Suppression of nitrosative stress and inflammation of the knee joint synovium in collagen type ii-induced rheumatoid arthritis by the inhibition of glycogen synthase kinase-3ß / Supresión del estrés nitrosativo e inflamación de la sinovial de la articulación de la rodilla en la artritis reumatoide inducida por colágeno tipo ii mediante la inhibición de la glucógeno sintasa quinasa-3 ß

SUMMARY: Rheumatoid arthritis (RA), an inflammatory autoimmune disease that causes cartilage degradation and tissue destruction, can affect synovial joints such as the knee joint. The link between the nitrosative stress enzyme inducible nitric oxide synthase (iNOS) and the cytokine interleukin-1 (IL-1β) in RA-induced knee joint synovial membrane damage with and without the incorporation of the GSK3β inhibitor TDZD-8 has never been studied. As a result, we used active immunization method with collagen type II (COII) for twenty one days to induce RA in rats. TDZD-8 (1 mg/kg; i.p.) was given daily into matched immunized rats for three weeks after day 21 (COII+TDZD-8). Blood and tissue samples were taken 42 days after immunization. A dramatic increase in rheumatoid factor (RF) blood levels, as well as considerable synovial tissue damage and inflammatory cell infiltration of the synovial membrane, were used to validate the onset of RA following COII immunization. COII immunization increased tissue levels of iNOS protein and IL- 1β mRNA and protein expression, which TDZD-8 suppressed considerably (p<0.0001). Furthermore, there was a significantly (p<0.001) positive correlation between iNOS, inflammatory biomarkers, and RF. We concluded that TDZD-8 reduced RA-induced IL-1β -iNOS axis-mediated arthritis in the rat knee joint synovium.

RESUMEN: La artritis reumatoide (AR), es una enfermedad autoinmune inflamatoria que causa la degradación del cartílago y la destrucción del tejido, pudiendo afectar las articulaciones sinoviales, como la articulación de la rodilla. No se ha estudiado el vínculo entre la óxido nítrico sintasa inducible por la enzima del estrés nitrosativo (iNOS) y la citocina interleucina-1 (IL-1β) en el daño de la membrana sinovial de la articulación de la rodilla provocado por AR con y sin la incorporación del inhibidor de GSK3β TDZD-8. Utilizamos el método de inmunización activa con colágeno tipo II (COII) durante veintiún días para inducir AR en ratas. Se administró TDZD-8 (1 mg/kg; i.p.) diariamente a ratas inmunizadas emparejadas durante tres semanas después del día 21 (COII+TDZD- 8). Se tomaron muestras de sangre y tejido 42 días después de la inmunización. Se observó un gran aumento de los niveles sanguíneos del factor reumatoideo (FR), así como un daño considerable del tejido sinovial e infiltración de células inflamatorias en la membrana sinovial, para validar la aparición de la AR después de la inmunización con COII. La inmunización con COII aumentó los niveles tisulares de la proteína iNOS y la expresión de proteína y ARNm de IL-1β, que TDZD-8 suprimió considerablemente (p<0,0001). Además, hubo una correlación positiva significativa (p<0,001) entre iNOS, biomarcadores inflamatorios y FR. Concluimos que TDZD- 8 redujo la artritis mediada por el eje IL-1β-iNOS inducida por la AR en la sinovial de la articulación de la rodilla de rata.

Evaluation of disease modifying activity of Coriandrum sativum in experimental models.

Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. Methods: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF-α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA.

[Effect of isolated soy protien on prevention of rheumatoid arthritis in collagen-induced rats]

The aim of this study was to investigate the effect of isolated soy protein on prevention of rheumatoid arthritis in collagen-induced rats. A total of 24 female Sprague-Dawley rats [body weights: 180-200g] were randomly divided into four equal groups including normal; control of rheumatoid arthritis; rheumatoid arthritis + isolated soy protein [7g/kg]; rheumatoid arthritis + dexamethasone [1mg/kg]. Experimentally rheumatoid arthritis in rats was induced by subcutaneous injection of collagen II emolsified in Incomplete Frund s Adjuvant in days 1 and 7. Treatments were gavaged to animals for 30 days, once a day. The severity of rheumatoid arthritis symptoms in paws were daily measured in double blind format by standard method. The statistical comparison between the experimental groups was performed by Independent -samples t- test and One-Way ANOVA using SPSS software. The clinical symptoms of rheumatoid arthritis started from day 17.4 +/- 2.4, 20 +/- 4 and 14.1 +/- 1.9 in isolated soy protein, dexamethasone and control groups, respectively [P<0.05]. The severity of clinical symptoms of rheumatoid arthritis on day 30 was 3.84 +/- 2.04, 2 +/- 1.78 and 6.5 +/- 1.76 in isolated soy protein, dexa methasone and control groups, respectively [p<0.05]. At the end of the study, the incidence rates of rheumatoid arthritis in isolated soy protein and control groups was 83.33% and 100%, respectively. Isolated soy protein decreased the severity of clinical symptoms of rheumatoid arthritis. Therefore, it could be a key factor in prevention and even treatment of rheumatoid arthritis

