peripheral arterial disease (PAD), a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy on the ability of plasma, from patients undergoing PTA, to stimulate SMCs in vitro. We aimed to investigate the effect of combination treatment on levels of circulating adhesion molecules and factors which mediate SMC proliferation in experimental models. We also sought to demonstrate any association between changes in measured markers and the development of restenosis or vascular events. Methods Fifty patients were randomised to receive clopidogrel or placebo, for thirty days, in addition to their daily 75mg aspirin. To measure proliferative capacity, diluted plasma was incubated with 24h-growth-arrested rat vascular SMCs, and Extracellular-regulated-kinase (ERK)1/2 activation was analysed by Western blotting at baseline, 1-hour pre-PTA, and at 1-hour, 24-hours and 30-days post-PTA. Plasma platelet-derived growth factor (PDGF-BB), soluble (s)E-selectin, sICAM-1 (intracellular adhesion molecule-1) and von Willebrand factor (vWF) were measured by ELISA (Enzyme-linked immunosorbent assay), at the same time-points. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and 1-hour post-PTA. Patients’ notes and all investigations were reviewed for 2 years post-PTA to record restenosis or vascular events. Results Samples were available for all 50 patients at baseline, 1-hour pre-PTA and 1-hour post-PTA timepoints. In this cohort ERK1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups. Those who developed a symptomatic restenosis had a significantly higher level of SMC activation at the 1-hour post-PTA time-point. There was a statistically significant decrease in PDGF-BB, and increase in vWF, following loading with clopidogrel. sICAM-1 levels significantly decreased in the aspirin/placebo group following PTA. ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel therapy post-PTA. Conclusions This is the first study to show in-vitro ERK1/2 activation (a marker of SMC proliferation) increases post-PTA. Patients developing a symptomatic restenosis had a significantly higher level of SMC activation at the 1-hour post-PTA time-point. Clopidogrel therapy had no significant effect on ERK1/2 activation, although it did reduce PDGF-BB in the larger cohort of patients. Further work is required to evaluate potential therapeutic treatments which may reduce peripheral PTA-induced smooth muscle cell activation.

by William, Wai-lun Lam. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 85-95). / Chapter I. --- Introduction --- p.1 / Chapter II. --- Our Approach --- p.9 / Chapter III. --- Results and Discussion - Synthetic Strategy --- p.29 / Chapter IV. --- Results and Discussion - Pharmacological Activity --- p.44 / Chapter V. --- Conclusion --- p.49 / Chapter VI. --- Further Development --- p.53 / Chapter VII. --- Experimental Section --- p.55 / Chapter VIII. --- References --- p.85 / Chapter IX. --- Supplementary Materials --- p.96

by Chu, Pui-ya. / Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 115-126. / ACKNOWLEDGEMENT / LIST OF ABBREVIATIONS / ABSTRACT --- p.1 / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- PLATELET-ACTIVATING FACTOR (PAF) --- p.4 / Chapter 1.1.1 --- Metabolism of PAF --- p.4 / Chapter 1.1.1.1 --- Biosynthesis of PAF --- p.4 / Chapter 1.1.1.2 --- Degradation of PAF --- p.9 / Chapter 1.1.2 --- Systemic effects of PAF --- p.12 / Chapter 1.1.3 --- Structure - activity relationship of PAF --- p.16 / Chapter 1.2 --- PAF RECEPTORS --- p.19 / Chapter 1.2.1 --- PAF receptor on platelets --- p.19 / Chapter 1.2.2 --- PAF receptor on leukocytes --- p.20 / Chapter 1.2.3 --- PAF receptor on macrophages --- p.20 / Chapter 1.2.4 --- Antagonists of PAF --- p.20 / Chapter 1.2.4.1 --- Nonspecific inhibitors of PAF --- p.21 / Chapter 1.2.4.2 --- Specific antagonists of PAF --- p.21 / Chapter 1.3 --- SECOND MESSENGER SYSTEMS OF PAF --- p.22 / Chapter 1.3.1 --- Adenylate cyclase - cyclic