Recent studies indicated that Atherosclerosis was thought to the resulted from high blood lipid and oxidative stress. Dioscorea has been recognized as an edible medicinal herb as well as healthy plant. Related studies showed that Taiwannative yam (Dioscorea) exhibited hypoglycemic, antioxidative and hypolipidemic functions. However, researches regarding the best species of native Dioscorea revealing the efficacy with both antioxidative and hypolipidemic functions are limited. Previously our laboratory, found that three in five native species of Dioscorea provided by the Agricultural Research Institute had antioxidative effects. The goal of this study was to investigate the effects of this three Dioscorea species (TA01¡BTA03¡BTA05) on lipid metabolism and antioxidative ability of hamsters. Hyperlipidemia hamsters induced by feeding high fat and high cholesterol diet for 3 weeks, were randomly divided into five groups. Group 1 was the control group fed with a high fat and high cholesterol diet (HF, 0.2% cholesterol and 12% fat) ; group 2 was the positive control group fed with a HF diet supplemented with 0.08% atorvastatin (HF+ATS) ; group 3 was TA01 group fed with a HF diet supplemented with 10% TA01 yam powder (HF+TA01) ; group 4 was TA03 group fed with a HF diet supplemented with 10% TA03 yam powder (HF+TA03) ; group 5 was TA05 group fed with a HF diet supplemented with 10% TA05 yam powder (HF+TA05). The experiment was conducted for 12 weeks. Blood was collcted to determine serum total cholesterol (TC) and triglycerol (TG) at week 4 and 8. The hamsters were scarified and the blood, liver and epididymal fat pads were collected at week 12. The weight of body, liver, epididymal fat pads ; Serum TC, TG, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and oxidation of LDL (thiobarbituric acid reactive substances, TBARS) were determined ; TC, TG, TBARS, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) of liver were also analyzed. Results indicated that TA01 group had significantly decreased serum TG (P < 0.05) at 4 and 8 weeks. Serum TC and TG of TA03 group were significantly lower than those of the control group at 8 weeks. No significant difference for TC and TG was found between TA05 and the control groups. After 12 weeks of Dioscorea feeding, liver weight and liver to body weight ratio of TA01 and TA03 groups compared to that of control group were significantly reduced. Epididymal fat pads weight and that the body weight ratio tended to be less compared to that of the control group. Serum TG concentration of TA01 was significantly decreased to 89% of the control group. Serum TC, TG and LDL-C concentrations of TA03 group were significantly decreased to 82, 89 and 83% of the control group, respectively. Serum HDL-C of TA03 group was unaffected and LDL TBARS tended to be decreased (1.67 ¡Ó 0.79 vs. 1.06 ¡Ó 0.57) compared to that of the control group. Liver TC concentrations of TA01 and TA03 groups both were significantly decreased to 88% of the control group. Liver TG and TBARS of TA01 and TA03 groups were unchanged. Catalase activities of TA01 and TA03 groups and GR activity of TA01 group were significantly higher than those of the control group. No significant differences were found in GPx and SOD activities among all groups. In conclusion, TA01 and TA03 species of Taiwannative yam (Dioscorea) tubers exhibit beneficial effects on lipid profile and antioxidative status for hyperlipidemia induced by a high fat and high cholesterol diet. Among there species, TA03 reveals the best potential with both hypolipidemic and antioxidant effects, and was suggested to be used in the development of functional food for the modification of lipid profile and oxidative status in cardiovascular disease prevention .

Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Social and Clinical Pharmacy The analysis of pharmacotherapy in patients suffering from hyperlipidemia (Diploma Thesis) Mentor of Diploma Thesis Prof. PharmDr. Jiří Vlček, Ph.D. Mavrovouniotis Konstantinos- Parmenion Hradec Králové 2015 ABSTRACT ENGLISH The analysis of pharmacotherapy in patients suffering from hyperlipidemia Mavrovouniotis Konstantinos Mentor: Prof. Dr. Jiří Vlček, CSc. Introduction: Hyperlipidemia is a serious condition whereby the blood levels of lipids, cholesterol and triglycerides are abnormally elevated. This condition is generally asymptomatic but may lead to atherosclerotic heart disease and other types of cardiovascular pathology if not treated effectively. Various risk factors can affect the onset and severity of hyperlipidemia and those include genetic predisposition, hypertension, diabetes mellitus, obesity, poor diet, lack of regular exercise, smoking etc. Measurement and monitoring of blood levels of triglycerides, cholesterol and lipoproteins can be used as prevention method for assessing the risk for an individual to develop hyperlipidemia. Once a patient is diagnosed with the condition several approaches exist for the treatment. The main goal of the treatment is to reduce the risk of...

