No description available.

No description available.

Polycyclic aromatic hydrocarbons (PAH) are common aquatic contaminants found at industrially contaminated sites. Alkylated PAH have been identified as a component of oil that is chronically toxic to the early life stages of fish. These compounds are important target analytes in Natural Resource Damage Assessment following oil spills, and often the focus of remedial activities. However, the mechanisms of PAH and alkyl-PAH toxicity are not well understood. The enzymatic metabolism of alkyl-PAH generates ring (OH-ring) and chain hydroxylated (OH-chain) derivatives, and has been associated with the increased prevalence of toxicity in early life stages (ELS) of fish. The role of PAH metabolism in toxicity remains unclear, and may involve the byproducts of metabolism such as reactive oxygen species (ROS), reactive intermediates, metabolites themselves, or a combination thereof. Using 1-methylphenanthrene (1MP) as a model alkyl-PAH, this research describes the relative toxicity of a suite of hydroxylated alkyl-PAH to the early life stages of fish, proposing an association between the formation of para-quinones and enhanced toxicity. The results of this thesis demonstrate: (1) hydroxylated derivatives of 1MP differ in toxicity from their non-hydroxylated counterpart; (2) ring hydroxylated 1MP derivatives are more toxic than both chain-hydroxylated derivatives and 1MP itself; (3) the location of ring-hydroxylation can affect toxicity and (4) the octanol-water partition coefficient (Kow) is a poor predictor of toxicity for hydroxylated APs derivatives. / Thesis (Master, Environmental Studies) -- Queen's University, 2011-04-24 12:15:43.323

No description available.

Xenin, a gastrointestinal peptide, is structurally similar to neurotensin which functions as a satiety factor via neurotensin receptor 1 (Ntsr1). Metabolic effect of the adipocyte hormone leptin is partially mediated through the Ntsr1 and interleukin 1 type I receptor (IL-1RI) in the central nervous system (CNS). Xenin reduces food intake when administered centrally and peripherally. Apart from its acute feeding-suppressing effect, the distinct metabolic action of xenin and the mechanism of xenin-induced anorexia remain to be elucidated. We hypothesized that prolonged xenin treatment reduces food intake and body weight and increases energy expenditure. We also hypothesized that xenin reduces food intake by activating CNS signalling pathways including Ntsr1 and IL-1RI and by interacting with leptin. To address these hypotheses, we examined (1) the effect of xenin treatment on food intake, energy expenditure and body weight in wild-type, Ntsr1-deficient and IL-1RI-deficient mice, (2) the effect of xenin on hypothalamic Fos and interleukin 1β (IL-1β) expression in wild-type mice, and (3) the effect of co-injection of xenin and leptin on food intake and body weight in wild-type mice. Daily intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) xenin treatment (6-10 days) significantly reduced body weight gain and adiposity with a transient reduction in food intake in wild-type mice. Xenin treatment (i.p.) caused a significant reduction in respiratory quotient without changes in energy expenditure. Xenin treatment increased hormone sensitive lipase (HSL) mRNA levels and reduced acyl-coenzyme A: diacylglycerol acyltransferase 2 (DGAT2) mRNA levels in white adipose tissue. Xenin (i.p.) increased the number of Fos-immunoreactive cells in the hypothalamus and the brainstem and increased hypothalamic IL-1β mRNA levels. The anorectic effects of xenin and leptin were abolished or attenuated in mice lacking Ntsr1 or IL-1RI. I.p. co-administration of xenin and leptin caused greater reductions in food intake and body weight compared to leptin alone and xenin alone. These data suggest that long-term xenin treatment reduces body weight by reducing food intake and increasing fat oxidization. Xenin reduces food intake by activating CNS signalling pathways involving Ntsr1 and IL-1 possibly through the interaction with leptin. These findings implicate xenin and its downstream mediators as potential targets for anti-obesity drugs.

No description available.

No description available.

The purpose of this study was to examine the caloric intake and energy output of swimmers and runner during normal daily activities and training. Daily and energy expenditure of twenty college varsity swimmers and runners were measured. Four groups of subjects were categorized as male runners, female runners, male swimmers, and female swimmers with five subjects in each group. An additional twenty runners and swimmers recorded only dietary intake. Despite a large difference in body weight and body fat, the mean daily caloric intake was similar for the two groups (male swimmers: 3377 Kcal/d-1, male runners: 3463 Kcal/d-1, female swimmers: 2491 Kcal/d-1, female runners: 2037 Kcal/d-1). Comparison of data normalized for body weight showed that male runners were more active than swimmers. Male runners burned more calories (53.3 Kcal/kg. d-1) in a twenty four hour period than swimmers (47.6 Kcal/kg.d-1). In the case of the females, the trend was reversed. Female swimmers expended more calories (45 Kcal/kg .d-1) than runners (38.9 Kcal/kg.d-1) despite a lower food intake. Consequently, caloric intake and life style does not seem to explain body fat difference between runners and swimmers. The data in this study suggest that the greater body fat found in swimmers may be related to a physiological adaptation induced by swim training.

