Copper complexes of a range of ligands have been prepared and evaluated for antiinflammatory activity and irritancy after oral, subcutaneous, and local administration in rats and guinea pigs. The antiinflammatory activities were found to depend on the species used and the route of administration. When nonantiinflammatory ligands were used, the response was generally dose dependent. With D-penicillamine and when the ligands were themselves antiinflammatory in animal models of inflammation--as was the case with flufenamic acid, levamisole, aspirin, L-histidine, and 2-amino-2-thiazoline--differences in antiinflammatory activity were observed between the copper complexes and the free ligands. In some cases, the copper complexes were the more effective. There was a weak correlation between local (subplantar) irritation and the dose of copper but, for four compounds studied in more detail, the response in the local subplantar test and degree of antiinflammatory activity were not related, suggesting that the action of copper is not solely by a counterirritant mechanism. No obvious differences between the activities of copper(I) and copper(II) compounds were observed, suggesting that a common metabolite may be involved in the antiinflammatory action of copper.
A method for the direct determination of the level of copper in plasma ultrafiltrate using atomic-absorption spectrometry with carbon furnace atomisation is reported. The relative standard deviation and the detection limit expressed as 26 were 3.6% (50 pl of 0.05 p g ml-l copper solution) and 0.0036 p g ml-l, respectively. Interferences from the salt matrix, the use of background correction and the problems of contamination caused by the low level of copper are discussed. The method has been applied to the determination of the level of copper in the plasma ultrafiltrate of patients with rheumatoid arthritis.
SUMMARY Total serum copper and ultrafilterable copper levels in patients with rheumatoid arthritis were determined and related to articular index, erythrocyte sedimentation rate (ESR), and serum iron concentration. Relationships were found between serum copper and ESR, and between ultrafilterable copper and articular index. The relationship between serum copper and serum iron was found to be a drug-dependent.
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