Yeung Chi Hang, Thomas. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 126-146). / Abstracts in English and Chinese. / Table of content / ACKNOWLEDGEMENT --- p.i / ABSTRACT --- p.ii / LIST OF ABBREVIATION --- p.vi / TABLE OF CONTENTS --- p.vii / Chapter Chapter1 --- General Introduction / Chapter 1.1 --- INTRODUCTION --- p.1 / Chapter 1.2 --- FORMATION OF CLA --- p.1 / Chapter 1.3 --- OCCURRENCE OF CLA IN FOODS --- p.5 / Chapter 1.4 --- PHYSIOLOGICAL EFFECTS OF CLA --- p.8 / Chapter 1.4.1 --- Anticarcinogenic Effects of CLA --- p.8 / Chapter 1.4.2 --- Antiatherogenic Effect of CLA --- p.11 / Chapter 1.4.3 --- Antioxidant Effect of CLA --- p.12 / Chapter 1.4.4 --- CLA and Immune Response --- p.13 / Chapter 1.4.5 --- CLA and Body Composition --- p.14 / Chapter Chapter2 --- Protective Effect of CLA on Copper-Induced Human LDL Oxidation / Chapter 2.1 --- INTRODUCTION --- p.17 / Chapter 2.1.1 --- Oxidative Modification of LDL and Atherosclerosis --- p.20 / Chapter 2.1.1.1 --- Understanding of LDL --- p.20 / Chapter 2.1.1.2 --- Oxidative Modification of LDL --- p.20 / Chapter 2.1.1.3 --- Role of Oxidative Modified LDL in Atherogenesis --- p.23 / Chapter 2.1.2 --- Antioxidants and Atherosclerosis --- p.25 / Chapter 2.1.3 --- Measuring TBARS Formation as an in vitro Index to Monitor LDL Oxidation --- p.26 / Chapter 2.1.4 --- CLA and Atherogenesis --- p.27 / Chapter 2.2 --- OBJECTIVE OF THE PRESENT STUDY --- p.28 / Chapter 2.3 --- MATERIALS AND METHODS --- p.29 / Chapter 2.3.1 --- Human LDL Isolation --- p.29 / Chapter 2.3.2 --- LDL Oxidation --- p.30 / Chapter 2.3.3 --- Thiobarbituric Acid Reactive Substances (TBARS) Assay --- p.30 / Chapter 2.4 --- STATISTICS --- p.31 / Chapter 2.5 --- RESULTS --- p.32 / Chapter 2.5.1 --- Inhibitory Effect of BSA on Human LDL Oxidation --- p.32 / Chapter 2.5.2 --- Pro-oxidant Effect of LA on Human LDL Oxidation --- p.32 / Chapter 2.5.3 --- Inhibitory Effect of CLA on Human LDL Oxidation --- p.32 / Chapter 2.6 --- DISCUSSION --- p.37 / Chapter 2.6.1 --- Effect ofBSA on Copper-Induced LDL Oxidation --- p.37 / Chapter 2.6.2 --- Effect of LA on Copper-Induced LDL Oxidation --- p.38 / Chapter 2.6.3 --- Protective Effect of CLA on Copper-Induced Human LDL Oxidation --- p.39 / Chapter Chapter3 --- Hypolipidemic Activity of CLA / Chapter 3.1 --- INTRODUCTION --- p.42 / Chapter 3.1.1 --- Total Cholesterol and LDL Cholesterol --- p.42 / Chapter 3.1.2 --- Triglyceride (TG) --- p.44 / Chapter 3.1.3 --- Hypolipidemic Effect of CLA --- p.45 / Chapter 3.1.4 --- Golden Syrian Hamster as an Animal Model of Cholesterol Metabolism --- p.46 / Chapter 3.2 --- OBJECTIVES OF THE PRESENT STUDY --- p.48 / Chapter 3.3 --- MATERIALS AND METHODS --- p.48 / Chapter 3.3.1 --- LA and CLA --- p.49 / Chapter 3.3.2 --- Animals --- p.49 / Chapter 3.3.3 --- Experiment1 --- p.49 / Chapter 3.3.4 --- Experiment2 --- p.51 / Chapter 3.3.5 --- "Determination of Serum TC, HDL-Cholesterol (HDL-C) and TG" --- p.54 / Chapter 3.3.6 --- Lipid analysis of Liver and Adipose Tissue --- p.54 / Chapter 3.3.6.1 --- Lipid Extraction and Separation of Different Lipid Species --- p.54 / Chapter 3.3.6.2 --- Acid-Catalyzed Methylation of Fatty Acids --- p.55 / Chapter 3.3.6.3 --- GLC Analysis of FAME --- p.55 / Chapter 3.3.7 --- Quantification of Tissue Cholesterol --- p.56 / Chapter 3.3.7.1 --- Cholesterol Extraction and Silylation --- p.56 / Chapter 3.3.7.2 --- GLC Analysis of TMS-Ether Derivative of Cholesterol --- p.56 / Chapter 3.4 --- STATISTICS --- p.57 / Chapter 3.5 --- RESULTS --- p.59 / Chapter 3.5.1 --- Body Weight and Food Intake --- p.59 / Chapter 3.5.2 --- "Effect of Dietary CLA Supplementation on Serum TG, TC and HDL-C" --- p.59 / Chapter 3.5.3 --- "Effect of