Objetivos: Este trabalho objetivou avaliar e comparar a incidência de linfedema, dor, restrição na amplitude de movimento e déficit sensorial 1 dia, 15 dias, 3 meses, 6 meses e 18 meses no membro superior homolateral, após linfadenectomia axilar total (LAT) e biópsia de linfonodo sentinela (BLS) para tratamento do câncer de mama. MÉTODOS: Neste estudo incluiu-se pacientes que realizaram ressecção segmentar de mama e LAT ou BLS. As pacientes foram avaliadas entre Dezembro de 2003 e Dezembro de 2004 e foram constituídos por dois grupos, o grupo A (n=100) foi formado por casos submetidos à LAT e o Grupo B, por casos submetidos à BLS (n=50). As pacientes foram analisadas através de questionário com respostas afirmativas e negativas, onde foram incluídas questões avaliando os sintomas de linfedema, dor, restrição da amplitude de movimento e déficit sensorial 1 dia (n=30), 15 dias (n=30), 6 meses (n=30) e 18 meses (n=30), após o procedimento cirúrgico. Além disto efetuou-se avaliação fisioterapêutica na qual foi realizada perimetria de membros superiores, mensuração da amplitude de movimento através da goniometria, os testes de sensibilidade cutânea através dos monofilamentos de Semmes-Weinstein e teste eletrodiagnóstico, utilizando-se gerador universal de correntes. RESULTADOS: No grupo A houve diferenças significantes (p < 0,05) em todos os sintomas subjetivamente avaliados, existindo maior queixa de edema (31%), dor (58%), restrição do movimento (52%) e dormência (57%). No grupo B houve menor prevalência da sensação de edema (2%), dor (26%), restrição do movimento (24%) e dormência (20%), em todos os tempos estudados. No exame clínico, o exame sensorial com monofilamentos apresentou 82% de diminuição da sensibilidade tátil na região axilar e 73% na região braquial proximal no grupo de mulheres submetidas à LAT e no grupo de mulheres submetidas à BLS houve diminuição da sensibilidade tátil nas duas regiões avaliadas em 40% (p<0.05). Nas provas cronaximétricas, a sensibilidade estava diminuída no grupo de mulheres submetidas à LAT em 56% na região axilar e 48% na região braquial proximal medial e no grupo BLS a sensibilidade estava diminuída em 39% e 14% respectivamente. CONCLUSÕES: A morbidade é maior a e funcionalidade do braço é menor em mulheres submetidas à LAT, quando comparadas à BLS, em mulheres operadas por câncer de mama / OBJECTIVES: The aim of this study was to evaluate and compare occurrence of lymphedema, pain, motion restriction and sensory deficit in the upper homolateral limb at 1 day, 15 days, 3 months, 6 months and 18 months after axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) after breast cancer surgery. METHODS: A controlled study was designed to include patients who underwent breast conservative surgery and ALND or SLNB. Patients were evaluated between December 2003 and December 2004, and they were divided into two groups, group A (n=100) consisted who had ALND and group B, with patients after only SLNB (n=50). All of them subjectively answer a \"yes\" or \"no\" questionnaire in which were included questions about incidence of lymphedema, pain, motion restriction and arm numbness at 1day (n=30), 15 days (n=30), 3 months (n=30), 6 months (n=30) and 18 months (n=30) after surgery. Besides this a physiotherapy examination was performed measuring circunference, shoulder adbuction range by a goniometer, sensibility tests by pressure Semmes-Weinsten monofilaments and by eletrodiagnostic tests using an universal stimulator. RESULTS: In the group A significant differences (p < 0,05) were seen in subjectively sensations, with significantly higher incidence of subjective swelling (31%), pain (58%), motion restriction (52%), arm numbness (57%). In group B there were less symptoms of subjective swelling (2%), pain (58%), motion restriction (24%), arm numbness (20%). In clinical examination sensory deficit using monofilaments the occurrence of numbness was 82% on axillary fold and 73% on medial part of upper arm after ALND and in 40% on axillary fold and medial part of upper arm after SLNB, with significantly different between the groups (p < 0.05). At cronaximetric proofs the sensibility was decreased in 56% in the axillary fold and 48% in the medial part of upper arm for ALND and 39% in the axillary fold and 14% at medial part of upper arm on patients who underwent SLNB. CONCLUSIONS: Arm morbidity is higher and function is lower after ALND compared to SLNB, in women submitted to breast cancer surgery

