Over the last three decades, there has been a sharp rise in the incidence of oesophageal adenocracinoma (OA) in the UK. The cause of this rising trend remains unknown. Chronic symptomatic Gastro-Oesophageal Reflux Disease (GORD) has been associated with Barrett's oesophagus (BO), a premalignant stage of OA. The process how acid exposure drives the metaplasia-dysplasia-neoplasia sequence is not known. Oxidative stress plays vital role in carcinogenesis. Selenium is a trace metal element in our diet essential for anti-oxidant selenoproteins synthesis, such as glutathione peroxidases (GPxs). GPxs play a vital role in humans to fight oxidative stress. Epidemiological studies showed that high serum selenium levels are associated with a lower incidence of oesophageal and gastric cardia cancer. This thesis hypothesised that chronic GORD is an initiator of OA pathogenesis by exposing the lower oesophagus to chronic pulse acid, which results in radical oxygen species (ROS) production and oxidative stress damage. GORD patients with suboptimal selenium status are more susceptible to pulse-acid induced oxidative damage because of poor anti-oxidative defence system. The combination of pulse acid exposure and low selenium status potentially drives the OA pathogenesis. The study aims to investigate the effect of pulse-acid exposure, selenium status and its supplementation on cellular proliferation and apoptosis, key processes in carcinogenesis. The study also further investigated the potential pathways through which the pulse acid and low selenium could trigger the carcinogenesis. Ex vivo study was also conducted to examine the selenium status among BO and OA patients, including analysis of single nucleotide polymorphism (SNP) of GPx4 among these patients. The results showed that pulse-acid exposure increased cellular survival and suppressed apoptosis. This result was consistent with previous studies conducted by other researchers. Selenium supplementation at supra-optimal level (100 nM) was shown to potentially mitigate the proliferative effect induced by pulse-acid exposure. Pulse acid exposure was shown to induce ROS production in vitro. This could be mitigated by selenium supplementation. The mitigating effect was likely to be mediated by GPx1, and GPx4, selenoenzymes that are capable of reducing ROS. The study also revealed that apoptosis suppression by selenium supplementation was probably mediated by p53 tumour suppressor gene, but not via Bcl-2 protein. Ex vivo study results showed that OA patients have a 54% significant lower GPx4 mRNA expressions compared to the normal subjects, while the Barrett's subjects were in between OA and Normal. This is in line with the hypothesis that the severity of the disease is closely linked with the levels of anti-oxidant enzymes expression. Expectantly, patients with BO have higher, although not statistically significant, serum selenium compared to the control group. Single nucleotide polymorphism (SNP) of GPx4 could be an explanation for the reason OA and BO patients were unable to synthesise GPx despite an adequate serum selenium level, this rendered them more susceptible to ROS induced oxidative damage. These findings might have potential therapeutic implications for BO and OA. Targeted selenium supplementation could be a cost effective way of OA cancer prevention. Target screening to identify subjects with certain Genotype or SNP, could ensure early intervention to prevent cancer development. A long term, well designed, randomised, placebo controlled selenium supplementation trial to examine the clinical efficacy of selenium supplementation in OA prevention is warrant.

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Purpose: To determine the association of plasma and aqueous humor selenium with glaucoma; and to determine those factors influencing biological levels of selenium in patients with glaucoma and cataractMethods: 47 primary open angle glaucoma (POAG) cases and 54 controls were recruited from surgery patients at the University Physician's Ophthalmology Clinic in Tucson, Arizona. Aqueous humor and plasma selenium concentration was determined by high performance liquid chromatography ion channel plasma-mass spectrometry (HPLC ICP-MS). Potential confounders were assessed via questionnaire. Outcome measures included the odds of glaucoma in relation to plasma selenium and aqueous humor selenium. Factors driving plasma and aqueous humor selenium in the study population were determined via linear regression.Results: After adjustment for risk factors and multiple outcomes, the odds of glaucoma in the highest tertile of plasma selenium (OR = 13.51; p=.03) and the middle tertile of aqueous humor selenium (OR = 0.05; p=0.02) were significantly associated with glaucoma. Selenium concentration in plasma and aqueous humor was primarily driven by metabolic factors (cancer, DMII, and ARMD).Conclusions: Although a causal pathway cannot be inferred from the analysis, it may be prudent to explore these relations in a larger sample in varying areas of geographic selenium distribution. Such information could be helpful in examining a larger study population and comparing biological data. Evaluating a subject's selenium levels over time and in relation to glaucoma onset could also lend pertinent informationDriving forces behind selenium concentrations in this population are mainly metabolic in nature. Selenium levels fluctuate in most tissue as it is metabolized by the body. Selenium supplementation is a significant predictor but this effect is small and may be transient as supplementation only temporarily increases selenium pools. It is interesting to note that sex is a significant predictor of aqueous humor selenium but not of plasma selenium. In this model, female sex predicts a decrease in the selenium within the aqueous humor. This point should be explored in future studies that are powered to discern possibly subtle differences that sex plays in relation to selenium concentrations in plasma and aqueous humor and its possible role in glaucoma.

