published_or_final_version / Anatomy / Master / Master of Philosophy

Thesis (PH. D.)--Michigan State University. Chemical Engineering, 2008. / Title from PDF t.p. (viewed on Sept. 6, 2009) Includes bibliographical references (p. 116-119). Also issued in print.

No description available.

The primary aim of this research is to test the therapeutic potential of certain new generation corticosteroid drugs in order to develop safe and effective treatment for eye diseases that result in oedema, or swelling. The rising incidence of diabetes and the ageing population of developed countries mean that the prevalence of uveitis, diabetic retinopathy and age related macular degeneration will rise. Often, oedema is one of the reasons for vision loss. Corticosteroids are often used to reduce inflammation. Inflammation is one of several sources of oedema. Glucocorticoids, a class of corticosteroids that have anti-inflammatory properties, are thus used to treat ocular oedema. There is an unmet need to support clinical experience of the efficacy of steroids for ocular inflammation and oedema with more substantial scientific evidence. None of the drugs under investigation, with the exceptions of dexamethasone and triamcinolone, have been used for any ocular therapeutic purpose before. This thesis investigates “repurposing” fludrocortisone to the ophthalmic area. 11-Desoxycorticosterone (11D) and Deoxycorticosterone (DCS), other potentially valuable mineralocorticoids, remain completely untested. Lastly, Kenacort ®, or triamcinolone acetonide (TCA), is only used off-label by ophthalmologists. Methods: In the first study, corticosteroids, and especially mineralocorticoids, were investigated for their treatment efficacy in experimental uveitis, or intraocular inflammation (using a model known as endotoxin induced uveitis). In the second study, endothelial cells from choroidal blood vessels in the back of the eye were used in vitro to study whether corticosteroids reduce paracellular (between cells) permeability. Lastly, since endophthalmitis due to frequent injections is a side effect of corticosteroid use, the pharmacokinetics of different size formulations of corticosteroids were studied in an effort to find a formula that would have a prolonged dwell time within the eye.

published_or_final_version / Anatomy / Master / Master of Philosophy

Mice bearing the mutant gene Cat:Fr have dominantly inherited congenital cataracts, which are more extensive in the mutant homozygote than in the heterozygote. The biochemical and ultrastructural properties of these lenses were examined and compared with those of lenses in which cataracts were induced with acetaminophen and bleomycin. The Cat mutation induces a dominant, by inheritance, loss of beta-H crystallins, but this change is also seen in the bleomycin cataracts, and in the presence of 1 M sucrose, or at 4(DEGREES)C. There are codominantly inherited alterations in the relative proportions of crystallin and albuminoid components in the inherited cataracts, and in the presence of 1 M sucrose. Changes in amino acid composition of the lens proteins are dominantly inherited in the Cat mutation. There are also abnormalities of amino acid composition in the proteins from the acetaminophen cataracts, but these are different from those caused by the mutation. As to the ultrastructural changes, the inherited cataracts have a relatively normal anterior epithelium, but show marked degeneration of nuclear and deep cortical fibres. The bleomycin cataracts also show extensive nuclear destruction, but in addition, appear to be completely devoid of capsule, and have degenerating anterior epithelium cells, which are not seen in the inherited cataract. The acetaminophen cataracts, by contrast, retain normal overall structural architecture, but the individual fibres become swollen and flaky, and develop an increased number of interdigitating processes. These abnormal biochemical properties not unique to the Cat:Fr mouse are unlikely to be proximal effects of the mutant gene, and may be general consequences of the presence of a cataract, from whatever cause. The differences between ultrastructural abnormalities seen in the drug induced and inherited cataracts suggest that these etiological agents induce cataracts by different mechanisms, a fact that is not always apparent from

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Ashim K. Mitra. Typescript. Vita. Description based on contents viewed Feb. 23, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 142-169). Online version of the print edition.