published_or_final_version / Social Work / Master / Master of Social Work

Thesis (Ph. D.)--Brigham Young University. Dept. of Psychology, 2009. / Includes bibliographical references.

Thesis (doctoral)--Universität Hamburg, 1972. / Includes bibliographical references (p. iv-xxxiii).

Wu Wai Ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 163-177). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgement --- p.vi / Table of Contents --- p.vii / Abbreviations --- p.x / Chapter Chapter 1 --- General introduction --- p.11 / Chapter 1.1 --- Introduction --- p.11 / Chapter 1.1.1 --- "Origin, processing and delivery form of TCM" --- p.11 / Chapter 1.1.2 --- Problems about the uses of TCM --- p.13 / Chapter 1.1.2.1 --- Quality control --- p.13 / Chapter 1.1.2.2 --- Efficacy --- p.14 / Chapter 1.1.2.3 --- Herb-drug interactions --- p.14 / Chapter 1.1.2.4 --- Authentication --- p.15 / Chapter 1.1.3 --- Commonly used Traditional Chinese Medicine --- p.15 / Chapter 1.2 --- Interactions between TCM and warfarin --- p.17 / Chapter 1.2.1 --- Danshen-warfarin interactions --- p.19 / Chapter 1.3 --- Danshen --- p.20 / Chapter 1.3.1 --- Chemical constituents --- p.20 / Chapter 1.3.2 --- Pharmacological effects of danshen --- p.24 / Chapter 1.3.2.1 --- Anti-oxidant effects --- p.24 / Chapter 1.3.2.2 --- Effects on liver fibrosis --- p.25 / Chapter 1.3.2.3 --- Effects on tumours --- p.26 / Chapter 1.3.2.4 --- Effects on cardiovascular system --- p.26 / Chapter 1.3.2.5 --- Effect on platelet aggregation --- p.27 / Chapter 1.4 --- Warfarin --- p.27 / Chapter 1.4.1 --- Pharmacology --- p.28 / Chapter 1.4.2 --- Pharmacokinetics --- p.30 / Chapter 1.4.3 --- Metabolism --- p.30 / Chapter 1.4.4 --- Warfarin-drug interactions --- p.32 / Chapter 1.4.4.1 --- Pharmacokinetic Interactions --- p.32 / Chapter 1.4.4.2 --- Pharmacodynamic interactions --- p.34 / Chapter 1.5 --- Aim of study --- p.35 / Chapter Chapter 2 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in rat liver microsomes --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Materials and methods --- p.39 / Chapter 2.2.1 --- Chemicals and reagents --- p.39 / Chapter 2.2.2 --- Animals --- p.39 / Chapter 2.2.3 --- Preparation of rat hepatic microsomes --- p.40 / Chapter 2.2.4 --- Protein assay --- p.40 / Chapter 2.2.5 --- Preparation of aqueous fraction and ethanolic fractions of danshen from danshen roots --- p.41 / Chapter 2.2.5.1 --- Aqueous extract of danshen --- p.41 / Chapter 2.2.5.2 --- Ethanolic extract of danshen --- p.42 / Chapter 2.2.6 --- Incubation condition for warfarin metabolism --- p.42 / Chapter 2.2.7 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in vitro --- p.43 / Chapter 2.2.8 --- Effects of danshen extract and some of its sctive ingredients on enzyme kinetics of warfarin metabolism in vitro --- p.44 / Chapter 2.2.9 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.45 / Chapter 2.2.10 --- Calibration curves and validation of the HPLC systems --- p.48 / Chapter 2.2.11 --- Data analysis --- p.52 / Chapter 2.3 --- Results --- p.53 / Chapter 2.3.1 --- Effects of danshen extract on warfarin metabolism --- p.53 / Chapter 2.3.2 --- Effects of aqueous extract of danshen on warfarin metabolism --- p.60 / Chapter 2.3.3 --- Effects of ethanolic extract of danshen on warfarin metabolism --- p.62 / Chapter 2.3.4 --- Effects of tanshinone I on warfarin metabolism --- p.64 / Chapter 2.3.5 --- Effects of tanshinone IIA on warfarin metabolism --- p.70 / Chapter 2.3.6 --- Effects of cryptotanshinone on warfarin metabolism --- p.76 / Chapter 2.3.7 --- IC20 of danshen extract and its components on warfarin metabolism --- p.82 / Chapter 2.4 --- Discussion --- p.84 / Chapter Chapter 3 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in human pooled liver microsomes and the human CYP2C9 isoform --- p.89 / Chapter 3.1 --- Introduction --- p.89 / Chapter 3.2 --- Materials and methods --- p.92 / Chapter 3.2.1 --- Chemicals and reagents --- p.92 / Chapter 3.2.2 --- Incubation conditions for warfarin metabolism --- p.92 / Chapter 3.2.3 --- Effects of danshen extract and its components on warfarin metabolism in vitro --- p.93 / Chapter 3.2.4 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.94 / Chapter 3.2.5 --- Calibration curves --- p.95 / Chapter 3.2.6 --- Data analysis --- p.95 / Chapter 3.3 --- Results --- p.96 / Chapter 3.3.1 --- Effects of danshen extract and its components on warfarin metabolism by using human pooled liver microsomes --- p.96 / Chapter 3.3.2 --- Effects of danshen extract and its components on S-warfarin metabolism by using human lymphoblast CYP2C9 isoform --- p.103 / Chapter 3.4 --- Discussion --- p.111 / Chapter Chapter 4 --- Effects of acute and subchonic pretreatment of danshen extract on the pharmacokinetics of warfarin in the rats in vivo --- p.115 / Chapter 4.1 --- Introduction --- p.115 / Chapter 4.2 --- Materials and methods --- p.118 / Chapter 4.2.1 --- Chemicals and reagents --- p.118 / Chapter 4.2.2 --- Animals Table of Contents --- p.118 / Chapter 4.2.3 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.4 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.5 --- Steady state warfarin study --- p.120 / Chapter 4.2.6 --- Sample extraction --- p.120 / Chapter 4.2.7 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.121 / Chapter 4.2.8 --- Calibration curve --- p.121 / Chapter 4.4 --- Results --- p.123 / Chapter 4.3.1 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.123 / Chapter 4.3.2 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.128 / Chapter 4.3.3 --- Steady state warfarin study --- p.136 / Chapter 4.5 --- Discussion --- p.138 / Chapter Chapter 5 --- Effects of danshen extract on the absorption of warfarin by using Caco-2 cells model --- p.142 / Chapter 5.1 --- Introduction --- p.142 / Chapter 5.2 --- Materials and methods --- p.144 / Chapter 5.2.1 --- Materials for Caco-2 cells culture experiment --- p.144 / Chapter 5.2.2 --- Preparation of Caco-2 monolayer --- p.144 / Chapter 5.2.3 --- High Pressure Liquid Chromatography (HPLC) analysis for warfarin --- p.145 / Chapter 5.2.4 --- Calibration curve --- p.145 / Chapter 5.2.5 --- Stability test for warfarin and danshen extract --- p.145 / Chapter 5.2.6 --- Toxicity test of danshen extract on Caco-2 cells --- p.146 / Chapter 5.2.7 --- Transport study --- p.146 / Chapter 5.2.8 --- Data Analysis --- p.147 / Chapter 5.3 --- Results --- p.149 / Chapter 5.3.1 --- Stability of warfarin and danshen extract --- p.149 / Chapter 5.3.2 --- Toxicity test of danshen extract on Caco-2 cells --- p.149 / Chapter 5.3.3 --- Integrity of Caco-2 cells monolayer --- p.152 / Chapter 5.3.4 --- Transport study --- p.152 / Chapter 5.4 --- Discussion --- p.154 / Chapter Chapter 6 --- General discussion --- p.156 / References --- p.163

