IX. REQUIREMENTS 447 



was done by Greaves'® and by Dam and Glavind'^ and the curative effect 

 of vitamin K demonstrated. Some individual rats remained highly resistant 

 to depletion attempts. Flynn and Warner-*^ found that depleted bile fistula 

 rats required approximately 1000 7 of phthiocol or 2 7 of methylnaphtho- 

 quinone daily for moderate recovery of prothrombin level in 2 days. The 

 disulfuric acid ester of methylnaphthohydroquinone, which is much less 

 potent than the parent compound, was required at 8 7 per day to cure 

 depleted rats.^' 



3. Dog 



Dogs rendered vitamin K-deficient by cholecystnephrostomy were found 

 by Collentine and Quick-- to respond to 9 7 of phytyl menadione per kilo- 

 gram of body weight when administered intravenously. With this dose the 

 "prothrombin time" returned to normal in 4 hours and persisted at that 

 level for 24 hours. From this rapid response it seems likely that much smaller 

 doses would have appreciable effects. It should be stated that changes in 

 "prothrombin time" and in the actual prothrombin concentration bear no 

 fixed relationship to each other, so that no direct comparison can be made 

 of minimal dosages determined by the various methods. 



B. OF HUMAN BEINGS 

 CHARLES A. OWEN, JR. 



Few studies have been conducted on human beings to ascertain the 

 minimal quantities of vitamin K derivatives necessary to correct the clot- 

 ting changes of the vitamin's deficiency. Even in animals few reports have 

 been published, primarily because a severe deficiency of vitamin K which 

 will be uniform for a period sufficient to enable one to analyze various 

 dosages is difficult to obtain. Another problem which faces the investigator 

 is the one of vitamin K stores. Although only small amounts of vitamin K 

 can be recovered from the various organs of normal animals,^* - ^'* it is 

 apparent that these stores are significant when the minuteness of daily 

 needs is realized. Direct evidence that these stores are important may be 

 deduced from the observation that a prolonged vitamin K-free diet scarcely 

 alters the blood coagulability of rats; if ligation of the common duct is nov/ 



18 J. D. Greaves, Am. J. Phxjsiol. 125, 429 (1939). 



'8 H. Dam and J. Glavind, Z. Vitaminforsch. 9, 71 (1939). 



2" J. E. Flynn and E. D. Warner, Proc. Soc. Exptl. Biol. Med. 43, 190 (1940). 



21 E. D. Warner and J. E. Flynn, Proc. Soc. Exptl. Biol. Med. 44, G07 (1940). 



22 G. E. Collentine and A. J. Quick, Am. J. Med. Sci. 222, 7 (1951). 



23 H. J. Almquist and E. L. R. Stokstad, /. Nutrition 12, 329 (1936). 



2'» H. Dam, J. Glavind, L. Lewis, and E. Tage-Hansen, Skand. Arch. Physiol. Id, 

 Suppl. 121_(1938). 



