The physiological role of LCAT has been the subject of a number of recent articles (Glomset, 1979; Nilsson-Ehle et al., 1980). According to most current theories, the enzyme functions in combination with high-density lipoproteins in the reverse cholesterol transport pathway which presumably returns peripheral cholesterol to the liver where cholesterol catabolism takes place. Despite the exciting potential for studies on the catalytic function and the nature of the enzyme-substrate complex, the mechanism of action of LCAT remains largely unexplored. The relatively slow progress in the elucidation of the LCAT reaction mechanism is likely to be due to the difficulties in the isolation of the enzyme in sufficient quantities. Consequently, considerably less is known about the physical and chemical properties of the enzyme. Therefore, the first objective of this investigation was to isolate and purify sufficient amount of enzyme for subsequent characterization studies. The second objective of this investigation was to characterize the physical properties of the enzyme by techniques including analytical ultracentrifugation, ultraviolet spectroscopy, and circular dichroism and fluorescence spectroscopy. The third objective of this investigation was to characterize the chemical properties of the enzyme which deals with the amino acid and carbohydrate composition and with some basic structural features that are related to the chemical composition of LCAT.

No description available.

Total and high-density lipoprotein cholesterol (TC and HDL-C) and TC/HDL-C ratio were compared in 30 adult male recreational swimmers and 21 sedentary controls. Percentage of body fat, number of cigarettes smoked daily, and daily alcohol consumption were assessed for both groups. Maximum workout heartrate, weekly swim duration and weekly swim distance of the swimmers were also measured. Maximum workout heartrate (mean ± S. D. ) was 140 ± 24 beats per minute . Mean weekly swim duration was 142 ± 84 minutes, and mean weekly swim distance was 5317 ± 3217 yards. Swimmers and controls were nonsignificantly different in age, number of cigarettes smoked daily, and percent body fat. In this sample, the swimmers consumed significantly higher levels of alcohol than the non-swimmers. TC and HDL-C concentrations of swimmers were not significantly different than controls, (204 vs 199 mg/dl, and 48 vs 47 mg/dl, respectively). TC/HDL-C ratio of swimmers was 4.69, while that of controls was 4.65. This study showed that adult male recreational swimmers who train at low intensity do not differ significantly in total and HDL-C or TC/HDL-C ratio from male sedentary controls. / M.S.

The effect of diets with various dietary fiber sources on the plasma lipids, liver cholesterol, the histology of the gastrointestinal tract, heart, liver and kidney and the fecal neutral steroid excretion was investigated in hamsters. 155, 9-11 wk old, male Golden-syrian hamsters were fed a purified basal hypercholesterolemic diet (0.1% cholesterol, 10% fat, 4% dietary fiber) for 5 wk to elevate plasma lipid levels. Based on wk 4 plasma total cholesterol (TC) levels hamsters with elevated levels were randomly assigned, 16 animals/group, into six groups for another 4 wk: control, oat bran, guar gum, cellulose, xylan and sacrifice. After 4 wk of the fiber diets (10% dietary fiber), the plasma TC levels were significantly lowered in the oat bran, guar gum and xylan groups (16%, 12% and 15%, respectively) (p<.05). They were also significantly lower than the control and cellulose groups. Plasma HDL-C concentrations tended to be lower in all the treatment groups, but was significantly decreased only in the guar gum group (12%) (p<.05). The combined plasma VLDL-C + LDL-C was significantly lowered by the oat bran, cellulose and xylan diets (38%, 40% and 34%, respectively) (p<.05). The liver cholesterol concentration increased significantly from 1 mg cholesterol/g liver to 4.1 mg cholesterol/g liver (p<.05) after 4 wk of the control diet; this was further increased significantly only in the cellulose group (5.6 mg cholesterol/g liver), while the other treatment groups showed no significant changes or differences compared to the control diet group (wk 4). The total fecal neutral steroid excretion was significantly (p<.05) higher in the oat bran group compared to the other treatment groups. No major differences were observed in the tissue histology of the animals in the different treatment groups. In the present study, it appeared that oat bran, guar gum and xylan were effective hypocholesterolemic agents; however, their mechanism of action is still not clear. / Ph. D.

