Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 92-105).

Thesis (Ph. D.)--Biology, Georgia Institute of Technology, 2005. / Choi, Jung, Committee Chair ; Tornabene, Thomas, Committee Member ; Chernoff, Yuri, Committee Member ; Hall, Dwight, Committee Member ; Doyle, Donald, Committee Member. Includes bibliographical references.

Thesis [Ph. D.]--Cornell University, January, 2009. / Vita. Includes bibliographical references (leaves 158-173).

A possible interrelationship between serum cholesterol level and atherosclerosis has long interested investigators in the fields of physiology and biochemistry. Cholesterol is found in very high concentrations in the plaques that occlude coronary arteries in man and laboratory animals. It is generally agreed that hypercholesterolemia favors the appearance of atherosclerotic lesions.1<1 In recent years, much information has been accumulated regarding the factors which affect the serum cholesterol level. Exact and detailed biochemical mechanisms are still not clearly understood. However, it has been demonstrated that the serum cholesterol levels of man and several experimental animals can be lowered significantly by various dietary regimens and drug administrations.2,3,4,5 One antihypercholesteremic agent that has aroused considerable interest is the sitosterol group. The purpose of the present study is to investigate the effect of sitosterols from soya bean oil powder on the serum cholesterol levels and to evaluate that effect on the genetic differences two strains of laboratory mice. These two strains of mice, produced previously by selective breeding, differ from each other in their serum cholesterol concentrations.

No description available.

No description available.

高膽固醇血症是產生動脈粥樣硬化的危險因素，本研究旨在探討甾醇的氧化產物和植物化學物質在餵食高膽固醇食金黃地鼠模型中對脂蛋白代謝的影響及其相關機制。 / 本研究包含四個部分。食物中同時含有植物甾醇及其氧化產物。第一部分旨在研究β-穀甾醇（Si）、甾醇(St)、β-穀甾醇氧化產物(SiOP)和豆甾醇氧化產物(StOP)對金黃地鼠血脂的影響。本研究顯示，Si和St組能有效降低血總膽固醇（TC）、非高密度脂蛋白膽固醇（non-HDL-C）和甘油三酯（TAG）的水平，而SiOP和StOP則失去此能力。RT-PCR分析表明，Si和St而非SiOP和StOP，能下調腸道醯基輔酶A：膽固醇醯基轉移酶2（ACAT2）和微粒體甘油三酯轉移蛋白（MTP）的mRNA表達。Si和St而非SiOP和StOP能有效防止動脈粥樣硬，Si和St的動脈弓舒張能力強於對照組和SiOP、StOP組。 / 辣椒鹼是辣椒中的活性成分。本研究第二部分表明，辣椒鹼能降低TC，NON-HDL-C，TAG，而不影響高密度脂蛋白膽固醇。餵養辣椒鹼能增加糞便中總酸性固醇的排泄，此作用有可能是通過上調膽固醇7α-羥化酶（CYP7A1）和下調肝X受體α（LXRα）的基因表達來實驗。辣椒鹼可通過抑制COX-2基因表達來改善內皮依賴性收縮。 / 藍莓含有豐富的抗炎抗氧化劑，例如花青素。本研究第三部分表明，食物中添加0.5和1.0藍莓花青素能導致TC呈劑量效益地降低6-12%，其中還伴隨22-29的中性固醇和41-74%的膽汁酸排泄的增加。RT-PCR分析表明食物中添加的藍莓花青素能下調腸道Niemann-Pick C1 Like 1 (NPC1L1)，ACAT2，MTP， 腺苷三磷酸結合盒轉運體G8(ABCG8)和肝臟3-羥基-3-甲基戊二醯輔酶A還原酶(HMG-CoA　Reductase)的基因表達。 / 芝麻素是芝麻種子中含有抗氧化活性的木脂素類化合物。本研究第四部分表明，在食物中添加芝麻素可有效調控TC和non-HDL-C，同時不影響TAG，並導致非高密度脂蛋白膽固醇與高密度脂蛋白膽固醇比例的下降。這有可能與膽汁酸排泄增加、CYP7A1基因的上調，LXR的下調有關。 / 綜上所述，本研究證實了植物甾醇、辣椒鹼、藍莓花青素和芝麻素降低血膽固醇的能力。與此同時，本研究還表明植物甾醇被氧化後將失去其降低膽固醇的能力。 / Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Functional foods that can lower or regulate cholesterol concentration are of interest to both public and scientific communities. The present study was to investigate the effects of phytosterols, phytosterol oxidation products (POPs), capsaicinoids, blueberry anthocyanins and sesamin on plasma cholesterol concentration using hamsters as a model. / The whole project consisted of four parts. Human diets contain both phytosterols and POPs. Part I was to examine the effect of β-sitosterol (Si), stigmasterol (St), β-sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP) on plasma cholesterol concentration. Results showed both Si and St could reduce while SiOP and StOP lost the capacity of lowering plasma total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C) and triacylglycerols (TAG). Real-Time PCR analysis demonstrated Si and St but not SiOP and StOP down-regulated mRNA levels of intestinal acyl CoA: cholesterol acyltransferase 2 (ACAT2) and microsomal triglyceride protein (MTP). In addition, aortas from hamsters given diets containing Si and St relaxed better than those from the control and their corresponding SiOP- and StOP-treated hamsters, suggesting that Si and St not SiOP and StOP were beneficial in improving lipoprotein profile and aortic function. / Capsaicinoids refer to a group of pungent compounds that are the active components found in chili peppers. Part II was to investigate the cholesterol-lowering activity of capsaicinoids