M.Tech. (Homeopathy) / Insulin resistance (IR) is a metabolic derangement and a documented clinical feature of the metabolic syndrome. It is an important risk factor in the development of cardiovascular disease and Type 2 Diabetes mellitus. Insulin resistance is often characterized by an increased Homeostasis Model Assessment (HOMA) index and hyperinsulinaemia, but it may also be present without increased insulin levels. Metabolic syndrome is a cluster of risk factors characterized by visceral adiposity (a girth exceeding 102cm in men and 88cm in women), dyslipidaemia (low HDL and raised triglycerides levels), hypertension and dysglycaemia, particularly raised fasting blood glucose levels, predisposing individuals to cardiovascular disease and Type 2 Diabetes mellitus. Diaglukon™ Dr Reckeweg R40 is formulated as an adjunct in the treatment of type 2 diabetes mellitus to assist in lowering the blood glucose (hyperglycaemia). The aim of the research was to evaluate and document its efficacy in the treatment of insulin resistance. A cohort of forty five participants between the ages of nineteen to forty five years was randomized into a double blind placebo controlled, 16 week, clinical study. Participants were matched according to age, race and gender. Anthropometric evaluation consisted of weight, height, BMI, waist circumference and blood pressure readings; these were recorded at 4 weekly intervals for sixteen weeks. Metabolic data included fasting insulin, glucose and a full lipogram at baseline (Week 0) and at study conclusion (Week 16). The insulin and glucose was used to calculate the HOMA index as a measure of insulin resistance (IR). Non parametric statistical analysis was conducted on all parameters using the SPSS statistical programme...

OBJECTIVES: The aim of this study was to evaluate the bond strength of a low fusing veneering porcelain fired on Titanium grade V with different surface treatments. MATERIALS & METHODS: One hundred and twenty bars of Titanium grade V (25±1x 3±0.5x 0.5±0.05mm) were divided randomly into twelve groups: group 1 no surface treatment, group 2 Gold sputter coating, group 3 TiN sputter coating, group 4 Sandblasting Al2O3 125μm, group 5 Sandblasting Al2O3 180μm, group 6 Sandblasting Al2O3 250μm, group 7 Sandblasting Al2O3 125μm then gold sputter coating, group 8 Sandblasting Al2O3 180μm then gold sputter coating, group 9 Sandblasting Al2O3 250μm then gold sputter coating, group 10 Sandblasting Al2O3 125μm then TiN sputter coating, group 11 Sandblasting Al2O3 180μm then TiN sputter coating, group 12 Sandblasting Al2O3 250μm then TiN sputter coating. Vita Titankeramik porcelain was applied for all groups and built up manually with dimensions limited to 8x3x1mm and fired on Ti bars following the manufacturer’s instructions and ISO 9693 recommendations, and tested for bond strength by Schwickerath crack initiation test (ISO 9693) using an Instron universal testing machine (Model: 5566A). The mode of failure and bond interface were evaluated by SEM / EDS. RESULTS: The mean bond strength values of groups 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 were 2.31MPa (±0.2), 24.3MPa (±0.78), 46.94MPa (±1.29), 6.18MPa (±0.98), 9.46MPa (±1.08), 15.14MPa (±0.74), 24.84MPa (±1.73), 36.24MPa (±1.43), 41.49MPa (±2.13), 49.45MPa (±0.96), 69.36MPa (±0.96), 94.45MPa (±1.51), respectively. Two-way ANOVA with Tukey multiple comparisons test was performed to determine the groups that are statistically different. All tested groups (1-12) showed statistically significant difference except groups 2, and 7, P< 0.05. CONCLUSIONS: Within the limitations of this study, the following conclusions can be drawn: 1- Surface finish significantly affects the bond strength of low fusing porcelain to Ti grade V. 2- Larger Al2O3 particle size corresponded to higher bond strengths. 3- Sandblasting in combination with Au or TiN coatings produced the highest bond strength values. 4- Groups 1, 4, 5, & 6 showed Adhesive failure at the ceramic – metal interface; for groups 3, 10, 11, & 12 were found to be Cohesive failure within the porcelain layers; and for groups 2, 7, 8, & 9 were found to be mixed Adhesive / Cohesive failure. / 2018-09-28T00:00:00Z

