published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

Made available in DSpace on 2015-01-26T13:21:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-14Bitstream added on 2015-01-26T13:30:33Z : No. of bitstreams: 1 000797244_20160214.pdf: 149696 bytes, checksum: 84a123bb9f79677c0bdacb3d06842bdd (MD5) Bitstreams deleted on 2016-02-15T11:45:39Z: 000797244_20160214.pdf,. Added 1 bitstream(s) on 2016-02-15T11:46:17Z : No. of bitstreams: 1 000797244.pdf: 1139032 bytes, checksum: 6d99dacf9659c04ba2a94d63d2011eb2 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As dislipidemias têm sido frequentemente encontradas nas crianças e adolescentes devido a obesidade, maus hábitos alimentares e a falta de exercícios físicos. A rosuvastatina atua como inibidor da enzima HMG-CoA redutase e pode ser indicada para a prevenção de doenças cardiovasculares e para o tratamento das dislipidemias, devido a sua grande eficiência na redução das concentrações plasmáticas do colesterol sérico. Este estudo pretendeu investigar o desenvolvimento sexual inicial e os possíveis efeitos reprodutivos adversos na maturidade sexual decorrentes da exposição de ratos juvenis à rosuvastatina na pré-puberdade. Foram formados três grupos aleatoriamente com ratos recém-desmamados (n= 20/por grupo): grupo controle, que recebeu solução salina 0.9%, e os grupos tratados com 3 ou 10 mg/Kg de rosuvastatina por dia via gavagem, desde o dia pós-natal (DPN) 21 até a instalação da puberdade. Parte dos animais de cada grupo (n=10/por grupo) foi eutanasiada no DPN55 e os animais remanescentes foram mantidos até a maturidade sexual e foram eutanasiados no DPN110. No DPN55 foram avaliados as concentrações hormonais, histologia testicular e epididimária e expressão de receptores de andrógenos (AR) no testículo e epidídimo. Na maturidade sexual foram avaliados o comportamento sexual, concentrações hormonais, produção, morfologia e motilidade dos espermatozóides, além da histologia do testículo e epidídimo e imunohistoquímica para AR no testículo. Nos grupos tratados com rosuvastatina, os resultados demonstraram uma tendência para a diminuição das concentrações de testosterona, mas abaixo do nível de significância, bem como houve atraso na idade da instalação da puberdade e no desenvolvimento epididimário. Houve ainda alterações testiculares que podem estar relacionadas com o atraso na puberdade e a diminuição da testosterona. Na maturidade sexual, os animais ... / Dyslipidemias are frequently found in children due to obesity, bad eating habits and the lack of physical exercises. Rosuvastatin acts as an HMG-CoA reductase inhibitor and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to investigate initial sexual development and the possible reproductive adverse effects on sexual maturity due to juvenile male rats exposure to rosuvastatin during prepuberty. Three groups were formed with newly weaned rats (n= 20/per group): control, whose rats received saline solution 0.9%, rosuvastatin at doses of 3 or 10 mg/Kg daily by gavage, since post-natal day (PND) 21 until puberty onset. Part of each group (n=10/per group) was euthanized on PND55 and the remaining rats (n=10/per group) were maintained until sexual maturity and were euthanized on PND110. On PND55, we analyzed the hormonal concentrations, testicular and epididymal histology and the expression of androgen receptors (AR) on testis and epididymis. During sexual maturity, the parameters evaluated were sexual behavior, hormonal concentrations, sperm production, morphology and motility, besides testicular and epididymal histology and immunohistochemistry for AR. In the rosuvastatin-treated groups, the results demonstrated a trend towards a decrease in testosterone concentration, but below the significance level, as well as delays in both the age of puberty onset and in epididymal development. There were also testicular alterations that might be related to delayed puberty and decrease of serum testosterone. In the adulthood, the rosuvastatin-treated groups showed diminution in follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations, delay in the latency to the first penis intromission, pathologic alterations on testis and epididymis and decreased sperm ... / FAPESP: 11/15065-5