and the associated molecular mechanisms. Results demonstrated that capsaicinoids reduced plasma TC, non-HDL-C and TAG with high-density lipoprotein cholesterol (HDL-C) being unaffected. This was accompanied by an increase in the fecal excretion of total acidic sterols, possibly mediated by up-regulation of cholesterol 7α-hydroxylase (CYP7A1) and down-regulation of liver X receptor alpha (LXRα). Capsaicinoids could also improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2. / Blueberries are rich in anthocyanins. Results from Part III experiments demonstrated that dietary supplementation with 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12% in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 2229% and 4174%, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of intestinal Niemann-Pick C1-like 1 (NPC1L1), ACAT2, MTP, ABCG 8 and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase. / Sesamin is a major lignan in sesame seed and is known to exhibit antioxidative activity. Part IV was to investigate the mechanism by which sesamin decreased plasma cholesterol concentration. Results clearly demonstrated supplementation of sesamin into diets could favorably reduce serum TC and non-HDL-C with TAG being unaffected. In addition, dietary supplementation of 0.2 or 0.5% of sesamin could cause a significant decrease in the ratio of non-HDL-C to HDL-C. This was accompanied by a marked increase in bile acid excretion and up-regulation of CYP7A1 and down-regulation of LXRα. / In conclusion, phytosterols, capsaicinoids, blueberry anthocyanins and sesamin were beneficial in improving lipoprotein profile in hamsters fed a high-cholesterol diet. However, phytosterols lose the cholesterol-lowering capacity when they are oxidized. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liang, Yintong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 112-123). / Abstracts also in Chinese. / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- Cardiovascular diseases --- p.1 / Chapter 1.2 --- Cholesterol --- p.2 / Chapter 1.3 --- Lipoproteins --- p.4 / Chapter 1.4 --- Cholesterol homeostasis --- p.6 / Chapter 1.4.1 --- HMG-CoA reductase --- p.7 / Chapter 1.4.2 --- LDL receptor --- p.9 / Chapter 1.4.3 --- Intestine ACAT2 --- p.10 / Chapter 1.4.4 --- NPC1L1 --- p.11 / Chapter 1.4.5 --- CYP7A1 and LXRα --- p.12 / Chapter 1.4.6 --- SREBP2 --- p.14 / Chapter 1.4.7 --- ABCG5 and ABCG8 --- p.15 / Chapter 1.5 --- Phytochemicals --- p.16 / Chapter 1.5.1 --- Phytosterols --- p.16 / Chapter 1.5.2 --- Capsaicinoids --- p.17 / Chapter 1.5.3 --- Blueberry anthocyanins --- p.19 / Chapter 1.5.4 --- Sesamin --- p.20 / Chapter 1.6 --- Animal model --- p.22 / Chapter Chapter 2 --- Effect of Phytosterols and their Oxidation Products on Lipoprotein Profiles and Vascular Function / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Objective --- p.24 / Chapter 2.3 --- Materials and methods --- p.24 / Chapter 2.3.1 --- Preparation of sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP) / Chapter 2.3.2 --- Diets --- p.25 / Chapter 2.3.3 --- Hamsters --- p.25 / Chapter 2.3.4 --- Analysis of individual SiOP and StOP in serum and liver --- p.26 / Chapter 2.3.5 --- Analysis of plasma lipoproteins --- p.28 / Chapter 2.3.6 --- Measurement of atherosclerotic plaque --- p.28 / Chapter 2.3.7 --- Analysis of cholesterol in the liver and aorta --- p.28 / Chapter 2.3.8 --- Determination of fecal neutral and acidic sterols --- p.29 / Chapter 2.3.9 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP. --- p.29 / Chapter 2.3.10 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.32 / Chapter 2.3.11 --- Vascular reactivity --- p.32 / Chapter 2.4 --- Results --- p.34 / Chapter 2.4.1 --- Composition of SiOP and StOP --- p.34 / Chapter 2.4.2 --- Food intake, body and organ weights --- p.34 / Chapter 2.4.3 --- Plasma TC, HDL, non-HDL ,TAG, Non-HDL-C/HDL-C --- p.34 / Chapter 2.4.4 --- Aortic cholesterol and atherosclerotic plaque --- p.35 / Chapter 2.4.5 --- Liver cholesterol, SiOP and StOP --- p.35 / Chapter 2.4.6 --- Fecal neutral, acidic sterols and cholesterol balance --- p.35 / Chapter 2.4.7 --- Immunoblot and mRNA analysis --- p.36 / Chapter 2.4.8 --- Vascular reactivity --- p.36 / Chapter 2.4.9 --- Role of COX