Ana Caroline Rocha de Melo Leite

The snake venom metalloproteinase BaP1 induces joint hypernociception through TNF‐α and PGE2‐dependent mechanisms

Matrix metalloproteinases (MMPs) have been implicated in joint tissue destruction in arthritis. However, MMPs have not been assigned a role in joint pain. We investigated the ability of BaP1, a metalloproteinase from Bothrops asper snake venom, with structural homology to MMPs, to induce joint hypernociception.

Tadalafil analgesia in experimental arthritis involves suppression of intra-articular TNF release

BACKGROUND AND PURPOSE We investigated the effect of the phosphodiesterase‐5 inhibitor, tadalafil, on the acute hypernociception in rat models of arthritis.

Effects of nitric oxide on neutrophil influx depends on the tissue: role of leukotriene B4 and adhesion molecules

Background and purpose:  We investigated the effect of nitric oxide synthase (NOS) inhibition on polymorphonuclear cell (PMN) influx in zymosan or lipopolysaccharide (LPS)‐induced arthritis and peritonitis.

A Longterm Prospective Real-life Experience with Leflunomide in Juvenile Idiopathic Arthritis

Objective. To describe a clinical practice with leflunomide (LEF) in juvenile idiopathic arthritis (JIA). Methods. Patients with JIA seen between May 2008 and May 2012 and considered nonresponsive to methotrexate (MTX) were given LEF and prospectively followed. Primary outcome was a 28-joint Disease Activity Score (DAS28) of low disease activity (< 3.2) in less than 6 months. Childhood Health Assessment Questionnaire (CHAQ) scores and safety data were recorded. Results. Forty-three patients (33 female) were included with 25 (58.1%) polyarticular, 10 oligoarticular (7 extended; 3 persistent), 6 systemic, and 2 enthesitis-related. Ten (23.2%) were rheumatoid factor–positive and 7 (16.3%) had antinuclear antibodies. Prior drugs other than MTX: 11 (25.5%) chloroquine diphosphate + MTX and 2 (4.6%) sulfasalazine + MTX; mean prednisone dose was 6.4 ± 9.3 mg. The MTX dose prior to LEF was 14.5 ± 4.5 mg/m2/week. LEF dose and duration of therapy were 16.6 ± 5.2 mg/d and 3.6 ± 2.2 years, respectively. Nineteen patients (44.2%) interrupted LEF: 1 entered remission, 11 were nonresponsive, and 7 were intolerant (16.2%). Baseline DAS28 (5.57 ± 0.7) dropped to 3.7 ± 1.2 at final analysis (p < 0.001) and 16 patients (37.2%) had a low DAS28 [< 3.2; 12 (27.9%) while taking LEF + MTX and 4 (9.3%) while taking monotherapy]. At last followup, the number of patients with DAS28 > 5.1 dropped from 34 (79%) to 9 (20.9%) and CHAQ scores from 0.86 ± 0.7 to 0.44 ± 0.5 (p < 0.001). Conclusion. LEF isolated or combined with MTX is effective and safe to treat JIA in patients refractory to MTX.

Anti-inflammatory and Immunomodulatory Effect of an Extract of Coccidioides posadasii in Experimental Arthritis

Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1β, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.