Luo, Kewang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 278-305). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

by Cheng Yuen Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves [106]-113). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.iv / Research out puts --- p.v / Abbreviations --- p.vii / List of Figures --- p.viii / List of Tables --- p.xiii / Table of contents --- p.xiv / Chapter Chapter 1 --- Introduction & Hypothesis / Chapter 1.1. --- General Introduction --- p.1 / Chapter 1.2. --- Hypothesis --- p.4 / Chapter 1.3. --- Objectives --- p.4 / Chapter Chapter 2 --- An Overview of Giant Cell Tumour of Bone / Chapter 2.1. --- Introduction --- p.5 / Chapter 2.2. --- Pathobiological features of GCT --- p.6 / Chapter 2.2.1. --- Radiological appearances and clinical classifications of GCT --- p.7 / Chapter 2.2.2. --- Histological characteristics --- p.10 / Chapter 2.2.3. --- Metastatic GCT --- p.13 / Chapter 2.3. --- Histogenesis of GCT --- p.14 / Chapter 2.4. --- Treatment --- p.19 / Chapter 2.5. --- Summary --- p.22 / Chapter Chapter 3 --- Pharmacological aspect of bisphosphonates / Chapter 3.1. --- Introduction --- p.23 / Chapter 3.2. --- Chemical structures of bisphosphonates --- p.28 / Chapter 3.3. --- Mechanisms and actions --- p.28 / Chapter 3.3.1. --- Bisphosphonates induce osteoclast apoptosis --- p.30 / Chapter 3.3.2. --- Bisphosphonates induce cell apoptosis --- p.32 / Chapter 3.3.3. --- Apoptosis --- p.33 / Chapter 3.3.3.1. --- Morphological characteristic of apoptosis --- p.35 / Chapter 3.4. --- Clinical applications of bisphosphonates --- p.36 / Chapter 3.5. --- Bisphosphonates used in this study --- p.38 / Chapter 3.6. --- Summary --- p.43 / Chapter Chapter 4 --- Materials and methods / Chapter 4.1. --- Introduction --- p.44 / Chapter 4.2. --- Primary GCT cell culture and maintenance --- p.46 / Chapter 4.3. --- Drug preparation --- p.46 / Chapter 4.4. --- MTT assay --- p.47 / Chapter 4.5. --- Annexin-V-flous staining assay --- p.48 / Chapter 4.6. --- Haematoxyline and Eosin staining --- p.51 / Chapter 4.7. --- TUNEL assay (Terminal deoxynucleotidyltrasferase - mediated dUTP-biotin nick end labelling) --- p.52 / Chapter 4.8. --- TEM (Transmission Electron Microscopy) --- p.54 / Chapter 4.9. --- Statistical analysis --- p.54 / Chapter Chapter 5 --- Bisphosphonates induce apoptosis in giant cell tumour of bone -in vitro study / Chapter 5.1. --- Introduction --- p.56 / Chapter 5.2. --- Experimental design --- p.57 / Chapter 5.3. --- Results / Chapter 5.3.1. --- Bisphosphonates reduce cell viability of GCT stromal tumour cell --- p.59 / Chapter 5.3.2. --- Bisphosphonates induce morphological changesin GCT primary culture --- p.59 / Chapter 5.3.3. --- Bisphosphonate significantly induce apoptosis in GCT stromal cells in a dose dependent manner --- p.62 / Chapter 5.4. --- Discussions and Summary --- p.68 / Chapter Chapter 6 --- Bisphosphonates induce apoptosis in giant cell tumour of bone -in vivo study / Chapter 6.1. --- Introduction --- p.73 / Chapter 6.2. --- Experiment design --- p.74 / Chapter 6.3. --- Results / Chapter 6.3.1. --- H & E observations / Chapter 6.3.2. --- Pamidronate significantly induce apoptosis in both osteoclast-like giant cells and stromal tumour cells by TUNEL labelling assay --- p.79 / Chapter 6.3.3. --- Pamidronate induced cellular ultrastructural changes of GCT by TEM examination --- p.83 / Chapter 6.3.4. --- Pamidronate reduce the recurrent characteristic of GCT --- p.95 / Chapter 6.4. --- Discussions and Summary --- p.97 / Chapter Chapter 7 --- Summary and Future Study / Chapter 7.1. --- Summary --- p.101 / Chapter 7.2. --- Future directions --- p.103 / Chapter Chapter 8 --- Reference --- p.105 / Chapter Chapter 9 --- Appendix - solution preparation

