No description available.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / It has been proposed that the accumulation of microdamage in bone of aging individuals may play a causative and synergistic role in increased fracture incidence. If microdamage production were somehow increased, or reparative remodeling was somehow decreased, the scales may tip towards pathologic fracture. It is known that bisphosphonates increase microdamage accumulation in ribs, lumbar vertebrae, and ilium. The specific aim of this study was to histomorphometrically quantify the microdamage effect of the bisphosphonates alendronate and risedronate therapy on alveolar bone surrounding the first mandibular molar in the dog to determine if this response differs from that in non-bisphosphonate treated dogs. Thirty-four dogs were randomly assigned in two test, and one control groups. Test groups received pharmacologically equivalent doses of either alendronate (11 dogs) or risedronate (11 dogs). The control group (12 dogs) received subcutaneous injections of saline solution. The mandibular right first molar was analyzed for this study. Histomorphometric measurements were made using a x150 Nikon Optiphot-2 fluorescence microscope equipped with brightfield sources (Nikon, Inc.) using the semi-automatic Bioqant digitizing system (R & M Biometrics). There was no significant differences in cortical bone area across treatment groups for any of the regions, nor were any expected. Overall, there was almost twice as much crotical bone found in the Middle (Combined) regions compared with the Coronal (Combined) regions. The precent cortical area was universally high across all treatment groups averaging in the mid-90% range. The Apical region averaged 96.05%, followed by the Coronal region with 95.04% and the Middle region with 93.80%. The number of labeled osteons per cortical area in the alendronate and risedronate groups both tended to be lower relative to the control group (0.92/mm2 and 0.93/mm2 vs. 1.26mm2, respectively), but were not significantly different. On average, the coronal regions had nearly three times the LOn/CtAr as the Middle and Apical regions (1.90/mm2 vs. 0.63/mm2 and 0.57/mm2 respectively). Only in one region was MAR statistically higher in the Coronal (1mm) region, relative to all other regions compared. The Middle region demonstrated a low MAR. The WTh was significantly higher in the risedronate and alendronate groups than that of the control group for the Coronal region. This illustrates that with respect to the bisphosphonates, there is more formation and less resorption. In one region of a significantly lower WTh for the alendronate group relative to the risedronate group was noted. This implies a more potent inhibition in the risedronate treated groups. The WTh for the entire Coronal was statistically lower than every Middle measurement, but was not different than observed in the Apical region. This would tend to signify that in the Coronal, the turnover rate is more of a rapid nature, and therefore the osteons are not as large, while in the Apical, there were so many missing values due to the low rate of turnover, the numbers are skewed to the low end. In the Coronal (Combined) region, the risedronate (108.79 days) group exhibiting a significantly higher FP than the alendronate (62.88 days) and the control (56.13 days) groups. This would imply an increased potency of risedronate over alendronate. Regionally, the FP was significantly lower in the Coronal, relative to Middle or Apical. This is consistent with a more rapid turnover in the Coronal regions observed earlier. The Acf for alendronate (6.41/mm2 per day) and risedronate (5.69/mm2 per day) both tended to be lower by approximately 40% when compared with the control group (10.11/mm2 per day). Overall, the Acf for the Coronal