M.Sc. (Physiotherapy), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Low back pain (LBP) is one of the commonest and most costly medical problems in both the low and high income countries accounting for 75-90% of compensation costs. Compensation costs for LBP in South Africa in the year 2000 were approximately two hundred million rand and about 30 000 people suffer from neck and back problems on a daily basis. Physiotherapy treatment modalities are commonly used in the management of LBP but there is no consensus on the choice of treatment modalities. A cross-sectional survey was used to investigate the treatment modalities used by physiotherapists in Kwazulu-Natal (KZN) for the management of chronic low back pain (CLBP). The objectives of the study were to establish the commonly used physiotherapy modalities in the management of CLBP, the reasons behind the selection of those modalities and the extent to which the physiotherapists in KZN used evidence based modalities when managing CLBP. Self-Administered questionnaires were posted to all registered physiotherapists in KZN, that is, six hundred and eighty-five (685) physiotherapists. A 31% (213) response rate was achieved, of which 20.6% (141) met the inclusion criteria and 10.5% (72) were excluded. The results established that general exercises (30%); spinal mobilisation (28%); myofascial release (18%), education (12%) and training of local stabilisers (12%) were the commonly used treatment modalities in the management of CLBP. The key reasons for the selection of the treatment modalities were the undergraduate education received; own clinical experience and the attendance of postgraduate courses/physiotherapy conferences. Treatment modalities were not selected on the basis of the current available evidence hence evidence-based practice is not employed by physiotherapists in KZN in the management of patients with CLBP.

