Fetal pig islet-like cell clusters (ICCs) were transplanted into the thymus or omentum of STZ-induced diabetic pigs immunosuppressed with cyclosporine (CsA) and deoxyspergualin (DSG), as a potential treatment for type 1 diabetes. C-peptide levels in response to glucagon and arginine significantly increased over time using 1 litter of ICCs with highest levels obtained at 100 days post-transplantation. Increasing the number of ICCs to 2 litters was not advantageous. Histology of the graft showed all 4 pancreatic endocrine cells. Normoglycaemia was achieved for transient periods without insulin administration in 4 out of 12 pigs. These results suggest sub-optimal insulin production, possibly due to the adverse effects of CsA on the grafted β cells. The effect of CsA on adult porcine β cells was investigated and adverse effects were shown. Renal toxicity and adverse changes to the haematological parameters did not occur despite high CsA levels although minimal toxicity to the liver was observed. The results indicate that the use of CsA monotherapy in the maintenance phase to prevent rejection of allografted pancreatic β cells may become a subsequent problem over time. As an alternative to chronic immunossuppression, anti-CD3 monoclonal antibody was administered for 10 days in pigs. Using anti-CD3 alone, only 1 out 4 pigs showed cells positive for insulin. The addition of a 5-day CsA course administered the day before transplantation did not promote allograft survival. The use of DSG for 10 days with anti-CD3 promoted graft survival with the histology showing the 4 endocrine cells 3 weeks post-transplantation. An attempt was made to replace any form of immunossuppression by encapsulating fetal pig ICCs in barium alginate, which were able to remain viable when transplanted in NOD/SCID mice. Fibrosis was detected in BALB/c mice transplanted with encapsulated fetal ICCs suggesting that fetal pig ICCs shed antigens that elicit an immune response. Results from this study show that although fetal pig ICCs may be a viable source of insulin-producing cells, the use of CsA to prevent rejection has adverse effects on graft function. Encapsulation as well as transient immunosuppression is worthy of further investigation to prevent rejection of fetal pig ICCs.

published_or_final_version / Community Medicine / Master / Master of Public Health

Fetal pig islet-like cell clusters (ICCs) were transplanted into the thymus or omentum of STZ-induced diabetic pigs immunosuppressed with cyclosporine (CsA) and deoxyspergualin (DSG), as a potential treatment for type 1 diabetes. C-peptide levels in response to glucagon and arginine significantly increased over time using 1 litter of ICCs with highest levels obtained at 100 days post-transplantation. Increasing the number of ICCs to 2 litters was not advantageous. Histology of the graft showed all 4 pancreatic endocrine cells. Normoglycaemia was achieved for transient periods without insulin administration in 4 out of 12 pigs. These results suggest sub-optimal insulin production, possibly due to the adverse effects of CsA on the grafted β cells. The effect of CsA on adult porcine β cells was investigated and adverse effects were shown. Renal toxicity and adverse changes to the haematological parameters did not occur despite high CsA levels although minimal toxicity to the liver was observed. The results indicate that the use of CsA monotherapy in the maintenance phase to prevent rejection of allografted pancreatic β cells may become a subsequent problem over time. As an alternative to chronic immunossuppression, anti-CD3 monoclonal antibody was administered for 10 days in pigs. Using anti-CD3 alone, only 1 out 4 pigs showed cells positive for insulin. The addition of a 5-day CsA course administered the day before transplantation did not promote allograft survival. The use of DSG for 10 days with anti-CD3 promoted graft survival with the histology showing the 4 endocrine cells 3 weeks post-transplantation. An attempt was made to replace any form of immunossuppression by encapsulating fetal pig ICCs in barium alginate, which were able to remain viable when transplanted in NOD/SCID mice. Fibrosis was detected in BALB/c mice transplanted with encapsulated fetal ICCs suggesting that fetal pig ICCs shed antigens that elicit an immune response. Results from this study show that although fetal pig ICCs may be a viable source of insulin-producing cells, the use of CsA to prevent rejection has adverse effects on graft function. Encapsulation as well as transient immunosuppression is worthy of further investigation to prevent rejection of fetal pig ICCs.