published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Orientador: Edilson Ervolino / Resumo: Bisfosfonatos (BPs) são fármacos amplamente empregados no tratamento de condições que desencadeiam osteólise, atuando via inibição do processo de reabsorção óssea. Os BPs de maior potência, como o zoledronato, são utilizados para o controle da progressão de metástase óssea em neoplasias malignas osteotrópicas ou para o tratamento da osteoporose severa. Todavia, um dos seus efeitos adversos é a ocorrência da osteonecrose dos maxilares associada à terapia medicamentosa (ONM-M). Dentre os principais fatores de risco locais para a ONM-M destacam-se as intervenções odontológicas invasivas, como as cirurgias para instalação de implantes dentários osseointegráveis. Apesar do aumento no número de relatos clínicos de ONM-M após a instalação de implantes dentários em pacientes tratados com BPs, poucos são os estudos que visam compreender quais as alterações que desencadeiam esta condição. Diante disso, o objetivo deste estudo foi analisar o processo de reparo peri-implantar na tíbia de ratas tratadas com dose oncológica ou dose osteoporótica de zoledronato e avaliar a existência de correlação entre tal processo e a ocorrência de lesões osteonecróticas. Quarenta ratas (6 meses) foram distribuídas em dois experimentos: Experimento I: receberam injeções intraperitoneais (IP) de 0,45ml de solução de cloreto de sódio (NaCl) 0,9% (grupo VEI-ONC, n=10) ou desta mesma solução acrescida de 100µg/Kg de zoledronato (grupo ZOL-ONC, n=10), a cada 4 dias, durante 8 semanas; Experimento II: receberam... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Bisphosphonates (BPs) are drugs widely used for the treatment of conditions that cause osteolysis, by inhibition of the bone resorption process. High potency BPs, such as zoledronate, are used to control the progression of bone metastasis in osteotropic malignant neoplasms or for the treatment of severe osteoporosis. However, one of its adverse effects is the occurrence of medication-related osteonecrosis of the jaws (MRONJ). Among the main local risk factors for MRONJ are invasive dental procedures, such as surgeries for installation of osseointegratable dental implants. Despite the increased number of clinical reports of MRONJ after installation of dental implants in patients treated with BPs, there are few studies that aim to understand the changes triggering this condition. So, the objective of this study was to analyze the peri-implant repair process in the tibia of rats treated with oncologic dose or osteoporotic dose of zoledronate and to evaluate the existence of correlation between this process and the occurrence of osteonecrotic lesions. Forty female rats (6 months old) were distributed in two experiments: Experiment I: rats received intraperitoneal (IP) injections of 0.45ml of 0.9% sodium chloride (NaCl) solution (group VEI-ONC, n=10) or this same solution added by 100µg/Kg of zoledronate (group ZOL-ONC, n=10), every 4 days for 8 weeks; Experiment II: rats received IP injections of 0.45ml of 0.9% NaCl solution (group VEI-OST, n=10) or this same solution added by 10... (Complete abstract click electronic access below) / Mestre

Reproduction de : Thèse de doctorat : Chimie macromoléculaire et supramoléculaire : Toulouse 3 : 2007. / Titre provenant de l'écran-titre. Bibliogr. à la fin des chapitres.

Thesis (M.S.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on Feb. 3, 2010). Includes bibliographical references (p. 38-42).

