidemiological and nutrition transitions, it is usually the more affluent, higher socio–economic groups that are affected; in the later stages, it is the poor, lower socio–economic groups that display the consequences of these transitions. Therefore, in developing countries at the beginning of the transition, affluent people have higher prevalence of obesity and increased CVD risk. In developed countries, at much later stages of the transition, obesity and increased CVD risk is more prevalent in the lower socio–economic groups. In South Africa, the Transition and Health during Urbanisation of South Africans (THUSA) study which was done in 1996/1998 indicated that at that time, most of the risk factors for CVD were observed in the more urbanised (richer) subjects. It is not known if this pattern changed in any way due to the present rapid urbanisation of South African blacks. Therefore, in this study we explored the associations between socio–economic status (SES) (measured by level of urbanisation, education and employment) and CVD risk factors in an African population undergoing transition in the North–West Province of South Africa, that were prevalent in 2005 when the baseline data for in the Prospective Urban and Rural Epidemiology (PURE) study were collected. Objectives: The main objective of this dissertation was to examine the SDP in an African population in a nutrition and health transition, by: (i) Reviewing the literature on associations between socio–economic variables and biological health outcomes focusing on CVD risk factors in developed and developing countries; (ii) Analysing the baseline data from the 2005 PURE study to examine the relationships between components of SES, namely level of iii urbanisation, education and occupation, and nutrition–related CVD risk factors in men and women participating in the PURE study; and (iii) Comparing results on these associations between CVD risk factors and SES from the PURE study with those found in the THUSA study, which was conducted almost 10 years earlier, to examine if social drift in these associations has taken place. Study design: The dissertation is based on a comparison of the CVD risk factors and socio–economic status of the THUSA and PURE studies. Secondary analysis of the baseline cross–sectional epidemiological data from the PURE study was executed. The South African PURE study is part of a 12–year Prospective Urban and Rural Epidemiology study which investigates the health transition in urban and rural subjects in 22 different countries. The main selection criterion was that there should be migration stability within the chosen rural and urban communities. The rural community (A) was identified 450 km west of Potchefstroom on the highway to Botswana. A deep rural community (B), 35 km east from A and only accessible by gravel road, was also included. Both communities are still under tribal law. The urban communities (C and D) were chosen near the University in Potchefstroom. Community C was selected from Ikageng, the established part of the township next to Potchefstroom, and D from the informal settlements surrounding community C. The baseline data for PURE were collected from October to December 2005. A total of 2010 apparently healthy African volunteers (35 years and older), with no reported chronic diseases of lifestyle, tuberculosis (TB) or known human immunodeficiency virus (HIV) were recruited from a sample of 6000 randomly selected households. Methods: A variety of quantitative and qualitative research techniques was used by multidisciplinary teams to collect, measure and interpret data generated from biological samples and validated questionnaires. For this study, the statistical package for social sciences (SPSS) package (version 17.0, SPSS Inc) was used to analyze the data. Means and 95% confidence intervals (CI) of CVD risk and dietary factors were calculated. Participants of both genders were divided into different groups (according to urbanisation, education and employment levels) and compared. Estimated significant differences between rural and urban participants were determined with analysis of variance using the general linear model (GLM), multivariate procedure. Univariate analysis was used to explore further the influence of education on CVD risk factors and dietary intakes. Employment was used as a proxy for income, and pairwise comparisons using GLM, multivariate procedure were done for comparing the three groups (Not answered, employed and not employed). Tests were considered significant at P<0.05. Results: Comparison of urban with rural subjects participating in the PURE study showed that urban men had significantly higher systolic and diastolic blood pressures and lower fibrinogen levels than rural men. In women, systolic and diastolic blood pressure, fasting blood glucose and serum triglycerides were significantly higher in urban subjects whereas fibrinogen levels were significantly lower among urban subjects. After examining the relationship between the level of education and CVD risk factors, we observed that men with higher education levels had significantly higher BMI. In women, serum triglycerides and blood pressure were lower and BMI was