No description available.

The growing pandemic of diabetes mellitus (DM) is continuing to spread around the world with developing countries being most vulnerable. Diabetes mellitus is the direct cause of 5 percent of deaths worldwide at present, with an expected increase of 50percent in the next 10 years. Diabetes mellitus was virtually unknown in Africa at the start of the 20th century but the incidence is expected to increase by 80 percent by 2025. South African estimates indicate that at present there are up to four million people living with DM in South Africa, with an expected rise of 25 percent by 2020. If DM is not adequately controlled, life-threatening complications ensue, resulting in financial, physical and emotional costs both for people living with the condition and for their families. There is also a great financial burden on the state, both directly due to the cost of providing health care and indirectly due to loss of productivity and a reduced tax base. Global initiatives against DM include the Diabetes Strategy for Africa compiled by the International Diabetes Federation and World Health Organization. There are several forms of DM with Type 2 being the most common with an estimated 95% of cases. Optimal glycaemic control is essential for the management of DM, potentially allowing the course of the disease to be slowed or halted. The previous medical model of management of chronic disease has changed to an empowerment approach where the person living with the condition is a partner in the management process. This is particularly true of DM where all aspects of life are affected by the condition. During Phase One of this study, a qualitative, exploratory, descriptive, contextual approach was utilized to explore and describe the experiences of persons living with DM and of diabetes nurse educators who assist them in Nelson Mandela Bay. During Phase Two, a conceptual framework was created and utilized to develop strategies which professional nurses may use in facilitating self-management by persons living with DM. Persons living with DM experience a definite initial experience on diagnosis of DM but gradually gain an acceptance and acknowledgment of their condition. They have definite views on the concept of self-management and experience both positive and negative factors influencing self-management. They also have definite ideas on how professional nurses may assist them in achieving self-management. These findings were confirmed ii by the experiences of the diabetes nurse educators who formed the second group of participants in this study. The ACE approach to self-management of DM consists of an Action Strategy, a Coordination Strategy and an Education Strategy. The ACE approach makes use of grand and functional strategies implemented on the macro (national), meso (provincial) and micro (local) levels to enable the professional nurse to assist persons living with DM to achieve self-management of their condition. Grand strategies need to be implemented on a macro or meso level to enable the professional nurse to function effectively on a micro level. Assisting the patient has to go beyond merely improving knowledge about the condition but has to include individual goal setting as well as problem solving skills and coping strategies as part of a therapeutic relationship between the professional nurse and the person living with DM. The level of personal responsibility achieved by persons living with DM is affected by the memes which they hold regarding their level of health and their ability to address any barriers to self-management which they may experience. Making use of the process of the therapeutic relationship, the professional nurse is able to positively influence the memes held by persons living with DM and assist them in achieving a greater level of personal responsibility. The therapeutic relationship is potentially influenced by all three of the strategies described above. This study provides insight into the experiences of persons living with DM and of the diabetes nurse educators who assist them in Nelson Mandela Bay. Recommendations regarding the implementation of a National Diabetes Policy on a macro level are made, as well as recommendations for nursing practice, education and research. The strategies which were evaluated by an Expert Panel provide a tool for the professional nurse to use while assisting persons living with DM by facilitating the growth of personal responsibility leading to self-management.

