Assuntos
Clima , Acesso à Informação , Terminologia , Mudança Climática , Relatos de Casos , Haiti , Região do CaribeAssuntos
Mudança Climática , Pobreza , Relatos de Casos , Malaui , México , Região do Caribe , América CentralRESUMO
Cartilage-specific extracellular matrix synthesis is the prerequisite for chondrocyte survival and cartilage function, but is affected by the pro-inflammatory cytokine TNF-alpha in arthritis. The aim of the present study was to characterize whether the immunoregulatory cytokine IL-10 might modulate cartilage matrix and cytokine expression in response to TNF-alpha. Primary human articular chondrocytes were treated with either recombinant IL-10, TNF-alpha or a combination of both (at 10ng/mL each) or transduced with an adenoviral vector overexpressing human IL-10 and subsequently stimulated with 10ng/ml TNF-alpha for 6 or 24h. The effects of IL-10 on the cartilage-specific matrix proteins collagen type II, aggrecan, matrix-metalloproteinases (MMP)-3, -13 and pro-inflammatory cytokines were evaluated by real-time RT-PCR and immunohistochemistry. Transduced chondrocytes overexpressed high levels of IL-10 which significantly up-regulated collagen type II expression. TNF-alpha suppressed collagen type II and aggrecan, but increased MMP and cytokine expression in chondrocytes compared to the non-stimulated controls. The TNF-alpha mediated down-regulation of aggrecan expression was significantly antagonized by IL-10 overexpression, whereas the suppression of collagen type II was barely affected. The MMP-13 and IL-1beta expression by TNF-alpha was slightly reduced by IL-10. These results suggest that IL-10 overexpression modulates some catabolic features of TNF-alpha in chondrocytes.
Assuntos
Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Glicoproteínas/metabolismo , Interleucina-10/metabolismo , Adenoviridae/genética , Adenoviridae/metabolismo , Idoso , Idoso de 80 Anos ou mais , Artérias/metabolismo , Proteína de Matriz Oligomérica de Cartilagem , Células Cultivadas , Condrócitos/ultraestrutura , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Proteínas da Matriz Extracelular/genética , Vetores Genéticos/genética , Glicoproteínas/genética , Humanos , Interleucina-10/genética , Proteínas Matrilinas , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , RNA Mensageiro/genética , Fator de Necrose Tumoral alfaRESUMO
Nitric oxide (NO) appears to act as an inflammatory mediator on monocytic cells. Exogenous NO augmented release of chemokines from human promonocytic U937 cells and peripheral blood mononuclear cells. Pharmacological strategies aiming at modulation of NO-induced release of interleukin-8 (IL-8) were investigated in U937 cells in detail. Release of IL-8 was down-regulated by transforming growth factor beta2 (TGF-beta2), by the protein tyrosine-kinase inhibitor genistein, and via rises in intracellular cyclic AMP, generated by prostaglandin E(2), rolipram, pentoxifylline, forskolin, or dibutyryl-cyclic AMP. In addition, incubation with the synthetic glucocorticoid dexamethasone or suppression of activity of p38 mitogen-activated protein (MAP) kinases by SB-203580 modulated release of IL-8. Activation of p38 MAP kinases was confirmed by the demonstration of an augmented appearance of phosphorylated p38 in the presence of NO. The present data suggest that exposure to exogenous NO resembles activation of U937 cells by proinflammatory stimuli. The anti-inflammatory cytokine TGF-beta2, as well as anti-inflammatory or immunosuppressive agents such as genistein, pentoxifylline, rolipram, dexamethasone, and SB-203580 modulate inflammatory, chemokine-inducing actions of NO.
Assuntos
Quimiocinas/metabolismo , Inflamação/fisiopatologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Óxido Nítrico/farmacologia , Quimiocina CCL4 , AMP Cíclico/metabolismo , Dexametasona/farmacologia , Inibidores Enzimáticos/farmacologia , Genisteína/farmacologia , Humanos , Imidazóis/farmacologia , Interleucina-8/metabolismo , Proteínas Inflamatórias de Macrófagos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Doadores de Óxido Nítrico/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Piridinas/farmacologia , Transdução de Sinais , Acetato de Tetradecanoilforbol/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Triazenos/farmacologia , Células U937 , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Based on the Helkimo index we assessed the success of conservative and conservative-surgical forms of treatment for mandibular fractures in a total of 166 patients. The control group consisted of 50 probands. The Helkimo dysfunction index, which is based on various criteria, showed dysfunction in 81.9% of the patients with only slight functional impairment in 57.2% of these cases. 18.1% of the patients were clinically symptom-free. A comparison with the probands revealed no major differences in dysfunction between the two groups. Significant differences were observed only in the case of 2 isolated criteria (maximum mandibular protrusion, muscle pain). Severe dysfunction, however, was more common in the fracture patients. Based on the Helkimo occlusion index disorder were noted in 91.7% of the patients, while severe occlusion disorder were observed particularly in patients with combined mandibular body and condyle fractures (40.0%). In the control group a more favorable occlusion index was found to be due mainly to the greater number of present and/or occluding teeth. The Helkimo index, particularly the dysfunctionindex, is a very useful instrument for assessing the success of treatment measures in mandibular fracture cases. It should be more commonly used to improve the possibilites of objective comparisons between patients from different hospitals.
