L’os est un matériau vivant avec une structure hiérarchique complexe qui lui confère des propriétés mécaniques remarquables. L’os subit perpétuellement des contraintes mécaniques et physiologiques, ainsi sa qualité et sa résistance à la fracture évoluent constamment au cours du temps à travers le processus de remodelage osseux. La qualité osseuse est non seulement définie par la densité minérale osseuse mais également par les propriétés mécaniques ainsi que la microarchitecture. Dans le cadre de la présente thèse, on a développé une modélisation multiéchelle unifiée couplant à la fois les activités cellulaires au comportement mécanique de l'os tenant compte des différents niveaux hiérarchiques de l'os: de l’ultrastructure au remodelage osseux. Ce modèle permet d’étudier le comportement mécano-bibliologique de l’os et de prédire ses propriétés mécaniques apparentes à différentes échelles allant du nanoscopique au macroscopique en fonction des constituants élémentaires de l'os. Pour atteindre cet objectif, une démarche en quatre phases a été adoptée. La première phase consiste à décrire les constituants élémentaires de l’os. La deuxième phase avait pour objectif la modélisation multiéchelle de l'ultrastructure osseuse constituée de trois échelles nanoscopiques (microfibrille, fibrille et fibre) par la méthode des éléments finis et des réseaux de neurones. La troisième phase correspond à la modélisation des échelles micro-macroscopiques de l’os cortical (lamelle, ostéon, os cortical) en utilisant comme paramètres d’entrée les propriétés de la fibre déterminées dans la deuxième phase. Enfin, dans la dernière phase, on a développé un modèle mécano-biologique du remodelage osseux permettant de simuler le processus d'adaptation osseuse tenant compte explicitement des activités biologiques des cellules osseuses. Les propriétés mécaniques prédites par nos algorithmes multiéchelles ont servi pour alimenter le modèle de remodelage. Ce modèle a été implémenté au code de calcul d’éléments finis ABAQUS/Standard à travers sa routine utilisateur UMAT. Finalement, le modèle EF mécano-biologique multiéchelle du remodelage osseux a été appliqué pour simuler différents scénarii de remodelage sur des fémurs humains (2D et 3D). Différents facteurs ont été ainsi analysés tels que l'âge, le genre, l'amplitude des activités physiques, etc. Les résultats obtenus sont conformes (qualitativement) avec les observations cliniques et cohérents avec les différentes études expérimentales. En conclusion: (i) Les modèles unifiés ainsi développés (modèle multiéchelle, modèle mécano-biologique de remodelage osseux) contribuent à l'analyse fine du comportement de l'os humain. (ii) L'application des algorithmes a permis d'effectuer des essais virtuels pour analyser les effets combinés de nombreux facteurs caractérisant la qualité osseuse. / Bone is a living material with a complex hierarchical structure which entails exceptional mechanical properties. Bone undergoes permanent mechanical and physiological stresses, thus its quality and fracture toughness are constantly evolving over time through the process of bone remodeling. Bone quality is not only defined by bone mineral density but also by the mechanical properties and microarchitecture. The current thesis offers a multiscale modeling approach unifying the cell activity to the mechanical behavior, taking into consideration the hierarchical levels of bone, from the ultrastructure to bone remodeling. This model permits to study the mechanobiological behavior and to predict the mechanical properties of the bone at different scales from nano to macro depending on the elementary constituents of bone. To achieve the objective of the current work, an approach of four phases was adopted. The first phase is to describe the basic components of the bone. The second phase concerns the multiscale modeling of the three nanoscopic levels of bone ultrastructure (microfibril, fibril and fiber) by the finite element method and neural networks. The third phase aims to model the micro-macroscopic structures of cortical bone (lamella, osteon, cortical bone) using the fiber properties predicted from the second phase as input parameters. In the last phase, a mechano-biological model of bone remodeling was achieved to simulate the process of bone adaptation explicitly considering the biological activities of bone cells. Mechanical properties predicted by our multiscale algorithms were used to feed the remodeling model. This model has been implemented into the ABAQUS/Standard finite elements code as a user subroutine. Finally, the finite element mechano-biological multiscale model of bone remodeling was applied to simulate different scenarios on human femurs (2D and 3D). Hence, different factors such as: age, gender, physical activities, etc were analyzed. The obtained results are conformed (qualitatively) to clinical observations and consistent with the various experimental studies. In summary, (i) the models portrayed here (multiscale model, mechanical-biological model of bone remodeling) contribute by their unified approach to the realistic modeling of the response of human bone. (ii) The application of the algorithms permits to perform virtual experiments to scrutinize the combined effects of numerous factors dictating the bone quality.