Research has reported that increased levels of plasma TC are directly related, while low levels of plasma HDL-C are inversely related, to coronary heart disease. Regular physical exercise has been suggested as a method for reducing plasma TC and increasing plasma HDL-C. Thirty-one healthy, sedentary women (ages 18-30) were studied to determine the effects of a jogging, weight training, or a combined jogging and weight training program on plasma total cholesterol, high-density lipoproteins, body composition. Experimental subjects were randomly assigned to the treatment conditions. The subjects trained three days a week for nine weeks. The R group ran for 30 minutes a session at 75% predicted maximum HR. The W group trained with weights utilizing exercises to strengthen all major muscle groups for one hour at 60% one repetition maximum the first 3 weeks and 75% one repetition maximum weeks 4 - 9. The RW group ran for 25 minutes a session at 75% predicted maximum HR, then lifted weights using the leg-strengthening exercises for 30 minutes, similar to the W group. Preceding and following the treatment period, plasma TC, HDL-C, body weight, and percent body fat was assessed for all four groups. Plasma TC was not significantly altered, although a downward trend was observed for all three treatment groups. Plasma HDL-C did not change over the treatment period for any group. The plasma TC/HDL-C ratio changed significantly among groups over the treatment period, with the R group decreasing their ratio from 3.5 to 2.9 (p < .05). No changes were noted In percent body fat, fat-free mass, or body weight for any of the groups. The Pearson product-moment correlations performed between the changes in blood lipids and the changes in body composition found no significant relationships. The results of this study indicate that an exercise program consisting of endurance training for 30 minutes, 3 times per week, or weight training for one hour, 3 times per week, or a combination aerobic/weight training program 3 times per week is not adequate to significantly improve plasma TC or HDL-C in young females over a nine week period. However, significant improvements may be made in the plasma TC/HDL-C ratio which may decrease the risk for CHD. / Master of Science

No / Gram-positive bacterial lipoproteins are a functionally diverse and important class of peripheral membrane proteins. Recent advances in molecular biology and the availability of whole genome sequence data have overturned many long-held assumptions about the export and processing of these proteins, most notably the recent discovery that not all lipoproteins are exported as unfolded substrates through the general secretion pathway. Here, we review recent discoveries concerning the export and processing of these proteins, their role in virulence in Gram-positive bacteria and their potential as vaccine candidates or targets for new antimicrobials. / Biotechnology and Biological Sciences Research Council (grant numbers F009224/1, F009429/1, EGH16082), the Medical Research Council (MRC), the Commission of the European Community (grant LSHG-CT-2004–005257) and The Royal Society.

Como demonstrado em estudos prévios, quando injetada em indivíduos, a microemulsão lipídica rica em colesterol sem proteína (LDE) que mimetiza a composição da LDL adquire apoE no plasma e é captada por receptores de LDL. No presente estudo, a LDE marcada com colesterol-H3(CL) e oleato de colesterol-C14(OC) foi injetada em 20 pacientes com doença arterial coronária antes da cirurgia de revascularização miocárdica. Fragmentos de aorta, artéria radial, artéria torácica interna, veia safena e pericárdio descartados durante a cirurgia foram coletados e analisados para radioatividade juntos com amostras seriadas de plasma. A contagem radioativa de LDE-OC foi maior do que a de LDE-CL em todas amostras de plasma coletadas durante 24h, entretanto a captação de LDE-CL foi expressivamente maior do que a do OC em todos os fragmentos. A captação de LDE-CL pela aorta foi cinco vezes maior do que a de LDE-OC (p=0,0379), quatro vezes maior na artéria torácica interna (p=0,033), dez vezes maior na veia safena (p=0,006) e quatro vezes maior no pericárdio (p=0,010). Apenas na artéria radial a captação não obteve significância estatística (p=0,053). Os estudos in vitro de captação celular, bloqueio e das marcações imuno-histoquímicas confirmaram os achados in vivo. Concluindo, a expressiva captação vascular do CL comparada com à do OC sugere que o CL dissocia-se a partir das partículas da microemulsão e precipita-se nos vasos. Considerando a LDE como um modelo de microemulsão artificial para a LDL, os resultados sugerem que este tipo de deposição do CL na parede vascular pode constituir um novo mecanismo para a aterogênese. / As shown in previous studies, when injected into subjects, a protein-free cholesterol-rich microemulsion (LDE) that mimics LDL composition acquires apoE in the plasma and is taken-up by LDL receptors. In the current study, LDE labeled with H3-Cholesterol (FC) and C14-Cholesteryl Oleate(CO) was injected into 20 coronary artery disease patients 24h before myocardial revascularization surgery. Fragments of aortic, radial, internal thoracic arteries, safenous vein and pericardium discarded during surgery were collected and analyzed for radioactivity together with serial plasma samples. The radioactive counting of LDE-CO was greater than that of LDE-FC in all the plasma samples collected over 24h, but the uptake of LDE-FC was markedly greater than that of CO in all fragments. The uptake of LDE-FC by aorta was 5-fold greater than that of LDE-CO (p=0,0379), 4-fold greater in the internal thoracic artery (p=0,033), 10-fold greater in safenous vein (p=0,006) and 4-fold greater in pericardium (p=0,010). Only in the radial artery the uptake didn\'t attains statistical significance (p=0,053). The in vitro studies of cell uptake, blocking and immunohistochemistry marks confirm the in vivo finds. In conclusion, the remarkably greater vessel tissue uptake of FC compared with CO suggests that FC dissociate from the microemulsion particles and precipitate in the vessels. Considering LDE as an artificial microemulsion model for LDL, the results suggests that this type of FC deposition in the arterial wall, might constitute a novel atherogenic mechanism.

