O tecido ósseo é o maior sítio de acúmulo de flúor (F) do nosso organismo. Parte do F ingerido pode transitar através de um mecanismo de estado estacionário entre cristais da superfície óssea e plasma, ou quando da remodelação óssea, mantendo constantes os níveis plasmáticos algum tempo após a diminuição da ingestão de F. O objetivo deste estudo foi avaliar o período de tempo para que o F acumulado no osso de ratos, após uma exposição aguda, seja removido. Três grupos experimentais com 10 ratos Wistar (70 dias de idade) receberam, por via gástrica, dose única de 50 mg F/Kg peso corporal (como NaF) e 3 grupos controle, também com 10 animais cada, receberam água deionizada. A eutanásia dos animais ocorreu após 30, 90 ou 180 dias da administração de F. Os ratos foram anestesiados, sangue e fêmures removidos e analisados quanto à concentração de F. Para o fêmur, foi analisado o F solúvel em ácido removido por biópsia da superfície óssea, além do F presente no osso total, após calcinação. As cinzas e o plasma foram analisados para o F com o eletrodo, após difusão facilitada por HMDS. Os dados foram analisados pelo teste de Kruskal-Wallis, seguido pelo teste de Dunn (p<0,05). Os níveis plasmáticos de F do grupo controle foram constantes ao longo do tempo, e similares aos do grupo experimental eutanasiado aos 30 dias. Para os grupos experimentais eutanasiados após 90 e 180 dias, houve uma redução significativa nos níveis plasmáticos de F em relação ao grupo controle. A concentração de F na superfície do fêmur para o grupo experimental foi significativamente maior em relação ao grupo controle no tempo de eutanásia de 30 dias apenas, sendo que para os demais períodos experimentais, apesar de a concentração de F ser maior no grupo experimental quando comparado ao controle, esta diferença não foi estatisticamente significativa. Para ambos os grupos pôde ser observado um aumento nos níveis de F na superfície óssea longo do tempo. Para o osso total, o grupo experimental apresentou concentrações similares de F nos diferentes tempos de morte, e estes níveis foram similares aos encontrados para o grupo controle, no tempo de eutanásia de 180 dias. O grupo controle, nos tempos de morte 30 e 90 dias, apresentou valores significativamente menores quando comparado às demais situações. Os dados sugerem que o F incorporado à superfície óssea de ratos a partir de uma exposição aguda não é irreversivelmente ligado, mas vai sendo perdido ao longo do tempo, parecendo ser completamente perdido entre 90 e 180 dias após a exposição. Já os níveis de F incorporados no osso total 30 dias após uma ingestão aguda subletal não parecem ser perdidos ao longo do tempo. A não ocorrência de aumento ao longo do tempo nos níveis de F no osso total do grupo experimental sugere que existe um limite para a incorporação de F no osso total, provavelmente relacionado ao número de sítios possíveis para ligação irreversível do F. / Bone is the major site for fluoride (F) accumulation in the body. Part of the ingested F can transit between bone surface crystals and plasma, through a steady-state mechanism, which can also occur during bone remodeling. This could maintain constant plasma F levels for some time after the F intake is reduced. The aim of this study was to evaluate the lag time required to remove F accumulated in bone of rats after acute exposure. Three experimental groups, containing ten 70-day-old Wistar rats each, received, by gastrogavage, a single dose of 50 mgF/Kg body weight (as NaF), while 3 control groups received deionized water. The animals were euthanized 30, 90 or 180 days after F administration. The animals were anesthetized, blood and femurs were collected and analyzed for F. F on the femur surface was removed through an acid biopsy and F in whole bone was analyzed after ashing. Ash and plasma F were analyzed with the electrode following HMDS-facilitated diffusion. Data were analyzed by Kruskal-Wallis and Dunn\'s tests (p<0.05). Plasma F levels in control group were constant along time and similar to the levels found for the experimental group euthanized after 30 days. For the experimental groups euthanized after 90 and 180 days, a significant reduction in plasma F levels in respect to control was found. F in bone surface for the experimental group was significantly higher than for the control group only 30 days after F administration. For the other experimental times, despite F concentration was higher in the experimental group when compared to control, this difference was not significant. For both groups an increase in bone surface F levels along time was seen. For whole bone, the experimental group had similar F concentrations for all times of euthanasia and these levels were similar to those found for control group 30 days after F administration. Control group, 30 and 90 days after F administration had values significantly lower when compared to the other situations. Data suggest that F incorporated into bone surface of rats after acute exposure does not seem to be irreversibly bound and is lost along time. It seems to be completely lost between 90 and 180 days after F administration. On the other hand, F levels incorporated in whole bone 30 days after acute exposure to F do not seem to be lost along time. The lack of increase in whole bone F levels in the experimental group along time suggests that there is a limit for F uptake in whole bone, probably related to the number sites available to bind F irreversibly.