region was 14.15/mm2 per day vs. 2.98/mm2 per day for the Middle and 9.13/mm2 per day for the Apical regions. This shows a significantly increased amount of turnover events taking place not just in the Coronal region, but in the region immediately adjacent to the tooth in the Coronal region. In no region did bone formation differ significantly when treated with bisphosphonates. The Coronal (1mm) region was statistically greater than every region it was measured against, individual and combined. Based on this observation, the second hypothesis that within the first molar alveolar site, bisphosphonate therapy with alendronate, and risedronate would inhibit remodeling more in the coronal region than in the middle and apical region, is rejected. When measuring microdamage accumulation (CrDn), only in the Middle (1mm) region was a significant difference across treatment groups notes. There were no other statistical differences across groups for any other regions. This observation demonstrates that bisphosphonate treatment does not increase the accumulation of microcracks in the dentate alveolar bone. Therefore, the first hypothesis that within the dentate mandible, bisphosphonate therapy with alendronate and risedronate would increase microdamage accumulation around the first molar compound to control, is rejected. When CrDn was compared by region, significant differences were noted. As expected, the Coronal (1mm) region demonstrated a significantly increased CrDN compared with the Apical and Middle regions. Coupled with the information that the BFR is increased in the Coronal and Middle (1-3mm) regions would argue for a reparative function of remodeling in the Coronal and outer Middle regions, which is in response to microdamage accumulation. Significant differences were observed in the Middle (1mm) and Middle (Combined) regions, with the alendronate group demonstrating an increased CrSDn relative to control. There was no statistical difference across treatment groups for any of the regions studied. When compared by regions, the Coronal (1mm) was statistically higher than all regions it was measured against. The Middle regions demonstrated elevated CrSDn relative to the apical region, which displayed the lowest CrSDn values of all regions. One final measure of microdamage is mean crack length. There were no statistically significant differences across any groups for any regions. The only significant differences, when observed across regions, was in reference to the Middle (1mm) region, which was significantly larger than the Coronal (1mm), Coronal (Combined), and the Middle (1-3mm) region. Otherwise, there is no observable trend, and no significant difference between regions. In conclusion, this study found that there was no an increase in microdamage in the dentate mandible of the dogs with bisphosphonate therapy, thereby rejecting the first hypothesis. While there were isolated regions of remodeling inhibition, the hypothesis that bisphosphonate therapy would inhibit remodeling more in the coronal region than in the middle and apical region is rejected. Therefore, based on the findings of this study, we conclude that bisphosphonates do inhibit remodeling in the dentate alveolus generally, but inhibition is not localized to any particular region. Finally, the administration of bisphosphonates do not result in an increase in microdamage accumulation in the dentate alveolus of dogs.

No description available.