In a 6-week rat model it was demonstrated that a small dose of peri-implant zoledronic acid (ZA) increased local bone formation 3-fold compared with controls. Ancillary in vitro studies using 14C-labeled ZA implant doses demonstrated biphasic elution profiles for implants coated with hydroxyapatite; complete ZA release occurred within one to three weeks in serum compared with only 60% ZA release after 12 weeks in water. Implants without hydroxyapatite coating showed more burst-type release profiles and full ZA elution within 24 hours of hydration in serum or water. Canine studies at 6 weeks using implants with 14C-labeled ZA showed that the compound remained localized, with the greatest ZA concentration immediately adjacent to the implant. Although there was evidence of skeletal ZA distribution via diffusion into the circulation, the levels were two orders of magnitude less than at the implant site.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Orientador: Edilson Ervolino / Coorientadora: Letícia Helena Theodoro / Banca: Juliano Milanezi de Almeida / Banca: Maria Bernadete Sasso Stuani / Resumo: Objetivo: O objetivo do presente estudo foi avaliar a progressão da periodontite experimental (PE) em ratas diabéticas submetidas à terapia com dose oncológica de zoledronato. Materiais e métodos: 120 animais (12 meses de idade) foram distribuídos aleatoriamente em quatro grupos experimentais: VEI-NG (n=30); VEI-DM (n=30), ZOL-NG (n=30) e ZOL-DM (n=30). Durante 7 semanas, a cada 3 dias, administrou-se pela via intraperitoneal 0,45ml de solução de NaCl 0,9% (VEI-NG e VEI-DM) ou 0,45ml desta solução acrescida de 100 µg/Kg de zoledronato (ZOL-NG e ZOL-DM). No 14º dia todos os animais foram submetidos: 1) indução da PE; 2) indução da diabetes com dose única de 0,3 ml de solução de estreptozotocina (60 mg/kg) diluída em solução de tampão citrato de sódio 0,1M, pH 4,0 (VEI-DM e ZOL-DM) ou apenas o veículo de tampão citrato (VEI-NG e ZOL-NG). As eutanásias foram realizadas aos 14, 21 e 35 dias após indução da PE. Foi realizada análise microtomográfica das hemimandibulas direitas e histopatológica e imunohistoquiímica (TNF-α e IL-1β) das hemimandibulas esquerdas. Os resultados foram analisados em microscopia óptica e submetidos à estatística com nível de significância de 5%. Resultados: A análise micro-CT mostrou uma menor perda óssea alveolar (POA), maior volume ósseo na furca (VOF) e maior espessura do trabeculado ósseo em ZOL-NG e ZOL-DM. ZOL-NG e ZOL-DM apresentaram maior porcentagem de tecido ósseo na furca (PTO) e a porcentagem de tecido ósseo não vital na furca (PON) foi maior... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of the present study is to evaluate the progression of experimental periodontitis (PE) in diabetic female rats under therapy of oncological dosage of zoledronic acid. 120 female rats (12 months of age) were randomly assigned to four experimental groups: VEI-NG (n = 30); VEI-DM (n = 30), ZOL-NG (n = 30) and ZOL-DM (n = 30). For 7 weeks, every 3 days, 0.45 ml of 0.9% NaCl solution (VEI-NG and VEI-DM) or 0.45 ml of this solution plus 100 μg / kg zoledronate (ZOL) were administered intraperitoneally -NG and ZOL-DM). On the 14th day post-start of the experiment all animals were submitted to: 1) a ligature installation around the lower bilaterally first molar, which remained in position throughout the experimental period; 2) a caudal vein injection of 0.3 ml of streptozotocin solution (60mg/kg) diluted in 0.1 M sodium citrate buffer solution pH 4.0 (VEI-DM and ZOL-DM) or only the vehicle of sodium citrate buffer 0.1M, pH 4.0 (VEI-NG and ZOL-NG). As euthanasia were performed at 14, 21 and 35 days after the induction of PE by transcardiac perfusion with histological fixative. A microtomographic analysis of the right and posterior hemi-mandibles of the histological processing of the left hemi-jaw was performed. Patients with histories were submitted to hematoxylin-eosin staining or immunohistochemical reaction for: tumor necrosis factor alpha TNF-α and interleukin IL-1β. The results were analyzed by optical microscopy and submitted to statistical analysis with a significance l... (Complete abstract click electronic access below) / Mestre