O tecido ósseo é o maior sítio de acúmulo de flúor (F) do nosso organismo. Parte do F ingerido pode transitar através de um mecanismo de estado estacionário entre cristais da superfície óssea e plasma, ou quando da remodelação óssea, mantendo constantes os níveis plasmáticos algum tempo após a diminuição da ingestão de F. O objetivo deste estudo foi avaliar o período de tempo para que o F acumulado no osso de ratos, após uma exposição aguda, seja removido. Três grupos experimentais com 10 ratos Wistar (70 dias de idade) receberam, por via gástrica, dose única de 50 mg F/Kg peso corporal (como NaF) e 3 grupos controle, também com 10 animais cada, receberam água deionizada. A eutanásia dos animais ocorreu após 30, 90 ou 180 dias da administração de F. Os ratos foram anestesiados, sangue e fêmures removidos e analisados quanto à concentração de F. Para o fêmur, foi analisado o F solúvel em ácido removido por biópsia da superfície óssea, além do F presente no osso total, após calcinação. As cinzas e o plasma foram analisados para o F com o eletrodo, após difusão facilitada por HMDS. Os dados foram analisados pelo teste de Kruskal-Wallis, seguido pelo teste de Dunn (p<0,05). Os níveis plasmáticos de F do grupo controle foram constantes ao longo do tempo, e similares aos do grupo experimental eutanasiado aos 30 dias. Para os grupos experimentais eutanasiados após 90 e 180 dias, houve uma redução significativa nos níveis plasmáticos de F em relação ao grupo controle. A concentração de F na superfície do fêmur para o grupo experimental foi significativamente maior em relação ao grupo controle no tempo de eutanásia de 30 dias apenas, sendo que para os demais períodos experimentais, apesar de a concentração de F ser maior no grupo experimental quando comparado ao controle, esta diferença não foi estatisticamente significativa. Para ambos os grupos pôde ser observado um aumento nos níveis de F na superfície óssea longo do tempo. Para o osso total, o grupo experimental apresentou concentrações similares de F nos diferentes tempos de morte, e estes níveis foram similares aos encontrados para o grupo controle, no tempo de eutanásia de 180 dias. O grupo controle, nos tempos de morte 30 e 90 dias, apresentou valores significativamente menores quando comparado às demais situações. Os dados sugerem que o F incorporado à superfície óssea de ratos a partir de uma exposição aguda não é irreversivelmente ligado, mas vai sendo perdido ao longo do tempo, parecendo ser completamente perdido entre 90 e 180 dias após a exposição. Já os níveis de F incorporados no osso total 30 dias após uma ingestão aguda subletal não parecem ser perdidos ao longo do tempo. A não ocorrência de aumento ao longo do tempo nos níveis de F no osso total do grupo experimental sugere que existe um limite para a incorporação de F no osso total, provavelmente relacionado ao número de sítios possíveis para ligação irreversível do F. / Bone is the major site for fluoride (F) accumulation in the body. Part of the ingested F can transit between bone surface crystals and plasma, through a steady-state mechanism, which can also occur during bone remodeling. This could maintain constant plasma F levels for some time after the F intake is reduced. The aim of this study was to evaluate the lag time required to remove F accumulated in bone of rats after acute exposure. Three experimental groups, containing ten 70-day-old Wistar rats each, received, by gastrogavage, a single dose of 50 mgF/Kg body weight (as NaF), while 3 control groups received deionized water. The animals were euthanized 30, 90 or 180 days after F administration. The animals were anesthetized, blood and femurs were collected and analyzed for F. F on the femur surface was removed through