L-carnitine is an endogenous compound that has important roles in fatty acid oxidation. Patients with end-stage renal disease (ESRD) who are undergoing haemodialysis may develop a secondary L-carnitine deficiency. Following oral administration of L-carnitine, enterobacteria generate ??-butyrobetaine and trimethylamine with the latter substance extensively N-oxygenated in the liver, to form trimethylamine-N-oxide. Given that patients with ESRD have qualitatively different and higher bacterial populations in the small intestine as compared with healthy subjects, increased formation of trimethylamine and accumulation of trimethylamine-N-oxide would be expected. The clinical significance of these amines is related to their potential to form the carcinogen N-nitrosodimethylamine, contribution to neurological toxicity and "uraemic breath". / The pharmacokinetics of oral L-carnitine display clear non-linearity above a dose of 0.5 g three times a day with an associated increase in plasma concentrations of trimethylamine and trimethylamine-N-oxide. Oral administration of L-carnitine to patients with ESRD undergoing haemodialysis increased plasma concentrations of this substance to levels seen in individuals with normal kidney function and evidence was provided for the accumulation of trimethylamine-N-oxide. / Thesis (PhD)--University of South Australia, 2006.

L-carnitine is an endogenous compound that has important roles in fatty acid oxidation. Patients with end-stage renal disease (ESRD) who are undergoing haemodialysis may develop a secondary L-carnitine deficiency. Following oral administration of L-carnitine, enterobacteria generate ??-butyrobetaine and trimethylamine with the latter substance extensively N-oxygenated in the liver, to form trimethylamine-N-oxide. Given that patients with ESRD have qualitatively different and higher bacterial populations in the small intestine as compared with healthy subjects, increased formation of trimethylamine and accumulation of trimethylamine-N-oxide would be expected. The clinical significance of these amines is related to their potential to form the carcinogen N-nitrosodimethylamine, contribution to neurological toxicity and "uraemic breath". / The pharmacokinetics of oral L-carnitine display clear non-linearity above a dose of 0.5 g three times a day with an associated increase in plasma concentrations of trimethylamine and trimethylamine-N-oxide. Oral administration of L-carnitine to patients with ESRD undergoing haemodialysis increased plasma concentrations of this substance to levels seen in individuals with normal kidney function and evidence was provided for the accumulation of trimethylamine-N-oxide. / Thesis (PhD)--University of South Australia, 2006.

Thesis (Ph. D.)--University of Adelaide, Dept of Clinical and Experimental Pharmacology, 1988. / Spine title: Pharmacokinetic investigations of triamterine and its metabolites. Erratum slip inserted. Includes bibliographical references (leaves 227-239).

Cimetidine is a histamine H2-receptor antagonist that is among the most widely prescribed drugs in the world. In addition to its inhibitory action on gastric acid secretion, a possible role in kidney tubulointerstitial disease has been suggested. Isolated reports have also suggested an association between cimetidine administration and acute interstitial nephritis. The present study examined the effect of cimetidine on renal function in the rat. The nine rats used in this study had normal renal function and urinalyses before treatment with cimetidine. The cimetidine treated rats then developed a clinical picture of weakness, hematuria, proteinuria, casturia, oliguria, and increases in serum blood urea nitrogen and creatinine.Following the 6 weeks treatment period, all rats were sacrificed and their kidneys prepared for microscopic study. Histologically, the patchy, intense tubulointerstitial infiltration of lymphocytes, plasma cells, and other cells observed in the cortex of the rat kidneys is quite similar to findings described in human cases of drug-induce hypersensitivity tubulointerstitial disease. In addition, other pathologic conditions which can cause tubulointerstitial disease were adequately ruled out. Specifically, bacterial pyelonephritis was excluded as a result of the consistently sterile urine test. In conclusion, the author feels that the clinical, aboratory, and histologic findings in this study strongly suggests an association between of tubulointerstitial disease and the use of cimetidine. / Department of Physiology and Health Science

Thesis (PhD)--University of South Australia, 2001.

