Social Work / MA(SS)(MENTAL HEALTH)

In Africa, use of medicinal plants for the treatment of diabetes is very common. However, efficacy on co-administering of medicinal plants with therapeutic drugs hasn't been fully determined, especially for African medicinal plants. The current study focused on assessing the in vitro modulation effects of three popular African medicinal plants, namely: Aloe ferox, Sutherlandia frutescens and Prunus africana (including five commercial preparations containing these medicinal plants) on two of the most important anti-diabetic drug metabolising enzymes, Cytochrome P450 (CYP450) 2C9 and CYP3A4 and a key drug efflux transporter, P-glycoprotein (P-gp). Vivid® microsome-based screening kits were used to assess inhibitory potency of plants preparations on CYP2C9 and CYP3A4 enzymes activities. The study showed that P. africana was a more potent inhibitor of CYP2C9 and CYP3A4 activity than the corresponding positive controls Ginkgo biloba and St. John's wort, which are known to cause clinically significant drug-herb interactions. S. frutescens leaf extract demonstrated potent to moderate inhibition on both the tested CYP activities, while its commercial products (Promune® and Probetix®) possessed moderate to mild inhibitory effects on the activities of both CYPs. Potent inhibitory effect on CYP2C9 and CYP3A4 was seen with Aloe Ferox®. Prosit® and Aloes powder® showed potent to moderate inhibition on CYP2C9 activity and moderate to mild inhibition on CYP3A4 activity. In addition to CYP450 activity, the present study also investigated the effects of the selected medicinal plant products on the activity of the main drug efflux protein, P-gp. A screening assay was specifically developed to assess the potential for herbal remedies to interact with P-gp mediated drug absorption. The assay is based on the principle of the reversal of drug resistance in modified Caco-2 cells specifically altered to express high iv efflux protein activity. These cells display a multidrug resistance phenotype and the addition of a plant extract containing a P-gp inhibitor or substrate will inhibit or compete with any cytotoxic drug and consequently reverse the drug resistance. The suitability of the assay was confirmed using a known P-gp inhibitor. The study observed that the anti-proliferation effect of vinblastine was significantly enhanced in vinblastine-resistant Caco-2 cells, which have high P-gp expression, when they were exposed to the selected African herbal preparations. This observation indicates that the studied plant preparations may alter P-gp functionality and therefore lead to interference with the absorption of co-administered drugs. The outcomes of this study provide useful information on whether there are any potential drug-herb interactions between the commonly used African medicinal plants and oral anti-diabetic drugs, at the level of CYP and P-gp drug metabolism and could contribute to better therapeutic management of Type II diabetics. However these predicted interactions will need to be verified in a clinical setting.

THESIS SUBMITED IN FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF THE DEGREE OF DOCTOR OF TECHNOLOGY OF BIOMEDICAL TECHNOLOGTY IN THE FACULTY OF HEALTH AND WELLNESS SCIENCES AT THE CAPE PENINSULA UNIVERSITY OF TECHNOLOGY SUPERVISORS: PROF T.E. MATSHA PROF R.T. ERASMUS DR A. ZEMLIN SUBMITED DECEMBER 2013 / Introduction: Cardiovascular diseases (CVD) have become the leading cause of morbidity and mortality amongst the global population. Originally thought to be a health burden of high income countries, the prevalence is rapidly increasing in developing countries. For example, in 2008, an estimated 17.3 million died from CVD, and 80% of these (13.8 mil) were from low to middle income countries. Epidemiological data on CVD in Africa is scanty and of poor quality and national vital registration is available in only 5% of Africa’s 53 countries. Furthermore, data on CVD risk amongst the South African population and specifically the mixed ancestry community is poorly described. The increasing global population of people with CVD has been largely attributed to increasing rates of determinants and risk factors which include obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and chronic kidney diseases (CKD). The prevalence of DM in South Africa is known to be on the rise with more affected communities being South African Asians followed by coloureds. Aims and objectives: The aim of this study was to determine the CVD risk profile of the Bellville South community during a baseline and three year follow-up study, by assessment of known risk factors, MetS, type 2 DM, obesity and CKD. Methods: Participants for this study were drawn from an urban community of the Bellville South suburb of Cape Town. At baseline (January 2008 and March 2009) 946 individuals aged 16 to 95 participated. All participants received a standardized interview and physical examination during which anthropometric measurements were performed three times and their average used for analysis: weight (kg), height (cm), waist (cm) and hip (cm) circumferences. Body Mass Index (BMI) was calculated as weight per square metre (kg/m2). A blood sample was obtained from all participants after an overnight fast for the determination of biochemical profiles: glucose, glycated haemoglobin, creatinine, total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides and low density lipoprotein cholesterol (LDL-C) which was calculated using Friedewald’s formula. Kidney function test was assessed through estimated glomerular filtration rate (eGFR) using the cockcroft-Gault and MDRD equations. Blood pressure was measured according to the World Health Organisation (WHO) guidelines. Participants with no history of doctor diagnosed DM underwent a 75 g oral glucose tolerance test as recommended by the WHO. Metabolic syndrome was determined using JIS, NCEP ATPIII and IDF criteria. The follow-up examination was conducted in 2011 (3 years from vii baseline) using similar procedures. A total of 198 participants formed the follow-up cohort whose measurements were compared to those of the baseline. Finally, the prediction and processes/progression of the risk factors were determined. Results: At both baseline and follow-up studies, females had a higher BMI compared to their male counterparts. The crude prevalence of type 2 DM, including the previously diagnosed type 2 DM was 28.59% (age-adjusted = 33.5%, 95%CI: 30.01 – 36.92), and that of undiagnosed type 2 DM was 17.8% (age-adjusted = 12.4%, 95%CI: 9.8 – 14.8). The overall prevalence of CKD was 28.7% (269) and was higher in females (31.4%) compared to 20.2% in males. MetS was present in 46.5% of the participants. Gender-specific prediction for CVD risk calculated using the 30-year CVD interactive risk calculator showed that high CVD risk was present in normoglycaemic and younger subjects (under 35 years). At follow-up, the cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of MetS. Between baseline and 3-year evaluation glomerular filtration rate (eGFR) increased by 8.7 ml/min (95% confidence interval: 6.9-10.7), reflecting variables trajectories across baseline strata of kidney functions. Conclusion: Given the findings of this study and the estimated increases in the determinants and risk factors of CVD in the mixed ancestry population of South Africa this trend may continue to worsen if current trajectories do not change.

