VIII. EFFECTS OF DEFICIENCY I\ AXIMALS 321 



new bone is of small scale and cannot absorb the quantity of calcium made 

 free from the old bone. There ensues in the body a surplus of calcium, and 

 a precipitate excretion takes place. . . . Afterwards, in the progress of scurvy 

 a circumstance arises which acts in the opposite direction. Different paren- 

 chymal organs get more and more atrophic and necrotize partially. D\diig 

 tissue generally has greater affinity for calcium and thus we see in scorbutic 

 guinea pigs calcifications appear to a large extent in different organs, prin- 

 cipall}' muscles and liver. This may explain the calcium balance V)eing 

 positive during this stage. In healing, again a strong excretion sets in which 

 has been noted by several investigators." 



Another aspect of the problem of interrelations of ascorbic acid and 

 calcium is sho\\Ti in connection with toxic doses of these substances. Valen- 

 zuela*"^ studied the problem by injecting large doses of ascorbic acid intra- 

 venously into mice. The administration of 3.75 mg. per gram caused death 

 immediately. By perfusing frog hearts with Ringer's solution containing up 

 to 0.8 or 0.9 % ascorbic acid he observed a decrease in the amplitude and 

 frequency of the contractions with a decrease in the minimum volume and 

 final arrest in the diastole. Addition of calcium chloride or calcium gluconate 

 reduced the toxicity of the ascorbic acid, and similarly ascorl)ic acid in- 

 creased the tolerance against large doses of calcium salts injected intra- 

 venously. The evidence of a specific effect of ascorbic acid as a cause of the 

 toxicity is not convincing, since comparal)le tests were not made with other 

 tj'pes of acids. 



The interrelations of calcium and ascorbic acid with respect to cell sur- 

 faces and intercellular sul)stances were reviewed and discussed in 1943.'*^' 

 The special need of the x-itamin by those cells in which calcium metabolism 

 is \'er3' actiA'e is not without significance. Chamliers' studies^"*' ^"^ showed 

 that repair of injury to cells is impossible in the absence of calcium because 

 of inability of the protoplasm to form a new interface. That ascorbic acid 

 also plays a role in the formation of the cell V)oundary is shown by Harman 

 and Warren's finding^^ of indistinct cell walls in the tissues of embryos of 

 scorbutic animals. It seems quite possible that the vitamin acts in conjunc- 

 tion with calcium to produce coagulative changes in cell surfaces in both 

 plant and animal tissues and that the intercellular cement may be an end 

 product of this action. That the \'itamin functions also in the maintenance 

 of the wall is shown by the disappearance of cell ])Oundaries in scorbutic 

 tissues as observed by Ilojer and Meyer.^ Eichelberger et al?^'^ studied the 



'"• M. A. Valenzuela, Farmacotcrap. actual {Madrid) 2, 712 (1945). 



'" M. E. Reid, Physiol. Revs. 23, 76 (1943). 



"»« R. Chambers, Am. Naturali.'it 72, 141 (1938). 



^<" R. Chambers, Cold Spriny Harbor Symposia Quant. Biol. 8, 144 (1940). 



"» L. Eichelberger, F. C. McLean, and \. Catterall, ./. Biol. Chem. 142, 467 (1942). 



