Includes abstract. Includes bibliographical references (p. 245-262).

Includes abstract. / Includes bibliographical references. / Nutritional supplements are used by competitive and recreational athletes of all ages. As a consequence the supplement industry has grown to meet the increasing demand. The regulation of the supplement industry is unrefined, which increases the risk of the nutritional supplements being contaminated. Contamination may be intentional, where the companies “spike” their products with an ergogenic aid, or unintentional. A consequence of contamination is that an athlete may fail a drug test after ingesting a contaminated supplement or there may be negative health consequences. Without adequate legislation it is difficult to control the industry and reduce the risk of contamination in the supplement. Objectives: To investigate the industry associated with commercially available nutritional and traditional supplements. These are in the five specific areas; (i) to review the regulations and legislations, and labelling and claims associated with nutritional products in the USA, European Union and South Africa, (ii) to assess the labelling and claims information on nutritional supplement products imported into and manufactured or assembled in South Africa, (iii) to assess using a survey questionnaire the container labelling and other sources of information that assist consumers of nutritional products in their purchasing decisions, (iv) to assess traditional commercial supplements for contamination and consistency of trace elements and heavy metals using Inductively Coupled Plasma-Mass Spectrometry, and (v) to assess the content of nutritional commercial supplements for steroids, stimulants and other compounds of interest using Tandem Liquid Chromatography-Mass Spectrometry.Methods: The thesis is divided into 6 Chapters. Chapter 1 describes the background to the problem and Chapter 2 reviews the existing legislation. In Chapter 3 the labelling and claims information on 40 nutritional supplements products are analysed, and the self-administered questionnaire determined what product label and other information influences consumers of nutritional supplements in their purchasing decisions. In Chapter 4 the consistency of trace elements and heavy metals are analysed in selected nutritional supplements using Inductively Coupled Plasma Mass Spectrometry. In Chapter 5 selected nutritional supplements are analysed for steroids, stimulants and other compounds using Tandem Liquid Chromatography Mass Spectrometry. All the data of these sections are summarised in Chapter 6.

Includes bibliographical references.

Bibliography: p. 130-155.

No description available.

Includes abstract. / Includes bibliographical references (leaves 148-171). / Plasmodium falciparum is becoming increasingly more resistant to regular antimalarial drugs, making it necessary to identify novel drug candidates and drug targets. Components of the endocytic and secretory pathway in asexual stage parasites are attractive targets because they play a fundamental role in the normal processes of parasite metabolism. Adaptor protein complexes are components of protein coats that associate with transport vesicles of the endocytic and secretory pathways in mammalian cells. Homologues of several adaptor protein subunits are encoded by the parasite genome. The presence of these genes suggests that the parasite experiences clathrin-mediated transport processes. This study reports the cloning and characterization of selected malarial homologues of these adaptor proteins, namely three medium (μ) chain adaptin homologues and two sigma (σ) chains.

Following the completion of a detailed baseline study of malaria in the region, a model was developed to assess the cost-effectiveness of switching from chloroquine to sulfadoxine-pyrimetharnine as first line treatment in the Tonga district of Mpumalanga, South Africa, where malaria is seasonal and the population is non-immune. In vivo drug resistance was used to create a resistance variable, which was used to assess the 1997 relative costs to the health care system of employing the two drugs, analysing factors such as drug costs, staff time, transport costs, maintenance costs, utility costs, training costs and consumables costs to generate an average cost-effectiveness ratio. The model was subsequently used to estimate the average cost-effectiveness ratios of nine other potential agents for the treatment of first line malaria, including artesunate monotherapy, artesunate combinations, pyronaridine, atovaquone-proguanil, co-artemether, halofantrine, amodiaquine, and mefloquine. It was found that sulfadoxinepyrimethamine was 5 times more cost-effective as first line therapy than chloroquine. Of the other modelled drugs, it was recommended that an artesunate combination should be implemented when it becomes necessary to replace sulfadoxine-pyrimethamine; artesunate-mefloquine and artesunate-SP were estimated to be 6 times and 9 times as cost-effective as chloroquine, respectively.

Includes abstract. / Includes bibliographical references. / The World Health Organization recommends the use of isoniazid preventive therapy to reduce the incidence of tuberculosis disease in populations at risk for developing the disease. Adherence to isoniazid preventive therapy is needful for efficacy. A urine assay known as the Arkansas test is widely used to monitor the ingestion of isoniazid. However, this test is limited by a drop in sensitivity with increasing time post isoniazid dose. Furthermore, results from the test can be affected by observer variation in colour changes, concomitant medications, urinary dilution, and presence of other substances in urine. Moreover, the Arkansas test results have not been evaluated against objective measurement of isoniazid and acetylisoniazid urine concentrations. This study seeks to measure the urine concentrations of isoniazid and acetylisoniazid at different time points after a dose in children, in order to establish reference ranges for liquid chromatography tandem mass spectrometry measurements of urine isoniazid and acetylisoniazid, as well as the Arkansas method. The reference ranges would provide a standard which can be used to estimate the probability of adherence to prior doses.

Worldwide occurrence of chloroquine resistance is an expanding problem in prophylaxis and treatment of malaria. Similarities between the drug resistance phenotype in certain cancers and in malaria suggest that homologue multidrug resistance proteins might be involved in the mechanism of resistance. In this thesis, the expression of a putative multidrug resistance protein of the malaria parasite Plasmodium falciparum, the P-glycoprotein homologue1 (Pgh1), was quantified on food vacuoles, the site of action of chloroquine. Chloroquine susceptibility was determined in 8 different P. falciparum strains. Food vacuoles were isolated from trophozoites of two chloroquine-sensitive (307 and D10) and three chloroquine-resistant (FAC8, K1 and RSA 11) strains. Antibodies against an 18 amino acid long peptide of Pgh1 were raised, as well as two other antibodies against the N-terminal ATP-binding site and the C-terminus of Pgh1. With these antibodies, Pgh1 was detected on isolated food vac.uoles and on trophozoites by immunoblotting. The exact Pgh1 expression levels on food vacuoles were measured with digital image analysis. The chloroquine-sensitive strains 307 and D10 and the chloroquine-resistant strains K1 and RSA 11 expressed equal amounts of Pgh1. The chloroquine-resistant FAC8 strain expressed at least three times more vacuolar Pgh1. No correlation was found between chloroquine IC₅₀ and vacuolar Pgh1 expression levels. Phosphorylation studies on intact food vacuoles indicated that Pgh1 is not a major kinase substrate.

Includes bibliographical references (leaves 94-103). / By contrast to mammalian cells, very little is known about endocytosis in the malaria parasite. However, endocytosis via the cytostome is required by the parasite to ingest haemoglobin from its host cytosol which it transports within double membrane vesicles to the digestive vacuole, where digestion occurs and metabolites are used mostly for nutritional purposes. To gain a deeper understanding of the molecular basis and mechanisms of this vital process, a panel of inhibitors was used to inhibit the actin cytoskeleton and PI (3) kinases in the parasite. In this study Cytochalasin D and Latrunculin A, which depolymerise and prevent actin fimalment formation, Jasplakinolide, which stabilises actin filaments, and Wormannin and LY294002, which inhibit PI 93) kinase, were used to study actin disrupting and PI (3) kinase inhibiting drug effects on haemoglobin endocytosis and transport vesicle trafficking within the malaria parasite Plasmodium falciparum.