significantly higher in the educated subjects. Because it was difficult to distinguish between reported household and individual income levels, we compared CVD risk factors of employed and unemployed subjects. Employed men had significantly higher BMI whereas the unemployed men had significantly higher fasting glucose and fibrinogen levels. Although mean blood pressure of employed men was higher than that of unemployed men, the difference did not reach significance. In women, the only significant difference seen was that employed women had lower high density lipoprotein (HDL) cholesterol, fasting glucose, triglycerides and fibrinogen levels, but they had a significantly higher BMI. Employed women had significantly higher BMI than unemployed women (27.9 [26.3–29.4] versus 26.5 [26.0–27.0] kg/m2). It seems that most of the nutrition related CVD risk factors were still higher in the higher socio–economic group, a situation similar to that reported in the THUSA study. v Conclusion: The results of this study showed little evidence of a major social drift in CVD risk factors from subjects participating in the 1996/1998 THUSA study to those in the 2005 PURE study. Most cardiovascular disease risk factors are still higher in the higher SES groups. However, there were some indications (increased fibrinogen in both men and women living in rural areas; higher triglyceride and fasting glucose levels in unemployed women; no significant differences in blood pressure and total cholesterol across different SES groups which existed in the THUSA study) that a social drift in CVD risk factors in our African population is on the way. This means that promotion of healthy, prudent diets and lifestyles should be targeted to Africans from all socio–economic levels for the prevention of CVD. / Thesis (M.Sc (Dietetics))--North-West University, Potchefstroom Campus, 2011.

Background: The global burden of cardiovascular diseases (CVDs) is escalating as part of the rapid health transition that developing countries are experiencing. This increase is associated with shifts in demographics and economics, two of the major factors that affect diet and activity. The term social drift phenomenon (SDP) is used to describe the observations that: in the early stages of the epidemiological and nutrition transitions, it is usually the more affluent, higher socio–economic groups that are affected; in the later stages, it is the poor, lower socio–economic groups that display the consequences of these transitions. Therefore, in developing countries at the beginning of the transition, affluent people have higher prevalence of obesity and increased CVD risk. In developed countries, at much later stages of the transition, obesity and increased CVD risk is more prevalent in the lower socio–economic groups. In South Africa, the Transition and Health during Urbanisation of South Africans (THUSA) study which was done in 1996/1998 indicated that at that time, most of the risk factors for CVD were observed in the more urbanised (richer) subjects. It is not known if this pattern changed in any way due to the present rapid urbanisation of South African blacks. Therefore, in this study we explored the associations between socio–economic status (SES) (measured by level of urbanisation, education and employment) and CVD risk factors in an African population undergoing transition in the North–West Province of South Africa, that were prevalent in 2005 when the baseline data for in the Prospective Urban and Rural Epidemiology (PURE) study were collected. Objectives: The main objective of this dissertation was to examine the SDP in an African population in a nutrition and health transition, by: (i) Reviewing the literature on associations between socio–economic variables and biological health outcomes focusing on CVD risk factors in developed and developing countries; (ii) Analysing the baseline data from the 2005 PURE study to examine the relationships between components of SES, namely level of iii urbanisation, education and occupation, and nutrition–related CVD risk factors in men and women participating in the PURE study; and (iii) Comparing results on these associations between CVD risk factors and SES from the PURE study with those found in the THUSA study, which was conducted almost 10 years earlier, to examine if social drift in these associations has taken place. Study design: The dissertation is based on a comparison of the CVD risk factors and socio–economic status of the THUSA and PURE studies. Secondary analysis of the baseline cross–sectional epidemiological data from the PURE study was executed. The South African PURE study is part of a 12–year Prospective Urban and Rural Epidemiology study which investigates the health transition in urban and rural subjects in 22 different countries. The main selection criterion was that there should be migration stability within the chosen rural and urban communities. The rural community (A) was identified 450 km west of Potchefstroom on the highway to Botswana. A deep rural community (B), 35 km east from A and only accessible by gravel road, was also included. Both communities are still under tribal law. The urban communities (C and D) were chosen near