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

Introdução: Recentes pesquisas têm indicado o enorme potencial de certas substâncias alimentares, como polifenóis antioxidantes e fibras na redução de riscos de doenças crônicas. O bagaço de uva, subproduto do processamento de vinhos e sucos, representa uma ótima fonte de fibras e antioxidantes naturais de baixo custo. Objetivo: Avaliar o potencial hipolipemiante, antioxidante e sensorial de subprodutos do processamento do vinho e do suco. Métodos: Para avaliar a capacidade antioxidante in vitro, foi utilizado o método do DPPH. O potencial antioxidante e hipolipemiante in vivo foi avaliado mediante ensaio biológico, no qual sessenta hamsters foram divididos em seis grupos diferenciados pelas dietas: controle, hiperlipemiante, extrato de bagaço do vinho (BV), extrato de bagaço do suco (BS), suplementada com BV e suplementada com BS. Amostras de sangue e fígado foram coletadas após 4 semanas de experimento para avaliação do perfil lipídico, capacidade de inibição da oxidação de LDL-colesterol (LDL-c) e atividade das enzimas antioxidantes superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Para a avaliação sensorial, foram desenvolvidos sorbet e picolé de BV e BS, cujos atributos sensoriais foram avaliados por 43 pessoas aplicando-se o método afetivo de escala hedônica de 9 pontos. Resultados: Extratos de BV e BS apresentaram uma expressiva capacidade antioxidante in vitro. No modelo animal, os grupos tratados com BV e BS apresentaram uma melhora significativa do perfil lipídico e da atividade da enzima CAT, em relação aos grupos controle e hipercolesterolêmico (p<0,05). Com relação aos valores de SOD, GPx e inibição da oxidação de LDL-c, observou-se melhores resultados em relação ao grupo hipercolesterolêmico, embora não significativamente em todos os grupos tratados. Na análise sensorial, somente o picolé de BV não preencheu totalmente os requisitos de aceitação. Conclusão: Os subprodutos de ambas as espécies de uva apresentaram potencial biológico e sensorial para serem utilizados como ingredientes funcionais. / Introduction: Recent studies have shown the great potential of certain food components such as antioxidant polyphenols and fiber in reducing the risk of chronic diseases. Grape pomace, a wine and juice processing byproduct, is a low cost material and a very good source of fiber and natural antioxidants. Objectives: To evaluate the hypolipidemic, antioxidant and sensory potential of wine and grape byproducts. Methods: To evaluate the in vitro antioxidant capacity, the DPPH method was used. The in vivo antioxidant and hypolipidemic potential was evaluated through an animal model, in which sixty hamsters were divided into six groups according to their diets: control, hyperlipidemic, wine pomace (WP) extract, juice pomace (JP) extract, WP supplemented diet and JP supplemented diet. Samples of blood and liver were collected after a 4-week experimental period to evaluate the lipid profile, ability to inhibit the LDL-cholesterol (LDL-c) oxidation and antioxidant activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes. For the sensory evaluation, BV and BS sorbet and popsicle were developed, and the sensory attributes were evaluated by 43 tasters according to a 9- point affective hedonic scale. Results: WP and JP extracts showed a very good in vitro antioxidant capacity. In the animal model, both WP and JP treated groups presented a significant improvement in the lipid profile and CAT enzyme antioxidant activity in comparison to hypercholesterolemic and control groups (p <0.05). Regarding the values of SOD, GPx and inhibition of LDL-c oxidation, there values were better when compared to hypercholesterolemic group, even though they were not significant in all treated groups. In the sensory evaluation, only the BV popsicle was not fully accepted. Conclusion: Both grapes byproducts showed a biological and sensory potential to be used as functional ingredients.