Thesis (MSc(Biomedical Technology))--Cape Peninsula University of Technology, 2019 / Background: Maturity Onset Diabetes of the Young (MODY) is a monogenic type of diabetes caused by a single gene mutation. Up to date 14 different MODY subtypes have been identified. Mutations in the glucokinase (MODY 3) and hepatic nuclear factor 1 alpha (HNF1A) (MODY 2) are the most frequent causes of MODY in all populations studied. Patients with MODY are misdiagnosed with type 1 or type 2 diabetes. Identifying patients with MODY is important as it affects treatment, for example, MODY 2 patients need no treatment, whereas those diagnosed with MODY 3 are very sensitive to low doses of sulphonylureas. To date, no data is available on the prevalence of MODY in populations from Africa. Thus, we aimed to investigate and report on the incidence of MODY, specifically mutations in the HNF1A gene in a population from the Western Cape. Methods: In this study, we screened for HNF1A MODY (MODY 3) mutations (rs115080759, rs140491072 rs137853245, and rs142318174) in 1639 (males = 406) individuals using real-time PCR. Positive MODY samples were confirmed by subsequent sequencing. All individuals underwent an oral glucose tolerance test. Results: The mean age of participants was 47.1±15.6 in males and 49.9±15.1 females. We identified 12 (0.73%) individuals with HNF1A gene polymorphisms; 12/1642 of rs115080759. Seven participants with a SNP in rs115080759 presented with normoglycemia, one with prediabetes, and four with diabetes. No polymorphism was detected in three SNPs; rs140491072, rs137853245 and rs142318174. Discussion and conclusion: To our knowledge, this is the first African study on MODY, and the incidence is similar to that reported in other studies. The results suggest that MODY is misdiagnosed with other types of diabetes in Africa; therefore, our findings support the introduction of diagnostic genetic testing for MODY in South Africa.

Diabetes is a rapidly growing health concern in the developed world. Hypoglycaemia is a major risk factor in people with diabetes. Each year, about 7000 calls relating to hypoglycaemia are made to the Scottish Ambulance Service (SAS), including a considerable number of repeat callers. Very little is known about people’s experiences and explanations of recurrent hypoglycaemia; in particular, why some individuals manage their recurrent hypoglycaemic episodes independently, while others require more direct healthcare support. This thesis investigated participants’ experiences and individual explanations of recurrent hypoglycaemic episodes, in order to understand their health help-seeking behaviour. To do this, it compared the experiences of people who had called the emergency services within one month prior to recruitment (SAS participants), with those people who had not done so (non-SAS participants). The study employed a multiple methods longitudinal approach to prospectively capture participants’ experiences of hypoglycaemic episodes, using qualitative semi-structured interviews, hypoglycaemia and blood glucose diaries and follow-up telephone interviews over a six month period. Thirty participants were involved in the study, recruited through the Scottish Ambulance Service, Diabetes UK (Scotland), and the University of Stirling. All participants resided in the central belt of Scotland. Qualitative data was analysed using the framework method, and quantitative data was analysed using descriptive statistics. This study found that hypoglycaemic episodes had a wide ranging impact on people’s everyday life. It was not only the actual hypoglycaemic episode that affected participants’ everyday life, but also fears and worries about future hypoglycaemic episodes, the preparations that participants engaged in, and the process of recovery. Hypoglycaemia unawareness was found to be a major problem for many people living with diabetes. It appeared to be associated with the likelihood of needing external help. There were differences between participant groups with regard to management of hypoglycaemia unawareness. Non-SAS participants adopted strategies to prepare for future hypoglycaemic episodes, and appeared to be more knowledgeable about their diabetes and its management, resulting in needing less external help. SAS participants experienced more severe hypoglycaemic episodes. Consequently, they relied more on external help. Findings of this study call for a re-conceptualisation of the previously recognised ‘balancing act’ of managing diabetes and hypoglycaemic episodes. This study introduces the concept of a hypoglycaemic episode balancing continuum (HEBC) which enables a deeper understanding of the factors involved in this balancing act: it demonstrates that people balance the various risks differently, depending on whether they prioritised their fear of hypoglycaemia over fears of long-term complications. People’s position on the continuum directly affected their management strategies for hypoglycaemic episodes. Most hypoglycaemic episodes were managed by the individual without requiring any external help. However, participants’ ability to self-care differed and deficits occurred, resulting in participants being more likely to need involvement of others (family/friends). When the capacity of others to help broke down, participants’ were more likely to need SAS emergency care. In order to explain how hypoglycaemic episodes are managed, this thesis has developed a hypoglycaemic episode help-seeking network (HEHS network), which helps to identify the various agents involved in helping to manage hypoglycaemic episodes. Findings from this study have implications for clinical practice. For example, looking at hypoglycaemia unawareness, this study has shown that current understanding may fail to take account of participants’ real experiences, which show hypoglycaemia unawareness to be a fluid phenomenon that can affect people at various times. If blood glucose levels can fail to predict onset of hypoglycaemic episodes, healthcare professionals may need to broaden the range of blood glucose readings that might indicate a hypoglycaemic episode and tailor specific advice to individual patients. To reduce the use of emergency services, more attention must be paid to hypoglycaemia unawareness and better advice provided about this condition. Also, more education should be provided for family members/carers, given the crucial role they play in the management of diabetes and hypoglycaemic episodes, and being a link in the process leading to increased use of emergency services. The HEBC could be developed into a useful ‘screening tool’ to help healthcare professionals identify those at greater risk of hypoglycaemic episodes and those at greater risk of long-term complications, and to target advice more specifically to these patient groups. Further research could explore family member/carer knowledge in more detail to better understand their role in helping to manage hypoglycaemic episodes.

