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Yang, Chao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 137-146). / Abstracts in English and Chinese. / Thesis Committee --- p.i / Acknowledgements --- p.ii / Contents --- p.iii / Declaration --- p.vii / Abstract --- p.viii / 摘要 --- p.xi / Abbreviations --- p.xiii / Chapter CHAPTER ONE: --- INTRODUCTION / Chapter 1.1 --- Occurrence and Structure of Phytosterols in Plants --- p.P.1 / Chapter 1.2 --- Biological Effects of Phytosterols / Chapter 1.2.1 --- Cholesterol-lowering Effect of Phytosterols --- p.P.3 / Chapter 1.2.2 --- Anti-cancer Effect of Phytosterols --- p.P.5 / Chapter 1.2.3 --- Anti-proliferative Effect of Phytosterols --- p.P.5 / Chapter 1.3 --- Intake and Absorption of Phytosterols in Human Beings --- p.P.6 / Chapter 1.4 --- Occurrence and Physiological Levels of Phytosterol Oxidation Products (POPs) / Chapter 1.4.1 --- Occurrence of POPs --- p.P.8 / Chapter 1.4.2 --- Physiological Levels of POPs --- p.P.8 / Chapter 1.5 --- Endothelium and the Vascular Tone / Chapter 1.5.1 --- Role of Endothelium in the Control of Vascular Tone --- p.P.11 / Chapter 1.5.2 --- "Endothelial Dysfunction, Cholesterol Oxidation Products (COPs) and Phytosterol Oxidation Products (POPs)" --- p.P.12 / Chapter 1.6 --- Calcium Homeostasis in the Vascular Smooth Muscle Cells (VSMCs) / Chapter 1.6.1 --- Modes of Ca2+ Entry in VSMCs --- p.P.15 / Chapter 1.6.2 --- Modes of Ca2+ Efflux in VSMCs --- p.P.18 / Chapter 1.7 --- Objectives of the Study --- p.P.19 / Chapter CHAPTER TWO: --- β-SITOSTEROL OXIDATION PRODUCTS ATTENUATE VASORELAXATION BY INCREASING REACTIVE OXYGEN SPECIES AND CYCLOOXYGENASE-2 / Chapter 2.1 --- Introduction --- p.P.21 / Chapter 2.2 --- Materials and Methods / Chapter 2.2.1 --- Preparation of SOPs --- p.P.24 / Chapter 2.2.2 --- Gas Chromatography -mass Spectrometry (GC-MS) Identification of SOPs --- p.P.24 / Chapter 2.2.3 --- Analysis of SOPs --- p.P.25 / Chapter 2.2.4 --- Vessel Preparation --- p.P.25 / Chapter 2.2.5 --- Isometric Force Measurement --- p.P.26 / Chapter 2.2.6 --- Western Blotting --- p.P.27 / Chapter 2.2.7 --- Primary Culture of Rat Aortic Endothelial Cell --- p.P.28 / Chapter 2.2.8 --- Measurement of SOPs-induced Intracellular Oxidative Stress --- p.P.29 / Chapter 2.2.9 --- Drugs --- p.P.30 / Chapter 2.2.10 --- Data Analysis --- p.P.30 / Chapter 2.3 --- Results / Chapter 2.3.1 --- GC-MS Identification of SOPs --- p.P.32 / Chapter 2.3.2 --- Analysis of SOPs --- p.P.34 / Chapter 2.3.3 --- SOPs But Not β-Sitosterol Impaired ACh- and A23187-induced relaxations --- p.P.36 / Chapter 2.3.4 --- Inhibition of COX Pathway Reversed SOPs-induced Impairment in Relaxation --- p.P.39 / Chapter 2.3.5 --- SOPs Elevated Endothelial COX-2 Expression --- p.P.42 / Chapter 2.3.6 --- SOPs Increased COX-2 Expression via An Oxidative Stress-sensitive Pathway --- p.P.45 / Chapter 2.4 --- Discussion --- p.P.52 / Chapter 2.5 --- Conclusion --- p.P.56 / Chapter CHAPTER THREE: --- β-SITOSTEROL OXIDATION PRODUCTS POSSESS POTENTIAL VOCC BLOCKING EFFECT IN VSMCs / Chapter 3.1 --- Introduction / Chapter 3.1.1 --- 2+ Modes of Ca Entry and Efflux in Vascular Smooth Muscle Cells (VSMCs) --- p.P.57 / Chapter 3.1.2 --- Effect of Cholesterol and COPs on VSMCs --- p.P.57 / Chapter 3.2 --- Methodology and Materials / Chapter 3.2.1 --- Vessel Preparation --- p.P.59 / Chapter 3.2.2 --- Isometric Force Measurement iv --- p.P.59 / Chapter 3.2.3 --- Drugs --- p.P.60 / Chapter 3.2.4 --- Data Analysis --- p.P.61 / Chapter 3.3 --- Results / Chapter 3.3.1 --- SOPs but not β-Sitosterol Induced Relaxation in 60 mM K+ -preconstricted Endothelium-denuded Aorta --- p.P.62 / Chapter 3.3.2 --- Both SOPs and β-Sitosterol did not Relax U46619-preconstricted Endothelium-denuded Aorta --- p.P.64 / Chapter 3.3.3 --- Both SOPs and β-Sitosterol did not Relax PDA -preconstricted Endothelium-denuded Aorta --- p.P.66 / Chapter 3.3.4 --- SOPs Attenuated 60 mM K+-induced Contraction --- p.P.68 / Chapter 3.3.5 --- SOPs Attenuated Phenylephrine-induced Contraction --- p.P.70 / Chapter 3.3.6 --- Effect of SOPs on Concentration-dependent Responses to U46619 --- p.P.72 / Chapter 3.3.7 --- Preincubation with Bay K 8644 Abolished SOPs-induced Relaxation in 60 mM K+ -preconstricted Rings --- p.P.74 / Chapter 3.3.8 --- Preincubation with Thapsigargin did not Affect SOPs-induced Relaxation in 60 mM K+ -preconstricted Rings --- p.P.76 / Chapter 3.3.9 --- Preincubation with Ouabain did not Affect SOPs-induced Relaxation in 60 mM K+ -preconstricted Rings --- p.P.78 / Chapter 3.3.10 --- Preincubation with Nickel Potentiated SOPs-induced Relaxation in 60 mM K+ -preconstricted Rings --- p.P.80 / Chapter 3.4 --- Discussion --- p.P.84 / Chapter 3.5 --- Conclusion and Future Work --- p.P.88 / Chapter CHAPTER FOUR: --- INVOLEMENT OF NITRIC OXIDE IN THE PROTECTIVE EFFECTS OF PHYTOSTEROLS AGAINST HOMOCYSTEINE-INDUCED IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RELAXATIONS OF RAT AORTA / Chapter 4.1 --- Introduction --- p.P.89 / Chapter 4.2 --- Materials and Method / Chapter 4.2.1 --- Vessel Preparation --- p.P.93 / Chapter 4.2.2 --- Isometric Force Measurement --- p.P.93 / Chapter 4.2.3 --- Western Blotting --- p.P.94 / Chapter 4.2.4 --- "1,1 -diphenyl-2-picrylhydrazyl (DPPH) Radical Scavenging Capacity" --- p.P.96 / Chapter 4.2.5 --- Primary Culture of Rat Aortic Endothelial Cells V --- p.P.96 / Chapter 4.2.6 --- Measurement Intracellular Oxidative Stress --- p.P.97 / Chapter 4.2.7 --- Nitric Oxide (NO) Measurement --- p.P.97 / Chapter 4.2.8 --- Drugs --- p.P.98 / Chapter 4.2.9 --- Data Analysis --- p.P.99 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Impairment of Endothelium-dependent Relaxation by HC was Reversed by ROS Scavenger --- p.P.100 / Chapter 4.3.2 --- Brassicasterol Reversed HC-induced Endothelial Dysfunction In a Dose-dependent Manner --- p.P.102 / Chapter 4.3.3 --- β-Sitosterol and Stigmasterol Reversed HC-induced Endothelial Dysfunction --- p.P.104 / Chapter 4.3.4 --- Effects of β-Sitosterol Oxidation Products (SOPs) on HC-induced Endothelial Dysfunction --- p.P.106 / Chapter 4.3.5 --- Effects of Brassicasterol and β-Sitosterol on H2O2-induced Impairment of Endothelium-dependent Relaxation --- p.P.108 / Chapter 4.3.6 --- Phytosterols did not Directly Scavenge Free Radicals --- p.P.110 / Chapter 4.3.7 --- "HC and Brassicasterol did not Affect the Expression of SOD-1, SOD-2, eNOS, COX-1 and COX-2 in Aorta" --- p.P.112 / Chapter 4.3.8 --- HC Increased ROS Production in Primary Rat Aortic Endotelial