HYPERSENSITIVENESS, PROTEIN INTOXICATION 231 



form of toxicity towards animals has been shown by Novy and De Kruif, 

 through purely physical processes and even by the mere coagulation of shed 

 blood. That toxic substances may be formed in blood sernm by a great 

 variety of methods has indeed been amply demonstrated and already 

 referred to, but the exact explanation of the evolution of the inert serum 

 into a toxic one, and the toxic chemical substance, if there is one, which is 

 produced under these varying circumstances is as yet imperfectly under- 

 stood. 



It seems highly probable that whatever the method employed, the 

 toxic substance is derived from the serum itself, but whether by the ac- 

 tion of specific ferments, an explanation that seems unnecessary, or by non- 

 specific enzymes or through purely physico-chemical means is not definitely 

 known. That proteins may be split through hydrolysis to the amins, 

 many of which are toxic, has long been recognized but the identification of 

 many of these toxic amins and their importance as a constituent of the 

 proteins of higher molecular form, is in part a matter of conjecture. 



This whole subject has recently been discussed by Koessler who 

 states "that from the point of view of chemical composition, these amins 

 may be divided into two classes. The mono-amins, like isobutylamin, 

 isoamylamin phenylethylamin, p-hydroxphenylethylamin and indolethyl- 

 amin, which have one basic N group; and the diamins, as tetramethylin 

 diamin and pentamethylin diamin (petruscin and cadaverin), agmatin, the 

 amin derived from arginin, and imidazolethylamin, which have two basic 

 N groups. This difference in the chemical composition of each group is 

 associated with a corresponding diversity of physiologic action. The most 

 active compounds are those that have a ring structure with a side chain of 

 two carbon atoms. As representative of the mono-amins, p-hydroxphenyl- 

 ethylamin will serve as an example. The substance tyramin, which be- 

 longs to the first or mono-amins, has received considerable experimental 

 study, but for various reasons much more work has been devoted to a study 

 of the diamins which contain two nitrogen groups. To this group belong 

 indolethylamin, putrescin, and cadaverin ; agmatin, the amin derived from 

 argenin and imidazolethylamin or histamin, the base derived from the 

 amino acid histidin." It is to the latter substance, particularly, that ex- 

 tensive study has been devoted in recent years ; and the results of the ex- 

 periments of Barger and Dale(a), of Dale and Laidlaw(a) (6), Dale and 

 Richards, and of Abel and Kubato have increased our knowledge exten- 

 sively concerning the pharmacological and toxic action of this substance. 

 The similarity between the toxic effects obtained by this chemical and those 

 observed in anaphylactic shock have been extensively discussed by Dale 

 and already have been referred to, and it is only necessary to emphasize 

 the fact that this substance affects very markedly the smooth muscle of 

 the animal and acts furthermore as a capillary poison. Abel and Kubato 