the University in Potchefstroom. Community C was selected from Ikageng, the established part of the township next to Potchefstroom, and D from the informal settlements surrounding community C. The baseline data for PURE were collected from October to December 2005. A total of 2010 apparently healthy African volunteers (35 years and older), with no reported chronic diseases of lifestyle, tuberculosis (TB) or known human immunodeficiency virus (HIV) were recruited from a sample of 6000 randomly selected households. Methods: A variety of quantitative and qualitative research techniques was used by multidisciplinary teams to collect, measure and interpret data generated from biological samples and validated questionnaires. For this study, the statistical package for social sciences (SPSS) package (version 17.0, SPSS Inc) was used to analyze the data. Means and 95% confidence intervals (CI) of CVD risk and dietary factors were calculated. Participants of both genders were divided into different groups (according to urbanisation, education and employment levels) and compared. Estimated significant differences between rural and urban participants were determined with analysis of variance using the general linear model (GLM), multivariate procedure. Univariate analysis was used to explore further the influence of education on CVD risk factors and dietary intakes. Employment was used as a proxy for income, and pairwise comparisons using GLM, multivariate procedure were done for comparing the three groups (Not answered, employed and not employed). Tests were considered significant at P<0.05. Results: Comparison of urban with rural subjects participating in the PURE study showed that urban men had significantly higher systolic and diastolic blood pressures and lower fibrinogen levels than rural men. In women, systolic and diastolic blood pressure, fasting blood glucose and serum triglycerides were significantly higher in urban subjects whereas fibrinogen levels were significantly lower among urban subjects. After examining the relationship between the level of education and CVD risk factors, we observed that men with higher education levels had significantly higher BMI. In women, serum triglycerides and blood pressure were lower and BMI was significantly higher in the educated subjects. Because it was difficult to distinguish between reported household and individual income levels, we compared CVD risk factors of employed and unemployed subjects. Employed men had significantly higher BMI whereas the unemployed men had significantly higher fasting glucose and fibrinogen levels. Although mean blood pressure of employed men was higher than that of unemployed men, the difference did not reach significance. In women, the only significant difference seen was that employed women had lower high density lipoprotein (HDL) cholesterol, fasting glucose, triglycerides and fibrinogen levels, but they had a significantly higher BMI. Employed women had significantly higher BMI than unemployed women (27.9 [26.3–29.4] versus 26.5 [26.0–27.0] kg/m2). It seems that most of the nutrition related CVD risk factors were still higher in the higher socio–economic group, a situation similar to that reported in the THUSA study. v Conclusion: The results of this study showed little evidence of a major social drift in CVD risk factors from subjects participating in the 1996/1998 THUSA study to those in the 2005 PURE study. Most cardiovascular disease risk factors are still higher in the higher SES groups. However, there were some indications (increased fibrinogen in both men and women living in rural areas; higher triglyceride and fasting glucose levels in unemployed women; no significant differences in blood pressure and total cholesterol across different SES groups which existed in the THUSA study) that a social drift in CVD risk factors in our African population is on the way. This means that promotion of healthy, prudent diets and lifestyles should be targeted to Africans from all socio–economic levels for the prevention of CVD. / Thesis (M.Sc (Dietetics))--North-West University, Potchefstroom Campus, 2011.

Each year approximately 600 000 infants, most of them in Sub-Saharan Africa are born with HIV infection as a result of mother to child transmission of HIV. Whereas significant progress has been made in reduction of mother to child transmission of HIV in developed countries, the situation remains desperate in developing countries. Progress has been hampered by shortage of staff, facilities, limited access to voluntary counselling and testing and lack of support for women by their partners and communities. The challenge is to increase voluntary counselling and testing uptake during antenatal care. Onandjokwe district in Northern Namibia is currently introducing the Prevention of Mother to Child Transmission Program (PMTCT). It has been found the previous PMTCT programs have failed because they adopted a top down approach where there was no community consultation. This study was conducted to explore the community perceptions, knowledge and attitudes regarding mother to child transmission of HIV through focus group discussions and in-depth interviews of key community members.