Cheung Sao Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves xxiv-xxxvii). / Abstracts in English and Chinese. / Examination Committee List --- p.i / Declaration --- p.ii / Acknowledgements --- p.iii / Abstract --- p.v / Abstract in Chinese --- p.viii / List of Figures and Tables --- p.x / List of Abbreviations --- p.xix / Table of Content --- p.xxiii / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Human Liver Cancer --- p.1 / Chapter 1.1.1 --- Incidence of Hepatocellular Carcinoma --- p.1 / Chapter 1.1.2 --- Causes and Symptoms of Hepatocellular Carcinoma --- p.4 / Chapter 1.1.3 --- Treatment Options for Hepatocellular Carcinoma --- p.4 / Chapter 1.1.4 --- Multi-drug Resistance --- p.5 / Chapter 1.1.4.1 --- Mechanisms of Multi-drug Resistance --- p.5 / Chapter 1.2 --- Traditional Chinese Medicine --- p.10 / Chapter 1.2.1 --- Sophora flavescens and Radix Sophorae --- p.10 / Chapter 1.2.2 --- Flavonoid and its Sub-classification --- p.13 / Chapter 1.2.3 --- Flavonoid and Human Health --- p.15 / Chapter 1.3 --- Cell Death --- p.17 / Chapter 1.3.1 --- Necrosis --- p.17 / Chapter 1.3.2 --- Apoptosis --- p.17 / Chapter 1.3.3 --- Signaling Pathways in Apoptosis --- p.18 / Chapter 1.3.3.1 --- Extrinsic (Death Receptor-mediated) Pathway --- p.20 / Chapter 1.3.3.2 --- Intrinsic (Mitochondrial) Pathway --- p.21 / Chapter 1.3.3.3 --- Cysteine Aspartatic Acid Proteases --- p.21 / Chapter 1.4 --- Research Objective (s) --- p.22 / Chapter Chapter 2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.1.1 --- Cell Lines --- p.23 / Chapter 2.1.1.1 --- HepG2 --- p.24 / Chapter 2.1.1.2 --- RHepG2 --- p.24 / Chapter 2.1.1.3 --- WRL-68 --- p.25 / Chapter 2.1.2 --- Culture Media --- p.26 / Chapter 2.1.2.1 --- Rosewell Park Memorial Institute( RPMl) 1640 Medium --- p.26 / Chapter 2.1.2.2 --- Dulbecco's Modified Eagle's Medium (DMEM) --- p.26 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.2 --- Traditional Chinese Medicines and Conventional Anti-cancer Drugs --- p.27 / Chapter 2.3 --- Antibodies --- p.29 / Chapter 2.4 --- Chemicals --- p.30 / Chapter 2.5 --- Reagents and Buffers --- p.34 / Chapter 2.5.1 --- Reagents for Silica Gel Column Chromatography --- p.34 / Chapter 2.5.2 --- Buffers for Common Use --- p.34 / Chapter 2.5.3 --- Reagents for Cell Viability Assay --- p.35 / Chapter 2.5.4 --- Reagents and Buffers for Typical Apoptosis Experiments --- p.35 / Chapter 2.5.4.1 --- Cell Cycle Analysis --- p.35 / Chapter 2.5.4.2 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.35 / Chapter 2.5.4.3 --- DNA Fragmentation Detection --- p.35 / Chapter 2.5.5 --- Reagents and Buffers for Western Blot Study --- p.36 / Chapter 2.5.5.1 --- Whole-cell Protein Extraction --- p.38 / Chapter 2.5.5.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.38 / Chapter 2.5.6 --- Reagents and Buffers for Mitochondrial Transmembrane Potential Depolarization Measurement --- p.39 / Chapter 2.5.7 --- Reagents and Buffers for in vivo Animal Study --- p.39 / Chapter 2.5.8 --- Reagents and Buffers for Two-Dimensional Gel Electrophoresis --- p.40 / Chapter 2.5.8.1 --- Sample Preparation --- p.40 / Chapter 2.5.8.2 --- First Dimension Gel Electrophoresis - Isoelectric Focusing (IEF) --- p.40 / Chapter 2.5.8.3 --- Second Dimension Gel 日ectrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.40 / Chapter 2.5.8.4 --- Silver Staining --- p.41 / Chapter 2.5.9 --- Reagents for Mass Spectrometry Preparation --- p.42 / Chapter 2.5.9.1 --- Destaining --- p.42 / Chapter 2.5.9.2 --- Trypsin Digestion --- p.42 / Chapter 2.5.9.3 --- Desalting of Peptide Mixture --- p.43 / Chapter 2.5.10 --- Reagents and Buffers for Real-Time PCR --- p.43 / Chapter 2.6 --- Methods --- p.44 / Chapter 2.6.1 --- Isolation of Bioactive Constituents by Silica Gel Column Chromatography --- p.44 / Chapter 2.6.2 --- Cell Viability Assay --- p.45 / Chapter 2.6.3 --- Typical Apoptosis Experiments --- p.45 / Chapter 2.6.3.1 --- Cell Cycle Analysis --- p.46 / Chapter 2.6.3.2 --- Annexin V-FITC/ PI Staining Experiment --- p.47 / Chapter 2.6.3.3 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.48 / Chapter 2.6.3.4 --- DNA Fragmentation Reaction --- p.48 / Chapter 2.6.4 --- Western Blot Study --- p.49 / Chapter 2.6.4.1 --- Whole-cell Protein Extraction --- p.49 / Chapter 2.6.4.