Treatment Of Arthritic Joints Research Articles

Osmium tetroxide, used in the treatment of arthritic joints, is a fast mimic of superoxide dismutase

Aqueous solutions of osmium tetroxide (OsO 4) have been injected into arthritic knees for the past 45 years to chemically destroy diseased tissue, in a procedure termed “chemical synovectomy.” Arthritis is an inflammatory disease. The primary inflammatory chemical species are the superoxide anion radical (O 2 − ) and nitric oxide ( NO), which combine to form the peroxynitrite anion (ONOO −). Here we show that OsO 4 does not react with ONOO − but very efficiently catalyzes the dismutation of O 2 − to O 2 and H 2O 2. Using the pulse-radiolysis technique, the catalytic rate constant has been determined to be (1.43 ± 0.04) × 10 9 M −1 s −1, independent of the pH in the 5.1–8.7 range. This value is about half that for the natural Cu,Zn-superoxide dismutase (Cu,Zn-SOD). Per unit mass, OsO 4 is about 60 times more active than Cu,Zn-SOD. The catalytically active couple is Os VIII/Os VII, Os VIII oxidizing O 2 − to O 2 with a bimolecular rate constant of k = (2.6 ± 0.1) × 10 9 M −1 s −1 and Os VII reducing it to H 2O 2 with a bimolecular rate constant of (1.0 ± 0.1) × 10 9 M −1 s −1. Although lower valent osmium species are intrinsically poor catalysts, they are activated through oxidation by O 2 − to the catalytic Os VIII/Os VII redox couple. The Os VIII/Os VII catalyst is stable to biochemicals other than proteins and peptides comprising histidine, cysteine, and dithiols.

Treatment of Arthritic Joints

ARTHRITIC JOINTS One still hears too frequently the neglected cripple, on seeking hospital care, declare that her physician despairingly admitted to her or to members of her family that she had arthritis and that there was no treatment which would help her. It is to that physician in whatever community he may reside that this paper is written. Some idea of the relative importance of rheumatism may be gained from the estimated prevalence of specified chronic disease in the United States in 1937,1shown in the accompanying table. In Massachusetts alone, out of a population of about 4,250,000 in 1930, there were 140,000 persons2found afflicted with this king of human misery. Today it represents our greatest single cause of chronic disease. Yet four fifths of the poor and one half of the well-to-do who were suffering from chronic disease were not under the care of any physician.