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<p>Vitamin C inhibits the oxidation of biologically important molecules and may have a potential protective role against cancer, cardiovascular diseases, and aging. Clinically relevant models of vitamin C function are essential for understanding the role of the antioxidant in the pathogenesis of these complex diseases, and its therapeutic potential. In this thesis, we examine ascorbic acid synthesis and deficiency in animal models, and develop these animal models into powerful tools to examine specific questions of vitamin C function. This thesis first presents a review on the existing animal models for antioxidant function in human nutrition, focusing on their clinical relevance in chronic diseases. We concluded that equivocal proof of beneficial effects of high dose antioxidant supplementation has not been established, and further investigations of animal models of antioxidant function are needed to resolve outstanding questions.</p> <p>We then examined the feasibility and efficacy of an alternative vitamin C delivery method using gene therapeutic lentivirus vectors in a guinea pig model of vitamin C function. The guinea pig exhibits an inactivated gulonolactone oxidase gene (<em>Gulo</em>), which is required for endogenous ascorbic acid synthesis, and as such must acquire vitamin C from the diet. Using a lentivirus vector carrying the mouse <em>Gulo</em> under the murine cytomegalovirus (mCMV) promoter, which was previously developed as a part of my undergraduate thesis, we examined the ability of this gene therapeutic vector to mediate the expression of GULO and the production of ascorbic acid in guinea pigs. At a titre of 10¹⁰ viral particles per animal, the life of lentivirus-treated guinea pigs were prolonged by 35 days compared to the scorbutic control, which was given an ascorbic acid-free diet. Ascorbic acid was produced in the liver of the treated guinea pigs, but the amount produced was not sufficient to elevate plasma concentrations or fully correct the metabolic deficiency. We conclude that lenti-mCMV-<em>Gulo</em> is able to mediate the expression of GULO and endogenous production of vitamin C in guinea pigs.</p> <p>To test the role of vitamin C in cancer etiology and outcome, we are currently in the process of introgressing the <em>Gulo</em>^-/- inactivation mutation, developed by Maeda <em>et al.</em> in 2000, from the C57BL/6 strain background into the FVB/N strain background. The FVB/N strain is also the background for several models of <em>erbB2/neu</em> overexpression in human breast cancer, associated with increased metastasis and low patient survival rates. Taken together, this thesis develops two animal models of vitamin C function, which can be employed in future applications.</p> / Master of Science (MSc)

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Fruits and vegetables are highly perishable, produced seasonally, and large quantities (about 50-60% of production) are wasted during high season due to poor handling and lack of cold storage in Tanzania. Processing excess pineapple into vinegar which can be used for preservation of other fruits and vegetables may be a helpful strategy for reducing losses. Vinegar was produced from pineapple juice supplemented with sugar to produce different degrees of Brix (13, 20 and 30) and was fermented with Saccharomyces cereviciae, Acetobacter pasteurianus, and Gluconobacter oxydans. Levels of acetic acid were measured in the vinegar produced. High production (5.8%) of acetic acid was observed with pineapple juice concentrated to 130 Brix with the combination of Saccharomyces cerevisiae, A. pasteurianus and G. oxydans. The pineapple vinegar produced was used for preservation of carrot and mango. The pH of carrot pickle and mango chutney was monitored for three months. The pH of preserved carrot and mango was below 4 and no significant changes in pH were observed during three months storage at 29-320C. Chemical analysis of vitamin A and vitamin C showed high losses of Vitamin A in carrot and increased vitamin A in mango, but losses of about 74% and 85% of vitamin C were observed in carrot and mango after processing. Consumer sensory testing of pineapple vinegar, carrot pickle and mango chutney showed no significance different on overall consumer acceptability of products during storage. Pineapple vinegar can be used to rescue mango and carrots that would otherwise be lost, producing highly acceptable food products in Tanzania. / Master of Science in Life Sciences

The purpose of this investigation was to study the influence of the ration of the cow upon the vitamin C content of milk. The determinations were made by the biological assay method and by the chemical titration method. The cows were given four kinds of rations. Similar determinations have been made by other workers. A brief resume of their technique and conclusions follows: From the results of this investigation, it is concluded: 1. That the ascorbic acid content of milk decreases as the stage of lactation increases. 2. That the ascorbic acid of the milk of individual cows varies within the breed. 3. That the age of the cow does not influence the vitamin C content of the milk. 4. That the rate of gain of the assay animals over a period of 74 days was independent of the ascorbic acid content. 5. That the vitamin C content seems to be independent of the ration of the cow. 6. That the “spring milk” carried some factor which influenced a greater gain of weight than other “winter” milk rations. / Master of Science