Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.

Objective. To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).Methods. One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.Results. The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of

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Objective. To define the nature of structural bone changes in patients with rheumatoid arthritis (RA) compared with those in healthy individuals by using the novel technique of high-resolution microfocal computed tomography (micro-CT).Methods. Fifty-eight RA patients and 30 healthy individuals underwent a micro-CT scan of the proximal wrist and metacarpophalangeal joints. Bone lesions such as cortical breaks, osteophytes, and surface changes were quantified on 2-dimensional (2-D) slices as well as by using 3-D reconstruction images, and exact localization of lesions was recorded.Results. Micro-CT scans could detect bone lesions <0.5 mm in width or depth. Small erosions could be observed in healthy individuals and RA patients, whereas lesions >1.9 mm in diameter were highly specific for RA. Cortical breaks were mostly found along the radial sites of the metacarpal heads. No significant difference in the presence of osteophytes between healthy individuals and RA patients was found. Cortical surface changes, presumably cortical thinning and fenestration, became evident from 3-D reconstructions and were more pronounced in RA patients.Conclusion. Micro-CT allows exact detection of morphologic changes of juxtaarticular bone in healthy individuals and RA patients. Even healthy individuals occasionally show bone changes, but the severity of these lesions, with the exception of osteophytes, is greater in RA patients. Thus, micro-CT allows accurate differentiation among physiologic bone changes in joints and among types of pathologic bone damage resulting from RA.

The role of the T3/antigen receptor complex is summarized by the diagram presented in Figure 4. Signals transmitted through T3/Ti activate a phosphodiesterase. This enzyme acts on its substrate PIP2 to generate two important mediators, IP3 and diacylglycerol. IP3 mobilizes calcium from bound intracellular stones. This increase in [Ca2+]i is one intracellular signal which, in conjunction with others, induces expression of lymphokine genes by influencing pretranslational, presumably transcriptional, events. Several problems remain. Which of the five molecules in the T3/Ti complex serves as the effector molecule in the transmembrane signaling process is not known. Which molecules serve to link T3/Ti to the phosphodiesterase enzyme is under investigation. The role diacylglycerol protein kinase C and other mediators play in signalling activation is not established. Finally, for those events occurring after the early events pictured in Figure 4 that result in gene activation, the sequence is a black box. Approaches to address each of these questions are available, and answers should be forthcoming.