Dietary CLA Supplementation on Hepatic TG, Phospholipid and Cholesterol" --- p.64 / Chapter 3.5.4 --- Effect of Dietary CLA Supplementation on Adipose Tissue TG and Cholesterol --- p.73 / Chapter 3.5.5 --- Effect of CLA Supplementation on Cholesterol Levels of Different Tissues --- p.73 / Chapter 3.6 --- DISCUSSION --- p.79 / Chapter 3.6.1 --- "Effect of CLA Supplementation on Serum TG, TC and HDL-C" --- p.79 / Chapter 3.6.2 --- "Effect of CLA Supplementation on Hepatic TG, PL and Cholesterol" --- p.81 / Chapter 3.6.3 --- Effect of CLA on Adipose Tissue TG and Cholesterol --- p.83 / Chapter 3.6.4 --- Implication of CLA Intake in Humans --- p.84 / Chapter Chapter4 --- Influences of Dietary CLA on Cholesterol Homeostasis / Chapter 4.1 --- INTRODUCTION --- p.86 / Chapter 4.2 --- NEUTRAL EFFECT OF DIETARY CLA SUPPLEMENTATION ON HMG-COA REDUCTASE ACTIVITY --- p.88 / Chapter 4.2.1 --- HMG-CoA Reductase as the Rate-Limiting Enzyme in Cholesterol Synthesis --- p.88 / Chapter 4.2.2 --- Objective of The Present Study --- p.91 / Chapter 4.2.3 --- Materials and Methods --- p.92 / Chapter 4.2.3.1 --- Preparation of Hepatic Microsome --- p.92 / Chapter 4.2.3.2 --- HMG-GoA Reductase Activity Assay --- p.92 / Chapter 4.2.4 --- Statistics --- p.93 / Chapter 4.2.5 --- Results --- p.94 / Chapter 4.2.6 --- Discussion --- p.96 / Chapter 4.3 --- DOWN-REGULATION OF THE INTESTINAL ACAT ACTIVITY BY CLA FEEDING --- p.97 / Chapter 4.3.1 --- Role of ACAT in Cholesterol Absorption --- p.97 / Chapter 4.3.2 --- Objective of The Present Study --- p.99 / Chapter 4.3.3 --- Materials and Methods --- p.100 / Chapter 4.3.3.1 --- Preparation of Intestinal Microsome --- p.100 / Chapter 4.3.3.2 --- ACAT Activity Assay --- p.100 / Chapter 4.3.4 --- Statistics --- p.101 / Chapter 4.3.5 --- Results --- p.102 / Chapter 4.3.6 --- Discussion --- p.104 / Chapter 4.4 --- ALTERATION OF FECAL EXCRETION BY DIETARY CLA --- p.105 / Chapter 4.4.1 --- Objective of The Present Study --- p.108 / Chapter 4.4.2 --- Materials and Methods --- p.109 / Chapter 4.4.2.1 --- Separation of Neutral and Acidic Sterols --- p.109 / Chapter 4.4.2.2 --- Neutral Sterol Analysis --- p.109 / Chapter 4.4.2.3 --- Acidic Sterol Analysis --- p.110 / Chapter 4.4.2.4 --- GLC Analysis of Neutral and Acidic Sterols --- p.110 / Chapter 4.4.3 --- Statistics --- p.113 / Chapter 4.4.4 --- Results --- p.114 / Chapter 4.4.4.1 --- Effect of CLA Supplementation on Fecal Output of Neutral Sterols --- p.114 / Chapter 4.4.4.2 --- Effect of CLA Supplementation on Fecal Output of Acidic Sterols --- p.114 / Chapter 4.4.5 --- Discussion --- p.118 / Chapter Chapter5 --- Conclusions --- p.123 / References --- p.126

Chan Chi Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 100-109). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / List of Abbreviations --- p.v / List of Tables --- p.vi / List of Figures --- p.vii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- "Free radicals, oxidative stress and antioxidants" --- p.2 / Chapter 1.1.1 --- Free radical and ROS --- p.2 / Chapter 1.1.2 --- Oxidative stress --- p.6 / Chapter 1.1.3 --- Antioxidants --- p.8 / Chapter 1.2 --- Plant as a source of antioxidants --- p.13 / Chapter 1.2.1 --- Common food sources of antioxidants --- p.13 / Chapter 1.2.2 --- Legume seeds as antioxidant sources --- p.15 / Chapter 1.3 --- Methods used to evaluate the antioxidant activity --- p.16 / Chapter 1.3.1 --- β-carotene bleaching method --- p.17 / Chapter 1.3.2 --- DPPH. scavenging method --- p.17 / Chapter 1.3.3 --- High-performance liquid chromatograph (HPLC) --- p.18 / Chapter 1.3.4 --- Single cell gel electrophoresis (SCGE) --- p.20 / Chapter 1.4 --- Objectives of the study --- p.22 / Chapter 2 --- Materials and