an acid biopsy and F in whole bone was analyzed after ashing. Ash and plasma F were analyzed with the electrode following HMDS-facilitated diffusion. Data were analyzed by Kruskal-Wallis and Dunn\'s tests (p<0.05). Plasma F levels in control group were constant along time and similar to the levels found for the experimental group euthanized after 30 days. For the experimental groups euthanized after 90 and 180 days, a significant reduction in plasma F levels in respect to control was found. F in bone surface for the experimental group was significantly higher than for the control group only 30 days after F administration. For the other experimental times, despite F concentration was higher in the experimental group when compared to control, this difference was not significant. For both groups an increase in bone surface F levels along time was seen. For whole bone, the experimental group had similar F concentrations for all times of euthanasia and these levels were similar to those found for control group 30 days after F administration. Control group, 30 and 90 days after F administration had values significantly lower when compared to the other situations. Data suggest that F incorporated into bone surface of rats after acute exposure does not seem to be irreversibly bound and is lost along time. It seems to be completely lost between 90 and 180 days after F administration. On the other hand, F levels incorporated in whole bone 30 days after acute exposure to F do not seem to be lost along time. The lack of increase in whole bone F levels in the experimental group along time suggests that there is a limit for F uptake in whole bone, probably related to the number sites available to bind F irreversibly.

Resumo: Proposição: Avaliar a resposta tecidual ao enxerto xenógeno inorgânico de osso bovino, por meio de análise histomorfológica e histomorfométrica. Material e método: O enxerto foi obtido da costela de boi resfriada após 8 horas de sacrifício do animal e processado da seguinte maneira: imersão por 60 minutos em água oxigenada a temperatura ambiente, com trocas a cada 15 minutos; imersão em água oxigenada aquecida, a uma temperatura de 100ºC, por 30 segundos e resfriamento imediato com água destilada a uma temperatura variando de 6º a 8ºC; enxague em água destilada corrente por 6 horas; imersão em álcool 70º, 90º e 100º, respectivamente, sendo 15 minutos em cada álcool; esterilização em autoclave. Em seguida, 10 coelhos brancos (Nova Zelândia) foram utilizados, originando dois grupos: Grupo I - enxerto inserido no pavilhão auricular e Grupo II - enxerto inserido e fixado em tíbia. Decorridos 180 dias, foi realizado sacrifício dos animais por injeção excessiva de anestésico. Resultados: No Grupo I, o enxerto apresentou-se em íntimo contato com tecido subcutâneo. No Grupo II, o enxerto apresentou-se em justaposição com o leito ósseo receptor. E nos dois grupos havia espaços medulares preenchidos por medula óssea ativa e osso neoformado, além da ausência de osteócitos no osso bovino e presença destas células no osso neoformado, próximo aos espaços medulares. Conclusão: Em razão dos resultados obtidos o enxerto xenógeno inorgânico de osso bovino demonstrou biocompatibilidade, capacidade osteocondutora e discreta perda de volume, preenchendo requisitos importantes do material ideal para reconstrução óssea. / Abstract: Objective: To evaluate tissue response to inorganic bovine bone xenograft by histomorphological and histomorphometrical analyses. Material and methods: The bone grafts was obtained from cooled bovine rib 8 hours after slaughtering and were processed as follows: 60-minute immersion in hydrogen peroxide at room temperature, with changes at 15-minute intervals; 30-second immersion in