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.50 / Chapter 2.6.5 --- Caspase Activity Determination --- p.54 / Chapter 2.6.6 --- Mitochondrial Transmembrane Potential Depolarization Measurement --- p.55 / Chapter 2.6.7 --- in vivo Animal Study --- p.56 / Chapter 2.6.8 --- Two-Dimensional Gel Electrophoresis --- p.58 / Chapter 2.6.8.1 --- Sample Preparation --- p.58 / Chapter 2.6.8.2 --- First Dimension Electrophoresis - Isoelectric Focusing (IEF) --- p.59 / Chapter 2.6.8.3 --- Second Dimension Electrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.60 / Chapter 2.6.8.4 --- Silver Staining --- p.61 / Chapter 2.6.9 --- Mass Spectrometry Preparation --- p.63 / Chapter 2.6.9.1 --- Destaining and Trypsin Digestion --- p.63 / Chapter 2.6.9.2 --- Peptide Extraction --- p.63 / Chapter 2.6.9.3 --- Desalting of Peptide Mixture --- p.64 / Chapter 2.6.10 --- Real-Time PCR --- p.65 / Chapter 2.6.11 --- Cellular Glutathione Level Detection --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter Chapter 3 --- RESULTS AND DISCUSSIONS - CYTOTOXICITY OF FLAVONOIDS ISOLATED FROM RADIX SOPHORAE --- p.72 / Chapter 3.1 --- Screening of Cytotoxic Flavonoids from Radix Sophorae --- p.72 / Chapter 3.2 --- Cytotoxicity of Leachianone A on Human Hepatoma Cell Lines --- p.74 / Chapter 3.3 --- Cytotoxicity of Leachianone A on Human Normal Liver Cell Line --- p.77 / Chapter 3.4 --- Cytotoxicity of Sophoraflavone J on Human Hepatoma Cell Line --- p.79 / Chapter 3.5 --- Cytotoxicity of Sophoraflavone J on Human Normal Liver Cell Line --- p.79 / Chapter 3.6 --- Cytotoxicities of Cisplatin and Taxol on Human Hepatoma as well as Normal Liver Cell Lines --- p.81 / Chapter 3.7 --- Conclusion --- p.86 / Chapter Chapter 4 --- "RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF LEACHIANONE A-INDUCED CELL DEATH IN HEPATOMA CELLS, HepG2 and RHepG2" --- p.88 / Chapter 4.1 --- Promotion of Cell Cycle Arrest --- p.88 / Chapter 4.2 --- Induction of Apoptosis as Evidenced by Phosphatidylserine Externalization and DNA Fragmentation --- p.93 / Chapter 4.2.1 --- Occurrence of Phosphatidylserine Externalization --- p.94 / Chapter 4.2.2 --- DNA Fragmentation Detection --- p.99 / Chapter 4.2.2.1 --- Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.99 / Chapter 4.2.2.2 --- DNA Laddering Pattern in Agarose Gel Electrophoresis --- p.103 / Chapter 4.3 --- Recruitment of Multiple Signaling Pathways in Leachianone A-induced Apoptosis --- p.105 / Chapter 4.3.1 --- "Activation of Caspases-3, -8, and -9" --- p.105 / Chapter 4.3.2 --- Altered Expressions of Bcl-2 Family Proteins --- p.112 / Chapter 4.3.3 --- Loss of Mitochondrial Membrane Potential --- p.115 / Chapter 4.4 --- in vivo Tumor Growth Inhibition in HepG2-bearing Nude Mice --- p.121 / Chapter 4.5 --- Conclusion --- p.127 / Chapter Chapter 5 --- RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF SOPHORAFLAVONE J-INDUCED CELL DEATH IN HEPATOMA CELLS HepG2 --- p.132 / Chapter 5.1 --- Execution of Cellular Apoptosis --- p.133 / Chapter 5.2 --- Involvement of Multiple Signaling Pathways in Sophoraflavone J-induced Apoptosis --- p.138 / Chapter 5.3 --- Differential Proteomes of Control and Sophoraflavone J-treated HepG2 Cells --- p.148 / Chapter 5.4 --- Conclusion --- p.167 / Chapter Chapter 6 --- OVERALL CONCLUSION AND FUTURE PERSPECTIVES --- p.169 / References --- p.xxiv

The present study investigated the influence of a brief, intensive biofeedback-assisted imagery training regimen on psychological, physiological and neuroendocrinological measures of pain and stress in injury related chronic pain patients. The subjects were 36 patients (myelography examcandidates) who were assigned to the imagery or wait-list control group by order of referral presentation and to formulate equivalent groups.