Made available in DSpace on 2016-12-23T13:49:03Z (GMT). No. of bitstreams: 1 Fernanda S Pimentel.pdf: 2000885 bytes, checksum: 1bf180bc2109c67426e7ca0264e6b4ae (MD5) Previous issue date: 2010-07-29 / The bone is a specialized form of connective tissue that provides support for metabolic and biomechanical throughout the body. Thus, the bone is very dynamic, with constantly renewing itself. His integrity therefore depends on the balance between the processes of formation and resorption. The loss of this balance alters both the structure of organic matrix as bone mineralization. Moreover, imbalances in bone remodeling process may result in the development of systemic skeletal diseases such as osteoporosis. The osteoporosis is a chronic progressive disease that affects millions of people around the world. Only in Brazil some 10 million people suffer from osteoporosis. The hormone estrogen deficiency induced by ovariectomy (OVX) rats, demonstrably stimulates increased bone resorption, especially in long bones and spine, mimicking what happens in postmenopausal osteoporosis. In this work we used OVX rats to investigate the interaction of alendronate (a drug widely used to treat osteoporosis) and vitamin K (VK) (recent investigations have pointed anabolic bone tissue of osteoporotic patients) in the metabolism osteomineral. This study revealed that administration of alendronate (ALE) and VK with ALE (ALE+VK) produced significant recovery in bone mineral density (BMD) in OVX rats. However, the use of VK alone did not appear to make any significant effect on BMD in OVX rats. We observed an increased excretion of urinary deoxypyridinoline (DPD), a marker of bone resorption, in OVX group, and statistically significant reduction of DPD when the animals were treated with VK, ALE, or both. There was no statistically significant difference in bone mineral content and body surface area. Was verified statistically significant difference in the thickness of compact bone in the different study groups. There was also a statistically significant reduction in wet weight and endometrium of OVX rats, demonstrating the effectiveness of ovariectomy. Therefore, the animal model used in this study efficiently mimicked estrogen deficiency induced by ovariectomy, resulting in increased bone resorption; treatment with ALE and VK+ALE increases BMD in OVX rats, while the VK alone does not produce this effect; treatment with ALE and VK reduces bone resorption in OVX rats, verified by the reduction in the excretion of DPD. / O osso é uma forma especializada de tecido conjuntivo que fornece suporte biomecânico e metabólico para todo o corpo. Para tanto, o tecido ósseo é muito dinâmico, apresentando-se em constante renovação. Sua integridade depende, portanto, do equilíbrio entre os processos de formação e reabsorção óssea. Ademais, desequilíbrios no processo de remodelamento ósseo podem resultar no desenvolvimento de doenças esqueléticas sistêmicas, como a osteoporose. A osteoporose é uma doença crônica e progressiva que afeta milhões de pessoas em todo o mundo. Somente no Brasil cerca de 10 milhões de pessoas sofrem de osteoporose. A deficiência hormonal estrogênica, induzida pela ovariectomia (OVX) em ratos, comprovadamente estimula o aumento da reabsorção óssea, principalmente em ossos longos e coluna vertebral, mimetizando o que acontece na osteoporose pós-menopausa. No presente trabalho foram utilizadas ratas OVX para se investigar a interação do alendronato (fármaco extensamente utilizado no tratamento da osteoporose) e da vitamina K (VK) (recentes investigações apontam possuir ação anabólica do tecido ósseo de pacientes osteoporóticas) no metabolismo osteomineral. Este estudo revelou que a administração de alendronato (ALE) e de VK juntamente com ALE (VK+ALE) produziu significante recuperação na densidade mineral óssea (DMO) de ratas OVX. No entanto, a utilização da VK isoladamente não pareceu exercer nenhum efeito significante na DMO de ratas OVX. Observou-se uma maior excreção de deoxipiridinolinas urinárias (DPD), marcador de reabsorção óssea no grupo OVX, e redução estatisticamente significante da DPD quando os animais foram tratados com VK, ALE ou ambas. Não houve diferença estatisticamente significante do conteúdo mineral ósseo e da área corporal. Também não foi verificada diferença estatisticamente significante na espessura do osso compacto nos diferentes grupos de estudo. Verificou-se ainda redução estatisticamente significante do peso úmido e do endométrio de ratas OVX, comprovando a eficiência da ovariectomia. Portanto, o modelo animal utilizado neste estudo mimetizou eficientemente a deficiência estrogênica induzida pela ovariectomia, resultando em aumento da reabsorção óssea; o tratamento com ALE e VK+ALE aumenta a DMO de ratas OVX, embora a VK isoladamente não apresente esse efeito; o tratamento com ALE e VK reduz a reabsorção óssea de ratas OVX, verificada pela redução na excreção de DPD.