Efeito antiinflamatório da lama negra de Peruibe em diferentes modelos experimentais de artrite / Evaluation of the anti-inflammatory effects of mud therapy (Peruibe, Brasil) on different experimental models of arthritis

Investigar a eficácia da lama negra brasileira como tratamento para inflamação em modelos experimentais de artrite. O efeito antiinflamatório de aplicações de lama foi comparado ao tratamento com água aquecida e ausência de tratamento em modelos experimentais de artrite e osteoartrite induzidas em coelhos e em ratos, visando parâmetros inflamatórios e cartilagem. O tratamento com lama melhorou a infiltração de leucócitos e exerceu um efeito protetor parcial na sinóvia e cartilagem. Nossos resultados sugerem que a lama brasileira apresenta efeito antiinflamatório e pode ser útil como um método complementar ao tratamento de pacientes com doenças articulares crônicas / Investigate the effectiveness of a Brazilian black mud as treatment for inflammation in experimental models of arthritis. Effects of mud applications was compared with warm water and no treatment in experimental models of arthritis and osteoarthritis induced in rabbits and in rats, regarding inflammatory parameters and cartilage. Treatment with mud impaired leukocyte infiltration which was followed by a partial protective effect on synovium and cartilage. Our results show that Brazilian mud presents an anti-inflammatory effect and can be useful as a complementary approach to treat patients with chronicle articular diseases...

Rheumatoid arthritis probably induced by pegylated interferon in a patient with chronic hepatitis C.

We report a 47-year-old woman who developed features of rheumatoid arthritis 20 weeks after initiation of treatment with pegylated interferon and ribavirin for chronic hepatitis C. She continued to have symptoms six months after discontinuation of the drugs which she received for 24 weeks with rival clearance.

Efeitos do ultra-som na hiperalgesia e no edema de ratos artriticos / Effects of therapeutic ultrasound on the hyperalgesia and edema in arthritic rats

Com o envelhecimento populacional a prevalencia de doencas osteomusculares cronicas, que restringem a capacidade funcional dos idosos tem aumentado. A artrite reumatoide, integrante desse grupo de patologias, tem atualmente a sua abordagem terapeutica realizada atraves de medicamentos e de fisioterapia. Os tratamentos propostos consistem basicamente em reduzir os sintomas apresentados pela doenca tais como: a dor, o edema, a rigidez e a atrofia muscular, atraves da inibicao do processo inflamatorio. Foi observado o efeito do ultra- som no edema e na hiperalgesia das patas posteriores de ratos artriticos. A artrite reumatoide foi induzida experimentalmente atraves de uma injecao de uma emulsao oleo-agua contendo 400 mcg de Micobacterium butiricum. A hiperalgesia foi detectada no 11 dia e o edema no 12 dia apos a inducao da artrite. O ultra-som com uma frequencia de 1MHz, intensidade de 0,2 watts/cm2, aplicado por 5 minutos diariamente durante 15 dias, nao reduziu a hiperalgesia ou o edema das patas posteriores dos ratos artriticos. Para estudo comparativo, foi administrado um antiinflamatorio nao-esteroide, a indometacina, por via oral na dose de 0,5 mg/kg/dia durante 15 dias consecutivos onde nao foi observado a reducao da hiperalgesia, mas ocorreu a reducao do edema. A associacao do ultra-som com a indometacina, nas doses ja citadas anteriormente, conseguiu inibir significativamente hiperalgesia e o edema das patas dos ratos artriticos. Em nossos estudos, concluimos que o ultra-som associado a indometacina foi mais efetivo do que quando a indometacina ou ultra-som foram utilizados isoladamente na inibicao da hiperalgesia e no edema de ratos artriticos