Thesis (MAppSc) -- University of South Australia, 1998

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This dissertation experimentally explores digital optical computing and optical interconnects with theoretical supports, from the physics of materials and the optimization of devices to system realization. The trend of optical computing is highlighted with the emphasis on the current development of its basic constituent elements, and a couple of algorithms selected to pave the way for utilizing bistable devices for their optical implementations. Optical bistable devices function as "optical transistors" in optical computing. The physics of dispersive optical bistability is briefly described. Bistable ZnS interference filters are discussed in detail regarding their linear and nonlienar characteristics. The optimization of switching characteristics for a bistable ZnS interference filter is discussed, and experimental results are shown. Symbolic substitution which fully takes advantage of regular optical interconnects constitutes two steps: pattern recognition and symbol scription. Two experiments on two digital pattern recognitions and one on a simple but complete symbolic substitution have been demonstrated. The extension of these experiments is an implementation of a binary adder. A one-bit full adder which is a basic block for a computer has been explored experimentally and demonstrated in an all-optical way. The utilization of a bistable device as a nonlinear decision-making element is further demonstrated in an associative memory experiment by incorporating a Vander Lugt matched filter to discriminate two partial fingerprints. The thresholding function of a bistable device enhances the S/N ratio and helps discrimination in associative memory. As the clocking speed of a computer goes higher, e.g. greater than several GHz, the clock signal distribution and packaging become serious problems in VLSI technology. The use of optical interconnects introduces a possible solution. A unique element for holographic optical interconnects, which combines advantages of computer generated hologram and DCG recording material, is discussed. Pattern design of a specific computer generated hologram and a proposed fabrication process are described. Experimental results suggest that this unique element has the capability of being tailored to perform multiple fan-out with resulting uniform tightly-focussed spots, and coupling between devices, e.g. source-to-fiber and fiber-to-waveguides, etc.

It is well known that a variety of toxicants can cause damage to the renal proximal tubule. However, the early pathogenesis of these deleterious interactions between a toxicant and this region of the nephron remain poorly understood. Thus, the purpose of this research was to attempt to answer three interrelated questions. First, what are the earliest changes in kidney function and structure after administration of tubule toxicants in vivo? Secondly, how do these structural/functional alterations change over time? Finally, are certain indicators of renal "dysfunction" more sensitive then others to the early stages of proximal tubule injury? The basic experimental approach consisted of injecting laboratory animals with a selective proximal tubule toxicant, and then collecting blood and/or urine at several timepoints after dosing; a variety of renal function indicators were evaluated at each of these timepoints. These included blood urea nitrogen (BUN), the glomerular filtration rate (GFR), and the excretion of glucose, protein, salts, glutathione, enzymes, and other endogenous molecules into the urine. At the termination of the exposure period the kidneys were evaluated histopathologically, and were also assayed for levels of specific enzymes and glutathione. Enzyme histochemistry was used to visualize changes in renal enzyme distribution, and protein electrophoretic methods permitted quantification of urinary proteins. These studies showed that specific markers of renal dysfunction were more sensitive to acute proximal tubule injury than other indicators. Specifically, the urinary excretion of proteins and the brush border membrane marker γ-glutamyl transpeptidase (GGT) were the best indicators of proximal tubule injury. Glucosuria, lysozymuria, and glutathionuria were all less sensitive markers, and changes in BUN or GFR were the poorest indicators of acute proximal tubule injury. These results indicated that the brush border membrane is one of the most susceptible regions of the proximal tubule to acute renal injury. Analysis of urinary protein electrophoresis patterns and kidney histopathology confirmed this hypothesis. This research also demonstrated the progression of the toxicant-tubule interaction over time, and showed that both tubule structure and function may be altered within minutes of administering a nephro-toxicant.

