B Cronstein

..Results of ongoing trials of IL-1β antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis...

..Taken together, our work strongly suggests that pharmacological A2AR blockade can be used to diminish scarring while improving the collagen composition and tensile strength of the healed wound...

..This review focuses on the importance of extracellular adenosine acting at specific receptors as a regulatory mechanism to control the formation of foam cells under conditions of lipid loading...

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..The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects...

..Here we review the proposed mechanisms of action of methotrexate...

..These results suggest that the adenosine A(1) receptor pathway plays a role in the process by which perceived psychological stress influences the contact hypersensitivity response...

..These activities contribute to the complex and multifaceted mechanisms that make methotrexate efficacious in the treatment of inflammatory disorders...

..Because the results of small pharmacogenetic studies are often misleading, we undertook a metaanalysis of published studies to determine the role of polymorphisms in the therapeutic efficacy and toxicity of MTX...

..Toward that objective, the latest developments in the pharmacokinetics, mechanism of action, pharmacogenetics, and toxicity of methotrexate are herein discussed...

..To determine whether genetic factors or the model itself is responsible for the poor response to MTX, we directly compared the responses of 4 inbred mouse strains to MTX in the air-pouch model of acute inflammation...

..These mechanisms of action and the role of methotrexate in the suppression of rheumatoid arthritis are reviewed...

..In confirmation of this mechanism of action, recent studies in both animals and patients suggest that adenosine-receptor antagonists, among which is caffeine, reverse or prevent the anti-inflammatory effects of methotrexate...

..Current evidence thus strongly supports the association between IL-6 and RA symptoms and suggests that IL-6 blockade will be a useful therapeutic strategy for patients with this disease...

..The clinical relevance of COX-1 compared with COX-2 inhibition is discussed to provide a framework upon which clinicians can better appreciate current and future therapeutic applications of coxibs...

..Moreover, these results provide strong evidence that adenosine, acting at either or both of these receptors, mediates the antiinflammatory effects of methotrexate and its analog MX-68...

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..6. These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis...

..05 for all; n=3). These findings indicate that adenosine and adenosine A(2A)R play a critical role in promoting the proliferation and differentiation of mouse BM-MSCs...

..The loci identified by in silico mapping likely contain genes with differential roles in determining this phenotype between genders...

..The effects of adenosine A2A receptors on the cells and tissues of healing wounds have only recently been explored. We review here the known effects of adenosine A2A receptor occupancy on the cells involved in wound healing...

..In contrast, glucocorticoid action depended on the p105...

..Finally, we provide an overview of the current approach to gout, as well as what treatments are on the horizon...

..The effects of adenosine, acting at its receptors, on the functions of the cells that mediate innate immune responses, will be reviewed...

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