644 



SCIENCE 



[N. S. Vol. XLVI. No. 1200 



degree of toxicity was expressed by the older 

 animals becoming both albuminuric and gly- 

 cosuric at an earlier period following the use 

 of uranium than was the case with the young 

 animals. Furthermore, the quantitative out- 

 put in the urine of both albumin and glucose 

 was greater in the old animals than in the 

 young animals. When the kidneys of these 

 animals were studied histologically there was 

 found to exist more evidence of kidney injury 

 in the organs from old animals than in those 

 from young animals. In so far as the kidney 

 was concerned in the reaction, uranium was 

 more toxic in an old animal than in a young 



In a later series of experiments^ in which 

 the age of the animals was taken into account, 

 animals following an intoxication by uranium 

 gave evidence of developing an acid intoxica- 

 tion much earlier than did the younger ani- 

 mals. The experiments also demonstrated 

 that the acid intoxication in the older animals 

 was of a severer degree than in the young ani- 

 mals. The evidence for the development of an 

 acid intoxication in these animals of different 

 ages consisted in noting the time of appear- 

 ance and quantitative output in the urine of 

 acetone bodies, and in determining the rela- 

 tive degree of tolerance for an alkali by the 

 two groups of animals. The old animals 

 showed an earlier appearance in the urine of 

 acetone bodies, a greater quantitative output 

 of these bodies, and a greater tolerance for an 

 alkali than did the younger animals. 



In these experiments it was furthermore 

 shown, that by the intravenous use of an alkali 

 in a young animal the kidney could be success- 

 fully protected against the toxic effect of an 

 anesthetic while in the older animals the difS- 

 culty of furnishing this protection increased 

 with the age of the animal. 



Eesponse of Animals of Different Ages to a Con- 

 stant Quantity of Uranium Nitrate," Proc. Soc. 

 Exp. Biol, and Med., Vol. XI., 159, 1914. 



2MaeNider, W. deB., "The Inhibition of the 

 Toxicity of Uranium Nitrate by Sodium Carbon- 

 ate, and the Protection of the Kidney Acutely 

 Nephropathie from Uranium from the Toxic Ac- 

 tion of an Anesthetic by Sodium Carbonate," 

 Jour. Exp. Med., Vol. XXIII., 171, 1916. 



In a recent study^ of the relative toxicity 

 of uranium nitrate in animals of different 

 ages, the observation has been made that the 

 old animals not only show a severer grade of 

 acid intoxication as indicated by the appear- 

 ance of acetone bodies in the urine than do 

 the younger animals, but these old animals 

 also show a more marked increase in the hy- 

 drogen ion concentration of the blood, which is 

 associated with a more rapid depletion of the 

 alkali reserve of the blood and a greater re- 

 duction in the tension of alveolar air carbon 

 dioxide. Associated with this change in the 

 acid-base equilibrium of the blood there de- 

 velops a kidney injury which is histologically 

 more marked in the old animals than in the 

 young animals. 



In a final series of experiments* it has been 

 found possible to maintain in some measure 

 the functional capacity of the kidney and the 

 response of this organ to various diuretic sub- 

 stances by employing a solution of sodium 

 carbonate to restore the alkali reserve of the 

 blood and maintain an acid-base equilibrium 

 of the blood which approaches in degree the 

 reaction of normality. The ease with which 

 the acid-base equilibrium of the blood can be 

 restored and maintained in an animal intoxi- 

 cated by uranium, and the degree of protection 

 which is furnished the kidney is dependent 

 upon the animal's age. The acid-base equi- 

 librium is more easily restored and can be 

 maintained for a longer time in a young ani- 

 mal than in an old animal. The protection of 

 the animal against the toxic effect of uranium 

 is more perfect in a young animal than in an 

 old animal. 



From the experiments which have been 

 cited it would appear that there is a definite 

 association between the toxic effect of uranium 

 and its ability to induce an acid intoxication 



3 MaeNider, W. deB., ' ' A Consideration of the 

 Eelative Toxicity of Uranium Nitrate for Animals 

 of Different Ages," I., Jour. Exp. Med., Vol. 

 XXIV., p. 1, 1917. 



* MaeNider, W. deB., "The Efficiency of Vari- 

 ous Diuretics in the Acutely Nephropathie Kidney, 

 Protected and Unprotected by Sodium Carbonate, ' ' 

 Jour. Exp. Med., Vol. XXIV., 19, 1917. 