Cells --- p.P.116 / Chapter 4.3.9 --- Brassicasterol did not Reverse the ROS Production by HC treatment In the Endothelial Cells --- p.P.120 / Chapter 4.3.10 --- Effect of L-NAME on Reversing the Effect of Brassicasterol on ACh-induced Relaxation --- p.P.123 / Chapter 4.3.11 --- Brassicasterol Reversed the Inhibitory Effect of HC on ACh-induced NO Production in Endothelial Cells --- p.P.125 / Chapter 4.4 --- Discussion --- p.P.128 / Chapter 4.5 --- Conclusion and Future Work --- p.P.132 / Chapter CHAPTER FIVE: --- CONCLUSIONS AND FUTURE WORK --- p.P.134 / Chapter CHAPTER SIX: --- REFERENCES --- p.P.137

Abstract not available

Bibliography: leaves 184-220.

Bibliography: leaves 140-190.

Object Rupture of intracranial arteriovenous malformations is a leading cause of stroke in children and young adults. Treatment options include surgery and highly focused radiation (stereotactic radiosurgery). For large and deep seated lesions, the risks of surgery may be prohibitively high, while radiosurgery has a disappointingly low efficacy and long latency. Radiosurgery carries the most promise for significant advances, however the process by which radiosurgery achieves obliteration is incompletely understood. Inflammation and thrombosis are likely to be important in the radiation response and may be amenable to pharmacological manipulation to improve radiosurgical efficacy. Materials and methods Immunohistochemistry and electron microscopy were used to study normal cerebral vessels, cavernous malformations and AVMs, some of which had previously been irradiated. An attempt was made to culture AVM endothelial cells to study the immediate response of AVM endothelium to radiosurgery. The effects of radiosurgery in a rat model of AVM were studied using immunohistochemistry and the results used to determine the choice of a pharmacological strategy to enhance the thrombotic effects of radiosurgery. Results Vascular malformations have a different endothelial inflammatory phenotype than normal cerebral vessels. Radiosurgery may cause long term changes in inflammatory molecule expression and leads to endothelial loss with exposure of pro-thrombotic molecules. Ultrastructural effects of irradiation include widespread cell loss, smooth muscle cell (SMC) proliferation and thrombosis. Endothelial culture from AVMs proved difficult due to SMC predominance in initial cultures. Radiosurgery upregulated several endothelial inflammatory molecules in the animal model and may induce pro-thrombotic cell membrane alterations. The administration of lipopolysaccharide and soluble tissue factor to rats following radiosurgery led to selective thrombosis of irradiated vessels. Conclusions Inflammation and thrombosis are important in the radiosurgical response of AVMs. Lumen obliteration appears to be mediated by proliferation of cells within the vessel wall and thrombosis. Upregulation of inflammatory molecules and perhaps disruption of the normal phospholipid asymmetry of the endothelial and SMC membranes are some of the earliest responses to radiosurgery. The alterations induced by radiation may be harnessed to selectively initiate thrombus formation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing treatable lesion size and reducing latency.

