Background and purpose:  Recent findings suggest that the noxious gas H₂S is produced endogenously, and that physiological concentrations of H₂S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H₂S to modulate carrageenan‐induced synovitis in the rat knee.Experimental approach:  Synovitis was induced in Wistar rats by intra‐articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H₂S formation (dl‐propargylglycine) or an H₂S donor [Lawesson's reagent (LR)].Key results:  Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3‐NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters.Conclusions and implications:  Whereas exogenous H₂S delivered to the knee joint can produce a significant anti‐inflammatory and anti‐nociceptive effect, locally produced H₂S exerts little immunomodulatory effect. These data further support the development and use of H₂S donors as potential alternatives (or complementary therapies) to the available anti‐inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.

Non-steroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed agents for arthritic patients, although gastric effects limit their long-term use. Considering the reported gastric safety of hydrogen sulfide (H2S)-releasing NSAIDs, in addition to the anti-inflammatory effects of H2S administration to rats with synovitis, we decided to evaluate the effects of the H2S-releasing naproxen derivative ATB-346 in this animal model. Male Wistar rats were anesthetized with inhalatory halothane and pre-treated with equimolar oral doses of either naproxen (0.3, 1, 3 or 10 mg/kg) or ATB-346 (0.48, 1.6, 4.8, or 16 mg/kg) 30 min before the i.art. injection of 7.5 mg of carrageenan (CGN) into the right knee joint cavity. Joint swelling and pain score were assessed after 1, 3 and 5 h, and tactile allodynia after 2 and 4 h. After the last measurement, the joint cavity lavages were performed for counting of the recruited leukocytes. The drugs (at the highest doses) were also tested for their gastric effects by evaluating macroscopical damage score and neutrophil recruitment (measured as myeloperoxidase – MPO activity) in the stomachs 5 h after administration of the drugs. In addition, the serum naproxen pharmacokinetic profiles of both compounds, administered at the highest equimolar doses, were obtained during the first 6 h after dosing. At the two highest tested doses, both naproxen and ATB-346 reduced edema and pain score (measured 3 and 5 h after CGN; P < 0.001). Tactile allodynia was similarly inhibited by ~45% 4 h after CGN by both naproxen (at 1, 3 and 10 mg/kg) and ATB-346 (at 1.6 and 4.8 mg/kg; P < 0.001), as well as leukocyte infiltration. Naproxen (but not ATB-346) induced significant gastric damage and, despite the increased gastric MPO activity by ~130% in the naproxen-, but not in the ATB-346-treated rats, this effect was of no statistical significance. The presence of a H2S-releasing moiety in the ATB-346 structure does not impair the antiinflammatory activity of the parent compound in rats with CGN-induced synovitis. In addition, released H2S may account for the absence of deleterious gastric effects, thus making of ATB-346 a potentially useful therapeutic alternative to traditional naproxen for treatment of patients with arthritis.

Background: Despite the guidelines provided by the World Health Organization for the treatment of malaria, treatment failure occurs in many hospitalized patients. Objective: Evaluate whether blood cell count parameters may serve as predictors for malaria treatment. Methodology: A cross-sectional study with a quantitative approach. Results: Of the 219 patients, 21.5% showed failure to antimalarial treatment, Patient with 21 and 40 years (72.6%), male (53.4%), from peri-urban area (47.5%), with high parasitemia (59.8%), treated with Arthemeter (90.9%) and the mortality were 5.9%. Significant associations were observed between occupation, level of parasitemia and outcome with resistance to antimalarial treatment (p<0.05). Patients with normal Hb [OR: 0.75 (95% CI: 0.39–1.44), p = 0.393], RBC [OR: 0.83 (95% CI: 0.40–1.72), p = 0.632], RDW [OR: 0.54 (95% CI: 0.27–1.09), p = 0.088], MCV [OR: 0.61 (95% CI: 0.28–1.31), p = 0.204] were less likely to have malaria treatment failures after artemisinin-based therapy failure. In contrast, those with normal values of segmented neutrophils [OR: 0.32 (95% CI: 0.11–0.96), p = 0.042] and lymphocyte counts [OR: 0.24 (95% CI: 0.05–1.04), p = 0.055]. We also found that patients with significant low levels of Hct [OR: 0.31 (95% CI: 0.15–0.64) p = 0.002], and high leukocytes [OR: 8.88 (95% CI: 2.02–37.2), p = 0.004] and normal platelet values [OR: 1.42 (95% CI: 0.73–2.95), p = 0.280] demonstrated high probability of treatment failure. Conclusion: The importance of blood cell count parameters in monitoring malaria therapy necessitates the urgent need to re-evaluate Artemether-based therapy. Future studies involving more participants in different settings are needed to provide further evidence.