Submitted by JOÃO MARTINS DE MELLO NETO (joao_martins_182@hotmail.com) on 2018-05-05T04:28:36Z No. of bitstreams: 1 VERSÃO FINAL PARA A BIBLIOTECA JMMN.pdf: 3038526 bytes, checksum: 3833aa4fda2a808223e4a27b9eaba2b1 (MD5) / Approved for entry into archive by Ana Paula Rimoli de Oliveira null (anapaula@foa.unesp.br) on 2018-05-07T12:39:44Z (GMT) No. of bitstreams: 1 melloneto_jm_me_araca_int.pdf: 3038526 bytes, checksum: 3833aa4fda2a808223e4a27b9eaba2b1 (MD5) / Made available in DSpace on 2018-05-07T12:39:44Z (GMT). No. of bitstreams: 1 melloneto_jm_me_araca_int.pdf: 3038526 bytes, checksum: 3833aa4fda2a808223e4a27b9eaba2b1 (MD5) Previous issue date: 2018-03-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Objetivo: O objetivo do presente estudo foi avaliar a progressão da periodontite experimental (PE) em ratas diabéticas submetidas à terapia com dose oncológica de zoledronato. Materiais e métodos: 120 animais (12 meses de idade) foram distribuídos aleatoriamente em quatro grupos experimentais: VEI-NG (n=30); VEI-DM (n=30), ZOL-NG (n=30) e ZOL-DM (n=30). Durante 7 semanas, a cada 3 dias, administrou-se pela via intraperitoneal 0,45ml de solução de NaCl 0,9% (VEI-NG e VEI-DM) ou 0,45ml desta solução acrescida de 100 µg/Kg de zoledronato (ZOL-NG e ZOL-DM). No 14º dia todos os animais foram submetidos: 1) indução da PE; 2) indução da diabetes com dose única de 0,3 ml de solução de estreptozotocina (60 mg/kg) diluída em solução de tampão citrato de sódio 0,1M, pH 4,0 (VEI-DM e ZOL-DM) ou apenas o veículo de tampão citrato (VEI-NG e ZOL-NG). As eutanásias foram realizadas aos 14, 21 e 35 dias após indução da PE. Foi realizada análise microtomográfica das hemimandibulas direitas e histopatológica e imunohistoquiímica (TNF-α e IL-1β) das hemimandibulas esquerdas. Os resultados foram analisados em microscopia óptica e submetidos à estatística com nível de significância de 5%. Resultados: A análise micro-CT mostrou uma menor perda óssea alveolar (POA), maior volume ósseo na furca (VOF) e maior espessura do trabeculado ósseo em ZOL-NG e ZOL-DM. ZOL-NG e ZOL-DM apresentaram maior porcentagem de tecido ósseo na furca (PTO) e a porcentagem de tecido ósseo não vital na furca (PON) foi maior em ZOL-DM. A resposta inflamatória periodontal foi maior em ZOL-NG e ainda maior em ZOL-DM, com inflamação mais intensa e nível das principais citocinas com atividade pró-inflamatória (TNFα e IL-1β) maior em ZOL e ainda maior em ZOL-DM. Conclusão: O diabetes mellitus promove exacerbação da resposta inflamatória periodontal ao longo do tratamento com dose oncológica de zoledronato, o que o coloca, juntamente com a doença periodontal, como um importante fator de risco para a osteonecrose dos maxilares. / The aim of the present study is to evaluate the progression of experimental periodontitis (PE) in diabetic female rats under therapy of oncological dosage of zoledronic acid. 120 female rats (12 months of age) were randomly assigned to four experimental groups: VEI-NG (n = 30); VEI-DM (n = 30), ZOL-NG (n = 30) and ZOL-DM (n = 30). For 7 weeks, every 3 days, 0.45 ml of 0.9% NaCl solution (VEI-NG and VEI-DM) or 0.45 ml of this solution plus 100 μg / kg zoledronate (ZOL) were administered intraperitoneally -NG and ZOL-DM). On the 14th day post-start of the experiment all animals were submitted to: 1) a ligature installation around the lower bilaterally first molar, which remained in position throughout the experimental period; 2) a caudal vein injection of 0.3 ml of streptozotocin solution (60mg/kg) diluted in 0.1 M sodium citrate buffer solution pH 4.0 (VEI-DM and ZOL-DM) or only the vehicle of sodium citrate buffer 0.1M, pH 4.0 (VEI-NG and ZOL-NG). As euthanasia were performed at 14, 21 and 35 days after the induction of PE by transcardiac perfusion with histological fixative. A microtomographic analysis of the right and posterior hemi-mandibles of the histological processing of the left hemi-jaw was performed. Patients with histories were submitted to hematoxylin-eosin staining or immunohistochemical reaction for: tumor necrosis factor alpha TNF-α and interleukin IL-1β. The results were analyzed by optical microscopy and submitted to statistical analysis with a significance level of 5%. The micro-CT analysis showed lower alveolar bone loss (POA), greater bone volume in the furcation (VOF) and greater thickness of bone trabecule in ZOL-NG and ZOL-DM compared to the VEI-NG and VEI-DM groups. ZOL-NG and ZOL-DM presented a higher percentage of bone tissue in the furcation (PTO) and a percentage of non-vital bone tissue in the furcation (PON) was higher in ZOL-NG and much higher in ZOL-DM. The periodontal inflammatory response was higher in ZOL-NG and even higher in ZOL-DM, with more intense inflammation and major cytokines with the higher pro-inflammatory activity (TNFα and IL-1β) in ZOL and even higher in ZOL-DM. Diabetes mellitus promotes exacerbation of the periodontal inflammatory response during treatment with the oncologic dose of zoledronate, which causes, along with periodontal disease, an important risk factor for osteonecrosis of the jaw.