MSc (Chemistry) / Department of Chemistry / Bridelia micrantha (Hochst) Baill (B. micrantha) is a South African medicinal plant used by traditional healers in the treatment of different human ailments including diabetes, gastrointestinal ailments, joint aches, cough, conjunctivitis, skin problems and malaria. Previous studies have demonstrated the antidiabetic activities of B. micrantha crude extracts in in vivo studies. However, there are no studies on the compounds responsible for the antidiabetic activity of the plant. The purpose of this study was to isolate and characterize the antidiabetic constituents from B. micrantha. Materials and methods Crude methanolic extracts of root, stem and leaf were investigated using in vitro antidiabetic enzyme assays. Antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing power assays. The isolation of the antidiabetic constituents was carried out using column chromatography on silica gel. Purification of the active fraction was carried out using preparative thin layer chromatography (pTLC). Structure elucidation of the compound was carried out using Nuclear Magnetic Resonance (NMR) spectroscopy and by comparison with literature. Results The results obtained in this study indicated that root, stem and leaf extracts exhibited high inhibition activity against α-glucosidase (98.52, 98.62 and 81.62% respectively). A moderate inhibition against α-amylase enzyme was observed for root (65.62%) and stem (61.86%) extracts. Leaf fraction LFR5 exhibited a high inhibition activity of 96.19% against α-glucosidase. Moreover, the isolated compound showed 96.74% inhibition against α-glucosidase. DPPH results revealed that antioxidant activity of crude extracts was not significantly different and they were concentration-dependent. Reducing power results revealed that stem (119.31 μg/mL) extract had higher activities compared to root (125.17 μg/mL) and leaf (291.88 μg/mL) extracts. Conclusion Quercetin-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnoside was successfully isolated from B. micrantha leaves. Furthermore, quercetin-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnoside demonstrated the ability to inhibit significantly the carbohydrate hydrolysing enzyme α-glucosidase and therefore validate the ethnomedicinal use of B. micrantha in the management of diabetes / Bridelia micrantha (Hochst) Baill (B. micrantha) is a South African medicinal plant used by traditional healers in the treatment of different human ailments including diabetes, gastrointestinal ailments, joint aches, cough, conjunctivitis, skin problems and malaria. Previous studies have demonstrated the antidiabetic activities of B. micrantha crude extracts in in vivo studies. However, there are no studies on the compounds responsible for the antidiabetic activity of the plant. The purpose of this study was to isolate and characterize the antidiabetic constituents from B. micrantha. Materials and methods Crude methanolic extracts of root, stem and leaf were investigated using in vitro antidiabetic enzyme assays. Antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing power assays. The isolation of the antidiabetic constituents was carried out using column chromatography on silica gel. Purification of the active fraction was carried out using preparative thin layer chromatography (pTLC). Structure elucidation of the compound was carried out using Nuclear Magnetic Resonance (NMR) spectroscopy and by comparison with literature. Results The results obtained in this study indicated that root, stem and leaf extracts exhibited high inhibition activity against α-glucosidase (98.52, 98.62 and 81.62% respectively). A moderate inhibition against α-amylase enzyme was observed for root (65.62%) and stem (61.86%) extracts. Leaf fraction LFR5 exhibited a high inhibition activity of 96.19% against α-glucosidase. Moreover, the isolated compound showed 96.74% inhibition against α-glucosidase. DPPH results revealed that antioxidant activity of crude extracts was not significantly different and they were concentration-dependent. Reducing power results revealed that stem (119.31 μg/mL) extract had higher activities compared to root (125.17 μg/mL) and leaf (291.88 μg/mL) extracts. Conclusion Quercetin-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnoside was successfully isolated from B. micrantha leaves. Furthermore, quercetin-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnoside demonstrated the ability to inhibit significantly the carbohydrate hydrolysing enzyme α-glucosidase and therefore validate the ethnomedicinal use of B. micrantha in the management of diabetes.