Made available in DSpace on 2016-12-23T13:49:04Z (GMT). No. of bitstreams: 1 Dissertacao de Fernanda Scarpatti Pimentel.pdf: 2000878 bytes, checksum: cdfb57d1ceb94c6e6c0b410060dcfbfb (MD5) Previous issue date: 2010-07-29 / The bone is a specialized form of connective tissue that provides support for metabolic and biomechanical throughout the body. Thus, the bone is very dynamic, with constantly renewing itself. His integrity therefore depends on the balance between the processes of formation and resorption. The loss of this balance alters both the structure of organic matrix as bone mineralization. Moreover, imbalances in bone remodeling process may result in the development of systemic skeletal diseases such as osteoporosis. The osteoporosis is a chronic progressive disease that affects millions of people around the world. Only in Brazil some 10 million people suffer from osteoporosis. The hormone estrogen deficiency induced by ovariectomy (OVX) rats, demonstrably stimulates increased bone resorption, especially in long bones and spine, mimicking what happens in postmenopausal osteoporosis. In this work we used OVX rats to investigate the interaction of alendronate (a drug widely used to treat osteoporosis) and vitamin K (VK) (recent investigations have pointed anabolic bone tissue of osteoporotic patients) in the metabolism osteomineral. This study revealed that administration of alendronate (ALE) and VK with ALE (ALE+VK) produced significant recovery in bone mineral density (BMD) in OVX rats. However, the use of VK alone did not appear to make any significant effect on BMD in OVX rats. We observed an increased excretion of urinary deoxypyridinoline (DPD), a marker of bone resorption, in OVX group, and statistically significant reduction of DPD when the animals were treated with VK, ALE, or both. There was no statistically significant difference in bone mineral content and body surface area. Was verified statistically significant difference in the thickness of compact bone in the different study groups. There was also a statistically significant reduction in wet weight and endometrium of OVX rats, demonstrating the effectiveness of ovariectomy. Therefore, the animal model used in this study efficiently mimicked estrogen deficiency induced by ovariectomy, resulting in increased bone resorption; treatment with ALE and VK+ALE increases BMD in OVX rats, while the VK alone does not produce this effect; treatment with ALE and VK reduces bone resorption in OVX rats, verified by the reduction in the excretion of DPD / O osso é uma forma especializada de tecido conjuntivo que fornece suporte biomecânico e metabólico para todo o corpo. Para tanto, o tecido ósseo é muito dinâmico, apresentando-se em constante renovação. Sua integridade depende, portanto, do equilíbrio entre os processos de formação e reabsorção óssea. Ademais, desequilíbrios no processo de remodelamento ósseo podem resultar no desenvolvimento de doenças esqueléticas sistêmicas, como a osteoporose. A osteoporose é uma doença crônica e progressiva que afeta milhões de pessoas em todo o mundo. Somente no Brasil cerca de 10 milhões de pessoas sofrem de osteoporose. A deficiência hormonal estrogênica, induzida pela ovariectomia (OVX) em ratos, comprovadamente estimula o aumento da reabsorção óssea, principalmente em ossos longos e coluna vertebral, mimetizando o que acontece na osteoporose pós-menopausa. No presente trabalho foram utilizadas ratas OVX para se investigar a interação do alendronato (fármaco extensamente utilizado no tratamento da osteoporose) e da vitamina K (VK) (recentes investigações apontam possuir ação anabólica do tecido ósseo de pacientes osteoporóticas) no metabolismo osteomineral. Este estudo revelou que a administração de alendronato (ALE) e de VK juntamente com ALE (VK+ALE) produziu significante recuperação na densidade mineral óssea (DMO) de ratas OVX. No entanto, a utilização da VK isoladamente não pareceu exercer nenhum efeito significante na DMO de ratas OVX. Observou-se uma maior excreção de deoxipiridinolinas urinárias (DPD), marcador de reabsorção óssea no grupo OVX, e redução estatisticamente significante da DPD quando os animais foram tratados com VK, ALE ou ambas. Não houve diferença estatisticamente significante do conteúdo mineral ósseo e da área corporal. Também não foi verificada diferença estatisticamente significante na espessura do osso compacto nos diferentes grupos de estudo. Verificou-se ainda redução estatisticamente significante do peso úmido e do endométrio de ratas OVX, comprovando a eficiência da ovariectomia. Portanto, o modelo animal utilizado neste estudo mimetizou eficientemente a deficiência estrogênica induzida pela ovariectomia, resultando em aumento da reabsorção óssea; o tratamento com ALE e VK+ALE aumenta a DMO de ratas OVX, embora a VK isoladamente não apresente esse efeito; o tratamento com ALE e VK reduz a reabsorção óssea de ratas OVX, verificada pela redução na excreção de DPD