Ng Chi Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 147-160). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.VII / TABLE OF CONTENTS --- p.IX / Chapter CHAPTER 1 --- GENERAL INTRODUCTION / Chapter 1.1 --- Introduction of Low-density lipoprotein --- p.1 / Chapter 1.1.1 --- What are lipids? --- p.1 / Chapter 1.1.2 --- Function and structure of cholesterol --- p.1 / Chapter 1.1.3 --- Function and classification of lipoprotein --- p.1 / Chapter 1.2 --- Functions of low-density lipoprotein --- p.2 / Chapter 1.3 --- Basic structure of low-density lipoprotein --- p.4 / Chapter 1.4 --- Principle on isolation and purification of low-density lipoprotein --- p.4 / Chapter 1.5 --- Cholesterol transport system --- p.7 / Chapter 1.5.1 --- Exogenous pathway of cholesterol metabolism --- p.7 / Chapter 1.5.2 --- Endogenous pathway of cholesterol metabolism --- p.7 / Chapter 1.5.3 --- Reverse transport of Cholesterol --- p.8 / Chapter 1.6 --- Oxidation of LDL --- p.10 / Chapter 1.6.1 --- Agents that causes oxidation --- p.10 / Chapter 1.6.1.1 --- Lipoxygenases --- p.10 / Chapter 1.6.1.2 --- Myeloperoxidase --- p.10 / Chapter 1.6.1.3 --- Reactive nitrogen species --- p.11 / Chapter 1.6.1.4 --- Reactive oxygen species --- p.11 / Chapter 1.6.2 --- Factors that affect the susceptibility of LDL oxidation --- p.13 / Chapter 1.7 --- Hyperlipidaemia 一 chance to increase LDL oxidation --- p.13 / Chapter 1.7.1 --- Definition of hyperlipidemia and hypercholesterolemia --- p.13 / Chapter 1.7.2 --- Risk factors of hyperlipidaemia --- p.13 / Chapter 1.7.2.1 --- High fat low fibre diets: --- p.13 / Chapter 1.7.2.2 --- Obesity --- p.14 / Chapter 1.7.2.3 --- Type II diabetes --- p.14 / Chapter 1.7.2.4 --- Genetic factors (Familial hyperlipidemias) --- p.14 / Chapter 1.8 --- Diseases related to oxidized LDL --- p.15 / Chapter 1.8.1 --- Cardiovascular diseases --- p.15 / Chapter 1.8.1.1 --- Atherosclerosis and ischemic heart attack --- p.15 / Chapter 1.8.1.2 --- Factors that affect incidence of atherosclerosis --- p.16 / Chapter 1.8.1.2.1 --- Triglyceride-rich lipoprotein --- p.16 / Chapter 1.8.1.2.2 --- Small and dense LDL --- p.16 / Chapter 1.8.1.3 --- Stroke --- p.17 / Chapter 1.8.2 --- Common ways to reduce plasma cholesterol level --- p.17 / Chapter 1.8.2.1 --- Diet control --- p.17 / Chapter 1.8.2.2 --- Physical activity --- p.17 / Chapter 1.8.2.3 --- Drug therapy --- p.18 / Chapter CHAPTER 2 --- IMPAIRMENT OF OXIDIZED LDL ON ENDOTHELIUM-DEPENDENT RELAXATION / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- Properties and function of phenylephrine hydrochloride --- p.22 / Chapter 2.1.2 --- Properties and function of acetylcholine --- p.22 / Chapter 2.2 --- Objectives --- p.23 / Chapter 2.3 --- Materials and methods --- p.24 / Chapter 2.3.1 --- Preparation of drugs --- p.24 / Chapter 2.3.2 --- Preparation of human native LDL --- p.25 / Chapter 2.3.3 --- Preparation of oxidized LDL --- p.27 / Chapter 2.3.4 --- Preparation of aorta --- p.27 / Chapter 2.3.5 --- Measurement of Isometric Force in vitro --- p.30 / Chapter 2.3.5.1 --- Protocol 1- Dose effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.30 / Chapter 2.3.5.2 --- Protocol 2 - Time effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.30 / Chapter 2.3.5.3 --- Protocol 3 - Effect of co-incubation of LDL and copper(ll) sulphate on acetylcholine-induced vasorelaxation --- p.31 / Chapter 2.3.5.4 --- Protocol 4 - Effect of oxidized LDL