Utilizou-se um modelo de escolha discreta (MED) para avaliar as preferências e disposição-a-pagar (DAP) dos pacientes por diferentes atributos de risco-benefício do tratamento insulínico, entre eles a via de administração da insulina. Através de uma revisão da literatura, consulta com especialistas, e do desenvolvimento de um estudo qualitativo utilizando as técnicas de entrevistas individuais e grupos focais, os atributos (e níveis) mais importantes do tratamento insulínico foram identificados, sob o ponto de vista dos pacientes. Os atributos incluídos no MED foram: controle da glicemia de jejum, número de episódios de hipoglicemia, ganho de peso, via de administração para as insulinas de ação longa e rápida, e custo do tratamento. Pares de opções de tratamentos insulínicos hipotéticos contendo diferentes níveis dos atributos foram apresentados aos pacientes com DM1 ou DM2, e lhes foi solicitado que, para cada cenário, eles escolhessem a alternativa de sua preferência. Dados demográficos, nível sócio-econômico (NSE) e informações relacionadas ao diabetes também foram coletados. Para a análise dos dados utilizou-se um modelo logit condicional de regressão e modelos segmentados foram posteriormente utilizados para a análise das sub-populações. Um total de 274 questionários foram incluídos na análise final dos dados. A idade média (± DP) dos participantes foi de 56.7 ± 12.98 anos, e 53% eram homens. Quarenta e nove por cento dos participantes eram usuários de insulina e 47 eram portadores de DM1. O tratamento insulínico ideal, sob o ponto de vista dos pacientes, resultaria em um melhor controle glicêmico, menos reações adversas, menor custo, e seria administrado por via oral. Houve uma forte preferência e uma DAP mais elevada por um melhor controle glicêmico, seguido pelos atributos de risco ganho de peso e episódios de hipoglicemia. Surpreendentemente, a via de administração da insulina foi o atributo menos valorizado. A estratificação social revelou que pacientes com alta renda anual familiar apresentaram uma DAP mais elevada por um melhor controle glicêmico e por menos reações adversas em relação aos grupos com rendas inferiores. Ainda, quanto mais alto o nível de renda, maior o desejo por uma insulina oral, enquanto a via inalada torna-se menos importante para os pacientes. A estratificação da amostra pelo uso de insulina e tipo de diabetes revelaram uma forte aversão pela via subcutânea pelos não-usuários de insulina e pacientes com DM2. Tais resultados sugerem a existência de uma importante barreira psicológica em se iniciar uso da insulina; no entanto, os resultados também revelam que os pacientes tendem a se acomodar com a via subcutânea uma vez iniciado o tratamento insulínico. Este estudo demonstra a importância que os pacientes com DM atribuem ao atributo controle glicêmico, e como suas preferências e DAP pelo tratamento insulínico variam entre as sub-populações. Especificamente, esforços devem ser realizados no sentido de vencer a barreira psicológica em se iniciar o uso da insulina, o que contribuirá para que se alcance um melhor controle glicêmico, através da melhor aderência do paciente ao tratamento, resultando em uma redução dos custos do DM e melhora na qualidade de vida dos pacientes. / We used a discrete choice experiment (DCE) to evaluate patients preferences for various attributes of insulin treatment, including route of insulin delivery. Through a review of the literature, expert consultation, and a qualitative descriptive study using individual interviews and focus group techniques, the attributes (and levels) of diabetes treatment most important to patients were identified. The attributes included in the DCE were: glucose control, frequency of hypoglycaemic events, weight gain, route of administration for the long-acting and the short-acting insulin, and out-of-pocket cost. Patients with type 1 or type 2 diabetes were presented with pairs of hypothetical insulin therapy profiles (i.e. choice sets) with different levels of the attributes and were asked to choose the treatment option they preferred. Sociodemographic data and diabetes medication were also collected. Data were analysed using conditional logit regression and segmented models were also developed for the analysis of subgroups. A Two hundred and seventy four questionnaires were completed. The mean age (±SD) of participants was 56.7 ± 12.98 years, and 53% were men. Forty-nine percent of participants were insulin users, and 47 had type 1 diabetes. Overall, patients ideal insulin treatment would provide better glucose control, result in fewer adverse reactions, have the lowest cost, and be administered orally. There was a strong preference and highest mean WTP for glucose control followed by the risk attributes weight gain and hypoglycaemic events. Surprisingly, route of insulin administration was the least valued attribute. Stratification of the sample revealed that patients with higher incomes had a significant higher WTP for better glucose control and less adverse reactions compared to lower income groups. Moreover, the highest the income, the stronger the preference for an oral insulin, while inhaled insulin becomes less important for patients. Segmented models by insulin use and type of diabetes indicated that insulin naïve and type 2 diabetics had a greater aversion to the subcutaneous route. These findings suggest that there may be an important mental barrier to initiating insulin therapy; however, patients tend to accommodate to subcutaneous administration once they initiate therapy. This study illustrates the importance that patients with diabetes place on glucose control and how preferences for insulin therapy vary between subgroups. Specifically, efforts need to be made to overcome the mental barrier to initiating insulin therapy, which may lead to improved control, through improved compliance and ultimately reduce the financial burden of the disease and improve patients quality of life.