adenosine mono- phosphate system --- p.26 / Chapter 1.3.2 --- Phospholipase C - phosphatidylinositol system --- p.28 / Chapter 1.3.3 --- Intracellular calcium --- p.29 / Chapter 1.3.4 --- The role of prostaglandins and leukotrienes --- p.30 / Chapter 1.3.5 --- Protein kinase C --- p.30 / Chapter 1.3.5.1 --- Dual action of PKC --- p.31 / Chapter 1.3.5.2 --- Down regulation of PKC --- p.33 / Chapter 1.4 --- THE FUNCTION OF MACROPHAGES --- p.33 / Chapter 1.4.1 --- Phagocytosis --- p.34 / Chapter 1.4.2 --- Antigen presentation --- p.34 / Chapter 1.4.3 --- Release of cytokines --- p.34 / Chapter 1.4.4 --- Respiratory burst --- p.35 / Chapter CHAPTER 2 --- METHODS / Chapter 2.1 --- PREPARATION OF PERITONEAL MACROPHAGES --- p.37 / Chapter 2.1.1 --- Preparation of reagents --- p.37 / Chapter 2.1.2 --- Preparation of peritoneal macrophages --- p.37 / Chapter 2.2 --- RADIOLIGAND BINDING ASSAY --- p.38 / Chapter 2.2.1 --- Reagents --- p.38 / Chapter 2.2.2 --- [3H]-PAF binding to TG-PEC --- p.39 / Chapter 2.2.2.1 --- Preparation of thioglycollate-elicited peritoneal macrophages --- p.39 / Chapter 2.2.2.2 --- Preparation of working solutions --- p.39 / Chapter 2.2.2.3 --- Assay of [3H]-PAF binding --- p.40 / Chapter 2.2.3 --- [3H]-PAF binding to resident PEC --- p.40 / Chapter 2.2.3.1 --- Preparation of resident peritoneal mcrophages --- p.41 / Chapter 2.2.3.2 --- Preparation of working solutions --- p.41 / Chapter 2.2.3.3 --- Assay of [3H]-PAF binding --- p.41 / Chapter 2.2.4 --- Preparation of drugs --- p.41 / Chapter 2.2.5 --- Data analysis --- p.42 / Chapter 2.3 --- MEASUREMENT OF INOSITOL PHOSPHATES --- p.42 / Chapter 2.3.1 --- Preparation of reagents --- p.42 / Chapter 2.3.2 --- Dowex column preparation --- p.43 / Chapter 2.3.3 --- Cell plating in 24 - well plastic trays --- p.44 / Chapter 2.3.4 --- Determination of total inositol phosphates --- p.44 / Chapter 2.3.5 --- Column separation --- p.45 / Chapter 2.3.6 --- Determination of inositol trisphosphate (IP3) --- p.46 / Chapter 2.4 --- MEASUREMENT OF INOSITOL PHOSPHATES ACCUMULATION AFTER PROLONGED PMA PRETREATMENT --- p.46 / Chapter 2.4.1 --- Preparation of phorbol-12-myristate-13-acetate (PMA) solutions --- p.47 / Chapter 2.4.2 --- Preparation of cells with PMA --- p.47 / Chapter 2.5 --- DETERMINATION OF SUPEROXIDE ANION PRODUCTION --- p.47 / Chapter 2.5.1 --- Preparation of drugs --- p.47 / Chapter 2.5.2 --- Assay of superoxide anion production --- p.48 / Chapter 2.5.3 --- Data analysis --- p.48 / Chapter 2.6 --- STATISTICAL METHOD --- p.48 / Chapter CHAPTER 3 --- RESULTS / Chapter 3.1 --- [3H]-PAF BINDING TO TG-PEC --- p.50 / Chapter 3.1.1 --- General properties --- p.50 / Chapter 3.1.2 --- Stereospecific of PAF receptor --- p.57 / Chapter 3.1.3 --- Comparison of [3H]-PAF binding to TG-PEC and TG-PMΦ from Balb/c mice --- p.57 / Chapter 3.1.4 --- Inhibition of specific binding of [3H]-PAF to murine and guinea pig TG-PEC by PAF --- p.57 / Chapter 3.1.5 --- Effects of PAF antagonists on the binding of [3H]- PAF to TG-PEC from Balb/c mice and guinea pigs --- p.60 / Chapter 3.1.6 --- Scatchard analysis of [3H]-PAF binding to murine and guinea pig TG-PMΦ --- p.65 / Chapter 3.2 --- SUPEROXIDE ANION PRODUCTION IN PERITONEAL MACROPHAGES --- p.69 / Chapter 3.2.1 --- Superoxide anion production induced by PAFin murine and guinea pig TG-PMΦ --- p.69 / Chapter 3.2.2 --- Effect of PMA on superoxide anion production in murine and guinea pig TG-PMΦ --- p.69 / Chapter 3.2.3 --- Effect of calcium ionophore on superoxide anion production in murine and guinea pig TG-PMΦ --- p.75 / Chapter 3.2.4 --- Effect of PAF antagonists on PAF - induced superoxide anion production in guinea pig TG-PMΦ --- p.75 / Chapter 3.3 --- PHOSPHOLIPASE C - PHOSPHATIDYLINOSITOL SYSTEM IN PERITONEAL MACROPHAGES --- p.79 / Chapter 3.3.1 --- Effect of PAF on the accumulation of inositol phosphates in the absence of LiCl --- p.79 / Chapter 3.3.2 --- Effect of PAF on the accumulation