Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xv, 91 p.; also includes graphics (some col.) Includes bibliographical references (p. 82-91). Available online via OhioLINK's ETD Center

Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 223-230).

No description available.

Thesis (Ph.D.). / Written for the Dept. of Chemistry. Title from title page of PDF (viewed 2007/08/29). Includes bibliographical references.

Thesis--Auburn University, 2009. / Abstract. Includes bibl

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Fungicide discovery is relatively neglected when compared to the investment in the development of antibacterial, antiviral, and anti-cancer therapeutics. Due to extensive use of currently available fungicides in agriculture and medicine, resistance is emerging among plant and animal pathogenic fungi. This necessitates the search for novel antifungal agents that are effective and less toxic and that do not promote resistance. FG08 and K20 are novel aminoglycoside analogs synthesized from kanamycin B and A, respectively. The antimicrobial properties of these analogs were tested in vitro against a wide range of agriculturally and clinically important fungal pathogens. Both compounds showed broad-spectrum antifungal properties, but they did not inhibit bacteria such as Escherichia coli and Staphylococcus aureus. The hemolytic activities and cytotoxicities of FG08 and K20 were also evaluated. They showed no toxicity or lowered toxicity against animal cells at their antifungal minimum inhibitory concentrations (MICs). The fungicidal mechanisms of action of FG08 and K20 were examined using intact cells of Saccharomyces cerevisiae, Cryptococcus neoformans, hyphae of Fusarium graminearum. FG08 and K20 caused SYTOX Green dye uptake and potassium efflux by intact cells, indicating that they increase plasma membrane permeability. FG08 and K20 also caused leakage of pre-loaded calcein from small unilamellar vesicles (SUVs) composed of lipids that mimic the lipid composition of fungal membranes, further suggesting increased membrane permeability as their mechanism of action. The synergistic interactions of K20 with six azoles (such as itraconazole, and fluconazole) were investigated against a wide array of fungal pathogens. The in vitro results revealed strong synergy between K20 and azoles against plant and human pathogenic fungi. Their synergies were furthered confirmed by time kill curves and disk diffusion methods. In conclusion, FG08 and K20 are broad-spectrum antifungal agents that do not inhibit bacteria. At their antifungal MICs, they are not toxic to animal cells, but they inhibit fungi by interacting with the fungal plasma membrane, leading to pore formation. These novel aminoglycoside analogs appear attractive for applications as fungicides in agriculture and medicine.

by Stanton Hon-Lung Kok. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 142-147). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

This dissertation describes how to apply pharmacokinetic simulations and modeling in a clinical setting to monitor and adjust drug dosing in special patient populations. Pharmacokinetic simulations were used to investigate efficacy and risk of drug toxicity of a new dosing regimen for aminoglycoside antibiotics when administered to renal failure patients. The current method of administering aminoglycosides to renal failure patients is to dose the drug during the last half hour of dialysis sessions. The new proposed method suggests dosing the drug during the first half hour of the dialysis session. Using one-compartment model infusion equations, both methods were simulated to predict drug peaks, troughs and area under the curves. These parameters were used to compare both dosing regimens to find out if the proposed dosing regimen can be suggested in a clinical setting to obtain the same efficacy and lower risk of drug toxicity. The dissertation then describes a prospective clinical study in chronic renal failure patients who received the same tobramycin dose using current and proposed dosing regimens. Results from the clinical study confirm pharmacokinetic simulations and modeling outcomes. Results suggest that both regimens have the same efficacy, but the new proposed method is expected to have lower risk of drug toxicity. The dissertation also describes a retrospective study for vancomycin dosing in renal failure patients. The objective was to confirm that pharmacokinetic modeling could be used to predict and adjust vancomycin dosing for this special population. Vancomycin trough concentrations obtained from patient medical records were compared to predictions obtained using a pharmacokinetic model. It was concluded that there was no statistically significant difference between actual and predicted vancomycin trough concentrations. These results suggest that the pharmacokinetic model can be used to predict and adjust vancomycin dosing to chronic renal failure population. The last part of this dissertation describes evaluation of insulin glargine effect on glycemic control and weight change in a diabetic population. Glycemic control and weight of patients before and after initiation of insulin glargine were evaluated retrospectively. Results showed that initiation of insulin glargine improved glycemic control while weight remained relatively stable. / Graduation date: 2005

Rett syndrome is a neurological condition that affects primarily girls. Approximately 40% of Rett syndrome cases arise from nonsense mutations. Several studies have shown that certain aminoglycosides can suppress some types of nonsense mutations in a context dependent manner, and allow the generation of a full length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study I tested whether some nonsense mutations of MECP2 seen clinically in Rett syndrome girls can be partially suppressed by aminoglycoside administration. My results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK-293 cells, but with differing levels of efficiency. Furthermore, I also show that aminoglycosides increased the prevalence of full length MeCP2 protein in a lymphocyte cell line derived from a Rett girl with R255X mutation. This study establishes the “proof of principle” that some nonsense mutations causing Rett syndrome can be suppressed by drμg treatment.