TOXICOLOGY AND PHARMACOLOGY 361 



about the cell or cell group, or a chemical defense in the sense of P. 

 EHRLICH, who believes that in these cases there is no " receptor" for 

 the poison. Probably both methods are involved. 



Although "distribution" is a very difficult and as yet scarcely 

 investigated field, in the study of the organic changes due to drugs we 

 are met largely by unsurmounted difficulties, since in many cases no 

 external or even histological change may be recognized. It is our 

 hope that colloid research may also prove of great value here, since 

 it is not only profound changes in chemical constitution which in- 

 terfere with the function of an organ, but harm may be done even 

 by changes in turgescence, flocculatfon, reversible precipitation and 

 in fact even changes in the size of the particles. [This is the basis of 

 the explanation of changes of muscular activity in response to drugs, 

 offered by W. BURRIDGE, to which reference has been made. Tr.] 

 More particularly than heretofore, we must observe the course of an 

 injury; we shall have to observe whether a permanent local change 

 occurs as in the toxic action of most metals, or whether the process 

 is reversible as in the case of the narcotics, or whether after a severe 

 effect occurs, a moderately prolonged after-effect takes place in the 

 organs involved, suggesting an adsorption. 



Valuable suggestions for such a viewpoint are offered by the 

 classical observations of PAUL EHRLICH on the " Oxygen require- 

 ments of the body" and by his study of the histology of the blood 

 (P. G. UNNA* 3 ), and W. STRAUB'S* researches on the distribution of 

 various alkaloids (veratrine, strychnine, curarine) between heart 

 muscle (of a sea snail) and the surrounding solution. [W. BURRIDGE 

 has shown that digitalis and strychnine increase the utilization of 

 calcium by the heart. The action of strychnine on nerves is explained 

 by a relative calcification of the synapse, facilitating the passage of 

 the nerve impulse (see p. 354). Tr.] 



Cooperation of Indifferent Substances. 



On pages 55 and 334, we saw that the presence of many substances 

 might either increase or diminish the permeability of membranes; 

 from this fact we are justified in concluding that the addition of 

 an essentially indifferent substance may increase or diminish the 

 toxic or pharmacologic action of a substance by aiding or impeding 

 its arrival at the spot where it is active. We may in general assume 

 from this that such other substance is also stored in the same organ. 



We may exemplify this by several observations (see G. STOFFEL *), 

 which must be viewed from this standpoint. VON SCHRODER found 

 that the diuretic action of caffein was increased by chloral hydrate, 

 and yet that this effect did not depend on the ability of the chloral 