Orientador: Wilma De Grava Kempinas / Banca: Isabel Cristina Cherici Camargo / Banca: Maria Terezinha Serrão Peraçoli / Resumo: As dislipidemias têm sido frequentemente encontradas nas crianças e adolescentes devido a obesidade, maus hábitos alimentares e a falta de exercícios físicos. A rosuvastatina atua como inibidor da enzima HMG-CoA redutase e pode ser indicada para a prevenção de doenças cardiovasculares e para o tratamento das dislipidemias, devido a sua grande eficiência na redução das concentrações plasmáticas do colesterol sérico. Este estudo pretendeu investigar o desenvolvimento sexual inicial e os possíveis efeitos reprodutivos adversos na maturidade sexual decorrentes da exposição de ratos juvenis à rosuvastatina na pré-puberdade. Foram formados três grupos aleatoriamente com ratos recém-desmamados (n= 20/por grupo): grupo controle, que recebeu solução salina 0.9%, e os grupos tratados com 3 ou 10 mg/Kg de rosuvastatina por dia via gavagem, desde o dia pós-natal (DPN) 21 até a instalação da puberdade. Parte dos animais de cada grupo (n=10/por grupo) foi eutanasiada no DPN55 e os animais remanescentes foram mantidos até a maturidade sexual e foram eutanasiados no DPN110. No DPN55 foram avaliados as concentrações hormonais, histologia testicular e epididimária e expressão de receptores de andrógenos (AR) no testículo e epidídimo. Na maturidade sexual foram avaliados o comportamento sexual, concentrações hormonais, produção, morfologia e motilidade dos espermatozóides, além da histologia do testículo e epidídimo e imunohistoquímica para AR no testículo. Nos grupos tratados com rosuvastatina, os resultados demonstraram uma tendência para a diminuição das concentrações de testosterona, mas abaixo do nível de significância, bem como houve atraso na idade da instalação da puberdade e no desenvolvimento epididimário. Houve ainda alterações testiculares que podem estar relacionadas com o atraso na puberdade e a diminuição da testosterona. Na maturidade sexual, os animais ... / Abstract: Dyslipidemias are frequently found in children due to obesity, bad eating habits and the lack of physical exercises. Rosuvastatin acts as an HMG-CoA reductase inhibitor and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to investigate initial sexual development and the possible reproductive adverse effects on sexual maturity due to juvenile male rats exposure to rosuvastatin during prepuberty. Three groups were formed with newly weaned rats (n= 20/per group): control, whose rats received saline solution 0.9%, rosuvastatin at doses of 3 or 10 mg/Kg daily by gavage, since post-natal day (PND) 21 until puberty onset. Part of each group (n=10/per group) was euthanized on PND55 and the remaining rats (n=10/per group) were maintained until sexual maturity and were euthanized on PND110. On PND55, we analyzed the hormonal concentrations, testicular and epididymal histology and the expression of androgen receptors (AR) on testis and epididymis. During sexual maturity, the parameters evaluated were sexual behavior, hormonal concentrations, sperm production, morphology and motility, besides testicular and epididymal histology and immunohistochemistry for AR. In the rosuvastatin-treated groups, the results demonstrated a trend towards a decrease in testosterone concentration, but below the significance level, as well as delays in both the age of puberty onset and in epididymal development. There were also testicular alterations that might be related to delayed puberty and decrease of serum testosterone. In the adulthood, the rosuvastatin-treated groups showed diminution in follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations, delay in the latency to the first penis intromission, pathologic alterations on testis and epididymis and decreased sperm ... / Mestre

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Rhode Island, 2003. / Typescript. Includes bibliographical references (leaves 204-227).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 149-160).

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

<p><strong>Background:</strong> Coronary heart disease kills more than 7 million people worldwide each year. High levels of blood fat, cholesterol, contributes significantly to coronary heart disease. Lifestyle changes combined with lipid-lowering drugs, statins, is an effective treatment. But adherence to statins is low, not even a myocardial infarction always contributes to adherence. Adherence requires patient education and good communication between patient and physician. There is no deeper knowledge of why coronary heart patients stops with statin treatment. <strong>Objective:</strong> To describe how coronary heart patients experience the disease and the statin treatment, and furthermore, opportunities and difficulties to adhere with statin therapy. <strong>Design:</strong> An exploratory qualitative study. <strong>Method:</strong> 10 male coronary heart patients, 55-78 years were strategically selected from a cardiology clinic in a larger Swedish hospital. Patients were interviewed individually in a semi-structured form, 2009/2010. Data processing was done according to content analysis and yielded four themes: <em>empowerment, effects, decision basis, </em>and<em> trust.</em> <strong>Results:</strong> The patients did not mentioned heredity among the factors they could not affect in association with the disease. Several patients saw the medication as a limitation, doubted its efficacy, but mostly took it anyway, at least for a limited time. Medication and illness were associated with each other. Information requirements were in most patients. Many patients wanted to discontinue the statin therapy. <strong>Conclusion:</strong> Retention of power over the own body, good reference base for decision about adherence, and trust in health care. These are crucial components of patients’ adherence to statin therapy, in connection with coronary heart disease.</p> / <p><strong>Bakgrund:</strong><strong> Kranskärlssjukdom dödar drygt 7 miljoner människor i världen per år.</strong></p><p><strong>För höga halter av blodfettet kolesterol i blodet bidrar kraftigt till kranskärlssjukdom.</strong> <strong>Livsstilsförändringar kombinerat med blodfettssänkande läkemedel, statiner, är en effektiv behandling. Följsamheten till statiner är dock låg, inte ens genomgången hjärtinfarkt ökar följsamhet. Följsamhet kräver patientutbildning och god kommunikation mellan patient och läkare. Det saknas djupare kunskap om varför kranskärlspatienter slutar med statiner. Syfte: </strong><strong>att </strong><strong>beskriva hur kranskärlspatienter upplever sjukdomen och statinbehandlingen, samt möjligheter och svårigheter att följa statinbehandlingen. Design: </strong><strong>explorativ kvalitativ studie. Metod: </strong><strong>10 manliga kranskärlspatienter, 55-78 år valdes strategiskt via en kardiologklinik på ett större svenskt sjukhus. Patienterna intervjuades personligen i semistrukturerad form, 2009/2010. Databearbetning skedde enligt innehållsanalys och gav fyra teman:</strong><em> egenmakt, effekter</em><strong>, </strong><em>beslutsgrund, tilltro. </em><strong>Resultat:</strong><strong> Patienterna nämnde inte ärftlighet bland faktorer som ansågs opåverkbara i samband med kranskärlssjukdomen.</strong> Flera patienter såg medicinen som en begränsning och tvivlade på effekten, men tog den oftast ändå, åtminstone under en begränsad tid. Likhetstecken sattes mellan medicinering och sjukdom. Informationsbehov fanns hos flertalet patienter. Många patienter ville sluta med statinbehandlingen. <strong>Slutsats: </strong>Bibehållen makt över sin egen kropp, god referensgrund för beslut om följsamhet samt förtroende för sjukvården, är avgörande förutsättningar för kranskärlspatienters följsamhet till statinbehandling.<strong></strong></p>