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O propósito deste estudo foi analisar o comportamento do osso alveolar na remodelação óssea sob carga fisiológica e ortopédica após a disjunção rápida da sutura palatina mediana durante 14 dias, com e sem aplicação de laser de baixa potência e comparar imagens obtidas por técnica radiográfica convencional com microtomografias computadorizadas. O aparelho de laser utilizado foi de diodo de arsenieto de gálio-alumínio (AlGaAs) (830m; 100mW, onda contínua, 126J/cm2, 29 segundos) aplicado à sutura palatina mediana de ratos Wistar, machos, de 6 semanas de vida. Foram utilizados 65 ratos divididos em um grupo controle (GC) contendo 5 ratos e dois experimentais I e II (GE I e GE II), com 30 ratos cada, ambos GE submetidos à disjunção imediata, sendo que o GE II foi irradiado imediatamente após a disjunção. Os GE I e II foram subdivididos em períodos de disjunção imediata, 6, 24, 48 horas, 7 e 14 dias. Dois amostras de cada período dos GC e GE foram radiografadas (convencional) e processadas para captura de imagens em scanner micro-CT (Scanco Medical, Zurik, Suíça), com 24KV de energia e 3,8μm de resolução espacial e o restante foram processadas para serem analisadas histologicamente coradas com hematoxilina e eosina e tricrômico de Masson. Os resultados foram avaliados histológica e radiograficamente. O trabeculado ósseo recém-formado a partir dos bordos ósseos da sutura foi observado nos períodos de 2, 7 e 14 dias do GE II, 7 e 14 dias do GE I. O presente experimento demonstrou que a atividade osteoblástica aumenta a atividade da osteosíntese de modo mais expressivo após aplicação do laser de baixa potência, porem é necessários mais estudos em biologia molecular para desvendar os seus efeitos ao nível celular. As microtomografias computadorizadas mostraram maior riqueza de detalhes para analisar o rompimento da sutura palatina mediana e seu reparo com o depósito de tecido ósseo do que as radiografias convencionais. / The purpose of this study was to evaluate the behavior of the alveolar bone on bone remodeling under physiological load and on after rapid midpalatal suture expansion during a 14-day period, with and without low-level laser irradiation and to compare images obtained by conventional radiographic technique with microtomografias computed. The laser device was a gallium-aluminum-arsenide (GaAlAs) diode laser (830 m; 100 mW, continuous wave, 126 J/cm2, 29 seconds) applied to the midpalatal suture of 6-week-old male Wistar rats. Sixty-five rats were assigned in a control group (CG) containing 5 rats and two experimental I and II (EG I and EG II), with 30 rats each, both EG submitted to expansion immediately, while the EG II was irradiated pos expansion immediately. The EG I and II were divided into periods of immediate midpalatal suture expansion, 6 hours, 1, 2, 7 and 14 days). . Two samples of each period of CG and EG were radiographed (conventional) and processed to capture images in micro-CT scanner (Scancem Medical, Zurik, Switzerland) with 24kV of energy and 3.8 mm in spatial resolution and the rest were processed for are analyzed histologically stained with hematoxylin and eosin and Masson's trichrome.The results were evaluated histologically and radiographically. Bone trabeculae recently formed from the bone borders of the suture were observed in the periods of 2, 7 and 14 days of EG II, and 7 and 14 days of EG I. The present experiment demonstrated that the osteoblastic activity increases the osteosynthesis activity in a more manner after low-level laser irradiation. However, more studies in the field of molecular biology are necessary to determine its effects at cellular level. The computed microtomographs provided a more detailed analysis of midpalatal suture opening and its repair by bone tissue deposition than conventional radiographs.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este estudo teve como objetivo avaliar o papel da administração crônica de cafeína durante a gestação de camundongos C57BL/6 sobre o remodelamento cardíaco e a expressão de componentes do sistema renina-angiotensina (SRA) na prole macho adulta. Fêmeas C57BL/6 grávidas foram divididas em dois grupos (n = 10): grupo controle (C), progenitoras foram injetadas apenas com o veículo (solução salina NaCl 0,9%), e grupo cafeína (CF), progenitoras receberam diariamente uma injecção subcutânea contendo 20 mg/kg de cafeína (1 mg/ml de solução salina). Após o desmame, os filhotes tiveram livre acesso à ração padrão até 90 dias de idade quando foram sacrificados. Rim e ventrículo esquerdo (VE) foram coletados para análise estrutural e western blotting. O grupo cafeína mostrou uma redução significativa no ganho de massa corporal (MC) (-18%; P <0,0001). O grupo cafeína apresentou ainda um aumento da pressão arterial sistólica (+ 48%; P <0,0001) e freqüência cardíaca (+10%; P <0,01) em relação ao grupo controle. A massa do VE corrigida pela MC no grupo da cafeína foi maior que no grupo C (+10%; P <0,01). O grupo cafeína apresentou um aumento na área de cardiomiócitos (+40%; P <0,05), e reduzida densidade capilar (-25%; P <0,05). No rim, as expressões de renina (128%; P <0,05) e dos receptores 1 da angiotensina II (AT1R) (88%; P <0,05) foram significativamente maiores nos animais do grupo cafeína. No VE, o grupo cafeína demonstrou aumento da expressão de ECA (+30%; P <0,05), angiotensina II (+60%; P <0,01), e AT1R (+77%; P <0,01) e diminuição da expressão do