of inositol phosphates in the presence of LiCl --- p.79 / Chapter 3.3.2.1 --- Time course of [3H]-inositol phosphates accumulation induced by PAF in TG-PMΦ --- p.86 / Chapter 3.3.2.2 --- Effect of PAF on the accumulation of [3H]-IPs in TG- PMΦ from Balb/c mice and guinea pigs --- p.86 / Chapter 3.3.2.3 --- Effect of PAF antagonists on PAF-induced [3H]-IPs accumulation in TG-PMΦ from Balb/c mice and guinea pigs --- p.86 / Chapter 3.3.2.4 --- Effect of PMA on PAF-induced [3H]-IPs formation in TG-PMΦ from Balb/c mice and guinea pigs --- p.90 / Chapter 3.3.2.5 --- Effect of prolonged PMA pretreatment on PAF and PMA-induced [3H]-IPs accumulation in murine and guinea pig TG-PMΦ --- p.90 / Chapter 3.4 --- STUDIES OF RESIDENT PEC FROM Balb/c MICE --- p.96 / Chapter 3.4.1 --- Binding of 2nM [3H]-PAF to Balb/c mice resident PEC --- p.96 / Chapter 3.4.2 --- PAF-induced [3H]-IPs accumulation in murine resident PMΦ --- p.100 / Chapter 3.4.3 --- Binding of 0.2 nM [3H]-PAF to Balb/c mice resident PEC --- p.100 / Chapter 3.4.4 --- Superoxide anion production induced by PAF and PMA in murine resident PMΦ --- p.104 / Chapter CHAPTER 4 --- DISCUSSIONS / Chapter 4.1 --- PAF RECEPTOR ON PERITONEAL MACROPHAGES --- p.125 / Chapter 4.1.1 --- [3H]-PAF binding to peritoneal macrophages --- p.105 / Chapter 4.1.2 --- Expression of PAF receptor on Balb/c mice peritoneal macrophages --- p.107 / Chapter 4.2 --- SUPEROXIDE ANION PRODUCTION IN PERITONEAL MACROPHAGES --- p.108 / Chapter 4.3 --- PAF RECEPTOR AND POLYPHOSPHATIDYLINOSITOL SYSTEM IN PERITONEAL MACROPHAGES --- p.109 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.112 / REFERENCES --- p.115

Orientador: Luís Carlos Spolidorio / Banca: Joni Augusto Cirelli / Banca: Raquel Fernanda Gerlach / Resumo: O objetivo deste trabalho foi avaliar o efeito da administracao da aspirina (Asp), do clopidogrel (Clo) e da ticlopidina (Tic) sobre o processo de reparacao dos tecidos periodontais apos inducao experimental de periodontite em ratos. Primeiramente avaliou-se a acao destas drogas sobre a expressao das citocinas pro-inflamatorias: TNF-α, IL-6 e TXA2 no tecido gengival de 25 ratos subdivididos em 5 grupos (n=5), 15 dias apos a instalacao da ligadura ao redor do primeiro molar inferior. Para avaliacao do reparo dos tecidos periodontais, setenta e dois ratos (Rattus norvegicus albinus, Holtzman) foram distribuídos aleatoriamente em 6 grupos (n=12), sendo 1 controle e 5 submetidos a periodontite atraves da instalacao de ligadura bilateral na regiao de primeiro molar inferior. Apos 15 dias, o grupo controle e um grupo com periodontite foram sacrificados. Para a inducao do reparo dos tecidos periodontais, as ligaduras dos animais dos outros 4 grupos foram removidas e os ratos foram tratados com solucao de NaCl 0.9%, Asp (30mg/kg), Clo (75 mg/kg) e Tic (300 mg/kg), diariamente, via gavagem. Apos 15 dias de tratamento, os animais foram sacrificados, as hemi- mandibulas do lado direito removidas para analise histologica e as do lado esquerdo para avaliacao macroscopica, microtomografia computadorizada e analise da expressao, atividade especifica e co-localizacao das metaloproteinases de matriz (MMPs) -2 e -9 atraves de zimograma e zimografia in situ. Apos a retirada da ligadura, houve reparacao do osso alveolar e reparacao do tecido gengival representado pela recomposicao da arquitetura tecidual do epitélio e do tecido conjuntivo. O tratamento com Asp comprometeu a reparacao óssea alveolar na face mesial e acelerou na area de furca, ao passo que nao influenciou na recomposicao da arquitetura do tecido epitelial e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to evaluate the effect of administration of aspirin (Asp), clopidogrel (Clo) and ticlopidine (Tic) in the process of periodontal tissue repair after induction of experimental periodontitis in rats. First, we evaluated the action of these drugs on the expression of pro-inflammatory cytokines: TNF-α, IL-6 and