on selected vasodilators --- p.32 / Chapter 2.3.5.5 --- Protocol 5 - Effect of pretreatment of L-arginine on oxidized LDL impaired -endothelium-induced relaxation --- p.32 / Chapter 2.3.5.6 --- Protocol 6 - Effect of a -tocopherol on oxidized LDL-damaged acetylcholine- induced vasorelaxation --- p.33 / Chapter 2.3.5.7 --- Protocol 7 - Effect of a -tocopherol on LDL and copper(ll) sulphate- induced endothelial dysfunction --- p.33 / Chapter 2.3.6 --- Western blot analysis of endothelial nitric oxide synthase (eNOS) protein --- p.34 / Chapter 2.3.7 --- Statistics --- p.35 / Chapter 2.4 --- Results --- p.36 / Chapter 2.4.1 --- Dose effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.36 / Chapter 2.4.2 --- Time effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.36 / Chapter 2.4.3 --- Effect of co-incubation of LDL and copper(II) sulphate on acetylcholine- induced vasorelaxation --- p.39 / Chapter 2.4.4 --- Effect of oxidized LDL on selected vasodilators --- p.41 / Chapter 2.4.5 --- Effect of pretreatment of L-arginine on oxidized LDL impaired- acetylcholine-induced relaxation --- p.41 / Chapter 2.4.6 --- Effect of a-tocopherol on oxidized LDL-damaged acetylcholine- induced vasorelaxation --- p.48 / Chapter 2.4.7 --- Effect of a-tocopherol on LDL and copper(II) sulphate-induced endothelial dysfunction --- p.50 / Chapter 2.4.8 --- eNOS Protein expression --- p.50 / Chapter 2.5 --- Discussion --- p.53 / Chapter CHAPTER 3 --- EFFECTS OF LDL INJECTION ON THE ENDOTHELIAL FUNCTION OF RATS / Chapter 3.1 --- Introduction --- p.58 / Chapter 3.2 --- Objective --- p.60 / Chapter 3.3 --- Methods and Materials --- p.61 / Chapter 3.3.1 --- Preparation of Drugs --- p.61 / Chapter 3.3.2 --- Preparation of LDL --- p.61 / Chapter 3.3.3 --- Animal Treatment --- p.61 / Chapter 3.3.4 --- Serum lipid and lipoprotein determinations --- p.62 / Chapter 3.3.5 --- Measurement of serum MDA level by TBARS assay --- p.62 / Chapter 3.3.6 --- Preparation of aorta --- p.62 / Chapter 3.3.7 --- Organ bath experiment --- p.63 / Chapter 3.3.8 --- Statistics --- p.64 / Chapter 3.4 --- Result --- p.65 / Chapter 3.4.1 --- Growth and food intake --- p.65 / Chapter 3.4.2 --- "Effect of LDL injection on serum TC, TG and HDL-C" --- p.65 / Chapter 3.4.3 --- Effect of LDL injection on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.65 / Chapter 3.4.4 --- Serum MDA level --- p.68 / Chapter 3.4.5 --- Phenylephrine-induced contraction --- p.70 / Chapter 3.4.6 --- Endothelium-dependent and -independent relaxation --- p.75 / Chapter 3.5 --- Discussion --- p.79 / Chapter CHAPTER 4 --- EFFECTS OF INDIVIDUAL COMPONENT OF OXIDIZED LDL ON ENDOTHELIUM-DEPENDENT RELAXATION / Chapter 4.1 --- Introduction --- p.83 / Chapter 4.2 --- Objectives --- p.85 / Chapter 4.3 --- Materials and methods --- p.86 / Chapter 4.3.1 --- Preparation of drugs --- p.86 / Chapter 4.3.2 --- Preparation of human native LDL and oxidized LDL --- p.86 / Chapter 4.3.3 --- GC analysis of fatty acid composition in LDL --- p.86 / Chapter 4.3.4 --- TBARS assay analysis of MDA content in LDL --- p.87 / Chapter 4.3.5 --- GC analysis of cholesterol oxidation products in LDL --- p.89 / Chapter 4.3.6 --- Thin-layer chromatography analysis of LPC in LDL --- p.91 / Chapter 4.3.7 --- Preparation of aorta --- p.92 / Chapter 4.3.8 --- Measurement of Isometric Force in vitro --- p.92 / Chapter 4.3.8.1 --- Protocol 1- effect of LPC on acetylcholine-induced vasorelaxation --- p.92 / Chapter 4.3.8.2 --- Protocol 2- effect of cholesterol oxidation products on acetylcholine-induced vasorelaxation --- p.92 / Chapter 4.3.8.3 --- Protocol 3- effect of oxidized fatty acids on acetylcholine-induced vasorelaxation --- p.93 / Chapter 4.3.9 --- Statistics --- p.93 / Chapter 4.4 --- Results --- p.94 / Chapter 4.4.1 --- Compositional differences between native LDL and oxidized LDL.