Objetivos: Este trabalho objetivou avaliar e comparar a incidência de linfedema, dor, restrição na amplitude de movimento e déficit sensorial 1 dia, 15 dias, 3 meses, 6 meses e 18 meses no membro superior homolateral, após linfadenectomia axilar total (LAT) e biópsia de linfonodo sentinela (BLS) para tratamento do câncer de mama. MÉTODOS: Neste estudo incluiu-se pacientes que realizaram ressecção segmentar de mama e LAT ou BLS. As pacientes foram avaliadas entre Dezembro de 2003 e Dezembro de 2004 e foram constituídos por dois grupos, o grupo A (n=100) foi formado por casos submetidos à LAT e o Grupo B, por casos submetidos à BLS (n=50). As pacientes foram analisadas através de questionário com respostas afirmativas e negativas, onde foram incluídas questões avaliando os sintomas de linfedema, dor, restrição da amplitude de movimento e déficit sensorial 1 dia (n=30), 15 dias (n=30), 6 meses (n=30) e 18 meses (n=30), após o procedimento cirúrgico. Além disto efetuou-se avaliação fisioterapêutica na qual foi realizada perimetria de membros superiores, mensuração da amplitude de movimento através da goniometria, os testes de sensibilidade cutânea através dos monofilamentos de Semmes-Weinstein e teste eletrodiagnóstico, utilizando-se gerador universal de correntes. RESULTADOS: No grupo A houve diferenças significantes (p < 0,05) em todos os sintomas subjetivamente avaliados, existindo maior queixa de edema (31%), dor (58%), restrição do movimento (52%) e dormência (57%). No grupo B houve menor prevalência da sensação de edema (2%), dor (26%), restrição do movimento (24%) e dormência (20%), em todos os tempos estudados. No exame clínico, o exame sensorial com monofilamentos apresentou 82% de diminuição da sensibilidade tátil na região axilar e 73% na região braquial proximal no grupo de mulheres submetidas à LAT e no grupo de mulheres submetidas à BLS houve diminuição da sensibilidade tátil nas duas regiões avaliadas em 40% (p<0.05). Nas provas cronaximétricas, a sensibilidade estava diminuída no grupo de mulheres submetidas à LAT em 56% na região axilar e 48% na região braquial proximal medial e no grupo BLS a sensibilidade estava diminuída em 39% e 14% respectivamente. CONCLUSÕES: A morbidade é maior a e funcionalidade do braço é menor em mulheres submetidas à LAT, quando comparadas à BLS, em mulheres operadas por câncer de mama / OBJECTIVES: The aim of this study was to evaluate and compare occurrence of lymphedema, pain, motion restriction and sensory deficit in the upper homolateral limb at 1 day, 15 days, 3 months, 6 months and 18 months after axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) after breast cancer surgery. METHODS: A controlled study was designed to include patients who underwent breast conservative surgery and ALND or SLNB. Patients were evaluated between December 2003 and December 2004, and they were divided into two groups, group A (n=100) consisted who had ALND and group B, with patients after only SLNB (n=50). All of them subjectively answer a \"yes\" or \"no\" questionnaire in which were included questions about incidence of lymphedema, pain, motion restriction and arm numbness at 1day (n=30), 15 days (n=30), 3 months (n=30), 6 months (n=30) and 18 months (n=30) after surgery. Besides this a physiotherapy examination was performed measuring circunference, shoulder adbuction range by a goniometer, sensibility tests by pressure Semmes-Weinsten monofilaments and by eletrodiagnostic tests using an universal stimulator. RESULTS: In the group A significant differences (p < 0,05) were seen in subjectively sensations, with significantly higher incidence of subjective swelling (31%), pain (58%), motion restriction (52%), arm numbness (57%). In group B there were less symptoms of subjective swelling (2%), pain (58%), motion restriction (24%), arm numbness (20%). In clinical examination sensory deficit using monofilaments the occurrence of numbness was 82% on axillary fold and 73% on medial part of upper arm after ALND and in 40% on axillary fold and medial part of upper arm after SLNB, with significantly different between the groups (p < 0.05). At cronaximetric proofs the sensibility was decreased in 56% in the axillary fold and 48% in the medial part of upper arm for ALND and 39% in the axillary fold and 14% at medial part of upper arm on patients who underwent SLNB. CONCLUSIONS: Arm morbidity is higher and function is lower after ALND compared to SLNB, in women submitted to breast cancer surgery