receptor 2 de angiotensina II (-46%; P <0,05). Em conclusão, a administração crônica de cafeína durante a gestação, possivelmente programa a expressão de componentes de sistema renina-angiotensina, levando à ativação persistente do SRA renal e cardíaco local, que por sua vez promove o aumento da pressão sanguínea, remodelação e efeitos cardíacos adversos. / This study aimed to evaluate the role of caffeine chronic administration during gestation of C57BL/6 mice on cardiac remodeling and the expression of components of the renin-angiotensin system (RAS) in male offspring as adults. Pregnant C57BL/6 female mice were divided into two groups (n=10): Control group (C), dams were injected with the vehicle only (saline 0.9% NaCl), and Caffeine group (CF), dams received daily a subcutaneous injection containing 20 mg/kg of caffeine/day (1 mg/ml saline). After weaning, pups had free access to the standard chow until 90 days of age when they were killed. Kidney and left ventricle (LV) were collected for structural analysis and Western blot. Caffeine group showed a significant reduction in body mass (BM) gain (-18%;P<0.0001). Caffeine group had increased systolic blood pressure (+ 48%;P<0.0001) and higher heart rate (+10%;P<0.01) than control group. LV mass adjusted by BM in caffeine group was greater than in C group (+10%;P<0.01). Caffeine group had increase in the area of cardiomyocytes (+40%;P<0.05), and reduced capillary density (-25%;P<0.05). In the kidney, the expressions of renin (+128%; P<0.05) and angiotensin II receptor 1(AT1R) (+88%;P<0.05) were significantly greater in caffeine mice. In the LV, caffeine group showed increased expression of ACE (+30%; P <0.05), angiotensin II (+60%;P<0.01), and AT1R (+77%;P<0.01), and decreased expression of angiotensin II receptor 2 (-46%;P<0.05). In conclusion, chronic administration of caffeine during gestation possibly programs the expression of renin-angiotensin system components, leading to persistent activation of local renal and cardiac RAS, which in turn promotes increased BP and adverse cardiac remodeling.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O objetivo deste trabalho foi estudar a ação do fenofibrato, um agonista do receptor ativador da proliferação peroxissomal alfa, no remodelamento cardíaco e na expressão de componentes do sistema renina-angiotensina (SRA) em um modelo de obesidade induzida por dieta. Camundongos machos C57Bl/6 com três meses de idade foram alimentados durante 11 semanas com dieta controle (grupo C, 3,57 kcal/g de dieta) ou dieta hiperlipídica (grupo HL, 5,40 kcal/g de dieta), em seguida foram separados em quatro grupos e estudados durante cinco semanas: C; HL; C-L (C mais fenofibrato) e HL-F (HL mais fenofibrato). Os animais HL foram mais pesados e apresentaram maior pressão arterial (PA) comparados aos animais C, mas HL-F foram mais leves e tiveram PA menor que HL. A resistência insulínica vista nos camundongos HL foi melhorada com fenofibrato nos camundongos HL-F. Fenofibrato reduziu colesterol total, triglicerídeos e aumentou HDL-c. Os animais HL apresentou um ventrículo esquerdo (VE) mais pesado e com espessura da parede maior, como também cardiomiócitos maiores e uma menor razão cardiomiócito/capilares que os animais C. Fenofibrato foi eficiente em melhorar estas alterações. As expressões cardíacas de Angiotensina II (ANG II) e de seu receptor tipo 1 (AT1R) foram maiores, enquanto que a expressão de seu receptor tipo 2 (AT2R) foi menor nos animais HL que nos animais C, e fenofibrato foi eficiente em atenuar estas diferenças. Como conclusão, a dieta HL lidera para a obesidade, elevação da PA, hipertrofia cardíaca, alterações metabólicas e expressão proteica alterada do SRA em camundongos, sugerindo a participação do SRA nestas alterações. Fenofibrato é eficiente em diminuir a PA e controlar a expressão proteica do SRA, assim como no tratamento da resistência insulínica e do remodelamento cardíaco adverso, diminuindo a hipertrofia dos cardiomiócitos e melhorando a vascularização do miocárdio, desta maneira, diminuindo importantes fatores de risco para doenças cardiovasculares / The aim was to study the action of fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, in cardiac remodeling and protein expressions of RAS components in a model of obesity induced by diet. 3-mo-old C57BL/6 male were fed for 11 weeks with standard chow (SC group, 3.57 kcal/g of chow) or high-fat chow (HF group, 5.40 kcal/g of chow), then they were separated into four groups and studied for five weeks: SC; HF; SC-F (SC plus fenofibrate) and HF-F (HF plus fenofibrate). HF was heavier and had higher blood pressure (BP) than SC, but HF-F was lighter and had lower BP than HF. The insulin resistance seen in HF mice was corrected by fenofibrate in HF-F mice. Fenofibrate reduced total cholesterol, triglycerides and raised the HDL-c. HF had thicker and heavier left ventricle (LV) with bigger LV cardiomyocyte and smaller cardiomyocyte-to-capillaries ratio than SC, and fenofibrate was efficient in treating these alterations. Cardiac expressions of angiotensin II (ANG II) and ANG II receptor 1 were higher, and ANG II receptor 2 was lower in HF than in SC, and fenofibrate was efficient in attenuating these differences. In conclusion, HF diet leads to obesity, BP elevation, cardiac hypertrophy, metabolic changes and altered RAS protein expression in mice, suggesting that RAS is involved. Fenofibrate is efficient in decreasing BP and in controlling RAS protein expressions, and treats the insulin resistance and the adverse cardiac remodeling decreasing the cardiomyocyte hypertrophy and improving the myocardial vascularization, therefore, decreasing important cardiovascular risk factors

Le syndrome de vibration main-bras (HAVS) est généralement provoqué par l'utilisation d'outils électriques portatifs sur le long terme ; il se manifeste après une exposition au froid, en provoquant une forte et anormale vasoconstriction des vaisseaux sanguins. L'objectif de la thèse est d'établir un nouveau modèle prédictif des changements géométriques et structurels des parois des capillaires causés par l'exposition des membres supérieurs aux vibrations. Le contexte médical du HAVS est rappelé en premier lieu, en particulier les mécanismes pathologiques sous-jacents. Les modèles constitutifs des tissus mous de la pulpe de doigt et de la paroi du vaisseau en croissance issus de la littérature sont rappelés. Dans la troisième partie de la thèse, les paramètres élastiques et visqueux de la pulpe du doigt sont identifiés par le recalage des résultats de la simulation d'un modèle 2D d'une section transversale du bout du doigt avec des données expérimentales. La dernière partie de la thèse aborde la modélisation de la croissance des capillaires induite par la vibration de l'outil, en considérant des échelles spatiales et temporelles macroscopique et microscopique. Le problème spatial multi-échelles est résolu par une méthode de zoom structural, le champ de déformation calculé à l’échelle macroscopique définissant la condition limite appliquée ensuite à l’échelle microscopique. Le problème multi-échelle de temps est résolu en transformant le problème dynamique en un problème équivalent quasi-statique. Les résultats obtenus montrent que les vibrations induisent l'épaississement de la paroi du capillaire, l’effet étant maximum au voisinage de la fréquence de résonance. Des analyses paramétriques sont réalisées pour étudier la relation entre la croissance des capillaires en fonction de la localisation dans la pulpe du doigt, la fréquence de la vibration, l’amplitude de la pré-charge statique, et la dose de vibrations / Hand-Arm Vibration syndrome (HAVS) is usually caused by long-term use of hand-held power tools. It typically occurs after exposure to cold, causing an abnormally strong vasoconstriction of blood vessels. A model predicting the geometrical and structural changes of the arterial walls caused by vibration exposure is developed for the first time in this thesis. The medical context of HAVS is first recalled, especially the underlying pathological mechanisms. The constitutive models for the finger pulp and the growth of the vessel wall from the literature are used as a basis for the modeling of the arterial wall remodeling under exposure to vibration. The elastic and viscous parameters of the fingertip have been identified by adjusting the simulation results of a 2D model of fingertip cross-section to available experimental data. The last part of the thesis develops a first attempt to build the growth model of capillary induced by the tool vibration, considering multiscale spatial and temporal aspects. The two-scale spatial problem is solved by a structure focus, the deformation field computed at the macro level defining the boundary condition next applied at the microscopic level. The two-scale time problem is solved by transforming the dynamic problem into a quasi-static problem. The results obtained show that vibration induces an increase of the thickness of the capillary's wall. Parametric analyses were carried out to study the relationships between the capillary growth and their localization within finger’s pulp, the vibration frequency, the magnitude of the static preload and the vibration dose

Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-03-14Bitstream added on 2014-06-13T19:20:07Z : No. of bitstreams: 1 kayatt_fe_dr_araca.pdf: 743751 bytes, checksum: a6f9587cf07b5001b3dd1c88f814cb3e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Sin Implantes / A estabilidade primária na instalação de implantes dentários é uma das determinantes principais no processo de osseointegração. Algumas situações clínicas impossibilitam o travamento adequado do implante. A diástase provocada por sobrefresagem ou implantações pós-exodônticas indicam o uso de materiais para ocupar este espaço. O objetivo deste estudo foi analisar o uso de copolímero a base de ácido poliláctico na estabilidade primária de implantes osseointegráveis, realizando uma avaliação microscópica através de fluorocromos. Para isso, foram utilizados 14 cilindros de Ti cp GII instalados na tíbia de ratos, divididos em: Grupo Implante Travado (GIT) e Grupo Implante e Biomaterial (GIB), nos períodos de 7, 15 e 21 dias. Resultado: Os implantes suportaram 3N.cm de torque reverso e não foram encontradas diferenças estatisticamente significantes, nos períodos finais, entre as médias das áreas ao redor