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Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos / Biomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human kneesFranco, Renata Nogueron 28 February 2011 (has links)
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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.
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Influência da lesão condral na concentração de glicosaminoglicanas sulfatadas no líquido sinovial.Cintra Neto, Paulo Felix de Araujo 28 February 2006 (has links)
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Previous issue date: 2006-02-28 / Universidade Federal de Sao Carlos / Objective. To evaluate the influence of sulfated glycosaminoglycan (GAG) concentration in synovial
fluid from individuals with chondral injuries, either isolated or associated with anterior cruciate ligament
injury or meniscal injury, and check for an association between time since injury and the degree of
chondral injury. Material and Method. Twenty-nine adult subjects (25 men and 4 women, mean age
38.3 ± 10.9 years) were selected. Samples obtained from all subjects were quantified to determine the
GAG concentration using dimethylmethylene blue dye. The degree of chondral damage was
macroscopically evaluated by arthroscopy and rated according to the International Cartilage Repair
Society (ICRS) classification. Results. Significant differences were found concerning the GAG
concentration in the control group compared with the other groups (p<0.05). No significant differences
were found between the studied groups concerning time since injury and degree of chondral damage
according to the ICRS. A strong correlation was found between GAG concentration and time since injury
in the chondral injury group (r= -1). Conclusion. Damage to articular structures seems to be the
determining factor in the change of synovial fluid GAG concentration, being higher in isolated chondral
injury. When associated with anterior cruciate ligament rupture and/or meniscal injury, it will promote a
tendency to fall, and is not related to sex, age, time since injury and degree of chondral injury in all
groups studied. / Objetivo: Avaliar a influência da lesão condral na concentração de glicosaminoglicanas sulfatadas no
líquido sinovial de indivíduos portadores de lesões condrais isoladas ou associadas com lesões do
ligamento cruzado anterior e dos meniscos, bem como uma associação com o tempo da lesão e o grau de
osteoartrite. Desenho do estudo: Foram avaliados 29 indivíduos adultos de ambos os sexos. Os sujeitos
foram divididos em cinco grupos: grupo controle; grupo com lesão condral; grupo com lesão condral
associada à lesão meniscal; grupo com lesão condral associada à lesão do ligamento cruzado anterior e
grupo com lesão condral associado às lesões meniscal e do ligamento cruzado anterior. Métodos: As
amostras foram quantificadas em relação à concentração de glicosaminoglicanas pelo método
espectrofotométrico, utilizando o corante azul de dimetilmetileno. O grau de osteoartrite foi avaliado
macroscopicamente, por artroscopia e graduado segundo classificação da Internacional Cartilage Repair
Society, 2000, variando entre grau 0 e 4. Resultados: Encontramos diferenças significativas quando
comparamos a concentração de glicosaminoglicanas do grupo controle em relação aos outros grupos
(P<0,05), houve também correlação entre concentração de glicosaminoglicanas sulfatadas e o tempo pós
lesão no grupo com lesão condral, (r= -1). Não houve diferenças significativas entre os grupos estudados
quanto ao grau de osteoartrite e tempo após a lesão. Conclusão: A lesão condral isolada apresenta maior
concentração de glicosaminoglicanas, entretanto a presença de lesão do ligamento cruzado anterior e
meniscos influenciam uma tendência à queda desta concentração no líquido sinovial e sem apresentar
relação com o tempo de lesão e o grau de osteoartrite entre os grupos estudados.
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Le rôle de la leptine dans le métabolisme anormal des ostéoblastes de patients atteints d’ostéoarthroseMutabaruka, Marie Solange 12 1900 (has links)
No description available.
