Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (Ph. D. in Neuroscience)--Vanderbilt University, Dec. 2005. / Title from title screen. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Restricted as requested by author. Restricted access for 1 year 2007--03--28 ; approval pending. Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Dietary antioxidant curcumin derived from turmeric has been suggested to decrease the risk of many chronic diseases. Much of the existing data for curcumin stem from experiments performed at supra-physiological concentrations (μM-mM) that are impossible to attain through oral ingestion. It was therefore hypothesized that curcumin at low plasma achievable concentration, though itself not acting as a direct antioxidant might up-regulate the intracellular antioxidants and thus helping combat oxidative stress and protect β-islet cells. The results indicated that Curcumin, DMC and BDMC were able to scavenge hydroxyl radicals, but showed little scavenging ability against superoxide and nitric oxide radicals. Nanomolar concentrations of curcuminoids easily prevented the deleterious effects of H₂O₂ in pancreatic <i>β</i>-islet RINm5F cells. Non of the curcuminoids showed a detrimental effect on insulin secretion, but the model did not allow assessment of any potential positive effect on insulin secretion. The findings confirmed that nanomolar concentrations of curcumin offered protection in pancreatic <i>β</i>-islet cells against H₂O₂-indicated damage by modulating the proportion of oxidised GSH (GSSG): reduced GSH in the favour of GSH and the increasing the activity of SOD. This increase in GSH and SOD levels was, at least in part, on account of an increase in GR, SOD-1 and SOD-2 gene expression. The intracellular mechanism driving this modulation of antioxidant gene was, by virtue of blocking the H₂O₂ induced NF-κB activation.

Acid mine drainage is a major environmental pollution concern associated with the mining of sulphide-containing ore bodies. Both physicochemical and biological options have been investigated for the treatment of acid mine drainage with recent interest in biological processes targeting low-cost and passive treatment applications. All acid mine drainage biological treatment processes are based to some extent on the activity of sulphate reducing bacteria, and their ability to reduce sulphate to sulphide in the presence of a range of carbon and electron donor sources. A portion of the sulphide produced may be consumed in the precipitation of heavy metals present in the mine drainage. Residual sulphide must be removed, not only due to its toxicity, but especially to prevent its reoxidation to sulphate where salinity reduction is a target of the treatment process. The partial oxidation of sulphide to elemental sulphur is an option that has received considerable attention and both physicochemical and biological options have been investigated. Biological processes have substantial potential cost advantages and run at ambient temperatures and pressures. However, the oxidation of sulphide to elemental sulphur is poised over a narrow redox range and process control to maintain optimum conditions remains a serious problem. In addition little has been reported in the literature on process control of sulphide oxidation to elemental sulphur, in the heterotrophic conditions prevailing in the reaction environment following sulphate reduction. This study undertook an investigation of biological sulphide oxidation under heterotrophic conditions in order to establish the effect of organic compounds on biological sulphide oxidation, and to determine whether the presence of organics, and associated heterotrophic oxygen consumption, may be manipulated to maintain the defined redox conditions required for the production of elemental sulphur. Biological sulphide oxidation under heterotrophic conditions was investigated in a series of flask experiments. Based on these results three different reactor configurations, a Fixed-Film Trickle Filter Reactor, Submerged Fixed-Film Reactor and a Silicone Tubular Reactor were used to investigate sulphur production. The flask studies indicated that organics, and associated heterotrophic metabolism in the presence of excess oxygen in the sulphide oxidation reaction environment, did contribute to the poising of redox conditions and thereby enabling the production of elemental sulphur. While the Fixed-Film Trickle Filter Reactor was found to be redox unstable, probably due to excess oxygen ingress to the system, a reduced oxygen challenge in the Submerged Fixed-Film Reactor configuration was found to be more successful for production of elemental sulphur. However, due to the production of a predominantly filamentous sulphur producing microbial population, recovery of sulphur from the column was intermittent and unpredictable. Extended residence times for produced sulphur on the column increased the likelihood for its eventual oxidation to sulphate. The Silicone Tubular Reactor was found to support a vigorous sulphide oxidising biofilm and produced elemental sulphur effectively. Electron microscopic studies showed that this occurred as both biologically produced sulphur and, probably mainly, as crystalline sulphur in the ortho-rhomic form. Given the linear extension of the sulphur production reaction environment it is was possible to investigate the sequence of the reaction mechanism in grater detail than is possible in mixed systems. Based on these findings a model explaining sulphur production under heterotrophic conditions has been proposed and is presented. The commercial implications of the development have also been noted.

Oxidative assimilation of glucose-U-C¹⁴ by several aerobic bacteria was found to involve the assimilation of radioactivity into nitrogenous cell components, principally proteinaceous, in conjunction with the reincorporation of endogenously produced ammonia. In one of these bacteria, Pseudomonas aeruginosa, if the cells were starved or treated with chloramphenicol/ prior to glucose-C¹⁴ the amount of assimilation, especially into protein, was decreased. The incorporation into nucleic acids and lipids was increased by the antibiotic, but was only slightly affected by starvation. A determination of the cytological sites of the assimilated material showed that, in control cell extracts, the soluble proteins of the cytoplasm contained most of the C¹⁴. Starved or antibiotic treated cell fractions had substantially less of the label in these proteins, whereas the radioactivity incorporated into the ribosomal ribonucleic acid and the "membrane" lipids was greater. A study of the aminoacyl-soluble ribonucleic acid synthetases in P. aeruginosa revealed that these enzymes were present only in the cytoplasm. Starving the cells resulted in decreased activity of the synthetases, but they were rapidly reactivated during oxidative assimilation. The large amount of heterologous reactions between bacterial soluble ribonucleic acids and synthetases indicated that little species specificity existed. However, cross reactions between the systems in bakers' yeast and the bacteria were poor, showing that some degree of species specificity was present in these instances. Preliminary experiments on the route of assimilation of ammonia in P. aeruginosa and in P. fluorescens gave no evidence for the direct amination of pyruvate by alanine dehydrogenase, but did demonstrate a requirement for concurrent substrate oxidation while ammonia was being incorporated. In contrast, several lines of evidence indicated that ammonia was assimilated via ∝-ketoglutarate in P. aeruginosa. / Land and Food Systems, Faculty of / Graduate

University of Macau / Institute of Chinese Medical Sciences

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