Abstract
1. Since Sakurada and Sato's1) publication of the prophylactic effect of yakriton against urea poisoning, the classification of rabbits according to their individual susceptibility to urea intoxication has been studied, because the prophylactic efficacy of yakriton against urea intoxication will be best seen in those rabbits which would otherwise be expccted to die of a fatal convulsion due to urea poisoning.
2. Almcst all rabbits which have once devcloped the urea convulsion are unable to outlive it. Because of this fact the method of forctelling the prospective fatal convulsion of a given rabbit has been studied. This has been very difficult because of the fact that the individual ausceptibility of animals to urea is subject to a very wide range.
3. At least such a reliable method has been devised, as will be stated below. A certain number of fresh animals will on the first day of experiment receive an intraperitoncal injcction of 10% urea in an amount of 10 c. c. per kilogram of body weight and the injection will be repeated once a day up to the fourth day (and until this fourth test animals of class IV will have died or will die during this fourth test). On the fifth day (thus at the fifth test), the amount of urea solution to be injected is quadrupled and the symptom at the injection is to be carefully observed. If a given rabbit is disturbed and not calm at that time, it is most likely to die either within some time (usually one hour or so) of hypercarbamidemic convulsion (=then it is a rabbit of class III), or on the next day (thus at the sixth test) when the same injection as on the fifth day is repeated (=then it is a rabbit of class II). Animals of exceptionally strong urea detoxicating activity (=they are rabbits of class I) can now be excluded from the experiment, because they will remain utterly unaffccted at the above mentioned injection on the fifth day. Thus, on the fifth test rabbits of class IV are already dead and naturally excluded, and those of class III will be excluded (=die) during the coursc of the fifth test, while those of class I can be artificially excluded from a further experiment. So, there will remain rabbits of class II alone, -animals which are certain of fatal convulsion at the urea test of the next day (the sixth test). And only then we are justified in criticizing the effect of yakriton.
4. 50 R. A. U. of yakriton (per kilogram of body weight) saves rabbits of class II, if this is administered 5 minutes previous to the urea in jection, from the prospective fatal convulsion. This amount of yakriton may thus indeed seem to be more than the least amount of the hormone sufficient to save those animals, but it is in all probability much less than the real minimum amount, because that amount cannot remove all the injurious effects of hypercarbamidemia and keep those once saved from the sixth (final) injection of urea, still alive through further repetitions of urea tests. For the latter purpose at least 300 R. A. U. (per kilogram of body weight) are necessary. Thus, the least amount of yakriton to remove all the injurious effects of hypercarbamidemia will be about 300 R. A. U. (per kilogram of body weight of class II animals) which amount may be called the Rabbit-Urea-Units for the time being.
5. There can be no direct comparison between the Rabbit-Ammonia-Units and the Rabbit-Urea-Units, because there is no direct comparison between the ammonia- and the urea-detoxicating activities of the same individual. But it may be said for the sake of simplicity that the Rabbit-Urea-Units are about (300 R. A. U. can be contained in 1 c. c. of the extract).
6. As the previous work of Sakurada and Sato1) and the present paper show, it may be safely accepted that the urea is detoxicated by the liver, though the organ plays, as already known, a very important rôle also in the formation of urea.