Bibliography: leaves 140-190 / xiv, 190, [10] leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1987

People with diabetes are at a greater risk of burn injuries than those without diabetes. This stems from the epidemiological profiles of the conditions and the effects of morbidities associated with diabetes. Both conditions share some similarities in terms of metabolic alterations and suboptimal immune functions which may result in poor outcomes for patients. For that reason, it is reasonable to deduce that patients with diabetes are a challenging group to manage in burns units. However, this deduction should be taken cautiously because of lack of supporting evidence. Accordingly and after consulting with clinical experts, the research in this portfolio investigated the association between diabetes and burn injuries. In particular, two different aspects of this association were investigated in two individual quantitative and descriptive inquiries. The first was a case note review of patients hospitalised with a principal diagnosis of a foot burn injury in a large tertiary hospital in South Australia from 1999 to 2004. The second study investigated management of diabetes in burns units treating adults. This study is an e-mail survey of clinical leaders of burns units in Australia, New Zealand, Hong Kong and the United Kingdom. The clinical leaders were approached indirectly through key liaison persons in each identified unit. In the first study, outcomes for twelve subjects with and fifty-two without diabetes were described using descriptive and non-parametric statistics. In the second study, descriptive frequencies and content analysis were adopted to analyse twenty-nine responses from seventeen out of thirty burns units which participated in the study. Supporting findings in the literature, the first study showed that burn injuries among subjects with diabetes were mainly resulted from household devices. There were no statistically significant differences between subjects with and without diabetes in terms of size and depth of burn injuries and treatment received. In spite of this, there was a statistically significant association between diabetes and the experience of local post-burn complications and longer duration of hospitalisation. The second study indicated that more than twenty-five percent of the respondents believed that multidisciplinary centres should only occasionally be involved in the process of care. Participants reported that the individual profile of each patient plays a major role in determining the management of diabetes. Additionally, it was found that the insulin sliding scale was commonly used in the management of diabetes in burns units. The association between diabetes and a burn injury is a serious issue in terms of health and cost. This association need be addressed firstly and most importantly at the prevention level; secondly through proper management of both diabetes and burns. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1285462 / Thesis (D.Nurs.)--Population Health and Clinical Practice, 2007.

Common risk factors for CVD such as hyperlipidaemia, hypertriglyceridemia, low HDL-C, obesity, insulin resistance, impaired glucose tolerance, inflammation and hypertension may increase the risk of atherosclerosis through altering vascular function. Modification of dietary intake and weight loss can ameliorate these risk factors and may impede the development of atherosclerosis. CVD risk can be assessed by measurement of both traditional e.g. lipid levels, glucose and blood pressure and novel risk markers of CVD e.g. FMD, levels of adhesion molecules, inflammatory markers and adipokines. Changes in these measurements are used to determine effects, if any, of dietary interventions. The studies in this thesis focus on the relationship between nutrition and vascular function and the effects of modifying dietary composition either with, or without weight loss. The primary hypotheses addressed were that a high saturated fat diet would have adverse effects on markers of CVD risk., that short and long term weight loss would have beneficial effects on these markers, that a conventional low fat, high glycaemic load diet would also have adverse effects on these markers and that weight loss would attenuate the BP response to salt. Six studies were conducted to address these hypotheses. The effects of saturated fat were investigated in chapters 3 and 6. In chapter 3, a high saturated fat diet impaired FMD and increased the level of the adhesion molecule Pselectin compared with a high MUFA, a high PUFA, or a low fat, high glycaemic load diet in weight stability. The high fat, high glycaemic load caused increases of 23-39% in TG and decreases of 10-15% in HDL-C but despite these adverse effects there was no change in