Utilizou-se um modelo de escolha discreta (MED) para avaliar as preferências e disposição-a-pagar (DAP) dos pacientes por diferentes atributos de risco-benefício do tratamento insulínico, entre eles a via de administração da insulina. Através de uma revisão da literatura, consulta com especialistas, e do desenvolvimento de um estudo qualitativo utilizando as técnicas de entrevistas individuais e grupos focais, os atributos (e níveis) mais importantes do tratamento insulínico foram identificados, sob o ponto de vista dos pacientes. Os atributos incluídos no MED foram: controle da glicemia de jejum, número de episódios de hipoglicemia, ganho de peso, via de administração para as insulinas de ação longa e rápida, e custo do tratamento. Pares de opções de tratamentos insulínicos hipotéticos contendo diferentes níveis dos atributos foram apresentados aos pacientes com DM1 ou DM2, e lhes foi solicitado que, para cada cenário, eles escolhessem a alternativa de sua preferência. Dados demográficos, nível sócio-econômico (NSE) e informações relacionadas ao diabetes também foram coletados. Para a análise dos dados utilizou-se um modelo logit condicional de regressão e modelos segmentados foram posteriormente utilizados para a análise das sub-populações. Um total de 274 questionários foram incluídos na análise final dos dados. A idade média (± DP) dos participantes foi de 56.7 ± 12.98 anos, e 53% eram homens. Quarenta e nove por cento dos participantes eram usuários de insulina e 47 eram portadores de DM1. O tratamento insulínico ideal, sob o ponto de vista dos pacientes, resultaria em um melhor controle glicêmico, menos reações adversas, menor custo, e seria administrado por via oral. Houve uma forte preferência e uma DAP mais elevada por um melhor controle glicêmico, seguido pelos atributos de risco ganho de peso e episódios de hipoglicemia. Surpreendentemente, a via de administração da insulina foi o atributo menos valorizado. A estratificação social revelou que pacientes com alta renda anual familiar apresentaram uma DAP mais elevada por um melhor controle glicêmico e por menos reações adversas em relação aos grupos com rendas inferiores. Ainda, quanto mais alto o nível de renda, maior o desejo por uma insulina oral, enquanto a via inalada torna-se menos importante para os pacientes. A estratificação da amostra pelo uso de insulina e tipo de diabetes revelaram uma forte aversão pela via subcutânea pelos não-usuários de insulina e pacientes com DM2. Tais resultados sugerem a existência de uma importante barreira psicológica em se iniciar uso da insulina; no entanto, os resultados também revelam que os pacientes tendem a se acomodar com a via subcutânea uma vez iniciado o tratamento insulínico. Este estudo demonstra a importância que os pacientes com DM atribuem ao atributo controle glicêmico, e como suas preferências e DAP pelo tratamento insulínico variam entre as sub-populações. Especificamente, esforços devem ser realizados no sentido de vencer a barreira psicológica em se iniciar o uso da insulina, o que contribuirá para que se alcance um melhor controle glicêmico, através da melhor aderência do paciente ao tratamento, resultando em uma redução dos custos do DM e melhora na qualidade de vida dos pacientes. / We used a discrete choice experiment (DCE) to evaluate patients preferences for various attributes of insulin treatment, including route of insulin delivery. Through a review of the literature, expert consultation, and a qualitative descriptive study using individual interviews and focus group techniques, the attributes (and levels) of diabetes treatment most important to patients were identified. The attributes included in the DCE were: glucose control, frequency of hypoglycaemic events, weight gain, route of administration for the long-acting and the short-acting insulin, and out-of-pocket cost. Patients with type 1 or type 2 diabetes were presented with pairs of hypothetical insulin therapy profiles (i.e. choice sets) with different levels of the attributes and were asked to choose the treatment option they preferred. Sociodemographic data and diabetes medication were also collected. Data were analysed