MSc (Botany) / Department of Botany / Diabetes and arthritis are the most common chronic diseases. Arthritis is the leading cause of global disability and diabetes has become a major health problem which is increasing rapidly. The purpose of the study was to document medicinal plants that are used to treat and manage diabetes and arthritis by traditional medicinal practitioners around the Vhembe District Municipality as well as to evaluate their in vitro efficacy. Traditional practitioners were interviewed using semi-structured questionnaires. Seventeen plant species belonging to fourteen different families were found to be used in the treatment of diabetes as well as arthritis. Fabaceae family was dominating. Antioxidant, anti-inflammatory, cytotoxicity, alphaamylase and alpha-glucosidase) of five plant species, (Bridellia mollis, Elephantorrihiza burkei, Elaeodendron transvaalense, Senna petersiana and Searsia lancea) used traditionally to manage diabetes were investigated using the standard in vitro procedures. All extracts showed a good nitric oxide inhibition, with highest percentage inhibition found in the highest concentration of 100 μg/ml. They all had good percentage cell viability at lowest concentration which was comparable to quercetin. Only two plant extracts B. mollis (T2) and E. transvaalense (T3) had lower than inhibition of quercetin at 25 μg/ml than at 12.5 μg/ml. In vero cells low toxicity effect was observed at lowest concentration tested, and toxicity increased with the increase in concentration. In bovine dermis cell line all plant extracts had more cell viability at lower concentration than doxorubicin. Ethanol extracts of B. mollis and S. petersiana, and ethyl extract of E. transvaalense had a good alpha-amylase inhibitory activity with IC50 values 58.6, 81.9 and 131.5 mg/ml respectively. Hydro-ethanol, ethyl acetate and ethanol extracts of E. burkei exhibited a significant alpha-glucosidase inhibitory activity with IC50 values 56.9, 52.2 and 129.7 mg/ml respectively. Kinetic analysis revealed non-competitive and un-competitive inhibitions of the plant extracts on alpha-amylase and alpha-glucosidase enzymes respectively. The information obtained showed that people in Vhembe District Municipality still rely on medicinal plants to treat and manage diabetes and arthritis. All plant extracts were toxic to both bovine dermis and vero cell lines. S. lancea (T5) was found to be the most toxic plant extract. The observed good inhibitions of both alpha-amylase and alpha-glucosidase enzymes by plant extracts of B. mollis, S. petersiana, E. transvaalense and E. burkei validate their use in the traditional treatment of diabetes in the region to some extent. Aqueous extracts of these medicinal plants should also be investigated because water is the main solvent which is used by traditional practitioners in the preparation of their herbal medicines.