TXA2 in the gingival tissue of 25 rats randomly distributed in five equal groups (n=5), 15 days after ligature placement around lower first molars. For periodontal tissue evaluation, seventy-two rats (Rattus norvegicus albinus, Holtzman) were randomly distributed in 6 equal groups (n=12). One control and 5 submitted to a ligature-induced periodontitis model in the region of lower first molar bilaterally. After 15 days, the control group and a group with periodontitis were sacrificed. To induce periodontal tissue repair, ligatures from the other 4 groups were removed and the rats treated with NaCl 0.9%, Asp (30 mg/kg), Clo (75 mg/kg) and Tic (300 mg/kg) daily by gavage. After 15 days of treatment, animals were killed, the right mandibles were removed for histological analysis and the left side to macroscopic, microtomography evaluation and expression, activity and colocalization of matrix metalloproteinases (MMPs) -2 and -9 by zymogram and in situ zymography. After removal of the ligature, there was repair of the alveolar bone and gingival tissue represented by the restoration of tissue architecture of the epithelium and connective tissue. Treatment with Asp undertook the repair of the mesial alveolar bone and accelerated the repair of furcation area, while not influenced the restoration of tissue architecture and epithelial tissue. Treatment with Tic undertook the repair of mesial alveolar bone and furcation the area, as well as the repair of gingival epithelial... (Complete abstract, click electronic access below) / Mestre

Objetivo: Avaliar o uso de antitrombóticos em pacientes com fibrilação atrial (FA) em hospital cardiológico no Brasil (InCor).Métodos e resultados: Um estudo observacional transversal analisou os prontuários de todos os pacientes atendidos no InCor em cada um de 5 dias separados no ano de 2002 (Fase 1), sendo prospectivamente reanalisados após 1 ano (Fase 2). A prevalência da FA nos 3764 prontuários analisados foi de 8%. Antiplaquetários foram prescritos para 21,26% e 19,93%, anticoagulantes para 46,51% e 57,81%, e 32,23% e 22,26% não usavam nenhum antitrombótico nas Fases 1 e 2, respectivamente. Somente 15,60% e 23,25% apresentavam níveis de RNI terapêuticos.Conclusão: A anticoagulação é subutilizada nos pacientes com FA apesar do fato de serem tratados por cardiologistas em um hospital universitário / Objective: To assess antithrombotic therapy among atrial fibrillation (AF) patients in a Brazilian University Heart Hospital (InCor).Methods and results: A cross sectional study analyzed the charts of all patients treated at InCor in 5 separate days of 2002 (Phase 1), and prospectively reviewed them after one year (Phase 2). The prevalence of AF in the 3,764 assessed charts was of 8.0%. Antiplatelets were prescribed to 21.26% and 19.93%, anticoagulants to 46.51% and 57.81%, and 32.23% and 22.26% were not receiving any antithrombotic in Phases 1 and 2, respectively. Only 15.60% and 23.25% were within INR therapeutic range.Conclusion: Anticoagulation is underused in AF patients besides the fact of being treated by cardiologists in a University Hospital

Made available in DSpace on 2014-06-11T19:27:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-20Bitstream added on 2014-06-13T19:35:52Z : No. of bitstreams: 1 coimbra_ls_me_arafo.pdf: 5964104 bytes, checksum: 3c09044b764aa34e6190582152ee354a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho foi avaliar o efeito da administracao da aspirina (Asp), do clopidogrel (Clo) e da ticlopidina (Tic) sobre o processo de reparacao dos tecidos periodontais apos inducao experimental de periodontite em ratos. Primeiramente avaliou-se a acao destas drogas sobre a expressao das citocinas pro-inflamatorias: TNF-α, IL-6 e TXA2 no tecido gengival de 25 ratos subdivididos em 5 grupos (n=5), 15 dias apos a instalacao da ligadura ao redor do primeiro molar inferior. Para avaliacao do reparo dos tecidos periodontais, setenta e dois ratos (Rattus norvegicus albinus, Holtzman) foram distribuídos aleatoriamente em 6 grupos (n=12), sendo 1 controle e 5 submetidos a periodontite atraves da instalacao de ligadura bilateral na regiao de primeiro molar inferior. Apos 15 dias, o grupo controle e um grupo com periodontite foram sacrificados. Para a inducao do reparo dos tecidos periodontais, as ligaduras dos animais dos outros 4 grupos foram removidas e os ratos foram tratados com solucao de NaCl 0.9%, Asp (30mg/kg), Clo (75 mg/kg) e Tic (300 mg/kg), diariamente, via gavagem. Apos 15 dias de tratamento, os animais foram sacrificados, as hemi- mandibulas do lado direito removidas para analise histologica e as do lado esquerdo para avaliacao macroscopica, microtomografia computadorizada e analise da expressao, atividade especifica e co-localizacao das metaloproteinases de matriz (MMPs) -2 e -9 atraves de zimograma e zimografia in situ. Apos a retirada da ligadura, houve reparacao do osso alveolar e reparacao do tecido gengival representado pela recomposicao da arquitetura tecidual do epitélio e do tecido conjuntivo. O tratamento com Asp comprometeu a reparacao óssea alveolar na face mesial e acelerou na area de furca, ao passo que nao influenciou na recomposicao da arquitetura do tecido epitelial e... / The aim of this study was to evaluate the effect of administration of aspirin (Asp), clopidogrel (Clo) and ticlopidine (Tic) in the process of periodontal tissue repair after induction of experimental periodontitis in rats. First, we evaluated the action of these drugs on the expression of pro-inflammatory cytokines: TNF-α, IL-6 and TXA2 in the gingival tissue of 25 rats randomly distributed in five equal groups (n=5), 15 days after ligature placement around lower first molars. For periodontal tissue evaluation, seventy-two rats (Rattus norvegicus albinus, Holtzman) were randomly distributed in 6 equal groups (n=12). One control and 5 submitted to a ligature-induced periodontitis model in the region of lower first molar bilaterally. After 15 days, the control group and a group with periodontitis were sacrificed. To induce periodontal tissue repair, ligatures from the other 4 groups were removed and the rats treated with NaCl 0.9%, Asp (30 mg/kg), Clo (75 mg/kg) and Tic (300 mg/kg) daily by gavage. After 15 days of treatment, animals were killed, the right mandibles were removed for histological analysis and the left side to macroscopic, microtomography evaluation and expression, activity and colocalization of matrix metalloproteinases (MMPs) -2 and -9 by zymogram and in situ zymography. After removal of the ligature, there was repair of the alveolar bone and gingival tissue represented by the restoration of tissue architecture of the epithelium and connective tissue. Treatment with Asp undertook the repair of the mesial alveolar bone and accelerated the repair of furcation area, while not influenced the restoration of tissue architecture and epithelial tissue. Treatment with Tic undertook the repair of mesial alveolar bone and furcation the area, as well as the repair of gingival epithelial... (Complete abstract, click electronic access below)

Objetivo: Avaliar o uso de antitrombóticos em pacientes com fibrilação atrial (FA) em hospital cardiológico no Brasil (InCor).Métodos e resultados: Um estudo observacional transversal analisou os prontuários de todos os pacientes atendidos no InCor em cada um de 5 dias separados no ano de 2002 (Fase 1), sendo prospectivamente reanalisados após 1 ano (Fase 2). A prevalência da FA nos 3764 prontuários analisados foi de 8%. Antiplaquetários foram prescritos para 21,26% e 19,93%, anticoagulantes para 46,51% e 57,81%, e 32,23% e 22,26% não usavam nenhum antitrombótico nas Fases 1 e 2, respectivamente. Somente 15,60% e 23,25% apresentavam níveis de RNI terapêuticos.Conclusão: A anticoagulação é subutilizada nos pacientes com FA apesar do fato de serem tratados por cardiologistas em um