using conditional logit regression and segmented models were also developed for the analysis of subgroups. A Two hundred and seventy four questionnaires were completed. The mean age (±SD) of participants was 56.7 ± 12.98 years, and 53% were men. Forty-nine percent of participants were insulin users, and 47 had type 1 diabetes. Overall, patients ideal insulin treatment would provide better glucose control, result in fewer adverse reactions, have the lowest cost, and be administered orally. There was a strong preference and highest mean WTP for glucose control followed by the risk attributes weight gain and hypoglycaemic events. Surprisingly, route of insulin administration was the least valued attribute. Stratification of the sample revealed that patients with higher incomes had a significant higher WTP for better glucose control and less adverse reactions compared to lower income groups. Moreover, the highest the income, the stronger the preference for an oral insulin, while inhaled insulin becomes less important for patients. Segmented models by insulin use and type of diabetes indicated that insulin naïve and type 2 diabetics had a greater aversion to the subcutaneous route. These findings suggest that there may be an important mental barrier to initiating insulin therapy; however, patients tend to accommodate to subcutaneous administration once they initiate therapy. This study illustrates the importance that patients with diabetes place on glucose control and how preferences for insulin therapy vary between subgroups. Specifically, efforts need to be made to overcome the mental barrier to initiating insulin therapy, which may lead to improved control, through improved compliance and ultimately reduce the financial burden of the disease and improve patients quality of life.

Philosophiae Doctor - PhD / Diabetes mellitus (DM), being one of the most common metabolic disorders with an elevated morbidity and mortality rate around the world. It is characterised by deficiency in insulin secretion or degradation of secreted insulin. Many internal and external factors such as oxidative stress, obesity and sedentary lifestyle among others have been suggested as the major causes of these cell alterations. Diabetes I and II are the most common types of diabetes. Treatment of type I requires insulin injection, while type II can be managed using different synthetic antidiabetic agents. However, their effectiveness is limited as a result of low bioavailability, high cost of drug production, and unfavourable side effects. There is a great need to develop alternative and more active antidiabetic drugs from natural sources. Natural products are a well-known source for the discovery of new scaffold for drugs discovery, and South Africa is one of the most important megaflora with high percentage of endemism. / 2023-12-01

According to the World Health Organization (WHO), 15% of couples in reproductive age suffer from infertility problems, and up to 60% of cases are caused by male factor. Causes of this condition could be genetic background, environmental factors and various diseases, including diabetes mellitus (DM). The aim of this study was to investigate the effects of DM on reproductive parameters and expression of selected testicular genes using mouse model (FVB inbred mouse strain). DM (type 1) was artificially induced by chemical substance streptozotocin, which causes destruction of pancreatic β cells. These mice were exposed to diabetic condition for 6 weeks and then subjected to analysis. Our results have shown that diabetic condition had an impact on body weight, weight of reproductive organs as well as kidneys and livers. We also observed decreased concentration and viability of diabetic sperm compared to control. Moreover, we noticed increased staining with apoptotic marker annexin V. Further, we evaluated changes of sperm nuclear proteins - protamines. In diabetic animals, we observed higher number of sperm with insufficient protamination. Nevertheless, protamine 1 to protamine 2 ratio (P1/P2), a marker of male fertility, was not altered in sperm of diabetic animals compared to control. Regarding the...

