CHEMICAL CONSTITUTION AND PHARMACOLOGICAL ACTION 421 



say bilirubin is not neurotropic. In recent years a different view 

 has been promulgated, especially by Biedl, who ascribes a decisive 

 role in the distribution of poisons to the vessel wall. As a result 

 of my own long experience with the greatest variety of substances 

 I am unable to assume that the vascular endothelium as such exer- 

 cises different functions in different organs, so that, for example, 

 a liver capillary is permeable for certain substances which will not 

 pass through other capillaries. 1 



On the other hand the vascular system plays a very important 

 role in a different direction, as can be seen from the following strik- 

 ing example. Mice are fed according to my "biscuit method" with 

 derivatives of paraphenylendiamin (acetylparaphenylendiamin, thio- 

 sulfonic acid and mercaptan of paraphenylendiamin). On autopsying 

 the animals very peculiar changes are observed in the diaphragm. 

 The parts surrounding the central tendon are stained intensely brown, 

 while the peripheral portions are usually unstained. Frequently 

 the margin of the stain is wavy and marked by a more intense colora- 

 tion. At times I have observed similar changes in other muscular 

 regions, namely, in those of the eye, larynx, and tongue. Micro- 

 scopical examination shows that this is not a case of infarct, but 

 that there is apparently a uniform brown staining of the muscle 

 areas in question. The cross striation is preserved intact, and a 

 moderate degree of fatty degeneration is not infrequently observed. 

 Usually also there is a certain amount of hyperaemia. We are not 

 dealing with a derivative of haemoglobin; on the contrary it is much 

 more probable that we are dealing with a highly complex oxidation 

 product of the paraphenylendiamin. 2 



The question which now arises is why, in this feeding, only part 

 of the muscles, a very small part, show this vital staining. 



It was soon seen that the groups of muscles affected were analo- 

 gous in other respects. Thus with injections of methylene blue it 



* It was especially gratifying to note that Bruno, as a result of the investi- 

 gations which he made under the direction of R. Gottlieb, is also very skeptical 

 regarding Biedl's views (Deutsche med. Wochensch. 1899, No 23). 



"This assumption has subsequently been clearly confirmed by the work of 

 Dr. Rehne (Archiv internat. de Pharmacodynamie, Vol. VIII, p. 203) It 

 was found in animals poisoned acutely with paraphenylendiamin that the 

 muscles which were saturated with the poison assumed the typical brown color 

 when brought in contact with air I would also call attention to the fact that 

 both paraphenylendiamin and paramidophenol are employed, by oxidation, 

 for true brown and black dyes for hair and fur (Ursol dye) 