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Nouvelles stratégies thérapeutiques des affections articulaires du cheval : évaluation du potentiel thérapeutique des chondrocytes autologues et des cellules souches de cordon ombilical (sang et gelée de Wharton) : vers l'industrialisation de cellules médicaments. / New therapeutic strategies for articular disorders in the equine model : therapeutic potential evaluation of autologous chondrocytes and umbilical cord stem cells (from umbilical cord blood and Wharton jelly) : toward industrialization of drug cellsRakic, Rodolphe 05 September 2017 (has links)
Les affections articulaires touchant le cartilage, telles que les lésions focales et l’arthrose, correspondent aux principales causes de baisse de performance et d’arrêt prématuré de la carrière sportive du cheval. Ainsi, le traitement des affections du cartilage représente un enjeu vétérinaire majeur dans le monde équin, du fait des importantes pertes financières qu’elles occasionnent à la filière. Les faibles capacités de réparation intrinsèque du cartilage, ainsi que l’absence de thérapie à long terme des dommages cartilagineux, nécessitent le recours à des thérapies de nouvelles générations telle que l’ingénierie tissulaire du cartilage. Dans ce cadre, notre étude s’est attachée à comparer différents types cellulaires pour la génération de cartilage in vitro, afin d’envisager une implantation pour traiter les atteintes cartilagineuses chez le cheval. Une technique initialement développée chez l’Homme, la transplantation de chondrocytes autologues, représente toujours un « gold standard » en ingénierie tissulaire du cartilage. Dans ce travail de thèse, après avoir développé une nouvelle génération de substitut cartilagineux de haute qualité biologique, à partir de chondrocytes articulaires équins, des limites techniques et biologiques inhérentes au type cellulaire persistent. Ainsi, nos travaux se sont tournés vers la recherche de types cellulaires alternatifs. Les cellules souches/stromales mésenchymateuses (CSM) néonatales issues de cordon ombilical telles que les CSM de sang placentaire (CSM-SPL) et les CSM de gelée de Wharton (CSM-GW) pourraient représenter un avantage thérapeutique du fait de leur isolement non-invasif, de leur forte prolifération cellulaire et de leur capacité de différenciation en chondrocyte. Il est néanmoins indispensable de définir le meilleur candidat thérapeutique, parmi ces deux sources cellulaires, pour l’obtention d’un substitut cartilagineux de qualité biologique optimale. Ces résultats de thèse ont montré d’importantes différences dans le processus de chondrogenèse de ces deux sources de CSM néonatales et plaident en faveur de l’utilisation des CSM-SPL dans le cadre d’une stratégie thérapeutique d’ingénierie tissulaire du cartilage équin. Ces travaux ont permis une meilleure compréhension de la biologie du chondrocyte et des CSM. De surcroît, ces travaux permettent d’envisager de futurs essais cliniques chez le cheval, afin de traiter les affections articulaires de ce modèle gros animal. / Articular cartilage disorders, such as focal defects and osteoarthritis, are the main causes of decreased performance or early retirement of sport- and racehorses. Thus, cartilage disorders represent a major veterinary issue in the equine industry, due to significant financial losses. Poor intrinsic cartilage repair properties and the absence of long- term therapy for cartilage defects lead to the development and use of new generation therapies such as autologous chondrocytes implantation. In this context, our study aimed to compare different cell types for the in vitro cartilage generation, in order to implant the biological substitute to treat cartilage defects in the horse. A therapeutic strategy initially developed in human medicine, the autologous chondrocytes transplantation, always represents a "gold standard" in cartilage tissue engineering. In the present study, after developing a new generation of cartilaginous substitute of high biological quality, composed of equine articular chondrocytes, technical and biological limits inherent to the cell type persist. Thus, we have used alternative cell types such as neonatal mesenchymal stem/stromal cells (MSCs) from umbilical cord, such as umbilical cord blood MSC (UCB-MSCs) and umbilical cord matrix or Wharton jelly MSCs (UCM- MSCs). These MSCs sources could represent a therapeutic advantage due to their non-invasive isolation, their high cell proliferation and their ability to differentiate into chondrocytes. Nevertheless, it is essential to define the best therapeutic candidate between these two MSCs sources, to obtain an optimal quality for the neocartilaginous substitute. Our data highlighted important differences in the chondrogenesis process of these two neonatal MSCs sources, allowing us to consider UCB-MSCs as the best therapeutic candidate for equine cartilage tissue engineering. This work allows a better understanding of the chondrocyte and MSCs biology. Moreover, this work leads the way to setting-up future clinical trials in the horse, in order to treat articular defects of this large animal model.
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