Thesis (MNutr (Interdisciplinary Health Sciences. Human Nutrition))--University of Stellenbosch, 2006. / OBJECTIVE: The primary aim of the study was to determine the nutritional status of vegetarian and non-vegetarian students in relation to their dietary preferences and risk factors (dietary, physical inactivity and obesity) for CHD. DESIGN: Cross-sectional analytical study. Setting: The Adventist International Institute of Advanced Studies (AIIAS) situated in the province of Cavite, Philippines. METHODS: The sampling frame was all graduate students at AIIAS (n=203). Of these students 153 returned the distributed dietary questionnaires which determined dietary practices, thus yielding a stratified random sample of 70 registered students (≥20y and ≤50y) who met the inclusion criteria of the study. Three 24-hour recalls and a self-administered food frequency questionnaire assessed dietary practices. Lifestyle was assessed by means of questionnaires, which also included the socio-demographic characteristics of the subjects. Anthropometric measurements included height, weight and waist circumferences. RESULTS: Seventy subjects participated in the study [non-vegetarian (n=38) and vegetarian (n=32)]. The mean age of subjects was 33.3 [(SD) 1.6] and 38.4 (1.9) years for non-vegetarian and vegetarian males respectively, with the respective means for females being 35.7 (2.0) and 33.2 (2.1) years. The majority of the vegetarians’ income was insignificantly below $10.000 as compared with that of non-vegetarians’, in whom annual income earned was within the $10.000- $50.000 range per year. Variations in level of education between the dietary groups were small and inconsistent, most of whom were characterized by a high education level. Within this cohort, mean BMI and WC were insignificantly lower in the vegetarians when compared with the non-vegetarians. For males, the prevalence of overweight, pre-obese and obese (p>0.05) for non-vegetarians was insignificantly higher than vegetarians. Insignificantly, female vegetarians were more pre-obese than non-vegetarians. As far as waist circumference was concerned, the prevalence of subjects observed in the alerting (≥94cm) and action zone (≥102cm) (p≤0.05) was 21% and 4% for non-vegetarian males, while 0% and 6% for vegetarian males. For females, more vegetarians were insignificantly prevalent in the alerting zone (≥80cm) as compared to the nonvegetarians. Both dietary cohorts illustrated no considerable differences that exemplified moderate to a high level of physical activity. All subjects, regardless of dietary preference, were non-smokers and consumed no alcohol (p>0.05). Overall, mean daily nutrient intake met current recommendations and there was no statistically significant difference between the two cohorts, except for fat and saturated fatty acids (SFA), which was higher among the non-vegetarians. Carbohydrate and fiber consumption was greater in the vegetarians. According to the DRIs, there were no intakes above the UL, however inadequate intakes of calcium and zinc posed possible risk of deficiency for both dietary groups. CONCLUSIONS: A small percentage of subjects in both cohorts were at risk of CHD morbidity. Both groups followed good lifestyle habits with dietary choices being of greater concern among non-vegetarians.

