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Very little is known about why and how the Parkinson's disease (PD) neurodegenerative process begins and progresses. In the course of developments for treatment of PD, the discovery of the inhibition of monoamine oxidase (MAO B) was a conceptual breakthrough, and has now been firmly established. MAO B has also been implicated in the neurodegenerative processes resulting from exposure to xenobiotic amines. For example, MAO B catalyzes the first step of the bioactivation of the parkinsonian inducing pro-neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Additional insight into the mechanism of catalysis of MAO B and the mechanism of neurotoxicity by MPTP is therefore very valuable in the pursuit of the treatment of PD. / Thesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2008.

Very little is known about why and how the Parkinson's disease (PD) neurodegenerative process begins and progresses. In the course of developments for treatment of PD, the discovery of the inhibition of monoamine oxidase (MAO B) was a conceptual breakthrough, and has now been firmly established. MAO B has also been implicated in the neurodegenerative processes resulting from exposure to xenobiotic amines. For example, MAO B catalyzes the first step of the bioactivation of the parkinsonian inducing pro-neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Additional insight into the mechanism of catalysis of MAO B and the mechanism of neurotoxicity by MPTP is therefore very valuable in the pursuit of the treatment of PD. / Thesis (Ph.D. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2008.

Aphanomyces invadans is the pathogen that causes epizootic ulcerative syndrome (EUS), an economically devastating fish disease in southern Asia. The present thesis considered possible improvements to current methods of monitoring EUS, and examined the mechanisms of the host immune response to A. invadans in order to establish whether they could be enhanced to reduce the impact of EUS on aquaculture. Monoclonal antibody (MAb) technology was considered as a possible improvement to the histopathological methods currently used in diagnosis of EUS. Five MAbs were raised to day-old A. invadans germlings. Four gave weak reactions to A. invadans and cross-reacted with other Aphanomyces spp, though they may be useful for future studies on A. invadans. The other, designated MAb 3gJC9, only cross-reacted with the crayfish plague pathogen, A. astaci, and was used for the development of an immunohistochemistry protocol that may be of use in diagnosis. Immunohistochemistry with MAb 3gJC9, which recognised an extracellular product (ECP) of A. invadans, was specific to A. invadans in fish tissue, although it also recognised A. astaci in plague-infected crayfish. It also recognised the mycelium in fish infected with ulcerative mycosis, indicating that ulcerative mycosis is synonymous with EUS. Preliminary observations indicated that both ECPs and what appeared to be a hitherto unreported early stage of the mycelium are important in the pathology of EUS. Studies in vitro on the macrophages of EUS-susceptible giant gourami Osphronemus gouramy and silver barb Barbodes gonionotus, and EUS-resistant Nile tilapia Oreochromis niloticus, found that their macrophages were able to inhibit the growth of A. invadans. The macrophages of striped snakehead Channa striata did not inhibit A. invadans, which may account for their high EUS-susceptibility, especially as A. invadans strongly inhibited the respiratory burst of snakehead macrophages. Studies on humoral immune responses revealed that complement inhibited A. invadans in the case of snakeheads, gourami and barbs but not tilapia or swamp eels Monopterus albus. The humoral responses of the latter were very different to the four other species, and not elucidated. Low levels of anti A. invadans antibodies were found in tilapia and gourami from an EUS-endemic region, and high levels in snakehead. Snakehead antibodies appeared to be able to inhibit A. invadans even when complement was removed, but lower levels were produced at the low temperatures typically associated with EUS. A range of potential immunostimulants were screened for the ability to enhance resistance to EUS. The two successful products were administered as feed supplements to snakeheads and barbs that were subsequently injected intramuscularly with A. invadans. One, the algal extract Ergosan, showed some beneficial effects on snakeheads although the challenge was inconclusive. The other, the vitamin supplement Salar-bec, accelerated the cellular immune response and reduced mortality in snakeheads and barbs, and enhanced antibody production in snakeheads. The antibody response of snakeheads was further studied by comparing the anti- A. invadans antibody level, inhibitory activity of sera in vitro and protective capacity of sera from EUS-naïve snakeheads to that of snakeheads recently exposed to EUS and those subject to long term EUS-exposure. Sera of populations recently exposed to EUS showed an increased level of antibodies, but little improvement in inhibitory or protective activity. Sera from snakeheads that had endured long term exposure showed a wide range of antibody levels, but marked increases in inhibitory and protective activity. Antibodies cross-reacted with non-pathogenic Aphanomyces spp. in all cases.

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Crassulacean acid metabolism (CAM) provides desert plants with distinct advantages over the C3 and C4 photosynthetic pathways in harsh climates where water is scarce. CAM is, however more metabolically costly than C3 or C4 photosynthesis, and some plants, such as Mesembryanthemum crystallinum, facultatively utilize CAM when water is abundant, and water conservation unnecessary. In such situations, these plants behave akin to a C3 plant when photosynthesizing. CAM is divided into four phases, with each phase displaying unique metabolic processes. Certain changes, including changes in the timing of CO2 fixation, stable carbon isotope ratios, and tissue malic acid content accumulation patterns can indicate that a plant has shifted from CAM to C3 photosynthesis. Such shifts have been observed to be regulated primarily by water availability and ontogenic development. While facultative CAM is well documented in species like Mesembryanthemum crystallinum, and it has not been studied extensively in Agave with the exception of Agave deserti, and Agave angustifolia. A better understanding of this phenomenon would apply to the agricultural growth of this genus. This study aimed to trigger C3 to CAM shifts in Agave sensu lato species, in order to expand upon the findings of previous studies, and better understand the prevalence of facultative CAM expression in the genus. Gas exchange and stable carbon isotope measurements were taken from 2-month-old, 10-month-old, and mature agaves grown in controlled ocnditions. Tissue acid content measurements were taken from mature plants. Despite the Agave sensu lato species in this study being subjected to moisture applications ranging from dry to saturated, we were unable to observe any distinct shifts from CAM to C3 photosynthesis in any of the species tested for both seedlings and mature plants. Diel net CO2 fixation rates also increased with age, and water applications for seedlings, and decreased with heavy irrigation in mature plants. Stable carbon isotope ratios revealed that some carbon in the plant tissues was fixed by rubisco, and that some species (Polianthes tuberosa, Prochnyanthes mexicana) had carbon isotope ratios of a C3 plant, but these ratios did not change with different irrigation treatments. Malic acid accumulation remained typical of CAM plants for the species tested as well, with one exception in Polianthes tuberosa. As such, we conclude that the Agave sensu stricto species tested in this study are obligate CAM plants, and that they perform poorly mature individuals are over-watered. Additionally, the Agave sensu lato species P. mexicana, and P. tuberosa appear to be C3 plants given the results of this study.