Effect of pentoxifylline on adjuvant-induced arthritis in albino rats

Rheumatoid arthritis [RA] is a common inflammatory autoimmune disorder. Non-steroidal anti inflammatory drugs [NSAIDs] have become an integral part of RA therapy. Adverse effects of these drugs are widely expanding. Data implicate the cytokine tumor necrosis factor alpha [TNF-alpha] in the pathophysiology of RA as well as involved in the indomethacin induced gastrointestinal damage. Pentoxifylline [PTX], amethylxanthine derivative is documented to possess anti-inflammatory and anti-TNF-alpha properties. The present study was conducted to investigate the effect of PTX on edema, serum malondialdehyde [MDA] and TNF-alpha in experimentally induced collagen II adjuvant arthritis in albino-rats. Forty-two male albino rats weighing 200-250 grams were used throughout the study. The anti mals were divided into seven equal groups. Group [1]: Non-arthritic control rats received daily 0.5 ml intragastric isotonic saline for 6 weeks. Group [2]: Arthritic control rats received daily 0.5ml isotonic saline intragastricaliy for 6 weeks. Group [3]: Arthritic rats treated intragastrically with indomethacin [1.3 mg/kg/day] for 6 weeks. Group [4]: Arthritic rats treated with daily intragastric PTX [50 mg/kg] for 6 weeks. Group [5]: Arthritic rats treated with PTX [100 mg/kg/day], intragastrically for 6 weeks. Group [6]: Arthritic rats treated with PTX [50 mg/kg/day] given 30 minutes before administration of indomethacin [1.3 mg/kg/day], intragatrically for 6 weeks. Group [7]: Arthritic rats treated with PTX [100 mg/kg/day] administered 30 minutes before administration of indomethacin as above. It was found that administration of collagen II and complete freund's adjuvant to rats produced a significant arthritic changes as assessed by paw edema thickness, analgesmetric pressure and C-reactive protein, arthritic rats developed a significant increase in serum MDA and TNF-alpha. Daily intragastric administration of either indomethacin, PTX alone or in combination induced a significant decrease in paw edema thickness, CRP, MDA as well as induced increase in analgesmetric pressure tolerance. Administration of PTX [50 mg or 100mg/kg] to arthritic rats produced significant decrease in TNF-alpha. Mean while administration of indomethacin alone to arthritic rats produced significant increase in TNF-alpha. Administration of PTX [50 or 100 mg/kg/day] 30 minutes before indomethacin induced a significant decrease in TNF-alpha as compared to administration of indomethacin alone. These findings suggest that PTX is effective in treatment of collagen-II induced adjuvant arthritis. In addition the present work support the concept that antagonizing TNF-alpha is successful in treating inflammatory disorder as RA. PTX may have to be used as adjuvant therapy in RA

A monitorizaçäo plasmática das metilxantinas do guaraná e a importancia na agregaçäo plaquetária / The plasma monitoring of methylxanthines of guarana and its importance in platelet aggregation

Num estudo placebo randomizado, 14 voluntários sadios foram tratados durante dois dias com extrato bruto de Guaraná. A suspensäo aquosa foi administrada em doses de 4 e 8g, três vezes ao dia. Após um período de "wash out", seguiu-se o tratamento com placebo, no mesmo esquema anterior. Desenvolveu-se uma técnica de análise simultânea das metilxantinas envolvidas (teofilina, cafeína e teobromina) em cromatografia líquida de alta pressäo após extraçäo conveniente do plasma em meio ácido com solvente orgânico. O método proposto se mostrou sensível, linear, reprodutível, seletivo, específico e portanto adequado à análise destes compostos em plasma após ingestäo do componente terapêutico nas doses de 4 a 8g. A administraçäo do produto aos voluntários evidenciou níveis plasmáticos dose dependentes para as metilxantinas envolvidas. Verificou-se ainda que houve uma correlaçäo linear positiva apenas entre níveis plasmáticos da cafeína e a inibiçäo da agregaçäo plaquetária em sangue total, mas näo em plasma rico em plaquetas. Näo houve correlaçäo entre doses, efeito biológico e níveis plasmáticos das demais metilxantinas ou por estas näo exercem influência digna de nota sobre a agregaçäo plaquetária ou abtençäo de concentraçäo plasmática subterapêutica utilizando aquelas doses