hydrogen peroxide at 100ºC; immediate cooling with distilled water at temperatures ranging from 6º to 8ºC; rinsing in running distilled water for 6 hours; immersion in alcohol grades of 70º, 90º and 100ºGL (15-minute in each solution); autoclaving. Thereafter, 10 white New Zealand rabbits were distributed into two groups: Group I - graft inserted in the ear pavilion and Group II - graft inserted and fixed in the tibia. After 180 days, the animals were sacrificed by anesthetic overdose. Results: In Group I, the graft was in intimate contact with the subcutaneous tissue, while in Group II the graft was juxtaposed to the recipient site. Both groups presented medullar spaces filled with active bone marrow and newly formed bone. In addition, osteocytes were absent in the bovine bone graft and present in the newly formed bone, close to the medullar spaces. Conclusion: From the obtained results, the inorganic bovine bone xenograft showed biocompatibility. / Orientador: Wilson Roberto Poi / Coorientador: Idelmo Rangel Garcia Júnior / Banca: Osvaldo Magro Filho / Banca: Roberta Okamoto / Banca: José Luiz Rodrigues Leles / Banca: Eleonor Álvaro Garbin Júnior / Doutor

Hung Wing Yin Vivian. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 128-142). / Abstracts in English and Chinese ; appendix in Chinese. / ABSTRACT --- p.i / ABSTRACT (in Chinese) --- p.iv / ACKNOWLEDGMENT --- p.vii / TABLE OF CONTENTS --- p.viii / LIST OF TABLES --- p.xiv / LIST OF FIGURES --- p.xvi / LIST OF ABBREVIATIONS --- p.xix / Chapter I. --- INTRODUCTION --- p.1 / Chapter 1.1. --- Scoliosis --- p.1 / Chapter 1.1.1. --- Classification of scoliosis --- p.1 / Chapter 1.1.2. --- Idiopathic scoliosis --- p.1 / Chapter 1.1.3. --- Clinical examination --- p.2 / Chapter 1.1.4. --- Curve pattern --- p.2 / Chapter 1.2. --- Etiology of AIS --- p.3 / Chapter 1.2.1. --- Prevalence of AIS --- p.5 / Chapter 1.2.2. --- Anthropometric Measurement in AIS --- p.5 / Chapter 1.2.3. --- Bone mass --- p.6 / Chapter 1.2.4. --- Bone mineral density measurements --- p.6 / Chapter 1.2.5. --- Osteopenia in AIS --- p.7 / Chapter 1.3. --- Natural history ofAIS --- p.8 / Chapter 1.3.1. --- Curve progression --- p.9 / Chapter 1.3.2. --- Treatment of scoliosis --- p.11 / Chapter 1.4. --- Research questions --- p.12 / Chapter 1.5. --- Objectives --- p.13 / Chapter II. --- METHODOLOGY --- p.20 / Chapter 2.1 --- Study Design --- p.20 / Chapter 2.2 --- Subject recruitment --- p.20 / Chapter 2.2.1 --- AIS patients --- p.20 / Chapter 2.2.2 --- Inclusion criteria --- p.20 / Chapter 2.2.3 --- Exclusion criteria --- p.20 / Chapter 2.2.4 --- Informed consent --- p.21 / Chapter 2.3 --- Grouping for chronological age --- p.21 / Chapter 2.4 --- Radiography assessments --- p.21 / Chapter 2.4.1 --- Cobb angle measurement --- p.21 / Chapter 2.4.2 --- Curve pattern --- p.22 / Chapter 2.4.3 --- Risser grade --- p.22 / Chapter 2.5 --- Definition of curve progression --- p.22 / Chapter 2.6 --- Bone mineral density (BMD) measurements --- p.23 / Chapter 2.6.1 --- Dual energy X-ray Absorptiometry (DXA) --- p.23 / Chapter 2.6.2 --- Peripheral quantitative computed tomography (pQCT) --- p.24 / Chapter 2.6.3 --- Definition of osteopenia or low bone mass --- p.24 / Chapter 2.7 --- Anthropometric measurements --- p.25 / Chapter 2.7.1 --- Body height --- p.25 / Chapter 2.7.2 --- Body weight --- p.26 / Chapter 2.7.3 --- Arm span --- p.26 / Chapter 2.7.4 --- Sitting height --- p.27 / Chapter 2.8 --- Family history --- p.27 / Chapter 2.9 --- Menstrual status --- p.27 / Chapter 2.10 --- Medication and fracture history --- p.27 / Chapter 2.11 --- Statistical analysis --- p.27 / Chapter 2.11.1 --- Sample size power calculation --- p.28 / Chapter 2.11.2 --- Student t test --- p.28 / Chapter 