FMD. In chapter 6, subjects on a very low carbohydrate/high saturated fat diet lost approximately 1 kg more weight over 8 weeks than those on a conventional low fat diet. While other CVD risk factors, glucose, insulin, E and P-selectin, ICAM-1 and PAI-1 levels all improved FMD did not change in either diet. Reductions in LDL-C and CRP were greater on the conventional diet. The effects of weight loss on CVD risk factors were also investigated in the studies in chapters 4, 5, 7 & 8. In chapter 4, moderate weight loss using 2 different low fat diets resulted in improvements in PAI-1 and sICAM-1 but there was no change in FMD. Similarly in chapter 5 weight loss on a low carbohydrate/low saturated fat diet did not change FMD but there were other benefits including reductions in glucose and insulin, LDL-C, adhesion molecules, VCAM1 and ICAM1. Adiponectin did not change after short term weight loss in either of the studies in chapters 5 or 6. In chapter 7 salt loading increased ambulatory day time BP and this response was not altered by short term moderate weight loss. The long term effects of weight loss were investigated in chapters 5, 7 and 8. In chapter 5, after 52 weeks, there was sustained weight loss of 5% but no change in FMD while adiponectin levels increased and LDL-C and insulin were substantially reduced. In chapter 7 the BP response to salt loading remained unchanged despite weight loss maintenance. Finally in chapter 8 weight loss was predicted by protein intake and there were reductions in CVD risk demonstrated by decreases in insulin, TG and CRP and increases in HDL-C. The studies in this thesis demonstrate that moderate weight loss has beneficial effects on traditional and novel cardiovascular disease risk markers but does not have a beneficial effect on FMD regardless of dietary composition. A high saturated fat diet has detrimental effects on novel CVD risk markers in weight stability but weight loss attenuates this effect. A high saturated fat diet may have detrimental effects on adhesion molecules in weight stability and may attenuate the beneficial effects of weight loss on LDL-C and CRP. Moderate long term weight loss maintenance has beneficial effects on most but not all CVD risk markers. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1293779 / Thesis (Ph.D.) -- School of Medicine, 2007

In this study, we investigated the role of Ang II in pathological vascular remodeling. We sought to determine whether the humoral or the mechanical effects of Ang II are the dominant factor driving the remodeling process. The following experimental groups were used: control group (untreated mice), mice treated with an angiotensin receptor blocker (Candesartan, 0.5 mg/kg/day,SQ), an ACE inhibitor (Captopril, 6 mg/kg/day), and a calcium-channel blocker (Amlodipine, 7.5 mg/kg/day). All mice (n=6 per experimental group) were from the C57Bl/6 background. The carotid ligation model was implemented to study the differences in vascular remodeling. Additionally, multiple time points (7-, 14-, and 21-days post-surgery) were used to track the progression of remodeling. In Day-7 analysis, all three treatment groups yielded similar remodeling patterns as evidenced by a significant reduction in neointimal area, medial thickening and hypertrophy compared with the control group. Histomorphometric analysis of carotid sections collected 1mm below the ligation demonstrated that the Amlodipine group had 26% reduction in total vessel area, Candesartan a 36% reduction, and Captopril a 28% reduction (p less than 0.05 in all groups compared with Control), as well as a parallel 38-40% drop in medial thickness. In Day-14 analysis, no significant differences between the Controls and treatment groups were observed, although differences were emerging between the treatment groups. Candesartan was found to reduce the extent of negative remodeling observed between the 7- and 14-day Control data, whereas the Captopril group did not exhibit this trend. All treatment groups exhibited less neointimal formation than Controls, similar to Day-7. By the 21-day time point, the Captopril group underwent positive remodeling, resembling the Candesartan and Amlodipine groups. Although total vessel area was analogous among all groups, neointimal areas were significantly decreased in the treatment groups. Blood pressure plays a pivotal role in the modulation of vascular remodeling in response to mechanical injury. Although intermediate timepoint analysis suggests that humoral aspects of ACE inhibition or angiotensin-receptor blockade yielded unique effects on the overall vessel caliber, upon reaching the late, 21-day time point, the mechanical factors became predominant. These data support the importance of blood pressure control in the attenuation of pathological vascular remodeling.