Yeung Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 136-162). / Abstracts in English and Chinese. / THESIS COMMITTEE --- p.i / ACKNOWLEDGEMENTS --- p.ii / ABSTRACT (ENGLISH) --- p.iii~v / ABSTRACT (CHINESE) --- p.vi~vii / TABLE OF CONTENTS --- p.viii~xiii / LIST OF TABLES --- p.xiv~xv / LIST OF FIGURES --- p.xvi~xviii / LIST OF ABBREVIATIONS --- p.xix~xx / Chapter CHAPTER ONE: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Different lipoproteins and their functions --- p.1 / Chapter 1.1.1 --- Chylomicrons --- p.4 / Chapter 1.1.2 --- VLDL --- p.4 / Chapter 1.1.3 --- LDL --- p.4 / Chapter 1.1.4 --- HDL --- p.5 / Chapter 1.2 --- Risk factors of coronary heart disease (CHD) --- p.5 / Chapter 1.2.1 --- Background information of CHD --- p.6 / Chapter 1.2.2 --- "Relationship between serum total cholesterol (TC), Low-density lipoprotein (LDL) cholesterol and CHD" --- p.7 / Chapter 1.2.3 --- High-density lipoprotein (HDL) cholesterol and CHD --- p.8 / Chapter 1.2.4 --- Triglyceride and CHD --- p.9 / Chapter 1.3 --- Cholesterol homeostasis --- p.10 / Chapter 1.3.1 --- Roles of HMG-CoA reductase in cholesterol biosynthesis --- p.13 / Chapter 1.3.2 --- Roles of cholesterol 7α-hydroxylase (CYP7A) in cholesterol catabolism…… --- p.15 / Chapter 1.3.3 --- Effects of Short-Chain Fatty Acid (SCFA) --- p.17 / Chapter 1.3.4 --- Related hormone --- p.18 / Chapter 1.4 --- Possible mechanisms of hypolipidemic agents --- p.19 / Chapter 1.4.1 --- Hypolipidemic functional foods --- p.20 / Chapter 1.4.2 --- Pharmacological drugs --- p.26 / Chapter 1.5 --- Edible and medicinal mushrooms --- p.28 / Chapter 1.5.1 --- General introduction --- p.28 / Chapter 1.5.2 --- Hypolipidemic agents from Fungi --- p.31 / Chapter 1.6 --- Animal model --- p.35 / Chapter 1.7 --- Objectives --- p.36 / Chapter CHAPTER TWO: --- MATERIALS AND METHODS --- p.37 / Chapter 2.1 --- Materials --- p.37 / Chapter 2.1.1 --- Mushroom samples and control --- p.37 / Chapter 2.1.1.1 --- Sample introduction --- p.37 / Chapter 2.1.1.2 --- Sample collection --- p.40 / Chapter 2.1.1.3 --- Sample preparation --- p.41 / Chapter 2.1.1.4 --- Moisture content --- p.45 / Chapter 2.1.2 --- Animal diets for different experiments --- p.45 / Chapter 2.1.2.1 --- Basal diet --- p.45 / Chapter 2.1.2.2 --- Diet for preliminary screening --- p.46 / Chapter 2.1.2.3 --- Diet for dosage experiment --- p.46 / Chapter 2.1.2.4 --- Diet for active ingredient experiments --- p.47 / Chapter 2.1.2.5 --- Diet for long-term feeding experiment --- p.47 / Chapter 2.1.3 --- Animal model --- p.49 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- Nutritional components of mushroom samples --- p.49 / Chapter 2.2.1.1 --- Crude protein content (Kjeldahl method) --- p.49 / Chapter 2.2.1.2 --- Total dietary fiber content --- p.50 / Chapter 2.2.1.3 --- Crude lipid content --- p.52 / Chapter 2.2.1.4 --- Ash content --- p.53 / Chapter 2.2.1.5 --- Moisture content --- p.53 / Chapter 2.2.2 --- Animal handling experiments --- p.54 / Chapter 2.2.2.1 --- Feeding experiment standards --- p.54 / Chapter 2.2.2.1.1 --- Feeding experiments of preliminary screening test --- p.54 / Chapter 2.2.2.1.2 --- Feeding experiments of dosage test --- p.55 / Chapter 2.2.2.1.3 --- Feeding experiments of solvent extracts from Agrocybe aegerita (Brig) Sing (AA) --- p.56 / Chapter 2.2.2.1.3.1 --- Fractionation of ethanol & water soluble components of AA --- p.56 / Chapter 2.2.2.1.3.2 --- Feeding experiments of ethanol & water soluble components of AA --- p.57 / Chapter 2.2.2.1.4 --- Feeding experiment of long-term test --- p.58 / Chapter 2.2.2.2 --- Blood sample collection --- p.58 / Chapter 2.2.2.3 --- Serum preparation --- p.58 / Chapter 2.2.2.4 --- Liver sample preparation --- p.58 / Chapter 2.2.2.5 --- Fecal sample preparation --- p.59 / Chapter 2.2.3 --- Determination of serum lipid profiles --- p.59 / Chapter 2.2.3.1 --- Serum total cholesterol (TC) assay --- p.59 / Chapter 2.2.3.2 --- Serum triglyceride (TG) assay --- p.60 / Chapter 2.2.3.3 --- Serum high-density lipoprotein (HDL) cholesterol assay --- p.61 / Chapter 2.2.3.3.1 --- Separation of HDL fraction --- p.61 / Chapter 2.2.3.3.2 --- HDL cholesterol (HDL-c) determination --- p.61 / Chapter 2.2.4 --- Determination of liver lipid profiles --- p.62 / Chapter 2.2.4.1 --- Liver total cholesterol (TC) level determination --- p.62 / Chapter 2.2.4.2 --- Determination of liver total lipid (TL) level --- p.64 / Chapter 2.2.5 --- Quantitative determination of fecal neutral & acidic sterols --- p.64 / Chapter 2.2.5.1 --- Separation of fecal neutral & acidic sterols --- p.64 / Chapter 2.2.5.2 --- Derivatisation of fecal neutral sterols --- p.65 / Chapter 2.2.5.3 --- Derivatisation of fecal acidic sterols --- p.65 / Chapter 2.2.5.4 --- Gas chromatographic analysis of fecal neutral & acidic sterols --- p.66 / Chapter 2.2.6 --- Assays of liver key enzymes in cholesterol metabolism --- p.67 / Chapter 2.2.6.1 --- Preparation of hepatic microsome --- p.67 / Chapter 2.2.6.2 --- Assay of HMG-CoA reductase activity --- p.68 / Chapter 2.2.6.3 --- Assay of CYP7A activity --- p.69 / Chapter 2.3 --- Data statistics --- p.71 / Chapter CHAPTER THREE: --- RESULTS AND DISCUSSION --- p.72 / Chapter 3.1 --- Preliminary screening of eleven mushrooms for their hypolipidemic effect in hyperlipidemic S.D. rats --- p.72 / Chapter 3.1.1 --- Body weight and food intake --- p.73 / Chapter 3.1.2 --- Effect of mushroom supplementation on serum lipid profiles --- p.75 / Chapter 3.1.2.1. --- Effect of mushroom supplementation on serum TC levels --- p.75 / Chapter 3.1.2.2. --- Effect of mushroom supplementation on serum TG levels --- p.77 / Chapter 3.1.2.3. --- Effect of mushroom supplementation on serum HDL levels --- p.79 / Chapter 3.1.2.4 --- Discussion of serum lipid profiles of S.D. rats fed M.S. diets in mushroom screening experiments --- p.83 / Chapter 3.1.3 --- Effect and discussion of mushroom supplementation on hepatic lipid profiles --- p.84 / Chapter 3.1.4 --- Effect and discussion of mushroom supplementation on fecal neutral sterol excretion --- p.87 / Chapter 3.1.5 --- Summary (mushroom screening experiments) --- p.90 / Chapter 3.2 --- Hypolipidemic effect of Agrocybe aegerita (Brig.) Sing (AA) in a dose response study in hyperlipidemic S.D. rats --- p.91 / Chapter 3.2.1 --- Nutritional composition of AA mushroom --- p.91 / Chapter 3.2.2 --- Body weight and food intake --- p.91 / Chapter 3.2.3 --- Effect of three different dosages of AA mushroom supplementation on blood lipid profiles of S.D. rats --- p.93 / Chapter 3.2.3.1 --- Effect of different dosages of AA mushroom supplementation diets on serum TC level --- p.93 / Chapter 3.2.3.2 --- Effect of different dosages of AA mushroom supplementation diets on serum TG level --- p.93 / Chapter 3.2.3.3 --- Effect of different dosages of AA mushroom supplementation diets on serum HDL level --- p.95 / Chapter 3.2.3.4 --- Discussion of different dosages of AA mushroom supplementation diets on serum lipid profiles --- p.97 / Chapter 3.2.4 --- Effect and discussion of three different dosages of AA mushroom supplementation on hepatic lipid profiles --- p.98 / Chapter 3.2.5 --- Effect and discussion of three different dosages of AA mushroom supplementation on fecal neutral & acidic sterol excretion --- p.101 / Chapter 3.2.6 --- Summary (dose response study) --- p.105 / Chapter 3.3 --- Hypolipidemic effect of ethanol extract (E.E.) & water extract (W.E.) from AA in hyperlipidemic S.D. rats --- p.106 / Chapter 3.3.1 --- Extraction yield --- p.106 / Chapter 3.3.2 --- Body weight & food intake --- p.106 / Chapter 3.3.3 --- Effect of AA extract supplementation on serum lipid profiles --- p.107 / Chapter 3.3.3.1 --- Effect of AA extract supplementation on serum TC level --- p.107 / Chapter 3.3.3.2 --- Effect of AA extract supplementation on serum TG level --- p.108 / Chapter 3.3.3.3 --- Effect of AA extract supplementation on serum HDL level --- p.109 / Chapter 3.3.4 --- Effect of AA extract supplementation on hepatic lipid profiles --- p.111 / Chapter 3.3.5 --- Effect of AA extract supplementation on fecal neutral & acidic sterols excretion --- p.111 / Chapter 3.3.6 --- Discussion (active fraction extract study) --- p.113 / Chapter 3.4 --- Long-term evaluation of the hypolipidemic effect of AA supplementation in normolipic S.D. rats --- p.116 / Chapter 3.4.1 --- Body weight & food intake --- p.116 / Chapter 3.4.2 --- Effect of long term AA supplementation on serum lipid profiles --- p.117 / Chapter 3.4.2.1 --- Effect of long term AA supplementation on serum TC level --- p.117 / Chapter 3.4.2.2 --- Effect of long term AA supplementation on serum TG level --- p.118 / Chapter 3.4.2.3 --- Effect of long term AA supplementation on serum HDL level --- p.119 / Chapter 3.4.3 --- Effect of long term AA supplementation on hepatic lipid profiles --- p.119 / Chapter 3.4.4 --- Effect of long term AA supplementation on fecal neutral & acidic sterols excretion --- p.121 / Chapter 3.4.5 --- Effect of long term AA supplementation on hepatic key enzymes of cholesterol metabolism ´ؤ HMG-CoA reductase and CYP7A --- p.123 / Chapter 3.4.5.1 --- Quantitation of hepatic microsomal protein --- p.123 / Chapter 3.4.5.2 --- Effect of long term AA supplementation on HMG-CoA reductase activity in S.D. rats --- p.124 / Chapter 3.4.5.3 --- Effect of long term AA supplementation on CYP7A activity in S.D. rats --- p.124 / Chapter 3.4.7 --- Discussion (long-term study) --- p.126 / Chapter CHAPTER FOUR: --- CONCLUSION AND FUTURE PERSPECTIVES --- p.130 / References --- p.136

by Chan Ping Tim Timothy. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 129-141). / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.IV / TABLE OF CONTENTS --- p.VI / Chapter CHAPTER 1 --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- History of tea --- p.1 / Chapter 1.2 --- Botany and agriculture of tea --- p.1 / Chapter 1.3 --- Classification of tea --- p.2 / Chapter 1.4 --- Composition of tea --- p.4 / Chapter 1.5 --- Tea processing --- p.8 / Chapter 1.5.1 --- Manufacture of green tea --- p.8 / Chapter 1.5.2 --- Manufacture of black tea --- p.8 / Chapter 1.5.3 --- Manufacture of oolong tea --- p.10 / Chapter 1.6 --- Pharmacological effects of tea catechins --- p.13 / Chapter 1.6.1 --- Antioxidative activity --- p.13 / Chapter 1.6.2 --- Hypolipidemic activity --- p.14 / Chapter 1.6.3 --- Antimutagenic activity --- p.15 / Chapter 1.6.4 --- Anticarcinogenic activity --- p.15 / Chapter 1.6.5 --- Antibacterial activity --- p.16 / Chapter CHAPTER 2 --- ANTIOXIDATIVE ACTIVITIES OF TEA ETHANOL EXTRACTS AND GTC ON OXIDATION OF CANOLA OIL --- p.18 / Chapter 2.1 --- Introduction --- p.18 / Chapter 2.1.1 --- Lipid oxidation in food --- p.18 / Chapter 2.1.2 --- Phenolic antioxidants --- p.19 / Chapter 2.1.2.1 --- Major phenolic antioxidants used in food --- p.19 / Chapter 2.1.2.2 --- Mechanism of action of phenolic antioxidants --- p.20 / Chapter 2.1.2.3 --- BHA and its safety --- p.22 / Chapter 2.1.2.4 --- BHT and its safety --- p.24 / Chapter 2.1.3 --- Natural antioxidants --- p.24 / Chapter 2.2 --- Objectives --- p.26 / Chapter 2.3 --- Materials --- p.28 / Chapter 2.4 --- Methods --- p.28 / Chapter 2.4.1 --- GTC extraction --- p.28 / Chapter 2.4.2 --- "HPLC analysis of GTC," --- p.29 / Chapter 2.4.3 --- Isolation and purification of individual epicatechin isomers --- p.30 / Chapter 2.4.4 --- Ethanol extraction of tea --- p.30 / Chapter 2.4.5 --- Effect of tea ethanol extracts on oxygen consumption of canola --- p.31 / Chapter 2.4.6 --- Effect of GTC on oxygen consumption of canola oil --- p.32 / Chapter 2.4.7 --- Fatty acid analysis --- p.32 / Chapter 2.4.8 --- Thermal loss of BHT --- p.33 / Chapter 2.4.9 --- Thermal loss of GTC --- p.33 / Chapter 2.4.10 --- Statistics --- p.35 / Chapter 2.5 --- Results --- p.37 / Chapter 2.5.1 --- Antioxidative activities of tea ethanol extracts --- p.37 / Chapter 2.5.2 --- The yield and composition of GTC from jasmine tea --- p.51 / Chapter 2.5.3 --- Antioxidative activity of GTC --- p.55 / Chapter 2.5.4 --- Antioxidative activities of individual epicatechin isomers --- p.55 / Chapter 2.5.5 --- Thermal loss of GTC --- p.60 / Chapter 2.6 --- Discussion --- p.62 / Chapter 2.6.1 --- Contribution of catechins to the antioxidative effects of tea ethanol extracts --- p.62 / Chapter 2.6.2 --- Antioxidaitve activities of different types of teas --- p.62 / Chapter 2.6.3 --- Proposed mechanisms for the relative activity of epicatechin isomers --- p.63 / Chapter 2.6.4 --- Loss of BHT via volatilization --- p.66 / Chapter 2.6.5 --- Potential of tea catechins as food antioxidants --- p.67 / Chapter 2.6.5.1 --- Safety of GTC --- p.67 / Chapter 2.6.5.2 --- Solubility of GTC --- p.68 / Chapter 2.6.5.3 --- Effects of GTC on food quality --- p.68 / Chapter CHAPTER 3 --- INHIBITORY EFFECTS OF GTC AND EPICATECHIN ISOMERS ON IN VITRO CU2+-MEDIATED LDL OXIDATION --- p.70 / Chapter 3.1 --- Introduction --- p.70 / Chapter 3.1.1 --- Mechanisms of LDL oxidation --- p.71 / Chapter 3.1.1.1 --- Nature and sources of oxidants underlying LDL oxidation --- p.71 / Chapter 3.1.1.2 --- Structural changes of ox-LDL --- p.72 / Chapter 3.1.2 --- Biological effects of ox-LDL --- p.74 / Chapter 3.1.3 --- Antioxidants and atherosclerosis --- p.76 / Chapter 3.2 --- Objectives --- p.78 / Chapter 3.3 --- Materials and methods --- p.79 / Chapter 3.3.1 --- LDL isolation --- p.79 / Chapter 3.3.2 --- LDL oxidation --- p.79 / Chapter 3.3.3 --- Thiobarbituric acid-reactive substance (TBARS) assay --- p.80 / Chapter 3.3.4 --- Lipid analysis --- p.80 / Chapter 3.3.5 --- Statistics --- p.81 / Chapter 3.4 --- Results --- p.82 / Chapter 3.4.1 --- Protective effects of GTC against LDL oxidation --- p.82 / Chapter 3.4.2 --- Varying protective effects of individual epicatechin isomers --- p.82 / Chapter 3.4.3 --- Protective effects of GTC against oxidative degradation of PUFAs in LDL --- p.86 / Chapter 3.5 --- Discussion --- p.88 / Chapter 3.5.1 --- Tea catechins as anti-atherogenic agents --- p.88 / Chapter 3.5.2 --- Mechanisms of the protective effects of tea catechins against Cu2+-induced LDL oxidation --- p.88 / Chapter 3.5.3 --- Relative antioxidative activities of epicatchin isomers --- p.89 / Chapter 3.5.4 --- Absorption of tea catechins --- p.90 / Chapter 3.5.5 --- Pro-oxidant activities of tea catechins --- p.91 / Chapter CHAPTER 4 --- HYPOLIPIDEMIC ACTIVITY OF GTC --- p.93 / Chapter 4.1 --- Introduction --- p.93 / Chapter 4.1.1 --- High serum cholesterol as a risk factor of CHD --- p.93 / Chapter 4.1.2 --- Serum TG and CHD --- p.94 / Chapter 4.1.3 --- Hypolipidemic effect of tea --- p.95 / Chapter 4.1.4 --- Hamster as an animal model of cholesterol metabolism --- p.96 / Chapter 4.2 --- Objectives --- p.97 / Chapter 4.3 --- Materials and methods --- p.98 / Chapter 4.3.1 --- Animals --- p.98 / Chapter 4.3.2 --- Experiment 1 --- p.98 / Chapter 4.3.3 --- Experiment 2 --- p.100 / Chapter 4.3.4 --- Experiment 3 --- p.101 / Chapter 4.3.5 --- "Serum lipid, lipoprotein and apolipoprotein determinations" --- p.101 / Chapter 4.3.6 --- Lipid analysis of liver and carcass --- p.102 / Chapter 4.3.7 --- Analysis of fecal lipid content --- p.102 / Chapter 4.3.8 --- Determination of hepatic cholesterol content --- p.103 / Chapter 4.3.9 --- Assay of fatty acid synthase activity --- p.105 / Chapter 4.3.10 --- Statistics --- p.105 / Chapter 4.4 --- Results --- p.106 / Chapter 4.4.1 --- Growth and food intake --- p.106 / Chapter 4.4.2 --- Effects of different levels of dietary GTC on serum TG and cholesterol --- p.106 / Chapter 4.4.3 --- Time course study of the hypolipidemic effects of dietary GTC --- p.109 / Chapter 4.4.4 --- Effects of GTWE on serum lipid and apolipoprotein profiles --- p.113 / Chapter 4.4.5 --- "Effects of dietary GTC on hepatic TG, FFA and cholesterol contents" --- p.113 / Chapter 4.4.6 --- "Effects of dietary GTC on carcass TG, FFA and cholesterol contents" --- p.118 / Chapter 4.4.7 --- Effects of dietary GTC on fatty acid synthase activity --- p.118 / Chapter 4.4.8 --- Effects of dietary GTC on fecal lipids content --- p.118 / Chapter 4.5 --- Discussion --- p.120 / Chapter 4.5.1 --- Hypolipidemic effect of GTC --- p.120 / Chapter 4.5.2 --- Effects of GTC on serum apolipoproteins --- p.120 / Chapter 4.5.3 --- Implication of GTC intake in humans --- p.121 / Chapter 4.5.4 --- Mechanisms for the hypolipidemic activity of GTC --- p.122 / Chapter 4.5.5 --- Reduction in hepatic TG and FFA contents in GTC-fed hamsters --- p.123 / Chapter 4.5.6 --- Suppression of body lipid accumulation by dietary GTC --- p.124 / Chapter 4.5.7 --- Mechanisms for the hypocholesterolemic activity of GTC --- p.124 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.126 / REFERENCES --- p.129

Introdução: Recentes pesquisas têm indicado o enorme potencial de certas substâncias alimentares, como polifenóis antioxidantes e fibras na redução de riscos de doenças crônicas. O bagaço de uva, subproduto do processamento de vinhos e sucos, representa uma ótima fonte de fibras e antioxidantes naturais de baixo custo. Objetivo: Avaliar o potencial hipolipemiante, antioxidante e sensorial de subprodutos do processamento do vinho e do suco. Métodos: Para avaliar a capacidade antioxidante in vitro, foi utilizado o método do DPPH. O potencial antioxidante e hipolipemiante in vivo foi avaliado mediante ensaio biológico, no qual sessenta hamsters foram divididos em seis grupos diferenciados pelas dietas: controle, hiperlipemiante, extrato de bagaço do vinho (BV), extrato de bagaço do suco (BS), suplementada com BV e suplementada com BS. Amostras de sangue e fígado foram coletadas após 4 semanas de experimento para avaliação do perfil