Tang, Walfred. / "November 2011." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 151-165). / Abstracts in English and Chinese. / Title Page --- p.i / Thesis/Assessment Committee (English) --- p.ii / Acknowledgements --- p.iii / Table of Content --- p.iv / List of Figures --- p.ix / List of Graphs --- p.xi / List of Tables --- p.xiv / Abbreviations --- p.xviii / Abstract (English) --- p.xx / Abstract (Chinese) --- p.xxii / Chapter Chapter 1: --- General Introduction / Chapter 1.1 --- Renal Development --- p.2 / Chapter 1.1.1 --- The three embryonic excretory systems --- p.2 / Chapter 1.1.1.1 --- Pronephros and mesonephros --- p.2 / Chapter 1.1.1.2 --- Metanephros --- p.4 / Chapter 1.1.2 --- Renal malformations --- p.6 / Chapter 1.1.2.1 --- Causes of renal malformations --- p.8 / Chapter 1.1.2.1.1 --- Physical obstruction --- p.9 / Chapter 1.1.2.1.2 --- Mutation --- p.9 / Chapter 1.1.2.1.3 --- Environmental insults --- p.10 / Chapter 1.2 --- Retinoic Acid --- p.11 / Chapter 1.2.1 --- "Retinoic acid synthesis, signaling and degradation in the Embryo" --- p.12 / Chapter 1.2.2 --- Retinoic acid and embryonic development --- p.14 / Chapter 1.2.2.1 --- Retinoic acid and renal development --- p.15 / Chapter 1.2.3 --- Retinoic acid teratogenicity --- p.17 / Chapter 1.2.3.1 --- Retinoic acid teratogenic mechanism --- p.18 / Chapter 1.2.3.2 --- Retinoic acid-induced renal agenesis mouse model --- p.21 / Chapter 1.2.4 --- Induction of RA deficiency --- p.24 / Chapter 1.3 --- Strategy of the Thesis --- p.28 / Chapter Chapter 2: --- General Materials and Methods / Chapter 2.1 --- Mouse Maintenance and Mating Method --- p.31 / Chapter 2.2 --- Bisdiamine Preparation --- p.32 / Chapter 2.3 --- All-trans Retinoic Acid Preparation --- p.32 / Chapter 2.4 --- Embryo Dissection --- p.32 / Chapter 2.5 --- Real-time Quantitative Reverse Transcription- Polymerase Chain Reaction (RT-PCR) --- p.33 / Chapter 2.5.1 --- Sample collection --- p.33 / Chapter 2.5.2 --- Total RNA extraction --- p.33 / Chapter 2.5.3 --- Reverse transcription --- p.34 / Chapter 2.5.4 --- Polymerase chain reaction --- p.35 / Chapter 2.5.5 --- Preparation of DNA standards --- p.36 / Chapter 2.6 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick-end Labeling (TUNEL) Staining --- p.38 / Chapter 2.6.1 --- "Fixation, dehydration and embedding" --- p.38 / Chapter 2.6.2 --- Microtome sectioning --- p.39 / Chapter 2.6.3 --- TUNEL staining --- p.39 / Chapter Chapter 3: --- Induction of Renal Malformations by Bisdiamine via RA Deficien --- p.cy / Chapter 3.1 --- Introduction --- p.43 / Chapter 3.1.1 --- Time and dose responses to bisdiamine-induced renal malformations --- p.43 / Chapter 3.1.2 --- Methods to detect endogenous RA in embryonic tissues --- p.44 / Chapter 3.2 --- Experimental Design --- p.46 / Chapter 3.3 --- Materials and Methods --- p.48 / Chapter 3.3.1 --- Time and dose responses to bisdiamine administration --- p.48 / Chapter 3.3.2 --- Quantification of RA and retinol content in whole embryo by high pressure liquid chromatography (HPLC) --- p.49 / Chapter 3.3.2.1 --- Bisdiamine injection and sample collection --- p.49 / Chapter 3.3.2.2 --- Chromatographic system --- p.50 / Chapter 3.3.2.3 --- Preparation of standards --- p.50 / Chapter 3.3.2.4 --- Extraction of embryo samples --- p.51 / Chapter 3.3.2.5 --- Conditions of HPLC --- p.52 / Chapter 3.3.2.6 --- Recovery of sample --- p.53 / Chapter 3.3.2.7 --- Bradford protein assay --- p.53 / Chapter 3.3.3 --- X-gal staining of RARE-hsp-lacZ embryos --- p.54 / Chapter 3.3.4 --- Quantification of RA content in metanephroi by the RA-responsive cell line --- p.55 / Chapter 3.3.4.1 --- Bisdiamine injection and sample collection --- p.55 / Chapter 3.3.4.2 --- Maintenance of the RA-responsive cell line --- p.56 / Chapter 