do implante. O copolímero de PLA/PGA proporcionou o posicionamento dos implantes e não obstou a deposição óssea. / The primary stability in the installation of dental implants is one of the main prerequisite in the osseointegration process. Some clinical situations disable the adequate stability of the implantation. A gap occurred between the bone and the implant provoked by overdrilling or tooth extractions sockets implantations indicates the use of biomaterials to occupy this space. The aim of this study was to analyze the use of PLA/PGA copolymer in the primary stability of osseointegrated implants, through removal torque test and a microscopic evaluation with fluorescent bone markers. For this, 14 cylinders of Ti cp GII had been installed in the tibia of rats, divided in: Group Implant with Stability (GIT) and Group Implant and Biomaterial (GIB), in the periods of 7, 15 and 21 days. Result: The implantations had supported 3N.cm of removal torque and had not been found differences statistically significant, in the final periods, between the averages of the areas of the periphery of the implants. The PLA/PGA copolymer kept the implants position and did not hinder the bone deposition.

Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-17Bitstream added on 2014-06-13T18:41:42Z : No. of bitstreams: 1 almeidajunior_p_dr_araca.pdf: 1442119 bytes, checksum: ef1ca4851f34bc366b4409f8e330ec15 (MD5) / Proposição: O objetivo deste trabalho foi avaliar a influência de três meios de armazenamento temporário no processo de reparo de enxertos ósseos retirados de calota craniana e fixados em mandíbula de coelhos. Material e Método: Foram removidos dois blocos ósseos de 9mm da calota craniana de 40 coelhos machos e colocados no ângulo mandibular direito e esquerdo. O enxerto ósseo foi fixado ao leito receptor imediatamente após a sua remoção (G1), fixado 2 horas após armazenamento em meio seco (G2), 2 horas imerso em solução fisiológica (G3) e 2 horas imerso em solução de Euro Collins® (G4), todos a temperatura ambiente. Os animais foram sacrificados aos 7, 15, 30 e 60 dias pós-operatórios. Uma medida macroscópica padronizada da espessura do enxerto posicionado no leito receptor foi aferida no transoperatório e após o sacrifício de cada grupo. Os cortes histológicos foram corados pela hematoxilina e eosina e pela técnica de imunoistoquímica, através da expressão das proteínas osteocalcina (OC) e fosfatase ácida tartarato-resistente (TRAP). Resultado: A espessura do enxerto e rebordo evidenciou um comportamento uniforme entre os grupos, quando comparados no mesmo período, não havendo diferença estatisticamente significativa. A análise histométrica do percentual de osso neoformado na interface entre o leito receptor e o enxerto demonstrou não haver diferença estatística entre os grupos, no período de 7 e 15 dias pós-operatórios, exceto o grupo G1 que mostrou-se estatisticamente superior em relação ao grupo G4 (p=0,0227) aos 15 dias. Houve uma maior imunomarcação para TRAP e OC verificada no grupo G1, porém sem diferença significante entre os grupos do mesmo período. Conclusão: A solução fisiológica e de Euro Collins® utilizadas como meio de armazenamento temporário, demonstraram influenciar de forma semelhante na biocompatibilidade... / Purpose: The aim of this study was to evaluate the influence of three temporary storage environments in the repair process of bone grafts removed from the calvaria and fixed in rabbits’ mandible. Materials and Methods: Two bone blocks with 9 mm were removed from the calvaria of 40 male rabbits and placed on their right and left mandible angles. Bone graft was placed at the receptor site immediately after its removal (G1), placed 2 hours after storage in dry environment (G2), 2 hours immersed in physiological solution (G3) and 2 hours immersed in Euro Collins® solution (G4), all of them at room temperature. The animals were euthanized at 7, 15, 30 and 60 post-operative days. A standard macroscopic measurement of the graft thickness positioned at the receptor site was done at the trans-operative period and after the euthanasia of each group. Histological sections were stained by hematoxylin and eosin and by immunohistochemical technique, through the expression of the proteins osteocalcin (OC) and tartrate-resistant acid phosphatase (TRAP). Results: Ridge and graft thicknesses evidenced an uniform behavior among the groups, when the same periods were compared, and there was no statistically significant difference. Histometric analysis of the newly formed bone percentage at the interface between the receptor site and the graft showed no statistical difference among the groups in the post-operative periods of 7 and 15 days, except G1 group, which showed to be statistically higher when compared to G4 group (p=0,0227), at 15 days. There was a higher immunomarking for TRAP and OC, verified at G1 group, however without significant difference between the groups of the same period. Conclusion: Physiological and Euro Collins® solutions used as temporary storage environments showed to influence, similarly, the biocompatibility process of the autogenous bone graft, presenting a repair process dynamics close to immediate grafting procedure.