Thesis (MPhil)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: While there has been several studies that have been conducted targeting university students at state owned universities in South Africa, specifically on the impact of HIV/AIDS epidemic, no extensive study was conducted to establish what informs adoption of high risk sexual behaviour among university students in the context of HIV, STI and unplanned pregnancy epidemics at any of the state owned South African universities, let alone private universities. In order to address this identified gap in the body of knowledge, a cross-sectional study underpinned by the ‘social norms’ theory was undertaken at a private university in the Gauteng Province, South Africa to establish why undergraduate students engage in high risk sexual behaviour that puts them at risk of contracting HIV, STIs and unplanned pregnancy. Quantitative data was collected from 342 students through a questionnaire and qualitative data was collected from 38 students through the focus group discussions. Findings revealed that early sexual debut, intergenerational sex, multiple and concurrent partners, unprotected sex, sex under the influence of alcohol and illegal drugs and transactional sex constitute high risk sexual behaviour. The study concluded that peer pressure, independence, financial needs, drug and alcohol abuse, fear of being an outcast, need to identify with modernity, lack of individual perception of risk, campus culture and sexual partner influence are the factors influencing the adoption of high risk sexual behaviour on campus. Based on the findings and conclusions, recommendations are provided for the development of an HIV prevention programme on campus that is aimed at mitigating the negative consequences of the HIV/AIDS, STIs and unplanned pregnancy epidemics. / AFRIKAANSE OPSOMMING: Die literatuur toon aan dat daar alhoewel daar wel studies onderneem is ten einde die impak van die MIV epidemie onder studente aan openbare universiteite te bepaal onderneem is, daar nog steeds baie min kennis in hierdie verband bestaan. Die faktore wat ‘n rol vervul in hoërisiko seksuele gedrag onder studente aan hierdie universiteit is grootliks onbekend. Ten einde hierdie gaping te probeer oorbrug is hierdie studie onderneem aan ‘n privaat universiteit in Gauteng provinsie in Suid-Afrika. Die doel van die studie was om vas te stel wat voorgraadse studente motiveer om hoë seksuele gedrag te beoefen, wetende dat hulle hulleself blootstel aan MIV-infeksie en onbeplande swangerskappe. ‘n Steekproef van 342 student is in die studie gebruik en ‘n vraelys is deur hulle voltooi. ‘n Verdere 38 student het deelgeneem aan ‘n fokusgroepbespreking. Resultate toon aan dat studente dikwels meer as een seksuele maat het; dat seks beoefen word terwyl studente onder die invloed van alkohol is; dat seks dikwels onbeskermend plaasvind en dat alle hierdie faktore bydraend is tot hoë blootstelling aan MIV-infeksie. Die studie het verder gevind dat groepsdruk, finansiële probleme, dwelm- en alkoholmisbruik en groepsdruk verdere bydraende faktore tot hoë-risiko gedrag onder studente is. Resultate van die studie is gebruik om aanbevelings te maak vir die ontwikkeling van ‘n MIV-voorkomingsprogram wat daarop gerig is om die oordrag MIV en onbeplande swangerskappe aan die universiteit ( wat in die studie ondersoek is ) te bekamp.

Abstract Cardiovascular diseases (CVD), and especially atherosclerotic vascular diseases (ASVD), are the largest cause of morbidity and premature death worldwide. Coronary heart disease (CHD) and cerebrovascular disease (stroke) are common and severe manifestations of ASVD. Atherosclerosis is a chronic inflammatory disease and lipoprotein metabolism disorder. If the regulation of inflammatory process is disturbed, the systemic release of pro-inflammatory mediators, including matrix metalloproteinases (MMPs), may lead to a low-grade systemic inflammation, which is a risk factor for CVDs. MMPs are enzymes that are responsible for the degradation of the extracellular matrix (ECM) during growth and tissue renewal but also in many