Methods --- p.23 / Chapter 2.1 --- Plant materials and chemicals --- p.23 / Chapter 2.2 --- Sample preparation --- p.23 / Chapter 2.3 --- Determination of antioxidant activity using β-carotene bleaching method --- p.24 / Chapter 2.4 --- Evaluation of free radical scavenging ability --- p.26 / Chapter 2.5 --- HPLC separation of seed extract --- p.27 / Chapter 2.6 --- Evaluation of protective effects of legumes on the DNA damage using the comet assay --- p.28 / Chapter 2.6.1 --- Preparation of reagents --- p.28 / Chapter 2.6.2 --- Blood sample --- p.29 / Chapter 2.6.3 --- Hydrogen peroxide (H2O2) treatment --- p.29 / Chapter 2.6.4 --- Ethidium bromide-acridine orange (Et-Ac) viability determination --- p.31 / Chapter 2.6.5 --- Slide preparation --- p.31 / Chapter 2.6.6 --- Alkaline comet assay --- p.31 / Chapter 2.6.7 --- Quantification of DNA damage --- p.33 / Chapter 2.6.8 --- Statistical analysis --- p.33 / Chapter 3 --- Results --- p.40 / Chapter 3.1 --- General description of 24 selected legume seeds --- p.40 / Chapter 3.1 --- Determination of antioxidant activity using β-carotene bleaching method --- p.40 / Chapter 3.2 --- Evaluation of free radical scavenging ability --- p.43 / Chapter 3.3 --- Evaluation of protective effects of legumes on the DNA damage using the comet assay --- p.45 / Chapter 3.3.1 --- Optimal assay conditions --- p.46 / Chapter 3.3.2 --- Protective effects of seed extract and vitamin C --- p.47 / Chapter 3.3.3 --- Effects of heat treatment on the protective effect --- p.48 / Chapter 4 --- Discussion --- p.84 / Chapter 4.1 --- Methanolic extraction --- p.84 / Chapter 4.2 --- Antioxidant activities determined with β-carotene bleaching method and DPPH' scavenging method --- p.84 / Chapter 4.3 --- Evaluation of protective effects of legumes on the DNA damage using the comet assay --- p.93 / Chapter 4.3.1 --- H202-mediated DNA damage --- p.93 / Chapter 4.3.2 --- Protective effects of seed extracts and vitamin C --- p.94 / Chapter 5 --- Conclusion --- p.98 / References --- p.100

Major depressive disorder (MDD) and suicide have been associated with elevated indices of oxidative damage in the brain, as well as white matter pathology including reduced myelination by oligodendrocytes. Oligodendrocytes highly populate white matter and are inherently susceptible to oxidative damage. Pathology of white matter oligodendrocytes has been reported to occur in brain regions that process behaviors that are disrupted in MDD and that may contribute to suicidal behavior. The present study was designed to determine whether oligodendrocyte pathology related to oxidative damage extends to brain areas outside of those that are traditionally considered to contribute to the psychopathology of MDD and suicide. Relative telomere lengths and the gene expression of five antioxidant-related genes, SOD1, SOD2, GPX1, CAT, and AGPS were measured in oligodendrocytes laser captured from two non-limbic brain areas: occipital cortical white matter and the brainstem locus coeruleus. Postmortem brain tissues were obtained from brain donors that died by suicide and had an active MDD at the time of death, and from psychiatrically normal control donors. Relative telomere lengths were significantly reduced in oligodendrocytes of both brain regions in MDD donors as compared to control donors. Three antioxidant-related genes (SOD1, SOD2, GPX1) were significantly reduced and one was significantly elevated (AGPS) in oligodendrocytes from both brain regions in MDD as compared to control donors. These findings suggest that oligodendrocyte pathology in MDD and suicide is widespread in the brain and not restricted to brain areas commonly associated with depression psychopathology.