… --- p.94 / Chapter 4.4.2 --- Effect of LPC on endothelium-dependent relaxation --- p.98 / Chapter 4.4.3 --- Effect of COPs on endothelium-dependent relaxation --- p.98 / Chapter 4.4.4 --- Effect of oxidized fatty acids on endothelium-dependent relaxation --- p.101 / Chapter 4.5 --- Discussion --- p.103 / Chapter CHAPTER 5 --- EFFECTS OF DIETARY OXIDIZED CHOLESTEROL ON BLOOD CHOLESTEROL LEVEL IN HAMSTERS / Chapter 5.1 --- Introduction --- p.107 / Chapter 5.2 --- Objectives --- p.111 / Chapter 5.3 --- Materials and Methods --- p.112 / Chapter 5.3.1 --- Preparation of Oxidized Cholesterol --- p.112 / Chapter 5.3.2 --- Diet preparation --- p.112 / Chapter 5.3.3 --- Animals --- p.113 / Chapter 5.3.4 --- Serum lipid and lipoprotein determinations --- p.116 / Chapter 5.3.5 --- GC analysis of cholesterol and cholesterol oxidation products on organs --- p.116 / Chapter 5.3.6 --- Extraction of neutral and acidic sterols from fecal samples --- p.117 / Chapter 5.3.6.1 --- Determination of neutral sterols --- p.117 / Chapter 5.3.6.2 --- Determination of acidic sterols --- p.117 / Chapter 5.3.6.3 --- GLC analysis of neutral and acidic sterols --- p.118 / Chapter 5.3.7 --- Organ bath experiment --- p.121 / Chapter 5.3.7.1 --- Preparation of aorta --- p.121 / Chapter 5.3.7.2 --- Aortic relaxation --- p.121 / Chapter 5.3.8 --- Analysis of the total area of atherosclerotic plaque on aorta --- p.122 / Chapter 5.3.9 --- Statistics --- p.122 / Chapter 5.4 --- Results --- p.123 / Chapter 5.4.1 --- GC of oxidized cholesterol --- p.123 / Chapter 5.4.2 --- Growth and food intake --- p.123 / Chapter 5.4.3 --- "Effect of non-oxidized and oxidized cholesterol on serum TC, TG and HDL-C" --- p.123 / Chapter 5.4.4 --- Effect of non-oxidized and oxidized cholesterol on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.124 / Chapter 5.4.5 --- Effect ofnon-oxidized and oxidized cholesterol on concentration of hepatic cholesterol --- p.128 / Chapter 5.4.6 --- Effect of non-oxidized and oxidized cholesterol on concentration of cholesterol oxidation products accumulated in liver --- p.128 / Chapter 5.4.7 --- Effect of non-oxidized and oxidized cholesterol on concentration of brain and aortic cholesterol --- p.128 / Chapter 5.4.8 --- Effect of non-oxidized and oxidized cholesterol on fecal neutral and acidic sterols --- p.129 / Chapter 5.4.9 --- Effect of non-oxidized and oxidized cholesterol on aortic relaxation --- p.135 / Chapter 5.4.10 --- Effect of non-oxidzied and oxidized cholesterol on area of atherosclerotic plaque --- p.137 / Chapter 5.5 --- Discussion --- p.139 / Chapter CHAPTER 6 --- CONCLUSION --- p.143 / REFERENCES --- p.146