O ligamento cruzado anterior é o ligamento mais lesado dentre os ligamentos do joelho. Apesar de um aprimoramento das técnicas de reconstrução, existe ainda um porcentual de pacientes que apresenta resultado funcional insatisfatório. Possivelmente a causa dessa instabilidade rotatória estaria nas estruturas localizadas na porção anterolateral do joelho, não reconstruídas nas reconstruções intra-articulares isoladas. Uma dessas estruturas seria o ligamento anterolateral, estrutura estudada com detalhes nos últimos anos, ainda com controvérsias em relação a seus parâmetros anatômicos, histológicos e de visualização por ressonância magnética. Neste estudo, foram realizadas dissecções de 112 cadáveres para avaliação dos parâmetros anatômicos e histológicos do ligamento anterolateral, sendo que 13 deles foram submetidos ao exame de ressonância magnética previamente às dissecções. O estudo do ligamento anterolateral por ressonância magnética foi realizado também em 42 pacientes. Como resultados, o ligamento anterolateral foi encontrado com constância na região anterolateral do joelho, com origem próxima ao epicôndilo lateral, trajeto anterodistal em direção à tíbia e inserção na periferia do menisco lateral e na região anterolateral da tíbia, entre o tubérculo de Gerdy e a cabeça da fíbula. Sua análise histológica mostrou a presença de tecido conectivo denso e bem organizado, semelhante a tecido ligamentar. A avaliação por ressonância magnética mostrou parâmetros de origem, inserção e trajeto semelhantes às dissecções anatômicas, embora não sendo possível a visualização completa dessa estrutura em todos os exames. Existiu correlação entre as medidas encontradas nos exames de ressonância magnética e nas dissecções, exceto em relação à espessura do ligamento anterolateral / The anterior cruciate ligament is the most injured ligament of the knee. Despite an improvement in reconstruction techniques, there is still a percentage of patients with poor functional outcome after its reconstruction. Possibly, the cause of this rotational instability would be the structures located in the anterolateral portion of the knee, not addressed in the isolated intra-articular reconstructions. One of such structures would be the anterolateral ligament, a structure studied in detail in recent years, with controversies regarding its anatomical, histological and magnetic resonance imaging parameters. In this study, dissections of 112 cadavers were performed to evaluate anatomical and histological parameters of anterolateral ligament, and 13 of them underwent magnetic resonance imaging examination prior to dissection. The anterolateral ligament study by magnetic resonance imaging was also performed in 42 patients. As a result, the anterolateral ligament was found with constancy in the anterolateral region of the knee, with origin near the lateral epicondyle, antero-distal path towards the tibia and insertion in the periphery of the lateral meniscus and in the anterolateral region of the proximal tibia, between Gerdy\'s tubercle and the fibular head. Its histological analysis showed the presence of dense and well-organized connective tissue, similar to a ligamentous tissue. The magnetic resonance imaging evaluation showed origin, insertion and path parameters similar to the anatomical dissections, although it is not possible to fully visualize this structure in all the magnetic resonance imaging exams. There was a correlation between the measurements found in magnetic resonance imaging scans and dissections, except in relation to the anterolateral ligament thickness

