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Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science In Medicine / The interaction between miglitol, an a-glucosidase inhibitor used as an adjunct therapy in diabetes, and phenytoin, an anticonvulsant primarily used in the treatment of epilepsy, was studied over 26 days. Twenty-four healthy male volunteers took part in a placebo controlled, double blind, cross-over study in two phases, to determine the effects of multiple 100mg doses of miglitol on a single 400mg dose of phenytoin sodium. Miglitol or placebo was administered three times daily from Day 1 to Day 5. Phenytoin was administered as a single dose on Day 3 of each phase, after which blood samples were taken at regular intervals. A washout period of 14 days separated the two phases. / IT2018

by Wong Kwok Kong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 163-184). / Abstract --- p.2 / Preface / Acknowledgements --- p.6 / List of abbreviations --- p.7 / List of Tables --- p.8 / List of Figures --- p.13 / CONTENTS --- p.16 / Chapter Chapter One： --- Introduction --- p.23 / Chapter Chapter Two： --- Review of pharmacology of propofol --- p.26 / Chapter 1： --- Chemistry structure-Activity relationship --- p.27 / Chapter 2: --- Pharmacokinetics --- p.28 / Chapter 2.1： --- Distribution --- p.29 / Chapter 2.2： --- Elimination --- p.30 / Chapter 2.3: --- "Effects of age, sex, and hepatic and renal disease on the pharmacokinetics of propofol" --- p.35 / Chapter 2.3.1： --- Effects of age / Chapter 2.3.2： --- Effects of sex / Chapter 2.3.3: --- Effects of renal and hepatic disease / Chapter 3: --- Pharmacodynamic --- p.38 / Chapter 3.1： --- Anaesthetic concentrations --- p.38 / Chapter 3.2: --- Recovery characteristics --- p.39 / Chapter 3.3： --- Effects on the cardiovascular system --- p.40 / Chapter 3.4： --- Effects on the respiratory system --- p.43 / Chapter 3.5： --- Effects on cerebral blood flow and intracranial pressure --- p.44 / Chapter 3.6： --- Other effects --- p.45 / Chapter 3.6.1： --- Effects on liver function / Chapter 3.6.2： --- Effects on renal function / Chapter 3.6.3: --- Effects on coagulation / Chapter 3.6.4： --- Effects on adrenal steroidgenesis / Chapter 3.7： --- Side effects --- p.47 / Chapter 3.7.1： --- Pain on injection / Chapter 3.7.2: --- Excitatory & respiratory / Chapter 3.7.3: --- Nausea and vomiting / Chapter 3.7.4： --- Bradycardia / Chapter 3.7.5: --- Anaphylaxes / Chapter 4: --- Clinical use --- p.51 / Chapter 4.1： --- Anaesthesia induction --- p.52 / Chapter 4.2: --- Anaesthesia maintenance --- p.53 / Chapter 4.3: --- Use in sedation --- p.57 / Chapter Chapter Three ： --- Analytical Technique:Propofol content analysis --- p.58 / Chapter 1: --- Introduction high-pressure liquid chromatography --- p.58 / Chapter 2: --- Methods of propofol content analysis --- p.61 / Chapter 2.1: --- Reagents and solutions --- p.61 / Chapter 2.1.1: --- Sodium dihydrogen phosphate / Chapter 2.1.2： --- Cyclohexane / Chapter 2.1.3: --- Tetramethylammonium Hydroxide Solution / Chapter 2.1.4： --- Acetonitrile / Chapter 2.1.5: --- Acetic acid / Chapter 2.2: --- Standard solution --- p.62 / Chapter 2.2.1: --- Propofol standards / Chapter 2.2.2： --- Internal standard / Chapter 2.2.3： --- Control standard / Chapter 2.3： --- Mobile phase --- p.63 / Chapter 2.4： --- High-pressure liquid chromatography --- p.63 / Chapter 2.5: --- Quantification --- p.64 / Chapter 2.6： --- Procedure --- p.67 / Chapter 2.7： --- Throughput --- p.69 / Chapter 2.7.1： --- Fist working day / Chapter 2.7.2: --- Second working day / Chapter 2.7.3： --- Third working day / Chapter 2.7.4: --- Fourth working day / Chapter 2.7.5： --- Fifth working day / Chapter 3: --- Results of propofol content analysis --- p.71 / Chapter 3.1: --- Calibration standard of propofol (Linearity) --- p.71 / Chapter 3.2： --- Control standard of propofol --- p.74 / Chapter 3.2.1： --- Reproducibility / Chapter 3.2.2: --- Recovery / Chapter 3.2.3： --- Stability / Chapter 4: --- Discussion of propofol content analysis --- p.80 / Chapter 4.1： --- Calibration standard of propofol --- p.80 / Chapter 4.2: --- Precision and accuracy of analytical method --- p.86 / Chapter 4.3： --- Extraction efficiency of analytical method --- p.87 / Chapter 4.4： --- Stability of analytical met --- p.89 / Chapter Chapter Four： --- Analytical technique： Protein binding of propofol --- p.91 / Chapter 1: --- Introduction protein binding of propofol --- p.91 / Chapter 1.1: --- Ultrafiltration --- p.92 / Chapter 1.2： --- Equilibrium dialysis --- p.92 / Chapter 2: --- Methods of protein binding of propofol --- p.94 / Chapter 2.1： --- Material & Solution --- p.94 / Chapter 2.1.1: --- Dialysis buffer / Chapter 2.1.2: --- Molecularporous Dialysis Membrane / Chapter 2.2: --- Equilibrium dialysis --- p.96 / Chapter 2.3： --- Determine the optimum dialysis time to reach equilibrium --- p.97 / Chapter 2.3.1： --- Material / Chapter 2.3.2： --- Procedure / Chapter 3: --- Results of protein binding of propofol --- p.99 / Chapter 3.1： --- Results for optimum dialysis time to reach equilibrium --- p.99 / Chapter 3.2： --- Results for reproducibility --- p.101 / Chapter 3.2.1: --- Intraassay coefficient of variation (One analysis day) of propofol in plasma and in protein binding / Chapter 3.2.2: --- Interassay coefficient of variation (Seven analysis days) of propofol in plasma and in protein binding / Chapter 3.3: --- Results for recovery of propofol in plasma and in protein binding --- p.106 / Chapter 3.3.1: --- Recovery of propofol (unheated samples) / Chapter 3.3.2: --- Recovery of propofol (samples heated at 37°C) / Chapter 3.3.3: --- Recovery of propofol (after dialysis at 37°C) / Chapter 3.4： --- Results for stability of propofol in plasma --- p.112 / Chapter 4: --- Discussions of protein binding of propofol --- p.114 / Chapter 4.1: --- Optimum dialysis time to reach equilibrium --- p.114 / Chapter 4.2: --- Discussion for Intraassay & Interassay coefficient of variation of propofolin plasma and in protein binding --- p.114 / Chapter 4.3： --- Recovery of propofol in plasma and in protein binding --- p.116 / Chapter 4.4： --- Discussion for stability of propofolin plasma --- p.118 / Chapter Chapter Five： --- Clinical application of pharmacokinetic studies --- p.119 / Chapter 1: --- Introduction pharmacokinetic model controlled infusion / Chapter 1.1： --- Theoretical basis --- p.119 / Chapter 1.2: --- Use of computer & appropriate pump --- p.123 / Chapter 2: --- Results of propofol pharmacokinetic studies --- p.124 / Chapter 2.1: --- Sample prepare --- p.124 / Chapter 2.2: --- Computer control infusion of propofol according to pharmacokinetic model --- p.126 / Chapter 2.3: --- Comparison of measured and predicted blood concentrations of propofol --- p.129 / Chapter 2.4: --- Test the new paediatric pharmacokinetic model (the revised paediatric rate constants) --- p.136 / Chapter 3: --- Discussion of propofol pharmacokinetics studies： Infusion for Chinese children --- p.141 / Chapter Chapter Six： --- Clinical application on protein binding studies --- p.143 / Chapter 1: --- Plasma proteins and drug binding --- p.143 / Chapter 2: --- Methods of propofol protein binding studies --- p.145 / Chapter 2.1： --- Blood sample acquisition --- p.145 / Chapter 2.2: --- Population characteristics --- p.145 / Chapter 2.3： --- Methods of protein binding assay --- p.145 / Chapter 3: --- Results of propofol protein binding --- p.146 / Chapter 4: --- Discussion of propofol protein binding --- p.153 / Chapter 4.1: --- Protein binding of propofol in Chinese children --- p.154 / Chapter 4.2： --- Protein binding of propofol in pregnant women & neonate --- p.155 / Chapter Chapter Seven： --- Conclusions --- p.158 / References --- p.163 / Appendix --- p.180

by Wong Yick Fu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 201-224. / Acknowledgments --- p.V / Summary --- p.vi / Publications --- p.ix / Statement of Originality --- p.X / List of Abbreviations --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Preamble --- p.2 / Chapter 1.2 --- History of Trichosanthin --- p.6 / Chapter 1.3 --- Preparation of Trichosanthin --- p.8 / Chapter 1.4 --- Chemistry of Trichosanthin --- p.10 / Chapter 1.4.1 --- Primary structure --- p.10 / Chapter 1.4.2 --- Three dimensional structure --- p.12 / Chapter 1.5 --- Pharmacology of Trichosanthin --- p.14 / Chapter 1.5.1 --- Pharmacologic action --- p.14 / Chapter 1.5.2 --- Pharmacokinetics --- p.18 / Chapter 1.5.3 --- Toxicity --- p.21 / Chapter 1.6 --- Clinical Use of Trichosanthin --- p.24 / Chapter 1.6.1 --- Clinical application --- p.24 / Chapter 1.6.2 --- Mechanism of action --- p.29 / Chapter 1.6.3 --- Adverse reactions --- p.31 / Chapter 1.6.4 --- Contraindications --- p.33 / Chapter 1.7 --- Objectives of Project and Organization of Thesis --- p.35 / Chapter Chapter 2 --- Anti-tumour Activity of Trichosanthin In Vitro and In Vivo --- p.37 / Chapter 2.1 --- Cytotoxic Effects of Trichosanthin on Cultured Tumour Cells --- p.38 / Chapter 2.1.1 --- Introduction --- p.38 / Chapter 2.1.2 --- Materials and methods --- p.40 / Chapter 2.1.3 --- Results --- p.49 / Chapter 2.1.4 --- Discussion --- p.59 / Chapter 2.2 --- Effects of Trichosanthin on Co-cultured Cell Lines In Vitro --- p.64 / Chapter 2.2.1 --- Introduction --- p.64 / Chapter 2.2.2 --- Materials and methods --- p.65 / Chapter 2.2.3 --- Results --- p.66 / Chapter 2.2.4 --- Discussion --- p.77 / Chapter 2.3 --- Combination Effects of Trichosanthin with Adriamycin and Cisplatin on Cultured Tumour Cells --- p.80 / Chapter 2.3.1 --- Introduction --- p.80 / Chapter 2.3.2 --- Materials and methods --- p.81 / Chapter 2.3.3 --- Results --- p.84 / Chapter 2.3.4 --- Discussion --- p.93 / Chapter 2.4 --- Effects of Trichosanthin on Choriocarcinoma Cells In Vivo --- p.96 / Chapter 2.4.1 --- Introduction --- p.96 / Chapter 2.4.2 --- Materials and methods --- p.97 / Chapter 2.4.3 --- Results --- p.101 / Chapter 2.4.4 --- Discussion --- p.107 / Chapter 2.5 --- Effects of Trichosanthin Protein and Polysaccharide on Choriocarcinoma Cells In Vitro --- p.110 / Chapter 2.5.1 --- Introduction --- p.110 / Chapter 2.5.2 --- Materials and methods --- p.112 / Chapter 2.5.3 --- Results --- p.114 / Chapter 2.5.4 --- Discussion --- p.117 / Chapter Chapter 3 --- Mechanism of Action of Trichosanthin on Tumour Cells --- p.119 / Chapter 3.1 --- Morphological Study of Effects of Trichosanthin on Cultured Choriocarcinoma Cells --- p.120 / Chapter 3.1.1 --- Introduction --- p.120 / Chapter 3.1.2 --- Materials and methods --- p.121 / Chapter 3.1.3 --- Results --- p.124 / Chapter 3.1.4 --- Discussion --- p.133 / Chapter 3.2 --- Binding of Radiolabelled Trichosanthin with Tumour Cells In Vitro --- p.137 / Chapter 3.2.1 --- Introduction --- p.137 / Chapter 3.2.2 --- Materials and methods --- p.138 / Chapter 3.2.3 --- Results --- p.146 / Chapter 3.2.4 --- Discussion --- p.154 / Chapter 3.3 --- Effects of Trichosanthin on Macromolecule Synthesis of Choriocarcinoma Cells In vitro --- p.159 / Chapter 3.3.1 --- Introduction --- p.159 / Chapter 3.3.2 --- Materials and methods --- p.160 / Chapter 3.3.3 --- Results --- p.163 / Chapter 3.3.4 --- Discussion --- p.167 / Chapter Chapter 4 --- General Discussion --- p.169 / Chapter 4.1 --- Anti-tumour Activity of Trichosanthin --- p.170 / Chapter 4.2 --- Mechanism of Action of Trichosanthin --- p.180 / Chapter 4.3 --- Prospects of Research on Trichosanthin --- p.195 / References --- p.201 / Appendix 1 --- p.225 / Appendix 2 --- p.242

Lim Thiam Aun. / Thesis (M.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 142-154). / 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.