Objective. To determine the effects of peptidyl fluoromethyl ketones on the in vitro activity of purified cathepsins B and L, on tissue cysteine proteinase activity, and on cartilage and bone destruction in experimental arthritis.Methods. The effects of the fluoroketones on cathepsins B and L in vitro and the effects of oral administration of fluoroketones on ex vivo cysteine proteinase activity in tissue homogenates were determined by measuring the inhibition of fluorogenic substrate cleavage. To determine the effects on arthritis, animals were injected with adjuvant or type I1 collagen, treated orally with the fluoroketones, and the severity of arthritis was assessed by clinical, histologic, and radiologic methods.Results. All of the fluoroketones tested were potent inhibitors of purified cathepsins B and L activity.Oral administration of the fluoroketones reduced tissue cysteine proteinase activity by up to 77%. In addition,
Objective. To apply quantitative analytical methods to the evaluation of radiographic images in experimental arthritis.Methods. Adjuvant was used to induce arthritis in rats. Arthritis progression was followed by conventional methods. In addition, digitized images of radiographs of the calcaneus were examined for changes in the mean and in the distribution pattern of gray values. Periosteal new bone formation was measured as an increase in image area of the calcaneus.Results. Significant changes in the gray value profile and increases in periosteal bone formation occurred in arthritic rats. More extensive changes occurred in Lewis rats than in Sprague-Dawley rats. Analysis of serial radiographs revealed an initial decrease in the density of juxtaarticular bone, followed by progressive increases in gray value variation due to concurrent bone loss and bone formation. Eventually, bone formation in arthritic rats resulted in increased gray values above those in nonarthritic rats.Conclusion. Image analysis represents a sensitive, quantitative method for detecting radiographic changes in experimental arthritis.The adjuvant-and collagen-induced models of chronic arthritis are widely used for studies of the underlying pathophysiology of joint disease and for the evaluation of potential new therapeutic agents. In both models, grossly apparent joint inflammation rapidly
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