A instabilidade patelar é uma patologia comum dentro da especialidade da cirurgia do joelho. O principal fator estabilizador dessa articulação é o ligamento patelofemoral medial, sendo esta a principal estrutura a ser reconstruída no tratamento cirúrgico da instabilidade patelar. Apesar de sua reconstrução apresentar excelentes resultados clínicos, não se sabe ao certo o real efeito in vivo desse procedimento no movimento da patela ao redor do fêmur. A avaliação da articulação patelofemoral tradicionalmente é feita através de exames de imagem estáticos. Com a evolução dos aparelhos de tomografia computadorizada, se tornou possível realizar esse exame durante movimento ativo, técnica ainda pouco utilizada para estudo de articulações como o joelho. O objetivo deste estudo foi padronizar o uso da tomografia de 320 fileiras de detectores para estudo dinâmico da articulação patelofemoral em pacientes com instabilidade patelar recidivante pré e pós-reconstrução do ligamento patelofemoral medial, analisando o efeito da cirurgia no trajeto da patela ao longo do arco de movimento. Foram selecionados 10 pacientes com instabilidade patelar e indicação de reconstrução do ligamento patelofemoral medial isolada, que foram submetidos à tomografia antes e após um mínimo de 6 meses da cirurgia. Os parâmetros anatômicos avaliados foram os ângulos de inclinação da patela e distância da patela ao eixo da tróclea através de um programa de computador desenvolvido especificamente para esse fim. Foram aplicados os escores clínicos de Kujala e Tegner e calculada a radiação dos exames. O protocolo escolhido para aquisição de imagens na tomografia foi: potencial do tubo de 80 kV, carga transportável de 50 mA, espessura de corte de 0,5 mm e tempo de aquisição de 10 segundos, o que gerou um DLP (dose length product) de 254 mGycm e uma dose efetiva estimada de radiação de 0,2032 mSv. O paciente realizava uma extensão ativa do joelho contra a gravidade. Os resultados não mostraram mudança do trajeto da patela após a reconstrução do ligamento patelofemoral medial, apesar de não ter havido nenhuma recidiva da instabilidade e os escores clínicos apresentarem melhora média de 22,33 pontos no Kujala (p=0,011) e de 2 níveis no Tegner (p=0,017) / Patellar instability is a common pathology in the practice of knee surgeons. The most important stabilizing structure in the patellofemoral joint is the medial patellofemoral ligament. This ligament is the main structure to be reconstructed during surgery for patellofemoral instability. Although clinical results for this procedure are excellent, the real in vivo effect of medial patellofemoral ligament reconstruction on patellar tracking is unknown. The study of this joint is usually made with static imaging. With the recent evolution of tomographers, it is now possible to analyze anatomical structures moving during active range of motion. This technique (dynamic computerized tomography) has not been routinely used to study joints as the knee. This study had the purpose of standardizing the use of 320-detector row computerized tomography for the patellofemoral joint, analyzing patients before and after surgical reconstruction of medial patellofemoral ligament. We selected 10 patients with patellofemoral instability referred to isolated medial patellofemoral ligament reconstruction surgery, and submitted them to a dynamic computerized tomography before and at a minimum of 6 months after surgery. Patellar tilt angles and shift distance were analyzed using a computer software specifically designed for this purpose. Kujala and Tegner scores were applied and the radiation of the exams was recorded. The protocol for imaging acquisition was: tube potential of 80 kV, 50 mA, slice thickness of 0.5 mm and 10 seconds of acquisition duration. This produced a DLP (dose length product) of 254 mGycm and a radiation effective estimated dose of 0.2032 mSv. There were no changes in patellar tracking after medial patellofemoral ligament reconstruction. There was no instability relapse. Clinical scores showed an average improvement of 22.33 points for Kujala (p=0.011) and of 2 levels for Tegner (p=0.017)

No description available.