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I investigated, water, invertebrates and fishes from lakes in Banff National Park and Kananaskis Country, Alberta for selenium (Se), an element known to be toxic to vertebrates. At some depths, Se concentrations in sediment exceeded recognized thresholds for bird and fish reproductive impairment. Se concentrations in water were over USEPA guidelines after spring melt runoff. In aquatic invertebrates, Se concentrations exceeded values known to cause reproductive impairment in fish and bird predators. Se concentrations in all fish species exceeded known thresholds for reproductive impairment in avian consumers and the majority surpassed concentrations that would negatively affect wildlife and human consumers. Se concentrations in some fish species have significantly increased over the past 6-16 years. The strongest predictors of fish Se concentrations were growth rate, condition factor, age, weight, trophic position (within lakes) and vegetation type (among lakes). These results suggest that consumption advisories are desirable for several lakes in the Banff and Kananaskis area, and that Se concentrations in fish from other area lakes should be investigated. / Ecology

Titanium dioxide (TiO2) photocatalysis, which can oxidise or reduce organic and inorganic pollutants, is a developing technology for water and wastewater treatment. The current work investigates the photocatalytic reduction of cadmium and selenium species as the presence of these elements in water are of environmental concern. Although TiO2 has been widely used for the photocatalytic process, its light absorption is limited to the UV region of the solar spectrum. Hence, the current project also explores the possibility to deposit cadmium selenide (CdSe) onto TiO2 to extend the photoresponse to the visible region. This study demonstrated that cadmium (Cd(II)) could be reduced to its metallic form by photocatalysis. The choice of hole scavengers and reaction pH are of importance in determining whether the photocatalytic reduction reaction will occur. It is also essential that both Cd(II) and organic additives are adsorbed on the surface of TiO2. A mechanism for cadmium photoreduction in the presence of formate as the hole scavenger was proposed. The current investigation elucidated the mechanism for the photoreduction of selenite (Se(IV)). Selenite was found to be photoreduced to its elemental form (Se(0)) as films, by direct photoreduction of Se(IV), and as discrete particles, by the reaction between Se(IV) and selenide (Se(2-)) ions. The Se(2-) ions are believed to have been generated from the 6 electron photoreduction of Se(IV) and/or the further photoreduction of the Se(0) deposits. Photocatalytic reduction reactions of Se(IV) and selenate (Se(VI)) using different commercial TiO2 materials was also studied. The current work also successfully deposited CdSe by photocatalysis using Se-TiO2 obtained from the photoreduction of Se(IV) and Se(VI). The mechanism for CdSe deposition was clarified and attributed to the reaction of Cd(II) present in the system and the Se(2-) released from the reduction of Se(0) upon further illumination. The Se??TiO2 photocatalysts obtained from the photoreduction of different selenium precursors (Se(IV) and Se(VI)) resulted in the dominance of different morphologies of the CdSe particles. This suggests a new approach to manipulate the properties of CdSe during its formation, and hence control over electrical and optical properties of this semiconductor.

Thesis (Ph. D.)--University of Missouri--Rolla, 2007. / Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed January 28, 2008) Includes bibliographical references.

Dissertation (Ph.D.)--Auburn University, 2005. / Abstract. Includes bibliographic references.