We studied the course of adjuvant arthritis in rats by measuring clinical, biochemical, and histological parameters on day 36 after induction (representing the secondary reaction) and on day 171, which is at the stage of permanent deformity. The effect of SR 41319, a new diphosphonate, was evaluated on days 36 and 171, after three weeks of treatment (days 14-35 inclusive). In the absence of treatment all the measured parameters were markedly abnormal on day 36, indicating the presence of lesions that were still evolving. On day 171 clinical parameters and the lesion histological index remained the same, whereas the biochemical parameters and disease activity histological index had returned to normal, indicating that the lesions at this stage although severe were not inflammatory and consequently not progressing. SR 41319 treatment reduced the severity and progression of the disease both on day 36 and on day 171. We conclude that SR 41319 may be a potentially useful drug for the treatment of rheumatoid arthritis.
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