The aim of the present study was to investigate the interrelationship of the kinin system, nitric oxide and eicosanoids in the acute phase of antigen-induced arthritis (AIA) in rabbits. The arthritis was induced in immunized rabbits and the following parameters were evaluated 24 hours later: leukocyte influx (total and differential white cell count), vascular permeability (Evans's blue method), and synovial PMN cell infiltrate. PGE2 and LTB4 (radioimmunoassay) levels were quantified in the synovial fluid. The animals were pre-treated with 20mg/kg/day during 14 days with L-NAME or D-NAME and/or Enalapril (0.12 mg/kg/day-14 days), and/or the B2 antagonist of Bradykinin HOE 140 (0.9 mg/kg). Our results showed that L-NAME was effective in the prevention of AIA with reduction of all Inflammatory parameters analyzed. Enalapril partially reverted the L-NAME anti-inflammatory effects. The simultaneous treatment with HOE 140 abolished this reversion and returned the inflammatory parameters to the levels observed in L-NAME treated animals. Our results suggest that pressoric alterations induced by L-NAME could not account for all its anti-inflammatory action in this model of experimental arthritis. Additionally the contribution of the kinin system in AIA was characterized as well as its interaction with eicosanoids and nitric oxide.
BackgroundGuidelines and therapeutic strategies in the treatment of rheumatoid arthritis (RA) have been developed and adopted by most Societies of Rheumatology. However, the extent to which they have been supported by rheumatologists in their individual clinical practice is unclear.ObjectivesOur aim was to analyze, at private offices, adherence to guidelines and characteristics of RA patients in regular follow-up.MethodsThis was a cross-sectional study developed by a group of rheumatologists (n=13) working exclusively in private offices and hospitals in São Paulo, Brazil. It consisted of a web-based questionnaire addressing patient's demographics, social characteristics and treatment. Patients having the diagnosis of RA should be included sequentially. As Brazil's private health has no reference flowchart, patients can consult any physician from their insurance health program, or any physician at all if bearing the costs. Insurance programs can be either personal or tied to employers, in which case job changes imply in insurance and health professional changes.ResultsData from 235 RA patients were collected, 84% were female, mean age (SD) 57.3 (13.3) yrs., disease duration 9.5 (1–54) yrs., 73% RF positive (74% of the 61 RF negative patients had an anti-CCP test and 8 were positive), The mean duration of symptoms until diagnosis was 1.7yrs (0–23), number of physicians until diagnosis 2.4 (1 – 12), including GP (102 patients), orthopedists (110 patients) and rheumatologists (129 patients). Even after diagnosis, patients switched professionals at a mean number of 2 physicians (1–6), justified by shift of health insurance (66 patients), lack of resolution (33 patients), dislike of the physician (26 patients) and cost (11 patients). Regarding treatment, 51% of patients were on biologic agents: 23% adalimumab, 15% abatacept and rituximab, 14% etanercept, 12% tocilizumab, 7.6% golimumab, 5% certolizumab and infliximab and 4% tofacitinib. Interestingly, most patients (75%) using abatacept, tofacitinib and tocilizumab were not on methotrexate (MTX), while from the 65 patients on an anti-TNF agent, 75% were also using MTX or leflunomide (LFN). Regarding traditional DMARDs, 91% of patients were on (n=94) or had used MTX (n=120); 43% were on (n=37) or had used (n=64) LFN. Concerning treatment and disease activity, 91% of patients were considered adherent to the treatment with a mean number of 4 annual visits, 82% were also deemed to be in regular monitoring. According to rheumatologist's assessment, 63% of patients had RA “under control”. In fact, 72% of patients were on low disease activity (22%) or on remission (50%), according to the DAS28. However, when patients in disease activity were analyzed, few of them (0.28 CI 0.18–0.40) were on biologic or target DMARDS, pointing to a possible therapeutic transitional moment. Only 3 of these could be labeled “refractory”, having previously used 3 biologic agents.Conclusions Treat-to-target strategy seems to have been adopted by most rheumatologists in their individual practice, al...
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