Infertility is defined as an inability to conceive a child within one year of regular sexual intercourse. It affects up to 15 % of couples worldwide (WHO, 2010). The male factor contributes to the total infertility with more than 50 %. Fertility of a man is influenced by several factors such as genetic background, environment and various diseases such as diabetes mellitus (DM). Diabetes mellitus is a serious health problem that affects 451 million people worldwide (18-99 years) and the number of people with this disease still increases (Cho a spol., 2018). In addition, parenthood is postponed to middle age when the fertility decreases and metabolic diseases such as type 2 diabetes mellitus (DM2) appear. The aim of this thesis was to investigate the effect of type 2 diabetes on reproductive parameters of mouse inbred line C57BL/6J compared to the control group and the possible effect of paternal diabetes on the first filial generation. In the evaluation of the effect of DM2 on reproductive parameters, we used innovative methods to study internal state of sperm and testes. Results of our work showed that DM2 influenced the weight of body, prostate and liver. The weight of testes, epididymis and liver was reduced in the offspring. Furthermore, sperm morphology and intraacrosomal protein status were...

Magister Commercii - MCom / Introduction: Diabetes mellitus is a global health problem with a high mortality rate. Self-management is an essential part of diabetes management and it includes self-care behaviour tasks such as healthy eating, being active and taking prescribed medication. In the current digital age, the use of technology for self- management of the disease is an important consideration. As a first step towards this, individuals have to first accept and use the technology. However, the literature indicates low levels of technology use amongst diabetic patients in environments with low socio- economic indicators and amongst minority groups. Previous studies suggest that there are many factors that influence technology acceptance such as economic, social and cultural factors. Mobile health (m-health) received recognition in healthcare literature in recent years and are known for delivering effective and efficient interventions to patients with chronic conditions such as diabetes. An investigation into m-health acceptance for diabetes management is vital as it impacts the achievement of development goals, including the United Nations’ SDG 3. This research posits that the culture of patients is a possible reason for the low acceptance and use of technology. Research based on the proliferation of culture as a determinant for diabetes self-management at an individual level is limited, especially in the South African context. The main research question pursued in the study reported in this thesis is How does culture influence m-health acceptance of diabetic patients in disadvantaged communities? Research design and methodology: Using an interpretivist paradigm, a case study research design provided the basis to collect data from 20 diabetes patients in Mitchells Plain and Strandfontein. The theoretical model that was used as a lens for investigation comprised a juxtaposition of Hofstede’s cultural dimensions and Unified- Theory of Acceptance and Use of Technology 2 (UTAUT2). The analysis of the qualitative data was undertaken with Atlas Ti, using a thematic content analysis process. Results: Eight themes emerged from the data and key results of the study indicate that opinions towards medical practitioners, which reflects power distance has a positive impact on users and non-users. Diabetic patients comply with the opinions of their doctors as they fear disagreeing with them. As such, this may result in having a positive influence on a participant’s ability to adopt and use mobile applications. Caregiver influence, which reflects femininity, has a negative influence on users as a result of diabetic patients being responsible for taking care of their family and others are both home carers and providers for their families. This indicates that patients are more concerned with the quality of their life and family than with the adoption mobile applications. Future work: It is recommended that research should be conducted in other areas in the Western Cape, specifically in the Cape flats to see whether the same sorts of results will be achieved in different communities. This could help policymakers and application developers tailor mobile applications for this target population.

Diabetes mellitus belongs to diseases frequently occurring in childhood and adulthood. Insufficient knowledge of this disease and an unsatisfactory compensation for diabetes leads to development of late complications that have a negative impact on one's, as well as the family's, life and create an economic problem for society as a whole. The thesis focuses on the main characteristics of the disease, symptoms, diagnosis and treatment. Complications of the disease, including advice for patients themselves and their prevention are described in more detail. Social aspects (work inclusion of a diabetic, invalidity and reduced work capacity, driving of motor vehicles) are also emphasised. The research part containing 18 questions aims to find out to what extent the Czech public is informed about the problematic areas of this disease. It also assesses the feasibility of obtaining information from individuals of different ages and places of residence (city vs. village) regarding diabetes. These hypotheses were stated within the scope of the research: 1. Individuals older than 50 years of age are better informed about diabetes than individuals of a younger age. 1. Individuals living in a city have a better access to information concerning diabetes than individuals living in a village. The data was obtained from questionnaire research, in which respondents older than 18 years of age participated. The data collection took place in Bechyně Spa Ltd. 58 % of the resultant questionnaires were completed by women and 42 % by men.