3.3.4.3 --- Seeding of cells and addition of samples --- p.57 / Chapter 3.3.4.4 --- X-gal staining --- p.58 / Chapter 3.3.5 --- TUNEL staining --- p.59 / Chapter 3.3.6 --- Real-time quantitative RT-PCR --- p.60 / Chapter 3.3.7 --- Statistical analysis --- p.61 / Chapter 3.4 --- Results --- p.63 / Chapter 3.4.1 --- Time response to bisdiamine treatment --- p.63 / Chapter 3.4.1.1 --- Bisdiamine administration increased resorption and affected various growth parameters of the fetuses --- p.64 / Chapter 3.4.1.2 --- Bisdiamine administration resulted in renal malformations --- p.68 / Chapter 3.4.1.3 --- Bisdiamine administration resulted in non-renal malformations --- p.71 / Chapter 3.4.2 --- Dose response to bisdiamine treatment --- p.76 / Chapter 3.4.2.1 --- Dose response of resorption and various growth parameters --- p.77 / Chapter 3.4.2.2 --- Dose response to bisdiamine in inducing renal malformations --- p.80 / Chapter 3.4.2.3 --- Dose response to non-renal malformations --- p.83 / Chapter 3.4.3 --- RA deficiency induced by bisdiamine --- p.88 / Chapter 3.4.3.1 --- Comparison of endogenous RA and retinol levels in control and bisdiamine-treated whole embryos at different time points after treatment --- p.88 / Chapter 3.4.3.2 --- Comparison of RA signaling patterns in control and bisdiamine-treated embryos at different time points after treatment --- p.90 / Chapter 3.4.3.3 --- Comparison of endogenous RA levels in control and bisdiamine-treated metanephroi at different time points after treatment --- p.93 / Chapter 3.4.4 --- Increase in the number of apoptotic nuclei in the metanephros after bisdiamine treatment --- p.95 / Chapter 3.4.5 --- Alteration of genes expression in the metanephros after bisdiamine treatment --- p.96 / Chapter 3.5 --- Discussion --- p.99 / Figures / Graphs / Chapter Chapter 4: --- Rescuing Bisdiamine-treated Metanephroi by In Vitro Supplementation with Low Concentrations of RA / Chapter 4.1 --- Introduction --- p.107 / Chapter 4.1.1 --- Embryonic kidney culture --- p.107 / Chapter 4.1.2 --- In vitro culture of the RA-treated metanephros --- p.108 / Chapter 4.1.3 --- Effect of exogenous retinoic acid on in vitro development of metanephros --- p.109 / Chapter 4.2 --- Experimental Design --- p.111 / Chapter 4.3 --- Materials and Methods --- p.113 / Chapter 4.3.1 --- Supplementation of low concentrations of RA to metanephric explant culture --- p.113 / Chapter 4.3.1.1 --- Preparation of culture medium supplemented with low concentrations of RA --- p.113 / Chapter 4.3.1.2 --- Metanephric explant culture --- p.114 / Chapter 4.3.2 --- Whole-mount immunohistochemical staining of ureteric epithelium and nephric tubules in metanephric explants --- p.115 / Chapter 4.3.3 --- TUNEL staining of metanephric explants --- p.116 / Chapter 4.3.4 --- Real-time quantitative RT-PCR --- p.117 / Chapter 4.3.5 --- Statistical analysis --- p.117 / Chapter 4.4 --- Results --- p.119 / Chapter 4.4.1 --- Rescue of bisdiamine-treated metanephric explants by in vitro culture in medium supplemented with low concentrations of RA --- p.119 / Chapter 4.4.1.1 --- Assessment of metanephric development under various concentrations of RA by morphological grading of UB tips at different day of culture --- p.119 / Chapter 4.4.1.2 --- Effect of various concentrations of RA on the number of UB tips and nephric tubules in metanephric explants at day 6 of culture --- p.126 / Chapter 4.4.2 --- Effect of RA supplementation on apoptosis in bisdiamine-treated metanephric explants --- p.131 / Chapter 4.4.3 --- Effect of RA supplementation on genes expression in bisdiamine-treated metanephric explants --- p.133 / Chapter 4.5 --- Discussion --- p.136 / Figures / Graphs / Chapter Chapter 5: --- Conclusion and Future Perspectives --- p.141 / References --- p.150