Background: Coronary heart disease kills more than 7 million people worldwide each year. High levels of blood fat, cholesterol, contributes significantly to coronary heart disease. Lifestyle changes combined with lipid-lowering drugs, statins, is an effective treatment. But adherence to statins is low, not even a myocardial infarction always contributes to adherence. Adherence requires patient education and good communication between patient and physician. There is no deeper knowledge of why coronary heart patients stops with statin treatment. Objective: To describe how coronary heart patients experience the disease and the statin treatment, and furthermore, opportunities and difficulties to adhere with statin therapy. Design: An exploratory qualitative study. Method: 10 male coronary heart patients, 55-78 years were strategically selected from a cardiology clinic in a larger Swedish hospital. Patients were interviewed individually in a semi-structured form, 2009/2010. Data processing was done according to content analysis and yielded four themes: empowerment, effects, decision basis, and trust. Results: The patients did not mentioned heredity among the factors they could not affect in association with the disease. Several patients saw the medication as a limitation, doubted its efficacy, but mostly took it anyway, at least for a limited time. Medication and illness were associated with each other. Information requirements were in most patients. Many patients wanted to discontinue the statin therapy. Conclusion: Retention of power over the own body, good reference base for decision about adherence, and trust in health care. These are crucial components of patients’ adherence to statin therapy, in connection with coronary heart disease. / Bakgrund: Kranskärlssjukdom dödar drygt 7 miljoner människor i världen per år. För höga halter av blodfettet kolesterol i blodet bidrar kraftigt till kranskärlssjukdom. Livsstilsförändringar kombinerat med blodfettssänkande läkemedel, statiner, är en effektiv behandling. Följsamheten till statiner är dock låg, inte ens genomgången hjärtinfarkt ökar följsamhet. Följsamhet kräver patientutbildning och god kommunikation mellan patient och läkare. Det saknas djupare kunskap om varför kranskärlspatienter slutar med statiner. Syfte: att beskriva hur kranskärlspatienter upplever sjukdomen och statinbehandlingen, samt möjligheter och svårigheter att följa statinbehandlingen. Design: explorativ kvalitativ studie. Metod: 10 manliga kranskärlspatienter, 55-78 år valdes strategiskt via en kardiologklinik på ett större svenskt sjukhus. Patienterna intervjuades personligen i semistrukturerad form, 2009/2010. Databearbetning skedde enligt innehållsanalys och gav fyra teman: egenmakt, effekter, beslutsgrund, tilltro. Resultat: Patienterna nämnde inte ärftlighet bland faktorer som ansågs opåverkbara i samband med kranskärlssjukdomen. Flera patienter såg medicinen som en begränsning och tvivlade på effekten, men tog den oftast ändå, åtminstone under en begränsad tid. Likhetstecken sattes mellan medicinering och sjukdom. Informationsbehov fanns hos flertalet patienter. Många patienter ville sluta med statinbehandlingen. Slutsats: Bibehållen makt över sin egen kropp, god referensgrund för beslut om följsamhet samt förtroende för sjukvården, är avgörande förutsättningar för kranskärlspatienters följsamhet till statinbehandling.