Le développement et l'homéostasie des os requièrent l'orchestration spatio-temporelle d'un grand nombre de signaux moléculaires. Ces signaux entraînent l'activation ou l'inhibition de différents facteurs de transcription, lesquels sont en mesure de contrôler la prolifération et la différenciation des ostéoblastes et des chondrocytes. L'intégrité de ces différents mécanismes se doit d'être maintenu tout au long de la vie. Ainsi, une anomalie dans l'un de ces mécanismes conduit à l'apparition de pathologies osseuses et métaboliques telles qu’une hypophosphatémie, l'ostéoporose ou l'ostéoarthrite (OA). Afin d'en apprendre davantage sur la biologie osseuse, le projet décrit dans cette thèse a pour objectif de caractériser de nouveaux mécanismes de régulation transcriptionnelle pour deux gènes importants dans le développement des os et le maintien de leur intégrité. Il s’agit du Paired-like Homeodomain Transcription Factor 1 (PITX1) et du Phosphate-regulating gene with homology to endopeptidase on the X chromosome (PHEX). Le premier mécanisme présenté dans cette thèse concerne la régulation transcriptionnelle du gène PITX1, un facteur de transcription à homéodomaine nécessaire, notamment, au développement des os des membres inférieurs et au maintien de l'intégrité du cartilage articulaire chez l'adulte. Ainsi, dans les chondrocytes articulaires, on note que l'expression de PITX1 est assurée par le recrutement du facteur de transcription E2F1 à deux éléments de réponse présents dans la région proximale du promoteur de PITX1. Aussi, dans les chondrocytes articulaires de patients souffrant d'OA, dans lesquels l'expression de PITX1 est fortement diminuée, un mécanisme de répression transcriptionnelle, lequel implique la protéine multifonctionnelle Prohibitin (PHB1), semble être activé. En effet, dans ces chondroytes, on note une forte accumulation nucléaire de PHB1 comparativement aux chondrocytes articulaires de sujets sains. Le second mécanisme présenté dans cette thèse concerne la répression transcriptionnelle de PHEX, la peptidase mutée dans le syndrome d'hypophosphatémie lié au chromosome X (X-Linked Hypophosphatemia, XLH), lequel se caractérise par une hypophosphatémie et une ostéomalacie. Le traitement d'ostéoblastes à la Parathyroid hormone-related protein (PTHrP) permet d’observer la répression de PHEX. Afin de caractériser le mécanisme responsable de cette répression, des expériences de gènes rapporteurs ont révélé la présence de deux éléments de réponse pour le répresseur transcriptionnel E4BP4 dans le promoteur de PHEX. La suppression de l'expression d'E4BP4 par l'utilisation d'ARN d'interférence a permis de valider que ce facteur de transcription est responsable de la répression de PHEX suite au traitement d'ostéoblastes à la PTHrP. En somme ces nouveaux mécanismes de régulation transcriptionnelle permettent de mieux comprendre la régulation de l'expression de PITX1 et de PHEX. Aussi, cette nouvelle implication de PHB1 dans la pathogenèse de l'OA offre de nouvelles possibilités de traitement et pourrait servir pour le diagnostic précoce de cette pathologie. Enfin, la caractérisation d'E4BP4 en tant que médiateur pour la répression de PHEX par la PTHrP suggère que ce répresseur transcriptionnel pourrait être impliqué dans le contrôle de la minéralisation des os et des niveaux de phosphate sanguin. / Bone development and homeostasis need a large amount of molecular signals to be finely regulated in time and space. These signals lead to the activation or to the inhibition of different transcription factors, which are implicated in the control of osteoblast and chondrocyte proliferation and differentiation. The integrity of these mechanisms is required in order to have a healthy life. Indeed, if one of these mechanisms is dysfunctional, different diseases could develop such as hypophosphatemia, osteoporosis and osteoarthritis (OA). In order to contribute to the comprehension of bone biology, the present thesis describes new mechanisms for the transcriptional regulation of two genes implicated in bone development and regulation: PITX1 (Paired-like Homeodomain Transcription Factor 1) and PHEX (Phosphate-regulating gene with homology to endopeptidase on the X chromosome). The first mechanism described in this thesis relates to the transcriptional regulation of PITX1, a gene that encodes for a member of the homeobox family of transcription factors. PITX1 is required in bone development of inferior members and in the maintenance of the articular cartilage integrity in adults. Thereby, we showed that in articular chondrocytes, the expression of PITX1 is activated after the transcription factor E2F1 was recruited at two response elements in the proximal region of its promoter. Moreover, in articular chondrocytes from OA patients, we observed that the expression of PITX1 is strongly decreased. We proposed that the mechanism responsible for this repression requires the multitask protein Prohibitin (PHB1), which is strongly accumulated in OA chondrocyte nuclei, but not in chondrocyte nuclei from healthy individuals. The second mechanism described in this thesis reports a transcriptional mechanism by which PHEX, the gene that encodes for the peptidase mutated in the syndrome X-Linked Hypophosphatemia (XLH)and characterized by hypophosphatemia and osteomalecia, is repressed. We showed that the treatment of osteoblasts with the Parathyroid hormone-related protein (PTHrP) induced a decrease in PHEX expression. In order to characterize the mechanism responsible for this repression, we performed gene reporter experiments and identified two response elements for the transcription factor E4BP4 in the PHEX promoter. The downregulation of E4BP4 by siRNA led to the validation that this repressor decreased the expression of PHEX in osteoblasts after their treatment with PTHrP. In conclusion, the new transcriptional mechanisms presented in this thesis allow a better understanding of PITX1 and PHEX expression. Moreover, the potential role of PHB1 in the establishment of OA presents many interesting possibilities regarding the treatment and diagnosis of this disease. Finally, the characterization of E4BP4 as a mediator of PHEX repression by the PTHrP suggests that E4BP4 could be implicated in the control of bone mineralization and phosphate levels in the blood.

La structure du cartilage articulaire adulte est caractérisée par la présence de couches créées par l’orientation des fibres de collagène (Benninghoff, 1925). Avant de présenter la structure adulte classique en arcades “de Benninghoff”, le cartilage subit une série de changements au cours de sa maturation (Julkunen et al., 2010; Lecocq et al., 2008). Toutefois, un faible nombre d’études s’est intéressé à la structure du collagène du cartilage articulaire in utero. Notre objectif était d’étudier la maturation de la surface articulaire de l’épiphyse fémorale distale chez le cheval, en employant à la fois l’imagerie par résonance magnétique (IRM) et la microscopie en lumière polarisée après coloration au rouge picrosirius, au niveau de sites utilisés dans les études de réparation tissulaire et de sites prédisposés à l’ostéochondrose (OC). Le but était de décrire le développement normal du réseau de collagène et la relation entre les images IRM et la structure histologique. Des sections provenant de cinq sites de l’épiphyse fémorale distale de 14 fœtus et 10 poulains et adultes ont été colorées au rouge picrosirius, après que le grasset ait été imagé par IRM, dans l’optique de visualiser l’agencement des fibres de collagène de type II. Les deux modalités utilisées, IRM et microscopie en lumière polarisée, ont démontré la mise en place progressive d’une structure en couches du réseau de collagène, avant la naissance et la mise en charge de l’articulation. / Adult articular cartilage has a zonal or layered structure, created by the predominant collagen fibre orientation (Benninghoff, 1925). Before reaching the classical “Benninghoff structure”, major changes take place with maturation from juvenile to adult cartilage (Julkunen et al., 2010; Lecocq et al., 2008). However, there have been few studies addressing the in utero collagen structure of articular cartilage. Our objective was to study the maturation of the distal femoral epiphysis articular surface, employing