in endothelium-dependent contractions --- p.37 / Chapter 2.5 --- Discussion --- p.50 / Chapter Chapter 3 --- Cholesterol-Lowering Activity of Capsaicinoids Is Mediated by Increasing Sterol Excretion in Hamsters Fed a High Cholesterol Diet / Chapter 3.1 --- Introduction --- p.54 / Chapter 3.2 --- Objective --- p.55 / Chapter 3.3 --- Materials and methods --- p.55 / Chapter 3.3.1 --- Diets --- p.55 / Chapter 3.3.2 --- Hamsters --- p.57 / Chapter 3.3.3 --- Analysis of plasma lipoproteins --- p.57 / Chapter 3.3.4 --- Measurement of atherosclerotic plaque --- p.57 / Chapter 3.3.5 --- Analysis of cholesterol in the liver and aorta --- p.57 / Chapter 3.3.6 --- Determination of fecal neutral and acidic sterols --- p.57 / Chapter 3.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.57 / Chapter 3.3.8 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.58 / Chapter 3.3.9 --- Vascular reactivity --- p.58 / Chapter 3.4 --- Results --- p.59 / Chapter 3.4.1 --- Food intake, body and organ weights --- p.59 / Chapter 3.4.2 --- Plasma TC, HDL, non-HDL,TAG, Non-HDL-C/HDL-C --- p.59 / Chapter 3.4.3 --- Aortic cholesterol and atherosclerotic plaque --- p.59 / Chapter 3.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.59 / Chapter 3.4.5 --- Immunoblot and mRNA analysis --- p.60 / Chapter 3.4.6 --- Vascular reactivity --- p.60 / Chapter 3.4.7 --- Role of COX in endothelium-dependent contractions --- p.61 / Chapter 3.5 --- Discussion --- p.74 / Chapter Chapter 4 --- Effect of Blueberry Anthocyanins on Lipoprotein Profiles in Hamsters Fed a Cholesterol Diet / Chapter 4.1 --- Introduction --- p.77 / Chapter 4.2 --- Objective --- p.78 / Chapter 4.3 --- Materials and methods --- p.78 / Chapter 4.3.1 --- HPLC analysis of blueberry anthocyanins --- p.78 / Chapter 4.3.2 --- Diet --- p.79 / Chapter 4.3.3 --- Hamsters --- p.80 / Chapter 4.3.4 --- Analysis of plasma lipoproteins --- p.80 / Chapter 4.3.5 --- Analysis of cholesterol in the liver --- p.80 / Chapter 4.3.6 --- Determination of fecal neutral and acidic sterols --- p.81 / Chapter 4.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL Receptor, HMG-CoA Reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.81 / Chapter 4.3.8 --- Western blotting analysis of hepatic SREBP2, LDL Receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.81 / Chapter 4.4 --- Results --- p.82 / Chapter 4.4.1 --- Food intake, body, and organ weights --- p.82 / Chapter 4.4.2 --- Plasma TC, HDL-C, non-HDL-C, and TAG --- p.82 / Chapter 4.4.3 --- Liver cholesterol concentration --- p.82 / Chapter 4.4.4 --- Fecal total sterols and apparent sterol retention --- p.82 / Chapter 4.4.5 --- Immunoblot and mRNA analysis --- p.83 / Chapter 4.5 --- Discussion --- p.92 / Chapter Chapter 5 --- Effect of Sesamin on Lipoprotein Profiles in Hamsters Fed a high Cholesterol Diet / Chapter 5.1 --- Introduction --- p.95 / Chapter 5.2 --- Objective --- p.95 / Chapter 5.3 --- Materials and methods --- p.96 / Chapter 5.3.1 --- Diets --- p.96 / Chapter 5.3.2 --- Hamsters --- p.96 / Chapter 5.3.3 --- Methods --- p.97 / Chapter 5.4 --- Results --- p.98 / Chapter 5.4.1 --- Food intake, body and organ weights --- p.98 / Chapter 5.4.2 --- Plasma TC, HDL-C, non-HDL-C ,TAG, Non-HDL-C/HDL-C --- p.98 / Chapter 5.4.3 --- Liver cholesterol --- p.98 / Chapter 5.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.98 / Chapter 5.4.5 --- Immunoblot and mRNA analysis --- p.99 / Chapter 5.5 --- Discussion --- p.109 / References --- p.112

Faecal indicator bacteria have traditionally been used in the detection of faecal pollution in water, but due to concerns about the lack of reliability of these indicators, alternative methods have been developed. One of which is the detection of sterols present in human and animal excreta via GC-MS analysis of water in this study. The Szűcs method was used to detect six target sterols (coprostanol, cholesterol, dehydrocholesterol, stigmasterol, β-sitosterol, and stigmastanol) in environmental water samples. An initial study was done by analysing raw sewage and effluent (human faecal sterol biomarkers) and water samples were spiked with excreta from cattle, chickens, horses, pigs, and sheep to determine faecal sterol fingerprints. The method was evaluated for quantitation