This study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) > 10uM genistein > 70uM genistein. The chi-square test for comparing necrosis, apoptosis and life cells showed that Vitamin C could impact genistein-induced apoptosis in LNCaP cells (p = 0.0003). This study forms the basis for in vivo studies of the impact of vitamin C on genistein-induced apoptosis in LNCaP prostate cancer cells. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

In a mouse model of pulmonary thromboembolism induced by a collagen-adrenaline mixture, the SFE extract and ligustilide reduced the paralysis-death ratio, and the anti-thrombotic response of senkyunolide A was more pronounced. The effect of BDPH was not significant. Neither the SFE extract nor the three phthalides prolonged bleeding time in tail-transected mice. / In a rat myocardial ischemia-reperfusion model involving coronary artery ligation, 7-day pre-treatment with the SFE extract and ligustilide reduced ventricular arrhythmias in isolated hearts. BDPH and senkyunolide A were without significant effects. / In rat platelet-rich plasma, platelet aggregation induced by collagen and U46619 but not by adenosine diphosphate was inhibited by the SFE extract. Ligustilide inhibited the responses of all three agonists, while BDPH and senkyunolide A inhibited the collagen response only. / Raw Rhizoma Chuanxiong herb and its crude extract as obtained by supercritical fluid extraction (SFE) comprised mainly phthalides. The SFE extract and three representative phthalides, butylidenephthalide (BDPH), ligustilide and senkyunolide A, were studied on vasorelaxation, myocardial ischemia, platelet aggregation and thrombosis. The mechanisms underlying BDPH-mediated vasorelaxation were also explored. / Rhizoma Chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort., is a common traditional Chinese medicine used for the treatment of cardiovascular diseases. Surprisingly, the scientific basis of its action is poorly understood. The current study aims to establish the pharmacological basis of the cardiovascular effects of Rhizoma Chuanxiong and its active constituents by examining their effects in several cardiovascular domains. / The current study demonstrated various cardiovascular actions of Rhizoma Chuanxiong, and thereby established the pharmacological basis of the effects of the herb. Phthalides, in particular BDPH, ligustilide and senkyunolide A, were important contributors to such actions. Future investigation of the SFE extract and/or individual phthalides related to the progression from in vitro and in vivo effectiveness to clinical efficacy is much anticipated. / The SFE extract, BDPH, ligustilide and senkyunolide A produced vasorelaxation on isolated preparations of rat aorta, rat saphenous vein and pig coronary artery. BDPH-mediated relaxation appeared to involve both extracellular Ca 2+-dependent (L-type voltage-operated, receptor-operated and store-operated Ca2+ channels) and independent (NO modulation, Ca2+ release from internal stores and Ca2+ desensitization) mechanisms. BDPH was also observed to augment relaxation induced by sodium nitroprusside and forskolin through mechanisms that remain undefined. / Chan Sun Kin Sunny. / "July 2005." / Advisers: G. Lin; R. L. Jones. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1575. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 190-209). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Chan Yin Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 147-167). / Abstracts in English and Chinese. / ABSTRACT --- p.III / ACKNOWLEDGEMENT --- p.X / TABLE OF CONTENTS --- p.XI / ABBREVIATIONS --- p.XV / LIST OF FIGURES --- p.XVII / LIST OF TABLES --- p.XXI / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Introduction to Cardiovascular Disease and Atherosclerosis --- p.1 / Chapter 1.1.1 --- Cardiovascular Disease --- p.1 / Chapter 1.1.2 --- A therosclerosis --- p.3 / Chapter 1.1.2.1 --- Structure of Arteries --- p.4 / Chapter 1.1.2.2 --- Pathophysiology of Atherosclerosis --- p.5 / Chapter 1.1.2.3 --- Endothelial Dysfunction --- p.8 / Chapter 1.1.3 --- Current Western Therapies --- p.11 / Chapter 1.1.3.1 --- Surgery --- p.11 / Chapter 1.1.3.2 --- Western Medications --- p.13 / Chapter 1.1.4 --- Traditional Chinese Medicine --- p.17 / Chapter 1.1.4.1 --- Long History --- p.17 / Chapter 1.1.4.2 --- As Alternative Medicine --- p.18 / Chapter 1.1.4.3 --- Modernization of Chinese Medicine --- p.19 / Chapter 1.2 --- Introduction and Selection of Chinese Medicine --- p.20 / Chapter 1.2.1 --- Selection ofTCM Formulation from Pharmacopoeia --- p.20 / Chapter 1.2.1.1 --- Compound Formulation --- p.20 / Chapter 1.2.2 --- Introduction to the Herbal Medicines --- p.21 / Chapter 1.2.2.1 --- Danshen (Salvia miltiorrhiza) --- p.21 / Chapter 1.2.2.2 --- Gegen (Puerariae thomsonii and Puerariae lobata) --- p.22 / Chapter 1.2.2.3 --- Yanhu (Corydalis yanhusuo) and its Exclusion --- p.24 / Chapter 1.2.3 --- Source and Authentication of the Herbal Medicines --- p.25 / Chapter CHAPTER 2 --- OPTIMIZATION OF DANSHEN-GEGEN FORMULA --- p.26 / Chapter 2.1 --- Project History --- p.26 / Chapter 2.2 --- aims for the present study --- p.27 / Chapter 2.3 --- Methods and Materials --- p.30 / Chapter 2.3.1 --- Extracts --- p.30 / Chapter 2.3.2 --- Extraction Process --- p.31 / Chapter 2.3.3 --- In vitro Antioxidation Model --- p.33 / Chapter 2.3.4 --- Ex vivo Vasodilation Model --- p.35 / Chapter 2.3.5 --- Statistical Analysis --- p.38 / Chapter 2.4 --- Results --- p.39 / Chapter 2.4.1 --- Vasodilation Results --- p.39 / Chapter 2.4.2 --- Antioxidation Results --- p.43 / Chapter 2.5 --- Discussion --- p.46 / Chapter 2.6 --- Further Modification of the Formula --- p.49 / Chapter 2.6.1 --- Extracts --- p.49 / Chapter 2.6.2 --- Results --- p.49 / Chapter 2.7 --- discussion --- p.52 / Chapter CHAPTER 3 --- MARKER CHEMICAL CONTENTS OF HERBAL EXTRACTS AND THEIR PHARMACOLOGICAL PROPERTIES --- p.56 / Chapter 3.1 --- HPLC Analysis of Marker Contents --- p.56 / Chapter 3.1.1 --- Methods --- p.57 / Chapter 3.1.2 --- Results --- p.58 / Chapter 3.1.2.1 --- HPLC Chromatograms --- p.59 / Chapter 3.1.2.2 --- Content Percentage of Marker Compounds --- p.63 / Chapter 3.1.3 --- Discussion --- p.64 / Chapter 3.2 --- Studies on Marker Compounds --- p.65 / Chapter 3.2.1 --- Introduction --- p.65 / Chapter 3.2.2 --- Methods and Materials --- p.67 / Chapter 3.2.2.1 --- Source of Pure Compounds --- p.67 / Chapter 3.2.2.2 --- Purification and Identification of SAB --- p.68 / Chapter 3.2.2.3 --- Vasodilation model --- p.70 / Chapter 3.2.2.4 --- Antioxidation Model --- p.71 / Chapter 3.2.2.5 --- Structures of Pure Compounds --- p.72 / Chapter 3.2.3 --- Results --- p.73 / Chapter 3.2.3.1 --- Vasodilation Results --- p.73 / Chapter 3.2.3.2 --- Antioxidation Results --- p.76 / Chapter 3.3 --- Discussion --- p.79 / Chapter 3.4 --- Synergistic Effect Study --- p.85 / Chapter 3.4.1 --- Introduction --- p.85 / Chapter 3.4.2 --- Methods --- p.85 / Chapter 3.4.3 --- Results --- p.86 / Chapter 3.4.4 --- Discussion --- p.88 / Chapter 3.5 --- STUDY ON 3'-HYDROXYPlIERARIN AND 3'-METHOXYPUERARIN PURIFIED FROM YFGE --- p.90 / Chapter 3.5.1 --- 3 '-hydroxypuerarin and 3'-methoxypuerarin --- p.90 / Chapter 3.5.2 --- Methods and Materials --- p.91 / Chapter 3.5.2.1 --- Purification by HPLC semi-preparation --- p.91 / Chapter 3.5.2.2 --- Bioassays --- p.93 / Chapter 3.5.3 --- Results --- p.94 / Chapter 3.5.3.1 --- Vasodilation Study --- p.94 / Chapter 3.5.3.2 --- Antioxidative Effect of Yege --- p.95 / Chapter 3.5.4 --- Discussion / Chapter CHAPTER 4 --- MECHANISTIC STUDY --- p.98 / Chapter 4.1 --- Introduction --- p.98 / Chapter 4.1.1 --- Nitric Oxide-mediated Vasodilation --- p.99 / Chapter 4.1.2 --- Prostacyclin-mediated Vasodilation --- p.100 / Chapter 4.1.3 --- EDHF-mediated Vasodilation --- p.101 / Chapter 4.1.4 --- Endothelium-dependent and -independent Vasodilations --- p.103 / Chapter 4.2 --- Methods and Materials --- p.104 / Chapter 4.3 --- Results --- p.107 / Chapter 4.3.1 --- Danshen-Gegen Formula (DY80) --- p.107 / Chapter 4.3.2 --- Salvianolic acid B --- p.112 / Chapter 4.3.3 --- Daidzein --- p.117 / Chapter 4.4 --- Discussion --- p.121 / Chapter CHAPTER 5 --- STUDY ON LIPID PEROXIDATION AND UPTAKE BY MACROPHAGES --- p.128 / Chapter 5.1 --- Study of DY 80 and SAB on Copper-ion induced Low Density