both magnetic resonance imaging and polarized light microscopy with picrosirius red staining, at sites employed for cartilage repair studies or susceptible to osteochondrosis to describe normal development of the spatial architecture of the collagen network at these sites and the relationship between magnetic resonance images and histology. Samples were harvested from five sites from the distal femoral epiphysis of 14 fetuses and 10 foals and adults, after the stifle was imaged with magnetic resonance imaging. Sections were stained with picrosirius red to determine the structural arrangement of the type II collagen fibres. Both magnetic resonance imaging and polarized light microscopy revealed an early progressive structural laminar/zonal organization of the collagen network, prior to birth and postnatal load-bearing.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Les maladies ostéoarticulaires représentent environ 10% de l’ensemble des pathologies identifiées en France chaque année. Ces maladies inflammatoires et dégénératives des articulations sont pour la plupart consécutives au vieillissement ou à un traumatisme et évoluent vers l’usure des cartilages, d’où un handicap sévère. Comme aucun traitement ne permet la réparation totale du tissu cartilagineux, la recherche médicale développe des techniques d’ingénierie tissulaire. Ces techniques utilisent des substrats polymériques et des cellules souches qui sont « contraints » de se développer pour former du tissu cartilagineux. Cependant, ces techniques ne peuvent pas encore être utilisées à l’échelle d’une articulation complète car il n’est pas possible de reproduire ex vivo à grande échelle la structure et les propriétés mécaniques et physicochimiques du cartilage articulaire. Dans ce contexte, les travaux de cette thèse ont permis de développer des matériaux polymères capables d’être implantés à l’échelle macroscopique dans les articulations pathologiques afin de combler l’usure des cartilages. Pour se faire, de nouveaux biomatériaux - hydrogels p(HEMA) - ont été obtenus en contrôlant le caractère hydrophile des hydrogels p(HEMA) au cours de leur synthèse chimique en présence de différents co-monomères (acide acrylique, acrylamide, acrylate d'éthylène et acrylate de butyle). Partant de là, les propriétés physicochimiques, mécaniques et tribologiques de ces nouveaux hydrogels ont été optimisées afin d’obtenir des propriétés similaires à celles du cartilage articulaire sain. Ensuite, la libération contrôlée de médicaments par ces hydrogels a été étudiée afin de minimiser les risques inflammatoires lors de leur utilisation en ingénierie tissulaire du cartilage articulaire. / Osteoarticular diseases re present approximately 10% of all diseases identified in France each year. These inflammatory and degenerative joint disease are mostly consecutive with age or injuries and the wear progress of cartilage, resulting in severe disability. Because no treatment will total repair the cartilage tissue, medical research is developing techniques based on tissue engineering. These techniques use polymer substrates and stem cells that are "forced" to develop into cartilage tissue. However, these techniques cannot be used across a run articulation because Il is not possible-to replicate ex vivo a large-scale structure and the physicochemical and mechanical properties of articular cartilage. In this context, the purpose of this thesis is to develop polymer materials that can be implanted at the macroscopic level in the joints disease that will fill the wear of the cartilage. To do so, new biomaterials - hydrogels p (HEMA)- were obtained by controlling the hydrophilic nature of hydrogels p (HEMA) during their chemical synthesis in the presence of various co-monomers (acrylic acid, acrylamide, acrylate ethylene and butyl acrylate). From there, physicochemical, mechanical and tribological properties of these novel hydrogels have been optimized to obtain similar properties to those of healthy articular cartilage. Then, the controlled release of drugs from these hydrogels was studied to minimize inflammatory when used in tissue engineering of articular cartilage.