MCur / Department of Advanced Nursing Science / Diabetes mellitus is a global health issue affecting people of all ages. It is defined as a non-communicable chronic disease caused by abnormal insulin production, impaired insulin utilization or both. Its prevalence and complications is increasing rapidly. The aim of this study was to assess knowledge of Diabetes mellitus chronic complications among diabetic patients in the Vhembe district of the Limpopo Province, South Africa. The study objectives were: to assess the knowledge of Diabetes mellitus chronic complications amongst diabetic patients; to determine the knowledge of diabetic patients regarding self-care practice, control and management of diabetes in the Vhembe District, and to identify challenges faced by diabetic patients regarding chronic complications of Diabetes mellitus in the Vhembe District A quantitative descriptive design was used. The study population was diabetic patients who were visiting the selected 4 hospitals, 2 health centers and 2 clinics were in Thulamela Municipality. Convenient sampling was used to sample 259 respondents (184(71%) females and 75(29%) males) and to select the 8 health care services. A structured, closed-ended selfadministered questionnaire in Tshivenda was used to collect data on the day that diabetic patients were coming for follow-up treatment, and after they had been attended to by the health care providers. Data were analyzed using the / NRF

The aim of this research project was to assess and compare cardiovascular disease (CVD) risk in black males and females from an urban, working population in the Makana (Grahamstown) region of the Eastern Cape, South Africa. Two-hundred and ninety one individuals (males: n = 143, females: n = 148) with a mean age of 42.6 (±8.1) years were voluntarily recruited from the greater urban Makana (Grahamstown) area. Eight Cardiovascular disease (CVD) risks were assessed: stature and mass were obtained in order to calculate body mass index (BMI) (mass/stature2). Obesity, defined as a morphological risk, was classified according to the World Health Organisation (WHO) BMI criteria (BMI>30kg.m-2), as well as according to measures of waist circumference (WC) and body composition. Hypertension, hypercholesterolemia and type II diabetes, were grouped as cardiovascular (CV) risks. Hypertension was defined as a blood pressure greater than 140/90mmHg (JNC-7); hypercholesterolemia, as total cholesterol greater than 6.2mmol.L-1 (NCEP); and type II diabetes, as total glucose greater than 12mmol.L-1 (WHO). Physical activity, diet, tobacco use, and alcohol consumption and dependence were grouped as lifestyle-related risks. These were assessed by means of self-reporting through the use of various validated questionnaires. Finally, self-reporting of obesity, hypertension, hypercholesterolemia and type II diabetes was assessed, in addition to perception questions on individuals’ perceived body shape and size (Ziebland figures). Self-reported and perceived responses were then compared to actual measures. Females were significantly (p<0.001) heavier than the males (92.7kg compared to 72.1kg) and had significantly (p<0.001) higher BMIs than their male counterparts (37.6kg.m-2 compared to 25.7 kg.-2). They also recorded significantly (p<0.001) higher waist circumference (WC) values and had significantly (p<0.001) higher percentage and total body fat. Significantly (p<0.001) more females were obese (81%) compared to males (17%). While a higher percentage of males (25 % compared to 22%) presented with stage I hypertension (≥140/90mmHg, <160/95mmHg), significantly (p<0.05) more females (14% compared to 8%) presented with stage II hypertension (>160/95mmHg). The prevalence of hypercholesterolemia at a high level of risk (>6.2mmol.L-1) was relatively low (2.1 % of males, 3.4% of females), but notably more participants (22% of males and 26% of females) presented with the condition at a moderate level of risk (>5mmol.L-1). Type II diabetes was the least prevalent CV risk factor, with no males and only 3% of females presenting with the condition. Males consumed significantly (p<0.05) more in terms of total energy intake (9024 vs. 7234 kJ) and were significantly (p<0.05) more active (3315 compared to 2660 MET-mins.week). A significantly (p<0.05) higher percentage of males smoked (51.1% compared to 3.4%), consumed alcohol (73.4% compared to 46.6%) and were alcohol dependent (40% compared to 33.5%). Both males and females tended to be ignorant of their health status, with both samples under-reporting obesity, hypertension and hypercholesterolemia, while over-reporting type II diabetes. Furthermore, obesity was significantly (p<0.05) underestimated, with both male and female individuals perceiving themselves to be notably smaller than they actually were. Physical activity and diet were important determinants of CVD risk in this black urban sample of individuals. Obesity, in particular central adiposity, was the most notable risk (particularly in females), followed by hypertension (particularly in males). Although some risks presented at a moderate level of risk, a clustering of risk factors was evident in both samples, with 12.6% and 41.2% of males and females presenting with two risk factors, and 2.8% and 8.1% of males and females respectively presenting with three risks.