lipídico, capacidade de inibição da oxidação de LDL-colesterol (LDL-c) e atividade das enzimas antioxidantes superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Para a avaliação sensorial, foram desenvolvidos sorbet e picolé de BV e BS, cujos atributos sensoriais foram avaliados por 43 pessoas aplicando-se o método afetivo de escala hedônica de 9 pontos. Resultados: Extratos de BV e BS apresentaram uma expressiva capacidade antioxidante in vitro. No modelo animal, os grupos tratados com BV e BS apresentaram uma melhora significativa do perfil lipídico e da atividade da enzima CAT, em relação aos grupos controle e hipercolesterolêmico (p<0,05). Com relação aos valores de SOD, GPx e inibição da oxidação de LDL-c, observou-se melhores resultados em relação ao grupo hipercolesterolêmico, embora não significativamente em todos os grupos tratados. Na análise sensorial, somente o picolé de BV não preencheu totalmente os requisitos de aceitação. Conclusão: Os subprodutos de ambas as espécies de uva apresentaram potencial biológico e sensorial para serem utilizados como ingredientes funcionais. / Introduction: Recent studies have shown the great potential of certain food components such as antioxidant polyphenols and fiber in reducing the risk of chronic diseases. Grape pomace, a wine and juice processing byproduct, is a low cost material and a very good source of fiber and natural antioxidants. Objectives: To evaluate the hypolipidemic, antioxidant and sensory potential of wine and grape byproducts. Methods: To evaluate the in vitro antioxidant capacity, the DPPH method was used. The in vivo antioxidant and hypolipidemic potential was evaluated through an animal model, in which sixty hamsters were divided into six groups according to their diets: control, hyperlipidemic, wine pomace (WP) extract, juice pomace (JP) extract, WP supplemented diet and JP supplemented diet. Samples of blood and liver were collected after a 4-week experimental period to evaluate the lipid profile, ability to inhibit the LDL-cholesterol (LDL-c) oxidation and antioxidant activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes. For the sensory evaluation, BV and BS sorbet and popsicle were developed, and the sensory attributes were evaluated by 43 tasters according to a 9- point affective hedonic scale. Results: WP and JP extracts showed a very good in vitro antioxidant capacity. In the animal model, both WP and JP treated groups presented a significant improvement in the lipid profile and CAT enzyme antioxidant activity in comparison to hypercholesterolemic and control groups (p <0.05). Regarding the values of SOD, GPx and inhibition of LDL-c oxidation, there values were better when compared to hypercholesterolemic group, even though they were not significant in all treated groups. In the sensory evaluation, only the BV popsicle was not fully accepted. Conclusion: Both grapes byproducts showed a biological and sensory potential to be used as functional ingredients.

by Zhang Ze Sheng. / "October 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 157-174). / 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. / Abstracts in English and Chinese.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jan Juhász Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Treatment of lower extremity peripheral artery disease The lower extremities ischemia is a disease caused most often by atherosclerosis during which the lumen in lower limb arteries becomes narrow. Its prevalence is increasing, especially in the developed countries. The disease can be asymptomatic and symptomatic. The symptoms are very unpleasant and decrease patient's quality of life. Advanced stages of the disease may be life threatening. Therefore, it is vital to timely and correctly diagnose the illness. During the therapy, it is possible to use pharmacological as well as non-pharmacological procedures, and, preferably, a combination of the two types of treatment. The pharmacotherapy can be divided into several parts. The prevention of atherosclerotic complications makes use of preventive measures and antiplatelet therapy to reduce the cardiovascular risk. The symptoms therapy focuses on improving patients' quality of life by prescribing the vasoactive medications cilostazol, naftidrofuryl or pentoxifylin. The critical limb ischemia therapy uses prostaglandin analogues alprostadil, iloprost, limaprost or...