Made available in DSpace on 2016-06-02T20:18:15Z (GMT). No. of bitstreams: 1 3931.pdf: 5591864 bytes, checksum: b4873ba462675328d3fc2005b8032afb (MD5) Previous issue date: 2011-02-28 / Osteoarthritis (OA), a degenerative joint disease, is one of the most frequent causes of pain in the musculoskeletal system and of the inability to work in Brazil and the world. It is a multifactor, chronic disease, leading to progressive functional inability. It can arise as a result of injuries to structures such as the anterior crossed ligament and/or meniscus (post-traumatic OA), which, in this case, can affect individuals in any age range. The development of osteoarthritis includes multiple changes in the extracellular cartilage matrix, altering the normal morphological configuration of the joint involved, leading to a lack of equilibrium between the synthesis and degradation of products in this matrix. Although OA is not considered primordially as an inflammatory disease, inflammation of the joint has been shown to be a potential amplifier of the degenerative process. Thus the objective of the present study was to analyze potential biological markers in the serum and synovial fluid, and then correlate them with one another and with the morphological, inflammatory and functional alterations found in individuals with chronic injury of the anterior crossed ligament (ACL). The following techniques were used in the study: zymography, to determine the activity of the metallopeptidases 2 and 9 (MMP-2 and MMP-9); an immune-enzymatic assay (ELISA) to determine the presence of systemic and local cytokines; and a manual count of inflammatory cells (mononuclear and polymorphonuclear) by optical microscopy and spectrophotometry, in order to analyze for sulfated glycosaminoglycans (GAGs). The results indicated joint and systemic inflammation in chronic injury of the ACL by the detection of systemic and local cytokines, by the activity of MMP-9 and by the inflow of neutrophils. There were interactions between systemic and local cytokines, in which a cytokine did not always exert the same function in the serum as in the synovial fluid. The interleucines (IL) connected to degradation of the cartilage in chronic injury of the ACL were IL-12, IL-6 and IL-8, and those connected to pain and loss of function were IL-6 and IL-9. In counterpart, MMP-2 showed a negative correlation with the damage to the cartilage. It was concluded that the molecules studied had potential as biomarkers, since alterations were suggestive of injury and degradation of the cartilage. In addition, after the traumatic event resulting in rupture of the ACL, the ambient remained chronically inflamed and this inflammation was crucial for the high index of posttraumatic OA. / A osteoartrite (OA), doença articular degenerativa, é uma das causas mais freqüentes de dor do sistema músculo-esquelético e de incapacidade para o trabalho no Brasil e no mundo. É uma doença crônica, multifatorial, que leva a uma incapacidade funcional progressiva. Pode surgir em decorrência de lesões em estruturas como ligamento cruzado anterior e/ou meniscos (OA pós-traumática), e neste caso, pode afetar indivíduos em qualquer faixa etária. O desenvolvimento da osteoartrite inclui múltiplas mudanças na matriz extracelular da cartilagem, o que altera a configuração morfológica normal da articulação envolvida, levando a um desequilíbrio entre a síntese e degradação dos produtos desta matriz. Apesar da OA não ser considerada primordialmente como uma doença inflamatória, a inflamação articular tem demonstrado um potencial amplificador do processo degenerativo. Sendo assim, o objetivo deste trabalho foi analisar potenciais marcadores biológicos no soro e no líquido sinovial, e em seguida correlacioná-los uns com os outros e com as alterações morfológicas, inflamatórias e funcionais encontradas em sujeitos com lesão crônica do ligamento cruzado anterior (LCA). Para este estudo foram utilizadas técnicas de: zimografia, para verificar a atividade das metalopeptidases 2 e 9 (MMP-2 e MMP-9); Ensaio imunoenzimático (ELISA), para constatar a presença das citocinas sistêmicas e locais; contagem manual de células inflamatórias (mononucleares e polimorfonucleares) por microscopia óptica e espectrofotometria para a análise dos glicosaminoglicanos sulfatados (GAGs). Os resultados apontaram para uma inflamação articular e sistêmica na lesão crônica do LCA, pela detecção de citocinas sistêmicas e locais, pela atividade das MMP-9 e pelo influxo de neutrófilos. Houve interações entre citocinas sistêmicas e locais, nas quais nem sempre uma citocina exerce a mesma função no soro e no líquido sinovial. As interleucinas (IL) ligadas à degradação da cartilagem na lesão crônica do LCA foram IL-12, IL-6 e IL-8 e as ligadas à dor e a perda de função foram IL-6 e IL-8. Em contrapartida, a MMP-2 apresentou correlação negativa com os danos na cartilagem. Conclui-se que, as moléculas estudadas apresentam potencial como biomarcadores, sendo suas alterações sugestivas de lesão e degradação da cartilagem. E ainda, que após o evento traumático responsável pelo rompimento do LCA, o ambiente permanece inflamado cronicamente e que esta inflamação é crucial para o alto índice de OA pós-traumática.