Chung, Jennifer Siu Toye. / "June 2008." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 145-157). / Abstracts in English and Chinese, some text in appendix also in Chinese. / Abstract of Thesis in English --- p.i / Abstract of Thesis in Chinese --- p.iii / Acknowledgments --- p.v / List of Tables --- p.xi / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / List of Publications and Presentations related to Thesis --- p.xvi / Contributions related to Thesis --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Introduction of the Thesis --- p.1 / Chapter 1.2 --- Review on Coronary Heart Disease --- p.3 / Chapter 1.2.1 --- Definition of Coronary Heart Disease --- p.3 / Chapter 1.2.2 --- Risk factors for the development of Coronary Heart Disease --- p.3 / Chapter 1.2.3 --- Worldwide Figures for Coronary Heart Disease --- p.9 / Chapter 1.2.4 --- Coronary Heart Disease in Asia Pacific --- p.10 / Chapter 1.2.5 --- Coronary Heart Disease in Hong Kong --- p.11 / Chapter 1.3 --- Dyslipidaemia --- p.14 / Chapter 1.3.1 --- Lipid Transport and Lipoprotein Metabolism --- p.14 / Chapter 1.3.2 --- Definition and Classification of Dyslipidaemia --- p.16 / Chapter 1.3.3 --- Coronary Heart Disease and Dyslipidaemia --- p.17 / Chapter 1.3.4 --- Lifestyle Modifications for the Management of Dyslipidaemia --- p.19 / Chapter 1.3.4.1 --- Dietary Measures --- p.20 / Chapter 1.3.4.2 --- Cigarette Smoking --- p.23 / Chapter 1.3.4.3 --- Physical Activity --- p.24 / Chapter 1.3.4.4 --- Weight Control --- p.25 / Chapter 1.3.5 --- Lipid-lowering Drug Therapy for Dyslipidaemia --- p.29 / Chapter 1.3.5.1 --- Statins --- p.31 / Chapter 1.3.5.2 --- Bile Acid Sequestrants --- p.35 / Chapter 1.3.5.3 --- Fibrates --- p.36 / Chapter 1.3.5.4 --- Ezetimibe --- p.37 / Chapter 1.3.5.5 --- Nicotinic Acid Group --- p.38 / Chapter 1.4 --- International Guidelines for Dyslipidaemic Management --- p.39 / Chapter 1.4.1 --- National Service Framework for Coronary Heart Disease (UK) --- p.39 / Chapter 1.4.1.1 --- National Service Framework Lipid-lowering Goals --- p.40 / Chapter 1.4.1.2 --- The Joint British Societies' Guidelines --- p.41 / Chapter 1.4.1.3 --- Achievement of the NSF Lipid Profile Targets --- p.42 / Chapter 1.4.2 --- National Cholesterol Education Program (United States) --- p.43 / Chapter 1.4.2.1 --- The Third Report of the National Cholesterol Education Program --- p.43 / Chapter 1.4.2.2 --- Review of Clinical Trials --- p.43 / Chapter 1.4.2.3 --- Low-Density Lipoprotein Cholesterol Goal Targets --- p.46 / Chapter 1.4.2.4 --- Compliance with the NCEP ATP III Guidelines --- p.48 / Chapter 1.4.3 --- Dyslipidaemic Guidelines for Study --- p.51 / Chapter 1.5 --- Clinical Pharmacy Services --- p.52 / Chapter 1.5.1 --- The Healthcare System in Hong Kong --- p.52 / Chapter 1.5.2 --- Clinical Pharmacy Services in Hong Kong --- p.54 / Chapter 1.5.3 --- Examples of successful Clinical Pharmacy Services --- p.55 / Chapter 1.5.3.1 --- Hypertension Clinic --- p.55 / Chapter 1.5.3.2 --- Diabetes Mellitus Clinic --- p.56 / Chapter 1.5.3.3 --- Smoking Cessation Clinic --- p.57 / Chapter 1.5.3.4 --- Anticoagulation Clinic --- p.57 / Chapter 1.5.3.5 --- Haematology-oncology Clinic --- p.57 / Chapter 1.5.4 --- Pharmacist-managed Lipid Clinics --- p.58 / Chapter 1.6 --- Objective & General Aims of the Study --- p.60 / Chapter 1.6.1 --- Objectives --- p.60 / Chapter 1.6.2 --- Study Hypothesis --- p.60 / Chapter 1.6.3 --- General Aims of the Study --- p.60 / Chapter Chapter 2 --- Methodology of Study --- p.62 / Chapter 2.1 --- Background Setting --- p.62 / Chapter 2.2 --- Subject Selection and Recruitment --- p.62 / Chapter 2.3 --- Intervention and Control Groups --- p.63 / Chapter 2.4 --- Validation of Survey --- p.67 / Chapter 2.5 --- Data Collection --- p.67 / Chapter 2.6 --- Outcome Measures --- p.68 / Chapter 