Xenin, a gastrointestinal peptide, is structurally similar to neurotensin which functions as a satiety factor via neurotensin receptor 1 (Ntsr1). Metabolic effect of the adipocyte hormone leptin is partially mediated through the Ntsr1 and interleukin 1 type I receptor (IL-1RI) in the central nervous system (CNS). Xenin reduces food intake when administered centrally and peripherally. Apart from its acute feeding-suppressing effect, the distinct metabolic action of xenin and the mechanism of xenin-induced anorexia remain to be elucidated. We hypothesized that prolonged xenin treatment reduces food intake and body weight and increases energy expenditure. We also hypothesized that xenin reduces food intake by activating CNS signalling pathways including Ntsr1 and IL-1RI and by interacting with leptin. To address these hypotheses, we examined (1) the effect of xenin treatment on food intake, energy expenditure and body weight in wild-type, Ntsr1-deficient and IL-1RI-deficient mice, (2) the effect of xenin on hypothalamic Fos and interleukin 1β (IL-1β) expression in wild-type mice, and (3) the effect of co-injection of xenin and leptin on food intake and body weight in wild-type mice. Daily intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) xenin treatment (6-10 days) significantly reduced body weight gain and adiposity with a transient reduction in food intake in wild-type mice. Xenin treatment (i.p.) caused a significant reduction in respiratory quotient without changes in energy expenditure. Xenin treatment increased hormone sensitive lipase (HSL) mRNA levels and reduced acyl-coenzyme A: diacylglycerol acyltransferase 2 (DGAT2) mRNA levels in white adipose tissue. Xenin (i.p.) increased the number of Fos-immunoreactive cells in the hypothalamus and the brainstem and increased hypothalamic IL-1β mRNA levels. The anorectic effects of xenin and leptin were abolished or attenuated in mice lacking Ntsr1 or IL-1RI. I.p. co-administration of xenin and leptin caused greater reductions in food intake and body weight compared to leptin alone and xenin alone. These data suggest that long-term xenin treatment reduces body weight by reducing food intake and increasing fat oxidization. Xenin reduces food intake by activating CNS signalling pathways involving Ntsr1 and IL-1 possibly through the interaction with leptin. These findings implicate xenin and its downstream mediators as potential targets for anti-obesity drugs.

Methylmalonyl-CoA is a key building block in the biosynthesis of propionate derived polyketide metabolites. There are several known metabolic sources of methylmalonyl-CoA, e.g. succinyl-CoA (citric acid cycle), valine and isoleudne. An objective of this research was to investigate the role of the DNA base, thymine, as a source of methyhnalonyl-CoA in Streptomyces and hence probe the link between primary and secondary metabolism. Feeding key intermediates of the thymine and valine cataboHc pathways, i.e. [(^13)C(^2)H(_3)-methyl]-thymine, [(^13)C-methyl]- and [l-(613)c]-β- aminoisobutyric acid, sodium [3-(^13)C]-isobutyrate, sodium [(^13)C-methyl]- methacrylate and sodium [l-(^13)C]-methacrylate, to the monensin A producer, Streptomyces cinnamonensis, provided evidence of the reductive catabolism of thymine occurring in Streptomyces, analogous to mammals. The results also provided evidence which supports the existence of a novel deaminase enzyme mediating the transformation of β-aminoisobutyric add and methacrylyl-CoA. Cubensic add, isolated from Xylaria cubensis, is a long chain fungal metabolite possessing eight pendant methyl groups. Its biosynthesis from acetate and L-methionine units was demonstrated with the aid of feeding experiments, proving a classical fungal mode of assembly. Attempts to incorporate an advanced methylated precursor into cubensic add were unsuccessful. Biological intramolecular Diels-Alder reactions are implicated in the biosynthesis of a wide range of polyketide metabolites, e.g. nargenicin, solanapyrones. Attempts to demonstrate, by feeding an isotopically labelled precursor, an intramolecular Diels-Alder mechanism for the formation of the sbc membered ring in cytochalasin D, proved inconclusive. In the event, the precursor was degraded to acetate. This degradation was suppressed in the second attempt by the addition of a β-oxidation inhibitor, but still no incorporation of labelled precursor was evident.