Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 183-216). Available also in a digital version from Dissertation Abstracts.

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Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Terrence J. Monks and Shawn B. Bratton. Vita. Includes bibliographical references.

Indiana University-Purdue University Indianapolis (IUPUI) / At the present time, gentamicin is used in the treatment of both Gram-negative and Gram-positive bacterial infections. However, the poorly understood side effect of nephrotoxicity is a serious problem and is one of the dose-limiting factors in the use of gentamicin. In our model system, Saccharomyces cerevisiae, which is relatively resistant to gentamicin, at least 20 genes are required for gentamicin resistance. Inspection of the physical and genetic interactions of the gentamicin sensitive mutants reveals a network centered on the ARF pathway which plays a key role in the regulation of retrograde trafficking. Our studies show that arf1ts arf1Δ arf2Δ cells, gea1ts gea1Δ gea2Δ cells, and gcs1ts gcs1Δ glo3Δ cells are all hypersensitive to gentamicin which indicates that impaired Arf1 function causes yeast cells to become hypersensitive to gentamicin. As evidence, cellular CPY trafficking and processing are blocked by the presence of gentamicin in some of these mutants. Interestingly, gentamicin can directly affect the level of the GTP-bound form of Arf1 in a cell growth phase-dependent manner; even though total Arf1 levels in S. cerevisiae are not affected. As predicted, we also find that gentamicin-bound resin can enrich both yeast Arf1-TAP protein and rat Arf1 protein in vitro. With the help of mass spectrometry, we also generated a gentamicin-binding protein list. Gentamicin hypersensitivity is also observed in S. cerevisiae double deletion strains that lack both ARF1 and ARF2 but are kept alive by the presence of hARF4 or bARF1. Increased -1 programmed ribosomal frameshifting efficiency is also observed in cells treated with gentamicin. Finally, a comparison of a gentamicin mixture and four of the gentamicin congeners reveals that gentamicin C1 is less toxic than other gentamicin congeners or the gentamicin total mixture.

Cisplatin is an antineoplastic drug used to treat malignant tumors in human beings and dogs. Nephrotoxicosis was initially considered dose limiting. The use of saline loading and hypertonic saline administration protocols allowed dose escalation, reduced nephrotoxicosis, and increased remission rates in the treatment previously poorly responsive malignant tumors in human beings. A pilot study was performed to determine efficacy of 4-hour saline loading in providing renal protection for dogs receiving high-dose cisplatin (150 mg/m² IV). Two beagles were saline loaded (25 ml/kg/hr of 0.9% NaCI, IV) for 4 hours and infused with cisplatin (150 mg/m²). We demonstrated that high-dose cisplatin (150 mg/m² IV) can be administered to dogs without biochemical evidence of acute nephrotoxicosis; however gastrointestinal toxicoses (fibrinonecrotic enteritis) and severe myelosuppression (leukopenia) were incompatible with patient survival and therefore, dose limiting. In another study we compared efficacy of hypertonic saline with normal saline in preventing nephrotoxicosis associated with administration of high-dose cisplatin (90 mg/m² IV) to dogs. In this study we demonstrated that a single IV dose of cisplatin (90mg/m²) can be administered to dogs in normal saline (0.9%) or hypertonic saline (7%) in combination with 4 hour saline loading (25 ml/kg/hr) without evidence of reduced renal function as measured by exogenous creatinine clearance. Platelet numbers were significantly increased in dogs that received cisplatin in hypertonic saline. Nephrotoxicosis was not dose limiting in either study. Future studies should attempt to determine the efficacy and toxicoses of multiple doses of cisplatin (90 mg/M² administered in hypertonic saline to tumor bearing dogs. / Master of Science

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 147-168.

Research to improve artificial renal replacement therapies is varied across the many different parts of a hemodialysis system. Work largely focuses on developing a better dialyzer - the component that is directly responsible for removing wastes from the blood - but less study is devoted to the entire hemodialysis system. This work seeks to improve hemodialysis in two ways: by proposing a new renal replacement therapy that does not rely on traditional hemodialysis components, and by investigating the feasibility of adapting current hemodialysis practices to a portable format. While an alternative renal replacement therapy may be the best solution to today's dialysis problems, this work further focuses on reducing hemodialysis to a portable format through systematic engineering design. In that process, a detailed system model is made in Simulink that can account for the large number of inputs of such a system - the blood flow rate, dialyzer size, treatment time, etc. - allowing for detailed exploration of the design space. Once the model is completed, it is verified through in vitro experiments carried out with porcine blood. Additionally, the model is verified against published human hemodialysis data. After model verification, hemodialysis concepts are generated that allow for maximum portability under different patient conditions.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Dissertation Abstracts International, Volume: 68-12, Section: B, page: 7975. Adviser: Mary Ann Smith. Includes bibliographical references.

Les acides aristolochiques (AA) présents dans les aristoloches sont impliqués dans le développement d’une insuffisance rénale progressive chez l’homme, appelée néphropathie aux plantes chinoises (CHN). Elle se caractérise par une atrophie tubulaire sévère et une fibrose interstitielle associée à une fréquence élevée de cancers urothéliaux. L’observation en clinique d’une protéinurie tubulaire a suggéré que le tubule proximal était la cible des AA.<p><p>\ / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished