EXPERIMENTAL STUDIES ON THE EFFECT OF SO-CALLED SECONDARY ANTITUBERCULOSIS DRUGS:(1) Combination Effects of SM-INH-PAS, SM-INH-TH and KM-TH-CS on Experimental Tuberculosis in Mice
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This experiment was carried out 1) to examine the difference in therapeutic effects between the so-called primary and secondary combined antituberculosis drugs, and 2) to establish the method clarifying the difference in the effect of the combined therapy.<BR>Young ddY female mice, intravenously infected with H<SUB>37</SUB>Rv (v. u. 8.5×10<SUP>6</SUP>) and left untreated for 3 weeks, were divided into 4 groups according to the treatment received: SM-INH-PAS, SM-INH-TH, KM-TH-CS and untreated control. Each of the groups was necropsied at the end of any one of the following periods: 3-week chemotherapy, 4-week non-treatment period following 3-week chemotherapy, 6-week chemotherapy, and 6-week non-treatment period following 6-week chemotherapy. SM 10mg/kg and KM 20mg/kg were administered twice weekly subcutaneously, and INH 2mg/kg, TH 4mg/kg, PAS 200mg/kg, and CS 10mg/kg orally once daily for six days weekly.<BR>Each mouse was examined for body weight, macroscopic changes of lung lesions, lung weight, spleen weight, and amount of viable tubercle bacilli in the lung and the liver at necropsy.<BR>Results: 1. In comparison of the effect of antituberculosis drugs on experimental tuberculosis in mice, it was thought suitable to necropsy the animals at the end of the 6 week treatment starting at the beginning of the 4th week of the infection, and to compare the degree of macroscopic involvement of the lung, lung weight, and the amount of viable tubercle bacilli in the lung.<BR>2. Spleen weight, the amount of tubercle bacilli in the liver and the change in body weight during chemotherapy were unrelated to the evaluation of the effect of chemotherapy. When mice were left untreated after the cessation of chemotherapy, the difference of the involvement between the treated and untreated animals became obscure.<BR>3. The effect of combined chemotherapy of SM-INH-PAS and SM-INH-TH were superior to that of KM-TH-CS. Comparing SM-INH-PAS with SM-INH-TH, the latter tended to be superior to the former, judging from the lung weight and the amount of viable tubercle bacilli in the total lung.
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