The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2008-2009 / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

A number of experimental studies have implied a link between diabetes-induced lipid accumulation in the myocardium and the development of cardiomyopathy. Since diabetics excrete large amounts of myo-inositol which is a lipotropic agent, this study was undertaken to investigate the effects of myo-inositol on the elevated myocardial lipid levels and the depressed cardiac performance of diabetic rats. Diabetes was induced in female Wistar rats (190-215 g) with streptozotocin (STZ) (55 mg/kg, i.v.). Three days after diabetes induction, myo-inositol was administered in the drinking water (2.5 g/kg/day) for a 8 week period. Untreated diabetics exhibited a loss of body weight, hyperglycemia, hypoinsulinemia and hypothyroidism. These effects were not altered after myo-inositol treatment. STZ-diabetes also produced a significant elevation of plasma and myocardial triacylglycerol, cholesterol and phospholipid. Myo-inositol treatment decreased these lipid levels. In addition, hearts from diabetic animals had a decreased ability to develop left ventricular developed pressure (LVDP) and both the rate of pressure rise (+dP/dt) and the rate of pressure decline (-dP/dt) were also reduced. Hearts from myo-inositol-treated diabetic animals showed a partial but definite improvement of cardiac function. As diabetes-induced hypothyroidism was not altered after myo-inositol supplementation, a combination treatment of both myo-inositol (2.5 g/kg/day, p.o. daily) and T₃ (30 ug/kg/day, s.c. daily) was then undertaken to determine whether heart function of diabetic rats could be further improved. STZ-diabetic rats were characterized by a loss of body weight, hyperglycemia and hypoinsulinemia; none of which were altered by either T₃ or myo-inositol plusT₃ treatment. T₃ treatment normalized the thyroid state of diabetic animals as shown by Tahiliani and McNeill (1984). However, plasma and myocardial triacylglycerol, cholesterol and phospholipid levels of diabetic rats either remained elevated or were further increased with T₃ or myo-inositol plus T₃ treatment. In addition, T₃ treatment alone did not prevent cardiac dysfunction in diabetic rats. There was, however, some improvement in heart function in the groups treated with both myo-inositol and T₃, but the improvement was not as pronounced as with myo-inositol treatment alone. / Pharmaceutical Sciences, Faculty of / Graduate

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