THE FOLIC ACID GROUP 569 



coccus faecalis R, a sigmoid curve is obtained on plotting the growth 

 response against concentration of the triglutamate. 78, 79 



Pteroyldi-y-glutamylglutamic acid, administered either orally or in- 

 travenously, is just as effective as folic acid in effecting an increase in 

 the urinary excretion of forms of folic acid active for Streptococcus 

 faecalis R; however, a very slight lag in the rate of excretion is noted. 38 

 Even so, most of the active substances derived from the triglutamate are 

 excreted during the first six hours. 38 



The earliest indication of a beneficial effect of the triglutamate in 

 human subjects was a report of slight activity in a patient with nutri- 

 tional macrocytic anemia. 41 Administration of 5 mg of the triglutamate 

 per day gave a reticulocyte response of 12 per cent on the ninth day, 

 with a subsequent increase in red cell count. 41 Subsequently, parenteral 

 administration of the triglutamate (daily dose equivalent to 3.1 mg of 

 folic acid) was shown to increase markedly the excretion of folic acid, 

 and to have pronounced beneficial effects in relieving the clinical and 

 hematologic manifestations of sprue in a patient previously treated with 

 liver extracts. 42 Treatment of a sprue patient with intramuscular injec- 

 tions of a crystalline sample of the pteroyldi-y-glutamylglutamic acid 

 (5 mg twice daily) alone resulted in a rise in erythrocyte count and 

 hemoglobin, clinical improvement, and maximum reticulocytosis of 38 

 per cent on the fourth day of therapy. 43 Administration of 3 mg daily of 

 the triglutamate by intramuscular injection to a patient with pernicious 

 anemia in relapse resulted in a submaximal hemopoietic response, accom- 

 panied by subjective improvement. 44 This is in contrast to an earlier 

 report indicating that a concentrate of the triglutamate was inactive 

 when administered to two patients in doses equivalent to 3.6 and 2.3 mg 

 of folic acid daily. 45 However, from more recent work, it appears that 

 the triglutamate is utilized by patients with pernicious anemia. 39 



Monkeys rendered anemic and leucopenic by vitamin M-deficient 

 diets respond to an intramuscular injection of 3 mg of pteroyldi-y-gluta- 

 mylglutamic acid. Administered in divided doses over a period of three 

 days, it produces prompt and complete remission lasting for ten to 

 thirty days. 54 



The deficiency of folic acid resulting from administration of succinyl- 

 sulfathiazole or sulfaguanidine in the diet of rats is corrected by pteroyldi- 

 y-glutamylglutamic acid as well as by folic acid. 55 The triglutamyl 

 derivative also has a preventive and corrective effect on anemia induced 

 by bleeding rats fed a purified diet containing succinylsulfathiazole. 56 

 The leucopenia which develops in rats given thyroid powder orally or 

 thyroxine injections and fed thiourea in a purified diet is relieved by the 

 triglutamate. 57 Granulocytopenia, which develops in rats on a purified 