FACT est une protéine clé, qui joue de multiples rôles, y compris dans la transcription et la réparation de l'ADN endommagé. Néanmoins, comment FACT participe à la réparation et à la transcription de la chromatine n'est pas élucidé. Dans ce travail nous avons tout d'abord étudié le rôle de FACT dans le processus de réparation par excision de base (BER). Nous avons utilisé des nucléosomes reconstitués avec de l'ADN à uracile incorporé au hasard. Nous avons trouvé que l'enzyme UDG est capable d'enlever les uraciles localisés du côté de la solution et pas les uraciles se trouvant en face de l'octamère d'histone. La présence simultanée de FACT et de RSC (facteur de remodelage de la chromatine, impliqué dans la réparation) permet un enlèvement efficace des uraciles localisés du côté de l'octamère d'histone par l'UDG. De plus, l'action concertée de FACT et RSC contribue à l'enlèvement de la lésion oxidative 8-oxoG, autrement inaccessible, de la matrice nucléosomale par l'enzyme OGG1. Ce résultat est obtenu grâce à une activité « co-remodelatrice » de la protéine FACT. Dans ce travail nous décrivons pour la première fois cette nouvelle propriété de FACT et nous montrons par une série d'expériences biochimiques que FACT est capable de stimuler l'activité de remodelage du RSC. Nos expériences montrent que la présence de FACT augmente l'efficacité de RSC à transformer l'énergie libérée par l'hydrolyse de l'ATP en travail « mécanique ». Les données obtenues suggèrent une nature stochastique du BER in vivo, FACT étant un facteur clé dans le processus de réparation. Nous avons également investigué l'implication de l'activité co-remodelatrice de FACT dans la fixation de NF-kB aux matrices nucléosomales. La production de nucléosomes remodelés, mais non - mobilisés (remosomes) n'est pas suffisante pour promouvoir la fixation de NF-kB. Pourtant, la mobilisation des nucléosomes par l'intermédiaire de RSC permet une interaction efficace entre NF-kB et l'ADN nucléosomal. Toutes ces données sont essentielles pour le décryptage du mécanisme moléculaire par lequel FACT agit dans le BER et dans la transcription médiée par NF-kB. / FACT is a vital protein which has multiple roles including one in transcription and repair of damaged DNA. However, how FACT assists repair and transcription remains elusive. In this work, we have first studied the role of FACT in Base Excision Repair (BER). We used nucleosomes containing DNA with randomly incorporated uracil. We found that the enzyme UDG is able to remove uracils facing the solution and not the uracils facing the histone octamer. The simultaneous presence of FACT and RSC (a chromatin remodeler involved in repair) allows, however, a very efficient removal of uracil facing the histone octamer by UDG. In addition, the concerted action of FACT and RSC permits the removal of the otherwise un-accessible oxidative lesion 8-oxoG from nucleosomal templates by OGG1. This was achieved thanks to the co-remodeling activity of FACT. Here we described for the first time this novel property of FACT and we show in a series of biochemical experiments that FACT is able to boost the remodeling activity of RSC. The experiments reveal that the presence of FACT increases the efficiency of RSC to transform the energy freed by ATP hydrolysis into “mechanical” work. The presented data suggest a stochastic nature of BER functioning in vivo, FACT being a key factor in the repair process. The implication of the co-remodeling activity of FACT in NF-kB factor binding to nucleosomal templates was also investigated. The generation of remodeled, but not mobilized nucleosomes (remosomes), was not sufficient to promote NF-kB binding. However, the RSC-induced nucleosome mobilization allows efficient NF-kB interaction with nucleosomal DNA. Our data are instrumental in deciphering the molecular mechanism of FACT implication in BER and NF-kB mediated transcription.