Objectif: Définir l’effet des lipides et du traitement de la dyslipidémie sur les cancers de la prostate et de la vessie en utilisant différents devis d’étude et en tenant compte de la présence de plusieurs biais, particulièrement le biais du temps immortel. Devis: Le premier volet utilise un devis rétrospectif de type cas témoins. Un questionnaire semi-quantitatif de fréquence de consommation alimentaire validé a été utilisé. Le génotype COX2 de neuf polymorphisme nucléotidique unique (SNP) a été mesuré avec une plateforme Taqman. Des modèles de régression logistique non conditionnelle ont été utilisés pour comparer le risque de diagnostic d’un cancer de la prostate et l’interaction. Le deuxième volet utilise un devis rétrospectif de type cohorte basée sur les données administratives de la Régie de l’assurance-maladie du Québec (RAMQ). Des modèles de régression de Cox ont été employés pour mesurer l’association entre les statines et l’évolution du cancer de la vessie. Le troisième volet, porte un regard méthodologique sur le biais du temps immortel en examinant sa présence dans la littérature oncologique. Son importance est illustrée avec les données de la cohorte du deuxième volet, et les méthodes de correction possibles son appliquées. Résultats: L’étude du premier volet démontre qu’une diète riche en acides gras oméga-3 d’origine marine était fortement associée à un risque diminué de cancer de la prostate agressif (p<0.0001 pour la tendance). Le ratio de cote pour le cancer de la prostate du quartile supérieur d’oméga-3 était de 0.37 (IC 95% = 0.25 à 0.54). L’effet diététique était modifié par le génotype COX-2 SNP rs4648310 (p=0.002 pour l’interaction). En particulier, les hommes avec faible apport en oméga-3 et la variante rs4648310 avait un risque accru de cancer de la prostate (ratio de cote = 5.49, IC 95%=1.80 à 16.7), effet renversé par un apport en oméga-3 plus grand. L’étude du deuxième volet a observé que l’utilisation de statines est associée à une diminution du risque de progression du cancer de la vessie (risque relatif = 0.44, IC 95% = 0.20 à 0.96, p=0.039). Cette association était encore plus forte pour le décès de toute cause (HR = 0.57, 95% CI = 0.43 to 0.76, p=0.0001). L’effet des statines semble être dose-dépendant. L’étude du troisième volet démontre que le biais du temps immortel est fréquent et important dans les études épidémiologiques oncologiques. Il comporte plusieurs aspects dont certains sont mieux prévenus au stade du choix du devis d’étude et différentes méthodes statistiques permettent un contrôle de ce biais. Conclusion: 1) Une diète riche en oméga-3 aurait un effet protecteur pour le cancer de la prostate. 2) L’utilisation de statines aurait un effet protecteur sur la progression du cancer non invasif de la vessie. Les lipides semblent avoir un effet sur les cancers urologiques. / Purpose: To define the effects of dietary lipids and of treatment of dyslipidemia with statins on prostate and bladder cancers, using different epidemiologic study designs and accounting for biases, particularly immortal time bias. Study Design: The first part used a retrospective a case-control study design. Diet was assessed with a semi-quantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNPs) were genotyped. We used logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values for association and interaction. The second part used a retrospective cohort study design based on administrative databases of Québec, Canada. Cox regression models were used to measure association between statin use and bladder cancer evolution. The third part focuses on the immortal time bias by describing its presence in the oncologic literature. The importance of this bias is illustrated with data from the cohort used in the second part and statistical correction methods are applied. Results: The first part showed that an increasing intake of omega-3 fatty acids of marine origin was strongly associated with a decreased risk of aggressive prostate cancer (trend p<=0.0001). The OR (95% CI) for prostate cancer comparing the highest to the lowest quartile of omega-3 intake was of 0.37 (0.25 – 0.54). The dietary effect was modified by the rs4648310 COX-2 SNP (interaction p=0.02). This reflected the observation that men with low marine omega-3 intake and the variant rs4648310 SNP had an increased risk of disease (OR = 5.49; 95% CI: 1.80-16.7), which was reversed by increasing intake of marine omega-3. The second part showed that statin use was associated with a decreased risk of bladder cancer progression (HR = 0.44, 95% CI = 0.20 to 0.96, p=0.0388). The inverse association was even stronger for risk of mortality from all causes (HR = 0.57, 95% CI = 0.43 to 0.76, p=0.0001). The statin use effect appears dose-dependent. The third part showed that the immortal time bias is frequent and important in many epidemiological studies in oncology. It has many aspects and some of these are better prevented at time of study design selection. Various statistical methods also allowed control of this bias. Conclusion. 1) Dietary omega-3 appears to decrease prostate cancer risk. 2) Statin use appears to decrease risk of bladder cancer progression. Lipids seem to have an effect on urological cancers.