2.6.1 --- Lipid value changes --- p.68 / Chapter 2.6.2 --- Compliance rate with medications --- p.68 / Chapter 2.6.3 --- Patient satisfaction survey assessment --- p.69 / Chapter 2.6.4 --- Time spent and Cost of clinical pharmacist --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter 2.7.1 --- Sample Size Calculation --- p.70 / Chapter 2.7.2 --- Methods of Statistical Analysis --- p.71 / Chapter Chapter 3 --- Results of Study --- p.72 / Chapter 3.1 --- Recruitment Details --- p.72 / Chapter 3.2 --- Demographic Characteristics of Patients --- p.73 / Chapter 3.3 --- Drug Therapy of Patients during Study Period --- p.75 / Chapter 3.4 --- LDL-C Lowering Potency of Statin Doses Prescribed --- p.80 / Chapter 3.5 --- Coronary Heart Disease Risk Category of Patients --- p.84 / Chapter 3.6 --- Lipid Profile Changes --- p.85 / Chapter 3.7 --- NCEP ATP III LDL-C Goal Attainment --- p.87 / Chapter 3.8 --- Relationship between Patient Characteristics and LDL-C Goal Attainment --- p.91 / Chapter 3.9 --- Compliance with Medications --- p.94 / Chapter 3.10 --- Pharmacist Intervention --- p.98 / Chapter 3.10.1 --- Range of Pharmacist Intervention --- p.98 / Chapter 3.10.2 --- Time spent by Pharmacist --- p.100 / Chapter 3.10.2.1 --- Time spent on Documentation --- p.100 / Chapter 3.10.2.2 --- Time spent on Direct Communication with Patients --- p.101 / Chapter 3.10.3 --- Cost of Clinical Pharmacy Service at the Lipid Clinic --- p.102 / Chapter 3.10.3.1 --- Cost of Pharmacist Involvement --- p.102 / Chapter 3.10.3.2 --- Potential Healthcare Cost Saving --- p.103 / Chapter 3.11 --- Clinical Pharmacy Service Satisfaction Survey --- p.105 / Chapter 3.11.1 --- Validation of Survey --- p.105 / Chapter 3.11.2 --- Questionnaire Survey for Intervention and Control Groups --- p.107 / Chapter 3.11.3 --- Physician Questionnaire Survey on Clinical Pharmacy Service --- p.110 / Chapter Chapter 4 --- Discussion --- p.111 / Chapter 4.1 --- Clinical Outcomes of Study --- p.111 / Chapter 4.1.1 --- Changes in Lipid Parameters --- p.111 / Chapter 4.1.2 --- Reduction in CHD risk --- p.113 / Chapter 4.1.3 --- Attainment in NCEP ATP III LDL-C goals --- p.114 / Chapter 4.1.4 --- Predictors for LDL-C Goal Attainment --- p.117 / Chapter 4.2 --- Drug-related Problems --- p.119 / Chapter 4.2.1 --- Statin Dosing and LDL-C Lowering Potency --- p.119 / Chapter 4.2.2 --- Adherence to Drug Therapy --- p.121 / Chapter 4.2.3 --- Polypharmacy --- p.126 / Chapter 4.2.4 --- Adverse Drug Events and Drug Interactions --- p.129 / Chapter 4.2.5 --- Patient Busy Lifestyle --- p.131 / Chapter 4.3 --- Role of Clinical Pharmacist --- p.133 / Chapter 4.3.1 --- Role of Pharmacist --- p.133 / Chapter 4.3.2 --- Multidisciplinary Team --- p.135 / Chapter 4.3.3 --- Healthcare Cost Saving --- p.137 / Chapter 4.4 --- Limitations of Study --- p.139 / Chapter 4.5 --- Further Study --- p.142 / Chapter Chapter 5 --- Conclusion --- p.144 / Chapter 5.1 --- Conclusion of Study --- p.144 / Bibliography --- p.145 / Appendices --- p.158 / Appendix I Data collection form --- p.158 / Appendix II Information sheet on study protocol to patient --- p.160 / Appendix III Patient consent form for study --- p.164 / Appendix IV Framingham risk scoring system for male --- p.165 / Appendix V Framingham risk scoring system for female --- p.166 / Appendix VI Patient educational leaflet --- p.167 / Appendix VII Physician-pharmacist communication sheet --- p.169 / Appendix VIII Telephone checklist --- p.170 / Appendix IX Questionnaire survey provided to Intervention Group --- p.172 / Appendix X Questionnaire survey provided to Control Group --- p.174 / Appendix XI Questionnaire survey provided to Physicians --- p.176