M.Pharm., Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 2011. / Ulcerative colitis (UC), notorious for its unpredictable attacks of inflammation of the large intestine, is estimated to affect as many as 1.4 million people in the USA and 2.2 million people in Europe with 15000-30000 new cases being diagnosed annually worldwide. The chronic inflammatory process is limited to various regions of the colonic mucosa and is postulated to occur due to a dysregulated mucosal response in the intestinal wall, facilitated by defects in the protective barrier function of the intestinal epithelium and mucosal immune system. Due to the range and extent of disease manifestations the goals of UC therapy are broad and non-specific. The focus of therapy is thus primarily placed on the treatment of active disease by ameliorating the signs and symptoms characteristic of the disease state with concurrent adjunctive and anti-inflammatory therapy. Thus, ideally a delivery system should facilitate a reduction in the pill burden, daily dosing requirements and allow for concurrent adjunctive and anti-inflammatory therapy with a single delivery system administration. Therefore, essentially the purpose of this work was to develop a novel stimuliresponsive oral tablet system (SROT) that provided targeted drug delivery of 5-ASA to the colon and loperamide HCl to the small intestine with a single delivery system. For this purpose, the employment of polymers that are termed ‘stimuli-responsive’ or ‘smart’ were established to be the most attractive approach for ‘activating’ drug release at the desired site in response to the pre-determined reliable stimulus. Thus, advantage is taken of the over 400 distinct species of anaerobic bacteria and their corresponding enzymatic activities in the colon. Investigations performed according to a Box-Behnken experimental design exposed an optimum enzyme-responsive colon-targeted tablet that effectively inhibited premature 5-ASA release in conditions simulating the upper gastrointestinal tract, whilst enabling an immediate initiation of drug release on exposure to colonic enzymes. The enzyme-responsiveness of the tablet was a direct result of the employment of only naturally-derived polysaccharides that were susceptible to colonic degradation. Furthermore, and more importantly, the prevention of premature drug release was achieved by the enzyme-responsive hydrophobic coating consisting of pectin and an aqueous ethycellulose dispersion that was applied to tablets until a ±10% total weight gain was achieved. In addition the in situ crosslinking between pectin and BaCl2 in the tablet matrix as well as the crosslinked 5-ASA-loaded granules resulted in a zero-order drug release throughout the 18 hour period in the simulated colonic environment containing enzymes. The development of the outer pepsin-responsive small intestinally-targeted coating was also conducted according to the Box-Behnken experimental design. Extensive investigations revealed an optimized pepsin-responsive coating after conducting the relevant studies on the 15 statisticallyderived formulations. Essentially, the tablets coated with the 40%w/v gelatine solutions resulted in the greatest increase in weight and shell thickness of the formulations however these were the least responsive to pepsin. The optimum pepsin-responsiveness was achieved from a gelatine coating of 14.379%w/v which was crosslinked for 6 hours in a glutaraldehyde-lactose dry mixture. Furthermore, the novel crosslinking method ensured that no entrapped loperamide HCl was prematurely lost during the crosslinking process. In addition, the optimum formulation also achieved 100% drug release in the small intestine-at its site of therapeutic action. In vivo investigations of the SROT in the large white pig model explicated the colon-targeting ability of the 5-ASA-loaded tablet as well as the benefits of the SROT compared to the conventional commercially available system, Asacol® (Aventis Pharma (Pty) Ltd.,Midrand, Johannesburg, South Africa). The success of the loperamide-loaded coating was evident from the minimal presence of loperamide HCl in plasma in the first 2 hours post-dosing compared to its commercially available counterpart Imodium® (Janssen Pharmaceutica (Pty) Ltd., Woodmead, Johannesburg, South Africa). Investigations into an alternate colon-targeted drug delivery system revealed 3 novel composite polyacrylamide-polysaccharide hydrolyzed electrolytic matrices consisting of either pectin, chitosan or a combination of both, complexed with hydrolyzed polyacrylamide. Each matrix presented with varying surface area and porositometric properties which influenced their drug release behaviour. These formulations hold potential for numerous controlled drug delivery applications and are not exclusively limited to colon-targeting.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the Degree of Doctor of Philosophy Submitted June 2016. / The work detailed in this PhD involves two distinct, separate areas of research. The first project involved an investigation into the synthesis, characterisation and metal-chelation of pyrido-imidazo[1,2-a]pyridines in the search for new compounds for the treatment of cancer. Previously in our laboratories at the University of the Witwatersrand a small library of imidazo[1,2-a]pyridines were synthesized that showed significant activity (IC50 values between 6.57-21.98 μM) against Caco-2 and HT-29 colorectal cancer cell lines while showing little cytotoxicity towards white blood cells; significantly less than camptothecin the ‘golden standard’. In an attempt to improve the overall activity of the imidazo[1,2-a]pyridines methodology was developed to coordinate zinc, copper and platinum to the imidazo[1,2-a]pyridines to generate novel metal-imidazo[1,2-a]pyridine complexes. These novel compounds were characterised by NMR spectroscopy (where possible) and Single Crystal X-ray Diffraction (SCXRD) and tested against colorectal (Caco-2 and HT-29), leukemic (K562 and HL-60) and breast (MCF-7 and MDA-MB231) cancer cell lines, where the copper-containing compounds showed the most significant activity. A library of 11 copper complexes screened showed excellent activity in all the cell lines tested, some of which were more active than camptothecin. The second part of this PhD involved a detailed investigation into novel methodology to synthesize xanthones and related diones, for example such as 4a-methoxy-2H-xanthene-2,9(4aH)-dione, discovered in our laboratory. Initially this reaction was reported to be mediated by ceric ammonium nitrate (CAN), however it was determined during the course of this investigation that the novel reaction was actually mediated by ceric ammonium sulfate (CAS) and that different products were isolated depending on which reagent (CAN or CAS) was used. In this thesis, the mechanism of the reaction was probed and it was determined that the electronic nature of the starting benzophenone (e.g. (2-hydroxyphenyl)(2,4,6-trimethoxyphenyl)methanone) plays a crucial role in the outcome of the reaction. In addition to the furnishing of xanthones (e.g. 4-methoxy-9H-xanthen-9-one) and spirofurans (such as 2',6'-dimethoxy-3H-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-dione) using this CAS-mediated reaction, novel biaryl-fused dimers (e.g. (4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-diyl)bis((2,4-dimethoxyphenyl)methanone)) were also isolated and these results were explained by the mechanisms detailed in this work. Reliable methodology was developed using a sodium dithionite-mediated method for the conversion of dione products (such as 4a-methoxy-2H-xanthene-2,9(4aH)-dione) to hydroxy-containing xanthones (such as 7-hydroxy-9H-xanthen-9-one). iv Finally, as a proof of concept, this novel CAS-mediated methodology was extended to the synthesis of the nitrogen-containing derivatives, the acridones, and a single acridone, 10-benzyl-2-methoxyacridin-9(10H)-one, was successfully synthesized using CAS as the reagent, albeit in a low yield. / LG2017

University of Macau / Faculty of Health Sciences

University of Macau / Faculty of Health Sciences

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Faculty of Health Sciences