hospital universitário / Objective: To assess antithrombotic therapy among atrial fibrillation (AF) patients in a Brazilian University Heart Hospital (InCor).Methods and results: A cross sectional study analyzed the charts of all patients treated at InCor in 5 separate days of 2002 (Phase 1), and prospectively reviewed them after one year (Phase 2). The prevalence of AF in the 3,764 assessed charts was of 8.0%. Antiplatelets were prescribed to 21.26% and 19.93%, anticoagulants to 46.51% and 57.81%, and 32.23% and 22.26% were not receiving any antithrombotic in Phases 1 and 2, respectively. Only 15.60% and 23.25% were within INR therapeutic range.Conclusion: Anticoagulation is underused in AF patients besides the fact of being treated by cardiologists in a University Hospital

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

En Si Wang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 126-140 (2nd gp.)). / Acknowledgements --- p.i / Contents --- p.ii / Abstract --- p.iv / List of Acronyms and Abbreviations --- p.vi / introduction --- p.1 / Chapter I. --- "Platelet Activating Factor (PAF)´ؤPast, Present, and Future" --- p.1 / Chapter I-1. --- What is PAF? --- p.1 / Chapter I-2. --- Biochemistry of PAF --- p.2 / Chapter I-2-1. --- Metabolic Cycle of PAF --- p.3 / Chapter I-2-1-A. --- Biosynthesis of PAF --- p.4 / Chapter I-2-1 -B. --- Inactivation of PAF --- p.6 / Chapter I-2-2. --- Role of Endogenous PAF in Cell --- p.7 / Chapter I-3. --- Chemistry of PAF --- p.8 / Chapter I-4. --- Pathobiology of PAF --- p.9 / Chapter II. --- PAF Receptor --- p.10 / Chapter II-1. --- Presence and Characteristics of PAF Receptor --- p.10 / Chapter II-l-l. --- Solubilization of PAF Receptor --- p.10 / Chapter II-1-2. --- G-Protein Involvement --- p.11 / Chapter II-1-3. --- Species Differences --- p.11 / Chapter II-1-4. --- Multiple Conformational States of PAF Receptor --- p.12 / Chapter II-1-5. --- PAF Receptor Heterogeneity --- p.12 / Chapter II-2. --- Putative Conformation of PAF Membrane Binding Sites --- p.13 / Chapter II-3. --- Recent Progress in PAF Receptor Research --- p.15 / Chapter III. --- PAF Receptor Antagonist --- p.18 / Chapter III-1. --- Classification of PAF Antagonists --- p.18 / Chapter III-2. --- Inhibition Types of PAF Receptor Antagonists --- p.19 / Chapter III-2-1. --- Nonspecific Inhibition of the Effects of PAF --- p.21 / Chapter III-2-2. --- Specific Inhibition of PAF --- p.22 / Chapter III-3. --- Recent Progress in PAF Receptor Antagonist Research --- p.22 / Chapter IV. --- Pharmacology and Syntheses of Spiro-Ether Structural Units --- p.26 / Chapter IV-1. --- Natural Products Containing Spiro-Ether and Related Structural Units --- p.30 / Chapter IV-1-1. --- Labdane Diterpenoids Containing Spiro-Ether Structural Units --- p.30 / Chapter IV-1-2. --- Leucodrin and Related Derivatives --- p.32 / Chapter IV-2. --- Synthetic Methods of Spiro-Ethers and Related Derivatives --- p.34 / Chapter V. --- Aim of the Present Work --- p.45 / RESULTS AND DISCUSSION --- p.47 / Chapter I. --- Isolation and Structure Elucidation of Prehispanolone (1) and Preleoheterin (3) --- p.47 / Chapter I-1. --- Material and Isolation --- p.47 / Chapter I-2. --- Structure Elucidation of Prehispanolone (1) and Preleoheterin (3) --- p.47 / Chapter II. --- Synthesis of Model Compounds --- p.53 / Chapter II-l. --- "Synthesis of 2-Methyl-1,7-dioxaspiro[4.4]nonane (137)" --- p.53 / Chapter II-2. --- "Synthesis of 2,2-Dimethyl-l,7-dioxaspiro[4.4]nonane (139)" --- p.68 / Chapter II-3. --- "Synthesis of 2,2-Diphenyl-1,7-dioxaspiro[4.4]nonane (141) and 2,2-Diphenyl-l,7-dioxaspiro[4.4]non-8-ene (142)" --- p.72 / Chapter III. --- "Partial Synthesis of 13R, 14,15-Dihydroprehispanolone (5)，13S,14,15-Di- hydroprehispanolone (135) and prehispanolone (1)" --- p.76 / CONCLUSION --- p.89 / EXPERIMENTAL SECTION --- p.91 / REFERENCES --- p.126 / APPENDIX --- p.141

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