Como demonstrado em estudos prévios, quando injetada em indivíduos, a microemulsão lipídica rica em colesterol sem proteína (LDE) que mimetiza a composição da LDL adquire apoE no plasma e é captada por receptores de LDL. No presente estudo, a LDE marcada com colesterol-H3(CL) e oleato de colesterol-C14(OC) foi injetada em 20 pacientes com doença arterial coronária antes da cirurgia de revascularização miocárdica. Fragmentos de aorta, artéria radial, artéria torácica interna, veia safena e pericárdio descartados durante a cirurgia foram coletados e analisados para radioatividade juntos com amostras seriadas de plasma. A contagem radioativa de LDE-OC foi maior do que a de LDE-CL em todas amostras de plasma coletadas durante 24h, entretanto a captação de LDE-CL foi expressivamente maior do que a do OC em todos os fragmentos. A captação de LDE-CL pela aorta foi cinco vezes maior do que a de LDE-OC (p=0,0379), quatro vezes maior na artéria torácica interna (p=0,033), dez vezes maior na veia safena (p=0,006) e quatro vezes maior no pericárdio (p=0,010). Apenas na artéria radial a captação não obteve significância estatística (p=0,053). Os estudos in vitro de captação celular, bloqueio e das marcações imuno-histoquímicas confirmaram os achados in vivo. Concluindo, a expressiva captação vascular do CL comparada com à do OC sugere que o CL dissocia-se a partir das partículas da microemulsão e precipita-se nos vasos. Considerando a LDE como um modelo de microemulsão artificial para a LDL, os resultados sugerem que este tipo de deposição do CL na parede vascular pode constituir um novo mecanismo para a aterogênese. / As shown in previous studies, when injected into subjects, a protein-free cholesterol-rich microemulsion (LDE) that mimics LDL composition acquires apoE in the plasma and is taken-up by LDL receptors. In the current study, LDE labeled with H3-Cholesterol (FC) and C14-Cholesteryl Oleate(CO) was injected into 20 coronary artery disease patients 24h before myocardial revascularization surgery. Fragments of aortic, radial, internal thoracic arteries, safenous vein and pericardium discarded during surgery were collected and analyzed for radioactivity together with serial plasma samples. The radioactive counting of LDE-CO was greater than that of LDE-FC in all the plasma samples collected over 24h, but the uptake of LDE-FC was markedly greater than that of CO in all fragments. The uptake of LDE-FC by aorta was 5-fold greater than that of LDE-CO (p=0,0379), 4-fold greater in the internal thoracic artery (p=0,033), 10-fold greater in safenous vein (p=0,006) and 4-fold greater in pericardium (p=0,010). Only in the radial artery the uptake didn\'t attains statistical significance (p=0,053). The in vitro studies of cell uptake, blocking and immunohistochemistry marks confirm the in vivo finds. In conclusion, the remarkably greater vessel tissue uptake of FC compared with CO suggests that FC dissociate from the microemulsion particles and precipitate in the vessels. Considering LDE as an artificial microemulsion model for LDL, the results suggests that this type of FC deposition in the arterial wall, might constitute a novel atherogenic mechanism.