2.11.3 --- Paired t-test --- p.28 / Chapter 2.11.4 --- Predicting the incidence of curve progression --- p.28 / Chapter 2.11.4.1 --- Predictive outcome --- p.28 / Chapter 2.11.4.2 --- Potential risk factors --- p.28 / Chapter 2.11.4.3 --- Coding system for categorical variables --- p.29 / Chapter 2.11.4.4 --- Univariate analysis --- p.30 / Chapter 2.11.4.5 --- Logistic regression --- p.30 / Chapter 2.11.4.6 --- Receiver operating characteristics (ROC) curves --- p.32 / Chapter III. --- RESULTS --- p.54 / Chapter 3.1 --- Patients Characteristics --- p.54 / Chapter 3.1.1 --- Sample size --- p.54 / Chapter 3.1.2 --- Distribution of patient characteristics --- p.54 / Chapter 3.1.3 --- Drop out --- p.54 / Chapter 3.1.4 --- Prevalence of osteopenia (BMDage-adjusted ≤ -1) and low bone mass (BMCage-adjusted ≤ -1) --- p.55 / Chapter 3.1.5 --- Comparison between the BMD of the bilateral hip and tibia --- p.55 / Chapter 3.2 --- Comparison of AIS patients with osteopenia and with normal bone status --- p.55 / Chapter 3.3 --- Univariate analysis --- p.56 / Chapter 3.3.1 --- Growth related factors --- p.56 / Chapter 3.3.2 --- "Skeletal related parameters (areal BMD, volumetric BMD and BMC)" --- p.56 / Chapter 3.3.2.1 --- DXA lumbar spine --- p.56 / Chapter 3.3.2.2 --- DXA proximal femur at the convex-side hip --- p.56 / Chapter 3.3.2.3 --- DXA proximal femur at the concave-side hip --- p.57 / Chapter 3.3.2.4 --- pQCT at non-dominant distal radius --- p.57 / Chapter 3.3.2.5 --- pQCT - vBMD at convex-side distal tibia --- p.57 / Chapter 3.3.2.6 --- pQCT - vBMD at concave-side distal tibia --- p.58 / Chapter 3.3.3 --- Curve related factors --- p.58 / Chapter 3.3.4 --- Anthropometrics parameters --- p.58 / Chapter 3.3.5 --- Family history --- p.58 / Chapter 3.3.6 --- Summary of univariate analysis --- p.59 / Chapter 3.4 --- Logistic regression model (single factor) --- p.59 / Chapter 3.5 --- Logistic regression model (multiple factors) --- p.60 / Chapter 3.5.1 --- BMD inclusive model --- p.60 / Chapter 3.5.2 --- BMC inclusive model --- p.61 / Chapter 3.5.3 --- Conventional model --- p.63 / Chapter 3.6 --- ROC curve --- p.63 / Chapter 3.6.1 --- BMD inclusive model --- p.64 / Chapter 3.6.2 --- Conventional model --- p.64 / Chapter 3.7 --- Predictive equation obtained from different logistic regression models --- p.64 / Chapter 3.7.1 --- BMD inclusive model --- p.65 / Chapter 3.7.2 --- Conventional model --- p.65 / Chapter IV. --- DISCUSSION --- p.105 / Chapter 4.1 --- Prognostic factors for curve progression --- p.105 / Chapter 4.1.1 --- Well-known prognostic factors --- p.105 / Chapter 4.1.1.1 --- Growth-related factors --- p.106 / Chapter 4.1.1.2 --- Initial curve magnitude --- p.107 / Chapter 4.1.2 --- A new predictor 一 Osteopenia --- p.107 / Chapter 4.2 --- Non-significant prognostic factors for curve progression --- p.109 / Chapter 4.2.1 --- Anthropometric parameters --- p.109 / Chapter 4.2.2 --- Family History --- p.110 / Chapter 4.2.3 --- Curve pattern --- p.110 / Chapter 4.3 --- Predictive model --- p.111 / Chapter 4.4 --- Comparison of predictive models between BMD inclusive model and conventional model derived from our population --- p.115 / Chapter 4.5 --- Possible relationship between osteopenia and etiopathogensis of AIS --- p.116 / Chapter 4.6 --- Axial measurement has a better predictive power in curve progression than peripheral measurement --- p.117 / Chapter 4.7 --- Discordance of BMD in bilateral hips --- p.118 / Chapter 4.8 --- Method justifications --- p.119 / Chapter 4.8.1 --- Definition of curve progression --- p.119 / Chapter 4.8.2 --- Incidence of progression as the outcome of prediction --- p.119 / Chapter 4.8.3 --- Selection on bone densitometers --- p.119 / Chapter 4.9 --- Clinical significance --- p.121 / Chapter 4.10 --- Limitations and Future Studies --- p.122 / Chapter 4.10.1 --- Limited follow-up time --- p.122 / Chapter 4.10.2 --- No defined cutoff value for 226}0´ببosteopenia 226}0ح or low BMC in paediatric area --- p.122 / Chapter 4.10.3 --- Predictive model could only applied in local population --- p.122 / Chapter 4.10.4 --- Intrinsic error in Risser grade measurement --- p.123 / Chapter 4.10.5 --- Further studies --- p.123 / Chapter 4.10.5.1 --- Validation of the newly developed predictive model --- p.123 / Chapter 4.10.5.2 --- Possible intervention of osteopenia --- p.124 / Chapter 4.10.5.3 --- Long term follow-up BMD measurements and fracture risk in AIS patients --- p.124 / Chapter 4.10.5.4 --- Discordance of bilateral hips BMD contributed by the shift of center of gravity --- p.125 / Chapter 4.10.5.5 --- Axial QCT can be an alternative method in assessing BMDin scoliotic patients --- p.125 / Chapter V. --- CONCLUSION --- p.126 / Chapter VI. --- APPENDIX --- p.127 / Chapter VII. --- BIBLIOGRAPHY --- p.128 / Chapter VIII. --- CONFERENCE PUBLICATIONS --- p.142

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010. / Härtill 4 uppsatser.

Skeletal development is a complex event that requires a delicate balance between bone formation and bone resorption. Multiple transcription factors expressed in the bone-forming cells, osteoblasts, play crucial roles during the process of bone formation. Among them, ATF4 (Activating Transcription Factor 4) is a basic domain-leucine zipper transcriptional activator that is responsible for osteoblast differentiation, osteoblast-specific genes expression, synthesis of type I collagen, and osteoclast differentiation. Mice deficient for ATF4 are runted and exhibit severe skeletal dysplasia. Our laboratory has discovered Factor Inhibiting ATF4-mediated Transcription (FIAT), whose name was coined for its interaction with ATF4 and subsequent repression of ATF4-mediated osteocalcin gene transcription. FIAT is a leucine zipper nuclear molecule lacking a basic domain for DNA binding. We hypothesize that FIAT suppresses the bone-forming activities of osteoblasts by interacting with ATF4 and thereby blocking ATF4 attachment to the DNA to mediate downstream signalling pathways. To prove this hypothesis, we monitored the expression profiles of FIAT in parallel with ATF4 during osteoblastogenesis. Mechanism of FIAT repression of ATF4 was investigated through structure-function and mutation analysis. The physiological significance of FIAT expression in osteoblasts was studied through silencing FIAT in osteoblasts by RNA interference, as well as through characterization of two genetic mouse models: FIAT transgenic mice which overexpress FIAT in osteoblasts, and osteoblast-specific FIAT knockout mice. These studies showed that FIAT and ATF4 are co-expressed in osteoblasts, and that FIAT inhibition of matrix mineralization requires dimerization with ATF4 through the second leucine zipper. Furthermore, transgenic mice overexpressing FIAT exhibited osteopenia whereas FIAT knockout mice showed enhanced bone formation. These results support our hypothesis and demonstrate that FIAT is a key transcriptional repressor that modulates osteoblast function.

No description available.

Thesis (M.S.)--University of Tennessee Health Science Center, 2007. / Title from title page screen (viewed October 10, 2007). Research advisor: Joo L. Ong, Ph.D. Document formatted into pages (vi, 22 p. : ill.) Vita. Abstract. Includes bibliographical references (p. 23-32).

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Thesis (M.Sc.). / Written for the Division of Experimental Medicine. Title from title page of PDF (viewed 2008/12/04). Includes bibliographical references.