THE RESISTANCE OF SPIROCHETES TO THE ACTION OF HEXAMETHYLENETETRAMINE DERIVATIVES AND MERCURIAL AND ARSENIC COMPOUNDS.
The majority of the 76 new compounds possessed spirocheticidal powers ranging between 1: 1,000 (30) to 1:2,500 (14), while only 2 attained the power of 1:5,000, 1 of 1: 25,000, and 2 of 1: 50,000. On the other hand, 8 killed the spirochetes in a dilution of 1: 750, 10 in 1:500, 7 in 1:250. 1 in 1: 100, and 1 in 1:50. It may be mentioned that the 2 (M1, M4) of 1:50,000 and 1 (M7) of 1:25,000 belong to the mercury compounds, and that mercuric chloride kills the organisms in a dilution of 1: 100,000 under the same experimental conditions. It is also interesting to compare some of the more common chemicals and therapeutic reagents. Phenol is spirocheticidal in a dilution of 1: 2,500, lysol in 1: 5,000, formalin in 1: 750, salvarsan in 1: 7,500, and neosalvarsan in 1: 2,500. Thus, of the new compounds there are at least 14 which have the same spirocheticidal power in vitro as has neosalvarsan. It is of interest to note that nine compounds possessing the 1:1,000 spirocheticidal power showed only one-tenth of the antiseptic action when tested upon Bacillus dysenteriae and Streptococcus, while some showed an even greater difference in this respect. Nos. 16, 21, 29, 218, and 244 were effective in a dilution of 1:2,500 for spirochetes and in a 1:100 or lower dilution for the bacteria just referred to. Preparations 46 and 84 appear to exert about the same effect both on the spirochetes and the bacteria, neither being very strong. Atoxyl killed the spirochetes in a 1:50 dilution. One of the most striking results was obtained with various hemolytic substances. Neufeld and von Prowazek found that spirochetes, unlike bacteria in general, are highly susceptible to the lytic action of sodium taurocholate and saponin, and they considered that this phenomenon was of differential diagnostic value in determining plant and animal organisms. Their observations were confirmed by Gonder, who found, however, that spirochetes, especially treponemata, offer a great deal of resistance at the beginning, but finally undergo lysis, with their cell bodies swollen up or macerated. In the present experiment we have found that these substances not only bring about cytolysis of the spirochetes in higher concentrations, but also kill them without causing a gross destruction of the cells in very high dilutions; thus, sodium cholate in 1: 5,000, sodium glycocholate and taurocholate in 1: 2,500 each, saponin in 1:7,500. Sodium oleate, one of the most powerful hemolytic agents killed the spirochetes in 1: 7,000, and cobra lecithide and native cobra venom in a dilution of 1:1,000 each. Neither sodium nor potassium iodide displayed any marked spirocheticidal property (1: 10 only), while iodine in the form of Lugol's solution was able to kill them at 1:75.
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Laboratories of The Rockefeller Institute for Medical Research.