Lipoprotein Oxidation --- p.128 / Chapter 5.1.1 --- Pathologic Role of oxidized Low Density Lipoprotein --- p.128 / Chapter 5.1.2 --- Antioxidants in Low Density Lipoprotein and Role of Transition Metals --- p.129 / Chapter 5.1.3 --- Methods and Materials --- p.130 / Chapter 5.1.4 --- Results --- p.131 / Chapter 5.1.5 --- Discussion --- p.133 / Chapter 5.2 --- Study of Scavenger Receptor Regulation in Macrophages --- p.135 / Chapter 5.2.1 --- Introduction --- p.135 / Chapter 5.2.2 --- Methods and Materials --- p.136 / Chapter 5.2.3 --- Results --- p.139 / Chapter 5.2.4 --- Discussions --- p.140 / Chapter CHAPTER 6 --- General Discussion --- p.143 / REFERENCES --- p.147

Conclusion. The present results indicate that, baicalein with optimal dosage of 30 muM suppressed collagen deposition in AngII stimulated SHR CF cultures. In animal model of hypertension, high dose of baicalein feeding for 12 week showed optimal antifibrotic effect in hypertensive hearts. (Abstract shortened by UMI.) / For in-vivo study, comparing to control group, HW/BW (x1000) of SHR was significantly reduced in 12 weeks-high dose baicalein and (-0.78+/-0.23, p=0.014) 12 weeks-Valsartan group (-0.71+/-0.22, p=0.021), however, no significant change was observed in the LW/BW ratio. / In Blood pressure control, no effects on attenuation of SBP were observed after 4 weeks and 12 weeks daily administration of baicalein, only 12 weeks feeding of Valsartan significantly down-regulated the systolic blood pressure by -19.25+/-10.09 mmHg, p=0.049. / In the in-vivo study, SHR was used as a model of genetic hypertension. The objectives were: firstly, to determine the efficacy of baicalein in the prevention of myocardial fibrosis (interstitial fibrosis) in SHR, & compared with WKY rats as normal controls. Secondly, to determine if over-expression of pro-collagen I (and III, if any) gene in the ventricles could be normalized by baicalein. Thirdly, to determine if left ventricular hypertrophy in SHR is improved by baicalein. Furthermore, to determine if blood pressure and blood biochemistry parameters (plasma level of brain natriuretic peptides (BNP), and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) level could be alternated by baicalein. Besides, to determine the body weight (BW), heart weight to body ratio (HW/BW), liver weight to body weight ratio (LW/BW), serum AST and ALT level could be alternated by baicalein. Finally to evaluate by echocardiography if there are changes of ivss and ivsd in SHR after administration of baicalein. / Keywords. baicalein, wogonin, collagen, cardiac fibrosis, hypertension / Objectives. In the in-vitro study, cardiac fibroblast culture was prepared from neonatal SHR and WKY rats. The objectives were multi-fold: firstly, to determine over-expression of pro-collagen I mRNA (and III, if any) in cardiac fibroblasts cultures could be normalized by baicalein and wogonin after AngII activation. Secondly, to evaluate the efficacy of baicalein and wogonin on the suppression of total collagen protein production in cardiac fibroblasts cultures after AngII activation. Thirdly, to evaluate the mechanism (in protein level) of baicalein and wogonin on regulating collagen deposition in cardiac fibroblasts after AngII activation. Furthermore, to determine if there were any effects on cytotoxicity and membrane integrity of baicalein and wogonin towards cardiac fibroblasts cultures. Finally, to determine the optimal concentration of baicalein and wogonin for the above actions in-vitro. / Results. For in-vitro study, incubation of AngII resulted in significant up-regulation of COL-I and COL-III mRNA and total collagen protein production. Addition of either baicalein or wogonin significantly suppressed the mRNA synthesis and total collagen protein in CF with an optimal dosage of 30 muM. No effects on viability and membrane integrity were observed on baicalein and wogonin towards cardiac fibroblasts cultures. / Kong, Kam Chuen Ebenezer. / Advisers: Cheuk-Man Yu; Gabriel W. K. Yip. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0242. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 176-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.