Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: John T. Koh, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Chan Yau Chi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 157-177). / Abstracts in English and Chinese. / Contents / Declaration --- p.i / Acknowledgement --- p.ii / Abbreviations --- p.iii-iv / Abstract in English --- p.v-viii / Abstract in Chinese --- p.ix-xi / Contents --- p.xii-xvi / Chapter CHAPTER I - --- Introduction / Chapter 1.1. --- Selective Estrogen Receptor Modulators (SERMs) --- p.1 / Chapter 1.1.1. --- Raloxifene --- p.6 / Chapter 1.2. --- Mechanisms of Action of SERMs in Vascular System --- p.7 / Chapter 1.2.1. --- Estrogen --- p.7 / Chapter 1.2.2. --- Estrogen Receptors (ERs) --- p.8 / Chapter 1.2.3. --- General Mechanisms of Action of SERMs --- p.13 / Chapter 1.2.4. --- Actions of Raloxifene --- p.14 / Chapter 1.3. --- Effects of SERMs in Cardiovascular System --- p.14 / Chapter 1.3.1. --- Effects of SERMs on Endothelial Function --- p.15 / Chapter 1.3.2. --- Effects of SERMs on Vascular Smooth Muscle --- p.17 / Chapter 1.4. --- Effects of Raloxifene on Vascular Circulations --- p.18 / Chapter 1.4.1. --- Effects of Raloxifene on Systemic Circulation --- p.18 / Chapter 1.4.1.1. --- Preclinical Data --- p.18 / Chapter 1.4.1.1.1. --- Effects on Serum Lipids --- p.18 / Chapter 1.4.1.1.2. --- Effects on Inflammation Markers and Blood Coagulation --- p.19 / Chapter 1.4.1.1.3. --- Antioxidative Effects --- p.19 / Chapter 1.4.1.1.4. --- Effects on Nitric Oxide and Endothelial Function --- p.19 / Chapter 1.4.1.1.5. --- Effects on Vascular Smooth Muscle --- p.20 / Chapter 1.4.1.1.6. --- "Vascular Injury, Atherosclerosis and Ischaemia-Reperfusion Injury" --- p.20 / Chapter 1.4.1.2. --- Clinical Studies - Effects in Post-Menopausal Women --- p.21 / Chapter 1.4.1.2.1. --- "Effects on Serum Lipids, Lipoproteins and Triglycerides" --- p.21 / Chapter 1.4.1.2.2. --- Effects on Inflammation Markers and Homocysteine --- p.22 / Chapter 1.4.1.2.3. --- Effects on Coagulation Markers --- p.23 / Chapter 1.4.1.2.4. --- Effects on Endothelial Function --- p.23 / Chapter 1.4.1.2.5. --- Cardiovascular Events --- p.23 / Chapter 1.5. --- Myogenic Response and Vascular System --- p.24 / Chapter 1.5.1. --- Initiation and Development of Myogenic Response --- p.25 / Chapter 1.5.2. --- Regulation of Myogenic Response --- p.26 / Chapter 1.5.2.1. --- 20-hydroxyeicosatetraenoic acid (20-HETE) --- p.26 / Chapter 1.5.2.2. --- "Protein Kinase C, Rho/Rho-Kinase, and Tyrosine Kinase" --- p.27 / Chapter 1.5.3. --- Myogenic Response and Endothelium --- p.31 / Chapter 1.5.4. --- Estrogen and Myogenic Tone --- p.31 / Chapter 1.6. --- Objectives of the Present Study --- p.32 / Chapter CHAPTER II - --- Methods and Materials / Chapter 2.1. --- Tissue and Cell Preparation --- p.34 / Chapter 2.1.1. --- Vessel Preparation --- p.34 / Chapter 2.1.2. --- Removal of a Functional Endothelium --- p.36 / Chapter 2.2. --- Myograph and Pressure Myograph Setups --- p.36 / Chapter 2.2.1. --- Myograph 一 Isometric Tension Measurement --- p.36 / Chapter 2.2.2. --- Pressure Myograph - Isobaric Diameter Measurement --- p.37 / Chapter 2.3. --- Intracellular [Ca2+] Measurement in Vascular Smooth Muscle --- p.42 / Chapter 2.4. --- Chronic Raloxifene Therapyin Spontaneously Hypertensive Rats (SHRs) and Wistar-Kyoto Rats (WKYs) --- p.42 / Chapter 2.4.1. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.42 / Chapter 2.4.2. --- "Body Weight, Mean Arterial Blood Pressure and Uterine Weight" --- p.42 / Chapter 2.4.3. --- Measurement of Raloxifene Tubing Consumption --- p.43 / Chapter 2.4.4. --- Effect of Chronic Raloxifene Treatment on Artery Reactivity --- p.43 / Chapter 2.5. --- Ovariectomy and Chronic Raloxifene Therapyin Syrian Golden Hamsters --- p.45 / Chapter 2.5.1. --- Surgical Procedure - Ovariectomy (OVX) --- p.45 / Chapter 2.5.2. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.45 / Chapter 2.5.3. --- High-Cholesterol Food Preparation --- p.45 / Chapter 2.5.4. --- "Body Weight, Food Consumption and Uterine Weight" --- p.46 / Chapter 2.5.5. --- Measurement of Raloxifene Tubing Consumption --- p.46 / Chapter 2.5.6. --- Serum Lipid and Lipoprotein Determinations --- p.46 / Chapter 2.5.7. --- Effect of Chronic Raloxifene on Artery Reactivity --- p.46 / Chapter 2.6. --- Solutions and Drugs --- p.49 / Chapter 2.6.1. --- "Drugs, Chemicals and Enzymes" --- p.49 / Chapter 2.6.2. --- Solutions --- p.51 / Chapter 2.6.3. --- Diet Composition for Syrian Golden Hamsters --- p.51 / Chapter 2.7. --- Statistical Analysis --- p.52 / Chapter CHAPTER III - --- "Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca Influx" / Chapter 3.1. --- Abstract --- p.53 / Chapter 3.2. --- Introduction --- p.54 / Chapter 3.3. --- Methods and Materials --- p.55 / Chapter 3.3.1. --- Blood Vessel Preparation --- p.55 / Chapter 3.3.2. --- Protocols --- p.55 / Chapter 3.3.3. --- Measurement of Vascular Smooth Muscle [Ca2+]i --- p.56 / Chapter 3.3.4. --- Drugs --- p.57 / Chapter 3.3.5. --- Data Analysis --- p.53 / Chapter 3.4. --- Results --- p.58 / Chapter 3.4.1. --- Effects of Raloxifene on Pulmonary Arteries --- p.53 / Chapter 3.4.2. --- Effect of Raloxifene on CaCl2-induced Constrictionin Pulmonary Arteries --- p.59 / Chapter 3.4.3. --- Effects of Raloxifene on Pulmonary Veins --- p.59 / Chapter 3.4.4. --- Effect of Raloxifene on CaCl2-stimulated Increases in [Ca2+]i in Pulmonary Arteries --- p.60 / Chapter 3.5. --- Discussion --- p.67 / Chapter 3.6. --- Conclusion --- p.69 / Chapter CHAPTER IV - --- Raloxifene Modulates Pulmonary Vascular Reactivity in Spontaneously Hypertensive Rats / Chapter 4.1. --- Abstract --- p.70 / Chapter 4.2. --- Introduction --- p.71 / Chapter 4.3. --- Methods and Materials --- p.72 / Chapter 4.3.1. --- Raloxifene Treatment --- p.72 / Chapter 4.3.2. --- Blood Vessel Preparation --- p.72 / Chapter 4.3.3. --- Protocols --- p.73 / Chapter 4.3.4. --- Chemicals and Drugs --- p.73 / Chapter 4.3.5. --- Data Analysis --- p.74 / Chapter 4.4. --- Results --- p.74 / Chapter 4.4.1. --- Blood Pressure --- p.74 / Chapter 4.4.2. --- Vasocontraction in Spontaneously Hypertensive Rats --- p.75 / Chapter 4.4.3. --- Vasorelaxation in Spontaneously Hypertensive Rats --- p.75 / Chapter 4.4.4. --- Vasocontraction in Wistar-Kyoto rats --- p.76 / Chapter 4.4.5. --- Vasorelaxation in Wistar-Kyoto rats --- p.77 / Chapter 4.4.6. --- Comparison of contraction between WKY and SHR rats --- p.78 / Chapter 4.4.7. --- Comparison of relaxation between WKY and SHR rats --- p.78 / Chapter 4.5. --- Discussion --- p.93 / Chapter 4.6. --- Conclusion --- p.96 / Chapter CHAPTER V - --- Effects of Therapeutic Concentrations of Raloxifene in Pressurized Rat Small Mesenteric Artery / Chapter 5.1. --- Abstract --- p.98 / Chapter 5.2. --- Introduction --- p.99 / Chapter 5.3. --- Methods and Materials --- p.101 / Chapter 5.3.1. --- Blood Vessel Preparation --- p.101 / Chapter 5.3.2. --- Experimental Protocols --- p.102 / Chapter 5.3.2.1. --- Myogenic Tone Development --- p.102 / Chapter 5.3.2.2. --- Effects of Raloxifene and 17β-EstradioI on Myogenic Constriction --- p.102 / Chapter 5.3.2.3. --- Effects of Pharmacological Inhibitors on Raloxifene- or 17β-Estradiol-induced Myogenic Constriction --- p.103 / Chapter 5.3.3. --- Drugs and Solutions --- p.103 / Chapter 5.3.4. --- Expression of Results and Statistical Analysis --- p.104 / Chapter 5.4. --- Results --- p.104 / Chapter 5.4.1. --- Effects of Raloxifene and 17β-Estradiol on Rat Resistance Mesenteric Arteries1 --- p.104 / Chapter 5.4.2. --- Effects of Inhibitors of NOS --- p.105 / Chapter 5.4.3. --- Effect of CTX plus Apamin --- p.106 / Chapter 5.4.4. --- "Effect of ICI 182,780" --- p.106 / Chapter 5.4.5. --- "Effects of Wortmannin, LY 294002 and Cycloheximide" --- p.106 / Chapter 5.5. --- Discussion --- p.122 / Chapter 5.6. --- Conclusion --- p.125 / Chapter CHAPTER VI - --- Effects of Chronic Raloxifene Treatment on Vascular Reactivity in Pressurized Septal Coronary Arteries from Hamsters Fed with High-Cholesterol Diet / Chapter 6.1. --- Abstract --- p.127 / Chapter 6.2. --- Introduction --- p.128 / Chapter 6.3. --- Methods and Materials --- p.129 / Chapter 6.3.1. --- Preparatory Work --- p.129 / Chapter 6.3.1.1. --- Animals and Diets --- p.129 / Chapter 6.3.1.2. --- Preparation of High-Cholesterol (HC) Food --- p.129 / Chapter 6.3.1.3. --- Surgical Procedure - Ovariectomy (OVX) --- p.129 / Chapter 6.3.1.4. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.130 / Chapter 6.3.1.5. --- Blood Vessel Preparation --- p.130 / Chapter 6.3.1.6. --- "Body Weight, Food Consumption and Uterine Weight" --- p.131 / Chapter 6.3.1.7. --- Measurement of Raloxifene Tubing Consumption --- p.131 / Chapter 6.3.1.8. --- Serum Lipid and Lipoprotein Determinations --- p.132 / Chapter 6.3.2. --- Experimental Protocols --- p.132 / Chapter 6.3.2.1. --- Development of Myogenic Tone --- p.132 / Chapter 6.3.2.2. --- Pressure-Diameter Relationships --- p.132 / Chapter 6.3.2.3. --- The Effect of Acetylcholine --- p.133 / Chapter 6.3.2.4. --- The Effect of U46619 --- p.133 / Chapter 6.3.2.5. --- The Effect of L-NAME --- p.133 / Chapter 6.3.3. --- Drugs and Solutions --- p.133 / Chapter 6.3.4. --- Expression of Results and Statistical Analysis --- p.134 / Chapter 6.4. --- Results --- p.135 / Chapter 6.4.1. --- Effects on Myogenic Response --- p.135 / Chapter 6.4.2. --- "Effects of Acetylcholine, U46619 and L-NAME" --- p.135 / Chapter 6.4.2.1. --- Comparison between OHHCD and OvxOHHCD --- p.135 / Chapter 6.4.2.2. --- Comparison between OvxOHHCD and OvxOHHCDRf --- p.135 / Chapter 6.4.2.3. --- Comparison between OHHCDRf and OvxOHHCDRf --- p.136 / Chapter 6.4.2.4. --- Comparison between OHHCD and OHHCDRf --- p.136 / Chapter 6.5. --- Discussion --- p.155 / Chapter 6.6. --- Conclusion --- p.156 / References --- p.157 / Publications --- p.176

Thesis (Ph. D.)--Ohio State University, 2006. / Full text release at OhioLINK's ETD Center delayed at author's request

Indiana University-Purdue University Indianapolis (IUPUI) / Current interventions used to reduce skeletal fragility are insufficient at enhancing bone across multiple hierarchical levels. Bisphosphonates, such as Zoledronate (ZOL), treat a variety of bone disorders by increasing bone mass and bone mineral density to decrease fracture risk. Despite the mass-based improvements, bisphosphonate use has been shown to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties by binding to collagen and increasing tissue hydration in a cell-independent manner. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality of bone. In this study, wildtype (WT) and heterozygous (OIM+/-) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or RAL and ZOL from 8 weeks to 16 weeks of age. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, direct measures of the tissue’s ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/- compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, bone volume fraction was significantly higher with combination treatment in both genotypes. Similar results were seen in trabecular number. Combination treatment resulted in higher ultimate stress in both genotypes, with RAL additionally increasing ultimate stress in OIM+/-. RAL and combination treatment in OIM+/- also produced a higher resilience compared to the control. Given no significant changes in cortical geometry, these mechanical alterations were likely driven by the quality-based effects of RAL. In conclusion, this study demonstrates the beneficial effects of using combination therapy to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a future mechanism to improve bone health and combat skeletal fragility on multiple hierarchical levels.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, 2005. / Bibliyografya var.

