Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [76]-86).

Thesis (M.Ed.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 100-109). Also available in print.

Thesis, PlanB (M.S.)--University of Wisconsin--Stout, 2005. / Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1984. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 44-48).

Thesis (M.Phil.) - University of Queensland, 2006. / Includes bibliography.

Thesis (M.S.) in Food Science and Human Nutrition--University of Maine, 2006. / Includes vita. Includes bibliographical references (leaves 72-77).

This research investigated the role of the intestinal microbiota in shaping host food intake and body weight through immunomodulation, the impact of refined and unrefined diets, and though fermentable fibre induced gastrointestinal hormone secretion. Gut-derived lipopolysaccharide activating TLR4 has been proposed to contribute to obesity. To investigate this, TLR4-/- or CD14-/- mice and C57BL/6J controls were fed a high-fat or low-fat diet. Neither TLR4-/- or CD14-/- were protected against high-fat diet-induced obesity. High-fat diet increased hypothalamic expression of SerpinA3N and SOCS3 regardless of genotype; however, inflammatory gene expression was not increased. To investigate the use of chow control diets in obesity-associated microbiota changes, C57BL/6J mice were fed a chow diet, refined high-fat, or low-fat diet. Both high-fat and low-fat refined diets resulted in similar dramatic alterations in the composition of the intestinal microbiota at the phylum, family, and species level compared to chow, while only high-fat diet feeding resulted in obesity and glucose intolerance. The roles of colonic GLP-1 and PYY in mediating fermentable fibre in reducing food intake and body fat were investigated using GLP-1R-/- and PYY-/- mice fed a high-fat diet supplemented with inulin or cellulose. Inulin supplementation reduced body fat and food intake in C57BL/6J control mice while GLP-1R-/- and PYY-/- mice showed an attenuated response to dietary inulin. In summary, this research questions the role of TLR4 and LPS in diet-induced obesity. These results demonstrate the importance of the control diet used in studies of obesity in mice and indicate that many of the obesity-associated changes in the gut microbiota are due to comparing refined high-fat diets with chow diets. These results also provide evidence for an essential role for both GLP-1 and PYY in mediating the food intake and bodyweight-reducing effects of fermentable fibre.

Gentamicin is an aminoglycoside antibiotic that possesses bactericidal activity against many gram-positive and gram-negative organisms. Clinically, it is used most often to treat life-threatening infections due to Pseudomonas, Proteus, and the Klebsiella-Enterobacter group. A relationship between gentamicin serum concentrations and clinical response has been demonstrated. Toxicities, notably ototoxicity and nephrotoxicity, are also associated with serum concentrations. Gentamicin is given intermittently either intramuscularly or intravenously resulting in peak and trough concentrations. The therapeutic range is defined as peak concentrations between 4-15mg/L (depending in part on the site of infection and the susceptibility of the infecting organism), and trough concentrations less than 2mg/L (to minimize toxicity). Gentamicin distributes into a space similar to the extracellular fluid volume (ECFV). Pathophysiologic changes which alter the extracellular fluid compartment also alter gentamicin volume of distribution (Vd). One intrinsic factor known to alter gentamicin Vd is obesity. Leanness is also thought to alter gentamicin Vd but its effect has not been quantitated. The objectives of this study were to: 1) accurately describe a Vd in "normal" patients, that is, those with no factors known to alter gentamicin volume of distribution; 2) determine if there is a continuous linear relationship between gentamicin volume of distribution (L/kg) and percent body fat; 3) determine if that relationship is associated with changes in ECFV; and 4) develop a formula for predicting Vd in a similar patient population. Twenty patients with no extrinsic factors known to alter gentamicin Vd participated in the study. Five blood samples were drawn around one steady state dose of gentamicin. A one-compartment model was used to calculate Vd. Tritiated water and anthropometric measurements were conducted simultaneously to provide estimates of body composition. Together these values were used to examine the relationship between gentamicin Vd and body composition. We have described a Vd for gentamicin that is larger but no less variable than is currently used to determine initial dosage regimens. This volume may be larger either due to the selection of patients or method of serum gentamicin analysis. This larger volume should be used to calculate empiric dosage regimens for similarly selected patients to decrease the risk of treatment failure. We were not able to describe a linear relationship between percent body fat and gentamicin volume of distribution. We have postulated several reasons as to why this relationship could not be detected; 1) the sample size may not have been large enough, 2) the relationship is not important in patients who are not at extremes of weight, or 3) the variations caused by changes in body composition were not as significant as other factors that may cause fluid alterations in hospitalized patients. There was a strong correlation between gentamicin Vd and total body water noted. Having eliminated all patients in whom the relationship between total body water and ECFV could not be assumed to be normal and constant, we have indirectly demonstrated a strong relationship between ECFV and gentamicin Vd. This relationship still leaves variability in gentamicin's distribution characteristics to be explained. The predictive formula is based on measurements of height, weight, and a larger Vd [L/kg(ideal body weight)] than has previously been used. The predictive formula recommended for clinical use in adults is Vd=0.30L/kg (Dosing Weight). Dosing weight equals ideal body weight (IBW) when actual body weight (ABW) is ≤ IBW, or 0.4(ABW-IBW)+IBW, when ABW is > IBW. The consequences of estimating a larger Vd are that patients empirically would receive larger doses than are currently being administered, thus more patients should obtain therapeutic serum concentrations within the first 24 hours of therapy. This information will be useful in our attempts to optimize gentamicin therapy. / Pharmaceutical Sciences, Faculty of / Graduate

No description available.

The investigation reported here involved truncation-type individual selection in divergent directions for body weight at eight weeks of age in White Rocks. Phenotypic changes of selection and unselected traits within lines were measured for females from the P₁ through the F₇ generation. Unselected traits were 24 and 38-week body weight, egg weight, age at first egg and percentage egg production to January 1. The following were analyzed and discussed: 1. Direct response of eight-week body weight to selection, 2. Correlated responses and estimates of realized heritabilities, 3. Genetic correlations between the selected and unselected traits, 4. Phenotypic and environmental correlations between selected and unselected traits, and 5. The prediction of correlated responses. The realized heritabilities of unselected traits based on the expected secondary selection differential were relatively uniform and consistent with those reported in the literature. Genetic correlations obtained from realized heritabilities of the selected and unselected traits were uniform and consistent with those of others. The significant increase of environmental correlations between selected trait and 24 and 38-week weight and percentage egg production during the eight generations indicated genotype-environment correlations. Such correlations may cause further difficulties in the development of a breeding stock possessing a large broiler weight, small adult weight and high egg production. Predicted correlated responses of these three traits were lower than the actual responses and may reflect these relationships. / Master of Science