No description available.

No description available.

The study was conducted on arsenicosis patients living in Laksham upazilla, a sub-district of Comilla district, Bangladesh between January 2003 and October 2004. It was designed to address (a) the relationship between clinical manifestations of arsenicosis and socio-demographic and other variables (b) the relationship between the clinical manifestations and the biochemical markers of arsenicosis (c) the effectiveness of the nutritional and anti-oxidant supplementation in reducing the clinical symptoms and biochemical markers of arsenicosis patients and (d) whether any improvements in either clinical manifestations or biochemical markers were sustained after supplementation ceased. The arsenicosis patients were between 10 and 80 years of age, of whom just over half were female. Nearly one third had received no education, nearly half were engaged in household word or were unemployed, about two-thirds were residing in temporary housing and the majority of the less well-off patients had no educational qualification or household assets. The first intervention group was administered nutritional supplementation and anti-oxidant tablets (NSAEC, n=100) for 6 months, the second group with nutritional supplementation and a placebo of anti-oxidant tablets (NS, n=79) and the third group was treated with anti-oxidant tablet only (AEC, n=85); 25 patients did not participate in the intervention and they were retained as a pseudo control group. There was little or no significant associations between the prevalences of either keratosis or hyperkeratosis with socio-economic variables. Durations of hyperpigmentation and keratosis were positively related and lower grades of arsenicosis were associated with shorter dimensions. No significant relationships were found between prevalences or durations of dermatological clinical manifestations with the biochemical markers or physiological variables except for hair arsenic concentration and respiratory rate which were higher in keratotic patients and longer durations of keratosis were associated with drinking more arsenic contaminated water. Skin melanin concentrations showed no significant associations with the other biochemical markers (urinary, nail and hair arsenic concentrations). On average, males had higher means than females and those with diffuse hyperpigmentation had lower means. Urinary arsenic concentration showed a positive association with nail arsenic concentration and urinary creatinine concentration. Very few significant associations were found between the biochemical markers, anthropometric variables and disease grading with the socio-demographic and other variables at the end of the intervention or at the post-intervention follow-up. Nail and hair arsenic concentrations showed positive relationships with urinary arsenic concentrations. Skin melanin concentrations did not show any significant association with urinary, nail or hair arsenic concentrations. Grading of arsenicosis was mainly accounted for by the duration of dermatological clinical manifestations.

In this thesis LC-MS has initially been applied to investigate metabolic changes associated with gender, diurnal variation and time to define how key physiological differences affect the metabolome in rats. In the case of gender, a clear metabolic separation of females from males was observed based upon the urinary excretion of a sulphated endogenous steroid metabolite and this illustrates the benefits attained by improving metabolome coverage, as this metabolite is not detected by ¹H NMR spectroscopy. After development of acquisition and data processing methods, ultra performance LC-MS (and ¹H NMR spectroscopy) was applied to a 3-dose level toxicological evaluation of bromobenzene. As well as increasing metabolome coverage, the sensitivity of LC-MS resulted in improved accuracy of measurement of a candidate biomarker, 5-oxoproline. This additional information lent weight to the possibility that 5-oxoproline could be used as a pre-emptive indicator of glutathione depletion (and oxidative stress) based upon smaller but convincing changes elicited in doses not found to result in the stark pathological damage of the high dose administration. LC-MS was then applied to investigations of dietary restriction, not only to characterise the metabolic changes observed due to reduce energy intake but also as a direct comparator to the bromobenzene study in an attempt to delineate the effects of reduced feeding from the toxicological impact on the metabolic profile. The metabolomic information was then combined with transcriptomic analyses to place the metabolomic output in a systems biology context. Alterations in energy metabolism were detected using both metabolomics and transcriptomics and many metabolic changes due to dietary restriction were also observed after administration of bromobenzene, particularly relating to glycolysis/gluconeogenesis, tricarboxyic acid cycle, amino acid metabolism and fatty acid metabolism.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.