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BACKGROUND AND PURPOSEPro-inflammatory cytokines are important in rheumatoid arthritis (RA) and their production is mainly regulated by NF-κB and inflammasomes. Carboxyamidotriazole (CAI) exhibits potent anti-inflammatory activities by decreasing cytokines. Here, we have investigated NACHT, LRR and PYD domains-containing protein (NALP) inflammasomes in a rat model of RA and explored the therapeutic effects of CAI in this model and the involvement of NF-κB and inflammasomes in the actions of CAI. EXPERIMENTAL APPROACHThe anti-arthritic effects of CAI were assessed in the adjuvant arthritis (AA) model in rats, using radiological and histological techniques. NALP1 and NALP3 inflammasomes, NF-κB pathway and pro-inflammatory cytokines levels were measured with Western blots, immunohistochemistry and ELISA. KEY RESULTSCAI decreased the arthritis index, improved radiological and histological changes, and reduced synovial IL-1β, IL-6, IL-18 and TNF-α levels in rats with AA. Compared with normal rats, the 70 kDa NALP1 isoform was up-regulated, NALP3 was down-regulated, and levels of the 165 kDa NALP1 isoform and the adaptor protein ASC were unchanged in synovial tissue from AA rats. CAI reduced the 70 kDa NALP1 isoform and restored NALP3 levels in AA rats; CAI inhibited caspase-1 activation in AA synovial tissue, but not its enzymic activity in vitro. In addition, CAI reduced expression of p65 NF-κB subunit and IκBα phosphorylation and degradation in AA rats. CONCLUSION AND IMPLICATIONSNALP1 inflammasomes were activated in synovial tissues from AA rats and appeared to be a novel therapeutic target for RA. CAI could have therapeutic value in RA by inhibiting activation of NF-κB and NALP1 inflammasomes and by decreasing pro-inflammatory cytokines.

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Dynamic simulations have played an important role in assessing the power system dynamic studies. The appropriate numerical model is the key to obtain correct dynamic simulation results. In addition, the appropriate model including the selection of the individual model component (such as protections, controls and capabilities) is different depending on the type of phenomena to be observed or examined. However, the proper selection of the model is not an easy task especially for Inverter Based Generators (IBGs). Considerable industry experience concerning power system dynamic studies and the dynamics of the IBGs is required for the proper selection of the IBG model. The established CIGRE C4/C6.35/CIRED Joint Working Group (JWG) has gathered a wide variety of experts which fully cover the required industry experience. The JWG provides the guidance on the model selection for analyzing the phenomena such as frequency deviation, large voltage deviation, and long-term voltage deviation, individually. This helps to reduce the computational burden as well as it clarifies the required characteristics/functions that should be represented for the power system dynamic studies with the IBGs.