Wong Chi Ming. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 182-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

QUALITATIVE ASPECTS OF ADHERENCE TO ANTIRESORPTIVE TREATMENT IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS Author: Aneta Ravingerová Supervisor: Magda Vytřísalová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Social and Clinical Pharmacy INTRODUCTION: Compliance is using of medication in accordance with a prescription drug regimen. Qualitative aspect of compliance represents use of drugs in correct way. significantly affects treatment outcomes.Suboptimal compliance The study aim was to assess qualitative compliance with bisphosphonates (BIS)AIMS: among Czech women with osteoporosis in common clinical practice. METHODS: Data collection was performed using anonymous questionnaire in five outpatient Compliance with fivecentres in the Czech Republic from November 2012 to March 2013. dosing instructions for safe use and adequate absorption of BIS was evaluated. : A total of 363 patients were involved in the analysisRESULTS (mean age 68.9 years). once a week dosing forms ofPatients were treated with BIS - alendronate, alendronate + once a month dosing formvitamine D in a fixed combination, risedronate (N = 36.6 %) or - Only 46.6 % of respondents from weekly subgroup were compliantibandronate (N = 63.4 %). with all five dosing recommendations in monthly subgroup....

Thesis (M.S.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 21, 2008) Includes bibliographical references.

Submitted by Ana Carolina da Silva (aninha_010@hotmail.com) on 2018-07-03T00:00:59Z No. of bitstreams: 1 Dissertação_AnaCarolinaSilva.pdf: 2472051 bytes, checksum: 6b85b8c0d79a2746f5c893ab3a192b5e (MD5) / Approved for entry into archive by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br) on 2018-07-03T12:37:12Z (GMT) No. of bitstreams: 1 silva_ac_me_bauru.pdf: 2472051 bytes, checksum: 6b85b8c0d79a2746f5c893ab3a192b5e (MD5) / Made available in DSpace on 2018-07-03T12:37:12Z (GMT). No. of bitstreams: 1 silva_ac_me_bauru.pdf: 2472051 bytes, checksum: 6b85b8c0d79a2746f5c893ab3a192b5e (MD5) Previous issue date: 2018-05-04 / Pesquisas científicas associadas à osseointegração promoveram grande avanço no tratamento para a reabilitação bucal com um prognóstico de sucesso superior a 90%. O fenômeno da osseointegração corresponde à conexão direta estrutural e funcional entre o tecido ósseo e o material do implante odontológico. O sucesso da osseointegração está associado primordialmente com a estabilidade primária durante o procedimento de instalação do implante e posteriormente com a estabilidade secundária após o procedimento. Altos índices de fracasso e perda de implantes têm sido atribuídos a implantes em osso de qualidade baixa e consequentemente com estabilidade diminuída, fato este recorrente em especial à pacientes com densidade mineral óssea (BMD) reduzida. Uma opção utilizada pela Implantologia é o uso materiais para enxerto ósseo, associado eventualmente à ingestão oral de fármacos que induzam a regeneração óssea. Os biovidros ativos são comumente utilizados como opção para enxertos, pois alegadamente promovem o crescimento ósseo. Dentre as opções de fármacos disponíveis no mercado farmacêutico, o Cloridato de Raloxifeno tem apresentado resultados satisfatórios quando comparado com a reposição hormonal à base de estrógeno ou ao uso de bifosfonatos de primeira geração. Este projeto tem como motivação o desenvolvimento de um material híbrido a base do biovidro ativo comercial BioGran® (enxerto ósseo) e o fármaco comercial Raloxifeno®, sintetizado pela técnica sonoquímica estudados os efeitos de indução ao crescimento ósseo do tempo de sonicação do biovidro e também de diferentes concentrações em massa do fármaco em relação à massa do biovidro. Os resultados mostraram que a variável tempo de sonicação não resultou em diferenças significativas da diminuição do tamanho das partículas do biovidro. Também, os resultados indicaram que o grupo com 20% em massa de raloxifeno apresentou os melhores resultados de regeneração óssea. / Scientific research associated to osseointegration promoted a great advance in the treatment for oral rehabilitation with a success prediction of over 90%. The phenomenon of osseointegration corresponds to the direct structural and functional connection between the bone tissue and the material of the dental implant, and a determinant concept in osseointegration is the primary stability, sought after the implant installation procedure. High failure rates and implant loss have been attributed to poor quality bone implants and consequently decreased primary stability, especially in patients with reduced bone mineral density (BMD). One of the options used in the filed of Implantology is the use of materials for bone grafting, associated with oral intake of drugs that induce bone regeneration. Active bio-biopsies are commonly used as an option for grafts because they allegedly promote bone growth. Among the drug options available in the pharmaceutical market, Raloxifene hydrochloride has shown satisfactory results when compared with estrogen-based hormone replacement or the use of first-generation bisphosphonates. This project has as a motivation in the development of a hybrid material based on BioGran® commercial active bioglass (bone graft) and the commercial drug Raloxifeno®, synthesized by the sonochemical technique studied the effects of induction to the bone growth of the sonication time of the bioglass and also of different concentrations of the drug in relation to the mass of the bioglass. The results showed that the sonication time variable did not result in significant differences in the decrease of the bioglass particle size. Also, the results indicated that the group with 20% in mass of raloxifene presented the best results of bone regeneration.

Made available in DSpace on 2014-06-11T19:23:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-18Bitstream added on 2014-06-13T18:51:19Z : No. of bitstreams: 1 luvizuto_er_me_araca.pdf: 1006198 bytes, checksum: 7f15315191ddd77cc08393427bd6824f (MD5) / Objetivos: Avaliar a interferência da ovariectomia (OVX) e seu tratamento com estrógeno (E2) ou com raloxifeno (RLX) no balanço entre RANKL/OPG na cronologia do processo de reparo alveolar em diferentes períodos (7, 14, 21 e 42 dias) através da imunofluorescência por co-localização e análise histomorfométrica. Materiais e Métodos: Os grupos estudados foram: sham, OVX, OVX+E2, OVX+RLX. Após obtenção dos cortes histológicos corados em hematoxilina e eosina e as reações de co-localização por imunofluorescência de RANKL/OPG, os resultados foram avaliados quantitativamente. Resultados:Aos 7 dias: menor neoformação de trabéculas ósseas,o grupo OVX+RLX apresentou menor valor médio. O grupo OVX apresentou o maior turnover ósseo representado pelas co-localizações de OPG e RANKL. Aos 14 dias o grupo OVX+RLX apresentou menor formação óssea. O grupo sham apresentou intensa atividade celular representada pela alta imunorreatividade à OPG e RANKL observada nas células. Aos 21 dias os grupos experimentais apresentaram maiores níveis de ossificação; não apresentaram diferença estatística. O grupo OVX apresentou o menor turnover ósseo. Aos 42 dias houve diferença estatística na quantidade de formação óssea entre o grupo sham comparado aos demais grupos (p<0,05) e o grupo OVX apresentou o maior turnover ósseo. Conclusão: A ovariectomia atrasou o processo de reparo alveolar e alterou o turnover ósseo. A reposição do estrógeno e o tratamento com raloxifeno melhoraram as respostas, mas não restabeleceram completamente os valores da histometria e da colocalização do grupo sham. / Objectives: To evaluate the influence of the ovariectomy (OVX), and its treatments with estrogen (E2) or with raloxifene (RLX) on the RANKL/OPG balance during the periods in the chronology of the alveolar wound healing process (7, 14, 21 end 42 pos operative days) in female rats by means of immunocolocalization and histomorphometric analysis. Methods: The studied groups were: sham, OVX, OVX with E2 replacement, OVX with (RLX) treatment. After obtaining the histological tissue pieces colored in hematoxilin and eosin and the immunocolocalization reaction for RANKL and OPG, the results were quantitatively evaluated. Results: At 7 days, was observed lesser neoformed trabeculae bone, the smaller medium value was observed to the OVX+RLX group. The OPG and RANKL immunocolocalization showed larger bone tunover to OVX group. At 14 days there was a larger quantity of neoformed trabeculae bone, the smaller medium value was observed to the OVX+RLX group, the sham group presented an intense cellular activity. At 21 days the experimental groups had a greater ossification levels; no statistical significance was observed. The OVX group had the lowest bone turnover. At 42 days there were statistically differences on the quantity of ossification within sham group compared to the other groups (p<0.05). The OVX group showed the largest bone turnover. Conclusions: Ovariectomy delays the alveolar wound healing process and interferes with the bone turnover. The E2 replacement and the RLX treatment improved the healing but not enough to reach histomorphometric and immunocolocalization valours of the sham group.