Role of the NLRP3 inflammasome in the transient release of IL-1ß induced by monosodium urate crystals in human fibroblast-like synoviocytes.

BACKGROUND: To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1ß in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism. METHODS: Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1ß, IL-6, TNF-α and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR. RESULTS: Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1ß expression in culture medium with a peak at 6 h. The mRNA level of IL-1ß in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1ß was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment. CONCLUSIONS: MSU crystals directly increased IL-1ß and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1ß in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1ß through the NLRP3 inflammasome in human synoviocytes.

[Comprehensive analysis on variation of cardiac enzyme and troponin induced by acute organophosphorous poisoning].

OBJECTIVE: To discuss the diagnostic value of cardiac enzyme and troponin in acute organophosphorus pesticide poisoning (AOPP). METHODS: A retrospective study was performed in the document published in domestic journals and PubMed from 1979 to 2010. The data of the cardiac enzyme and troponin were collected. Statistical analysis was conducted with one-way ANOVA and rank sum test. 2129 cases with AOPP were enrolled. RESULTS: The levels of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) in milder, moderate and severe poisoning groups were significantly elevated compared by the healthy control group (P < 0.05). The differences were also dramatic among three patients groups (P < 0.05). The ratios of CK-MB to CK in both moderate and severe groups were significantly lower than in healthy controls (P < 0.05). The levels of CK, CK-MB and cTnI were higher especially in patients with intermediate myasthenic syndrome (IMS) than patients without IMS. Meanwhile, the levels of CK and CK-MB were elevated in patients with respiratory failure compared by non-failure ones, but decreased in the ratios of CK-MB to CK (P < 0.05). CONCLUSIONS: The elevation of CK and CK-MB in serum could not be judged as the criteria of myocardial damage in AOPP, the ratio of CK-MB to CK were more valuable; the value of cTnI in myocardial damage was still in suspect. CK, CK-MB and cTnI could be used as auxiliary criteria of AOPP classification.

[Meta-analysis of the effectiveness of plasma exchange in treatment of severe and acute organophosphate poisoning].

OBJECTIVE: To discuss the effectiveness of severe and acute organophosphate poisoning (AOPP) treated with plasma exchange in China. METHODS: Researches about effectiveness of severe AOPP treated with plasma exchange were analyzed by Review Manager 4.2 and fixed effect model of meta-analysis method were used. RESULTS: Six trials including 433 patients were identified. Treatment group including 211 patients adopted traditional physician therapy plus plasma exchange, and control group including 222 patients received physician therapy only. The case-fatality rate of the treatment group was lower than the control one [RR=0.30, 95%CI (0.19-0.49), P<0.01]. CONCLUSION: Plasma exchange can improve the cure rate of severe AOPP.

[Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorvos and omethoate].

OBJECTIVE: To observe the treatments on the patients with acute methamidophos dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the rational treatments on these three organophosphorus pesticides poisoning. METHODS: 101 patients with AOPP in 7 hospitals were divided into three groups: Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the three groups. RESULTS: The AChE activities of all the three groups were inhibited on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was found (P > 0.05). All the patients recovered from acute cholinergic excitation or crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were obviously reactivated in group A three hours later after admission to hospital, each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/- 7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th, 24th, 48th, 72nd hour and discharge (P < 0.05), and the upgrade tendency was continuous. AChE activities in group B were also reactivated after treatment, each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55) U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade tendency turned slowly after 12 hours, the inhibited AChE activities were not reactivated in group C from the beginning to the end. CONCLUSION: After the treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos poisoning could be continuously reactivated, the AChE activities of the patients with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep stable, but the AChE activities of the patients with acute omethoate/dimethoate poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy against acute toxicity of all the three organophosphorus pesticides. Oximes should be vigorously used in the treatment of AOPP, including acute omethoate/dimethoate poisoning.