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

Thesis (PhD (Biomedical Sciences))--Cape Peninsula University of Technology, 2017. / The use of medicinal plants in the management of various health problems date back to the ancient times. However, only in recent years, researchers are starting to focus on the use of natural plant products as alternative treatment in disease control. Basella alba (Ba), commonly called Ceylon or Indian spinach is one of such medicinal plants, wildly cultivated and consumed mostly as vegetable. Studies have established many beneficial effects of Ba, including androgenic effects as well as antidiabetic effects which have been described in rats following oral administration of the leave extract. However, the actual mechanisms underlying the antihyperglyceamic effect of Ba have not been reported in any study and little or no research details are yet available on the potential beneficial effects of Ba in reproductive dysfunction resulting from diabetes mellitus. This study was aimed at investigating the mechanisms underlying the antidiabetic effect of Ba and the possibility of a role for the plant in correcting diabetic-induced reproductive dysfunctions in male Wistar rats. The first part of the study involved comparing of three different solvent extracts of Ba leaves namely ethyl acetate, methanolic and aqueous extracts for their antioxidant potentials, after which the aqueous extract was selected for further use in the experiments. Animal experimentation involved male rats (n=40) aged 8-10 weeks, randomly divided into four equal groups as follows: Healthy Control, Diabetic Control, Healthy Treatment and Diabetic Treatment. Diabetes was induced via a single intraperitoneal injection of streptozotocin (55mg/kg) and all animals subsequently received treatment via gavage (Rats in Control groups received 0.5ml/100g normal saline daily and treatment groups received 200mg/kg plant extract daily) for a period of four weeks. Fasting blood sugar and body weights were recorded weekly throughout the study. Animals were sacrificed upon completion of the treatment and blood samples and tissues collected for further analysis which included computer aided sperm analysis, Luminex® technology and enzyme-linked immunosorbent hormonal assays, inflammatory cytokine assays, analysis of oxidative stress markers and Histopathological analysis. The single intraperitoneal injection of a high streptozotocin dose resulted in hyperglycaemia, weight loss, subnormal sperm parameters, negative balance of inflammatory cytokines and endogenous antioxidants and degenerative changes in the pancreas, testes and epididymis as observed in the diabetic control rats. Oral administration with the aqueous extract of Ba for four weeks in diabetic treatment rats led to a significant reduction in blood sugar and improvement of sperm parameters by modulating the production of gonadal hormones, in vivo antioxidants and inflammatory cytokines. There was also significant recovery of normal islet histology and reduction in testicular and epididymal degeneration in the diabetic treatment rats when compared to their diabetic control counterparts. It was concluded from the findings of this study that the antidiabetic and profertility effects of Ba are largely dependent on the modulation of in vivo production of antioxidants, gonadal hormones and inflammatory cytokines, probably stimulated by one or more phytochemical component(s) that can be isolated in the aqueous extract of the plant.

Zhou, Yu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 89-107). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.