[An analysis of the morbid condition in adjuvant arthritic rats and a new method for evaluating anti-rheumatic drugs].
The progress of various symptoms in adjuvant arthritic rats (AA-rats) and the effects of anti-rheumatic drugs were continuously observed on the basis of the Weibull distribution function, and the following results were obtained: 1) The cumulative incidence rates F(t) of various symptoms and abnormalities of measured values gradually increased with the passage of time. The relationship between the F(t) and the days after adjuvant injection indicated a simple Weibull distribution function. On the other hand, the bone damages in the distal limb joints indicated a composite Weibull distribution function with two shape parameters (m1 and m2). It was possible to classify the animals into two groups, fast responders (m1) and slow responders (m2), according to the time of occurrence of bone damages. 2) By using the Weibull probability paper, it was possible to integrate and to evaluate in totality those cases with varying grades of symptoms and cases with different symptoms in the adjuvant-induced syndrome in rats. 3) Azathioprine (AZP) showed an inhibitory effect on the advents of pain and swelling and functional disorders, while indomethacin (IDM), prednisolone (PSL) and gold sodium thiomalate (GST) delayed the advents of these symptoms. As to bone damages in the distal limb joints, IDM, PSL and AZP showed an inhibitory effect in only the fast responder group, while GST showed both an inhibitory and delaying effect in both the fast responder group and the slow one. The above results suggest that the usage of the Weibull distribution function is useful not only for analysis of the morbid condition of AA-rats but also for the evaluation of anti-rheumatic drugs in AA-rats.
Kanezuka
T
T
Biological Section, Research Laboratory of Grelan Pharmaceutical Co., Ltd., Tokyo, Japan.
Hatanaka
Y
Y
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D001379:Azathioprine / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006052:Gold Sodium Thiomalate / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use*; D011336:Probability; D051381:Rats; D011919:Rats, Inbred Strains
D006052:Gold Sodium Thiomalate; D011239:Prednisolone; D001379:Azathioprine; D007213:Indomethacin