pathological conditions. These ECM degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture, leading to acute cardiovascular manifestations. The pivotal role of MMPs in atherosclerosis has raised interest in the development of drug therapies targeting these proteases. Doxycycline has inhibitory effects on some MMPs in addition to its antimicrobial properties. The main objective of this thesis project was to investigate the potential of these inflammatory mediators as biomarkers, risk factors, and therapeutic targets in CVD. The special focus was on MMP-8 and its main regulator, tissue inhibitor of matrix metalloproteinase (TIMP)-1. The results of this study show that a high serum MMP-8 concentration indicates an acute cardiac condition and predicts a future CVD event. In addition to MMP-8, MMP-7 is a potential biomarker for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture. Measurement of serum MMP-8 concentration is reliable, anti-invasive and inexpensive and can be done in hospital settings. We also show that regular-dose doxycycline decreases the systemic inflammatory burden in patients with earlier myocardial infarction and is a promising anti-inflammatory therapy in the prevention of CVDs with relatively minor side effects. In conclusion, MMP-8 and TIMP-1 can be considered inflammatory risk markers of CVD events and death, and they can be utilized both for diagnostic and screening purposes. The inhibition of MMP-8 by doxycycline may reduce the systemic inflammatory burden in patients with myocardial infarction. / Tiivistelmä Sydän- ja verisuonisairaudet, erityisesti ateroskleroottiset valtimosairaudet, ovat maailman yleisin sairastuvuuden ja ennenaikaisen kuoleman syy. Sepelvaltimotauti ja aivohaveri ovat ateroskleroottisen valtimosairauden yleisiä ja vakavia ilmenemismuotoja. Ateroskleroosi on krooninen tulehduksellinen sairaus ja lipoproteiiniaineenvaihdunnan häiriö. Jos tulehdustapahtuma häiriintyy, elimistöön vapautuvat tulehdusvälittäjäaineet, kuten matriksin metalloproteinaasit (MMP), voivat aiheuttaa elimistön matala-asteisen tulehduksen, joka on sydän- ja verisuonisairauksien riskitekijä. MMP:t ovat entsyymejä, jotka pilkkovat solunväliainetta kasvun ja kudosten uusiutumisen mutta myös monien tautitilojen yhteydessä. Nämä soluväliainetta hajottavat proteaasit ja niiden säätelijät ovat tärkeässä roolissa ateroskleroottisen plakin muodostumisessa ja repeämisessä, joka johtaa äkillisiin sydäntautitapahtumiin. Matriksin metalloproteinaasien keskeinen rooli ateroskleroosissa on herättänyt kiinnostusta niihin kohdistuvan lääkehoidon kehittämiseen. Doksisykliinillä on joidenkin MMP-entsyymien toimintaa estävä vaikutus antimikrobiaalisten ominaisuuksiensa lisäksi. Tämän väitöskirjatutkimuksen päätavoitteena oli tutkia näiden tulehdusvälittäjäaineiden mahdollisuuksia biomarkkereina, riskitekijöinä ja lääkehoidon kohteena sydän- ja verisuonisairauksissa. Erityinen kiinnostuksen kohde oli MMP-8 ja sen pääsäätelijä ja kudosestäjä, tissue inhibitor of matrix metalloproteinase (TIMP)-1. Tämän tutkimuksen tulokset osoittavat, että seerumin korkea MMP 8 pitoisuus viittaa akuuttiin sydäntautiin ja ennakoi tulevaa sydäntautitapahtumaa. MMP-8:n lisäksi MMP-7 on lupaava sydäntapahtuman biomarkkeri. Näiden matriksin metalloproteinaasien ja niiden kudossäätelijä TIMP-1:n välinen tasapaino voi liittyä ateroskleroottisen plakin haurauteen. Seerumin MMP-8:n mittaus on luotettavaa, kajoamatonta ja edullista, ja mahdollista toteuttaa myös sairaalaolosuhteissa. Näytämme myös, että doksisykliini vähentää elimistön tulehdustaakkaa sydäninfarktin sairastaneilla potilailla ja että se on sydäntautien ehkäisyssä lupaava anti-inflammatorinen lääke, jolla on suhteellisen vähän sivuvaikutuksia. Johtopäätöksenä on, että MMP-8:aa ja TIMP-1:tä voidaan pitää lupaavina sydän- ja verisuonitautien sekä kuoleman biomarkkereina sekä diagnostiikka- että seulontakäytössä. Lisäksi tutkimustulokset osoittavat, että MMP-8:n esto doksisykliinillä voi vähentää elimistön tulehdustaakkaa sydänkohtauksen sairastaneilla potilailla.

Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.