and differences between the water samples from each species. Following liquid-liquid extraction, silylation and derivatization, samples were analysed by GC-MS. Standard curve assays were linear up to 160ng and the limit for quantification was 20ng. The human faecal sterol biomarker was coprostanol, while herbivore profiles were dominated by terrestrial sterol biomarkers (stigmasterol and stigmastanol). Sterol fingerprints and differences in concentrations of sterols between various animals and between animals and humans occurred, providing the opportunity to determine whether faecal pollution was from humans or from animals. The method proved sensitive enough to evaluate faecal contamination in environmental water. Groundwater was collected from bore-holes and surface water samples were collected from the Baberspan Inland Lake. Physico-chemical parameters analysed indicated that pH for surface water samples was above 6.9. The total dissolved solids (TDS) in groundwater indicated that the water was not suitable for human consumption, but could be used for livestock watering. Surface water electrical conductivity (EC) and inorganic nitrates was too high to be used for irrigational purposes. Nitrates in groundwater were too high to be consumed by humans. In groundwater, the total coliform target water quality range (TWQR) was exceeded at 53% of sites analysed and faecal coliform TWQR were exceeded at 77% sites. Surface water samples complied with TWQR with regards to faecal coliforms for full contact recreational activities and livestock watering. The TWQR for E. coli, with regards to full contact recreational activities, was within a safe range for surface water. Faecal streptococci were found in 85% of groundwater sampling sites. And surface water faecal streptococci counts exceeded the TWQR for full contact recreational activities. There is no TWQR for faecal sterols in water, but concentrations of cholesterol and coprostanol was found at three of the groundwater sites analysed. This indicates faecal contamination from possible animal and human origin. Surface water samples analysed showed that the Harts River water is clean and free of faecal sterols, while the water analysed from the inflow, hotel and outflow, cholesterol eluted, which showed faecal contamination, possibly from animals. Faecal sterol markers could be detected in groundwater and surface water, adding an extra dimension to determining the quality of water systems. An optimization and sensitivity study of the method was done on waste water treatment plant (WWTP) raw sewage and effluent. The WWTP sample analysed form Potchefstroom and Carletonville WWTP yielded all six target sterols in the raw sewage water samples, but no sterols eluted in the effluent samples. The raw sewage water sample taken from the Fochville WWTP yielded all six target sterols as well, however, the effluent yielded an unknown compound as well as cholesterol. An alternative study was done where the effluent sample volume was increased. By increasing the volume of water, one can possibly increase the amount (“load”) of sterols extracted and analysed, resulting in a higher abundance of target sterols. By using the target qualifier ions of the six target sterols, and the GC-TOF/MS software, the target sterols could still be qualitatively determined. Optimal volume for raw sewage is 300 ml water sample as this is enough to yield all 6 target sterols. For optimum water quality monitoring via faecal sterol analysis of effluent and other environmental samples, at least 1L sample volume needs to be collected and analysed. The methods described here can be applied to the analysis of environmental water samples. The technical advantages also make it suitable for routine environmental monitoring of faecal pollution. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

