THE FOLIC ACID GROUP 579 



These symptoms are prevented by folic acid, but are aggravated by l-z- 

 methylfolic acid, which prevents the utilization of folic acid. 111 The 

 inhibition index is somewhat lower than 10,000. The symptoms of defi- 

 ciency resulting from 1 g of the inhibitor per kg of diet are completely 

 prevented by 10 mg of folic acid per kg of diet. 111 



L-z-Methylfolic acid (1 g per kg of diet) administered to pigs on a 

 purified diet deficient in folic acid and containing succinylsulfathiazole 

 causes the development of deficiency symptoms characterized by severe 

 anemia, profuse diarrhea, diminished appetite, decreased growth rate, 

 some loss of hair and unkempt appearance. 112 The formation of erythro- 

 cytes and granulocytes is inhibited. Adequate amounts of folic acid 

 prevent toxicity of the analogue. Administration daily of the extrinsic 

 factor for pernicious anemia (p. 415) derived from 100 g of crude casein 

 together with 80 to 150 cc of fresh neutralized human gastric juice re- 

 sulted in improved appetite in one pig, and both growth and hemato- 

 poiesis were initiated and continued for many weeks after cessation of 

 therapy. 112 Liver extracts corresponding to those used in treatment of 

 pernicious anemia also allow remissions, 113 but the pig apparently cannot 

 be maintained indefinitely without supplementation of folic acid. 113, 114 

 While the inhibitory effect of the antagonist can be modified to some 

 extent by these extracts, pigs receiving 2 g of the analogue per kg of a 

 diet which contained adequate quantities of extrinsic factor respond only 

 partially, if at all, to liver extract; however, administration of folic acid 

 to such animals allows rapid relief of the anemia. 114 The antipernicious 

 anemia principle of liver does not appear to be present in normal amounts 

 in the liver of pigs with remissions induced by folic acid, even with simul- 

 taneous feeding of extrinsic factor. 113 



Although dogs appear normal on a purified diet with folic acid omitted, 

 the animals on the diet supplemented with L-z-methylfolic acid develop 

 deficiency symptoms characterized by slow growth, or loss in weight, 

 emaciation, alopecia, anemia and ulceration of the skin. Liver extract 

 gives only a slight hemopoietic response, but administration of sufficient 

 folic acid prevents the toxic effects of the analogue and causes marked 

 responses in the deficient animals. 115 Rhesus monkeys appear to be re- 

 sistant to the L-x-methylfolic acid. 116 



The development of the larvae of Drosophila melanogaster in a syn- 

 thetic medium containing growing yeast is arrested by supplementing the 

 medium with L-ar-methylfolic acid. 117 ' 118 In medium containing 0.25 

 per cent of the analogue, only 0.53 per cent of the larvae survived, and at 

 a concentration of 1 per cent, all the larvae died. Supplementation of the 

 medium containing 1 per cent of antagonist with an adequate quantity 



