1907.] Experimental Treatment of Trypanosomiasis in Rats. 507 



(a dose being given every, or every other, day), even after as many as four, 

 recurrences the spleen was generally found post mortem to be very little or at 

 most moderately enlarged. A too large close apparently produced wasting, 

 and a bad condition of the hair, and, we think, a quicker return of the 

 trypanosomes. 



When atoxyl is given more continuously or too freely than is required, in 

 cases in which there have been many recurrences, and probably under some 

 other conditions of which we are ignorant, in a certain small proportion of 

 rats so treated a race of trypanosomes is produced which entirely resists 

 atoxyl, and continues to develop and multiply in spite of continued exhibition 

 of the drug. This strain, when inoculated into fresh rats, retains its resistance 

 to atoxyl. Ehrlich, who has produced such a strain in mice, calls them 

 " atoxyl-fest," and we have obtained this atoxyl-proof variety of trypano- 

 some in rats, both in Nagana and Surra, of which mention will be made 



later. 



1. Monophcnylarsenic acid. 



2. Nitrophenylarscnic acid. 



3. Paratolylarsenic acid. 



These three bodies were sent for experimental purposes to Professor 

 Cushny, F.K.S., by Professor Michaelis, who discovered them. They are of 

 interest in connection with the treatment of trypanosomiasis, since atoxyl is 

 an amido derivative of phenylarsenic acid, which was also discovered by 

 Michaelis. They are extremely poisonous substances, and were given in doses 

 of 1 c.c. of a solution of 1/400. 



1. Monophenylarsenic acid. — This, in common with other arsenic com- 

 pounds, notably affected the development of the trypanosomes. In doses of 

 1 c.c. of 1/400, repeated once or twice in untreated animals, it diminished 

 greatly the number of trypanosomes ; and in three recurrent cases, after 

 initial treatment with atoxyl, it caused the trypanosomes to disappear, but it 

 did not save any animal; and it is, as are all these three compounds' 

 poisonous in effective doses. 



2. Mtrophenylarsenic acid. — In untreated animals, and in two recurrent 

 cases after atoxyl, this caused a temporary disappearance of the trypanosomes ; 

 in a case of second recurrence after atoxyl, it produced no effect on the 

 trypanosomes. It is the most poisonous of the three. 



3. Paratolylarsenic acid.— This caused a more effective disappearance of the 

 trypanosomes than the other two compounds, and it was better borne. One 

 Nagana rat, treated only with it from the beginning, lived for 25 days, having 

 had, however, three recurrences during this period. At each recurrence the 

 trypanosomes disappeared after two doses of 1 c.c. of 1/400. In recurrent 



vol. lxxix. — b. 2 o 