Faecal indicator bacteria have traditionally been used in the detection of faecal pollution in water, but due to concerns about the lack of reliability of these indicators, alternative methods have been developed. One of which is the detection of sterols present in human and animal excreta via GC-MS analysis of water in this study. The Szűcs method was used to detect six target sterols (coprostanol, cholesterol, dehydrocholesterol, stigmasterol, β-sitosterol, and stigmastanol) in environmental water samples. An initial study was done by analysing raw sewage and effluent (human faecal sterol biomarkers) and water samples were spiked with excreta from cattle, chickens, horses, pigs, and sheep to determine faecal sterol fingerprints. The method was evaluated for quantitation and differences between the water samples from each species. Following liquid-liquid extraction, silylation and derivatization, samples were analysed by GC-MS. Standard curve assays were linear up to 160ng and the limit for quantification was 20ng. The human faecal sterol biomarker was coprostanol, while herbivore profiles were dominated by terrestrial sterol biomarkers (stigmasterol and stigmastanol). Sterol fingerprints and differences in concentrations of sterols between various animals and between animals and humans occurred, providing the opportunity to determine whether faecal pollution was from humans or from animals. The method proved sensitive enough to evaluate faecal contamination in environmental water. Groundwater was collected from bore-holes and surface water samples were collected from the Baberspan Inland Lake. Physico-chemical parameters analysed indicated that pH for surface water samples was above 6.9. The total dissolved solids (TDS) in groundwater indicated that the water was not suitable for human consumption, but could be used for livestock watering. Surface water electrical conductivity (EC) and inorganic nitrates was too high to be used for irrigational purposes. Nitrates in groundwater were too high to be consumed by humans. In groundwater, the total coliform target water quality range (TWQR) was exceeded at 53% of sites analysed and faecal coliform TWQR were exceeded at 77% sites. Surface water samples complied with TWQR with regards to faecal coliforms for full contact recreational activities and livestock watering. The TWQR for E. coli, with regards to full contact recreational activities, was within a safe range for surface water. Faecal streptococci were found in 85% of groundwater sampling sites. And surface water faecal streptococci counts exceeded the TWQR for full contact recreational activities. There is no TWQR for faecal sterols in water, but concentrations of cholesterol and coprostanol was found at three of the groundwater sites analysed. This indicates faecal contamination from possible animal and human origin. Surface water samples analysed showed that the Harts River water is clean and free of faecal sterols, while the water analysed from the inflow, hotel and outflow, cholesterol eluted, which showed faecal contamination, possibly from animals. Faecal sterol markers could be detected in groundwater and surface water, adding an extra dimension to determining the quality of water systems. An optimization and sensitivity study of the method was done on waste water treatment plant (WWTP) raw sewage and effluent. The WWTP sample analysed form Potchefstroom and Carletonville WWTP yielded all six target sterols in the raw sewage water samples, but no sterols eluted in the effluent samples. The raw sewage water sample taken from the Fochville WWTP yielded all six target sterols as well, however, the effluent yielded an unknown compound as well as cholesterol. An alternative study was done where the effluent sample volume was increased. By increasing the volume of water, one can possibly increase the amount (“load”) of sterols extracted and analysed, resulting in a higher abundance of target sterols. By using the target qualifier ions of the six target sterols, and the GC-TOF/MS software, the target sterols could still be qualitatively determined. Optimal volume for raw sewage is 300 ml water sample as this is enough to yield all 6 target sterols. For optimum water quality monitoring via faecal sterol analysis of effluent and other environmental samples, at least 1L sample volume needs to be collected and analysed. The methods described here can be applied to the analysis of environmental water samples. The technical advantages also make it suitable for routine environmental monitoring of faecal pollution. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015