VII. EFFECTS OF DEFICIENCY 423 



is less effective than the leafy plant (phytyl) one.-^ Presumably, then, the 

 intestinally synthesized vitamin exceeds that oV)tained from food, for, 

 though less potent, it can maintain an efficient clotting system, whereas 

 the reverse does not seem to be true. Fowls have a short, large intestine 

 which is believed to be inadecjiiate for absorption of the bacterially produced 

 vitamin K.^** Also, the mammalian lower colon is probably incapable of 

 absorbing the fat-soluble vitamins K even in the presence of bile, for re- 

 tention enemas of vitamin K have proved ineffective,^' and Greaves'^- was 

 able to produce a vitamin K deficiency in rats by means of bile fistulas into 

 the colon. However, the cecum may be an important site of bacterial syn- 

 thesis of the vitamin.^^ More careful attention to prevention of coprophagy 

 — the feces contain large amounts of vitamin K even when the diet is 

 vitamin K-free"' ^°' ^^ — may account for the greater than average success 

 that certain investigators^"- ^^ have had in inducing a dietary vitamin K 

 deficiency in mammals. 



Reduction of intestinal synthesis of vitamin K is most simply accom- 

 plished by bacteriostatic or bactericidal agents such as the sulfonamides^^ 

 and possibly by certain antibiotic agents.*® p-Aminobenzoic acid, whether 

 given orally or parenterally, concentrates in the bowel and prevents sulfon- 

 amide depression of the intestinal flora,^'^ thus it is not possible to assume a 

 non-intestinal effect of a parenterally administered drug. 



29 H. J. Almquist and A. A. Klose, Proc. Soc. Exptl. Biol. Med. 45, 55 (1940). 



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



31 H. P. Smith, S. E. Ziffren, C. A. Owen, G. R. Hoffman, and J. E. Flynn, J. Iowa 

 State Med. Soc. 29, 377 (1939). 



32 J. D. Greaves, Avi. J. Physiol. 125, 429 (1939). 



33 H. G. Day, K. G. Wakim, M. M. Krider, and E. E. O'Banion, J. Nutrition 26, 585 

 (1943). 



3* H. Dam, Advances in Enzijmol. 2, 285 (1942). 



35 The sulfonamides depress E. coli [H. J. White, Bull. Johns Hopkins Hosp. 71, 213 

 (1942)] and inhibit intestinal synthesis of vitamin K in the same order of effective- 

 ness [W. H. Sebrell, Harvey Lectures 39, 288 (1943-1944) (from most to least effec- 

 tive)]: sulfapyrazine, sulfadiazine [A. Kornberg, F. S. Daft, and W. H. Sebrell, 

 Publ. Health Repts. (U. S.) 59, Part 1, 832 (1944)], sulfathiazole [B. M. Braganca 

 and M. V. Radhakrishna Rao, Indian J. Med. Research 35, 15 (1947)], sulfasuxidine 

 [A. D. Welch and L. D. Wright, J. Nutrition 25, 555 (1943)], and sulfaguanidine 

 [S. Black, R. S. Overman, C. A. Elvehjem, and K. P. Link, /. Biol. Chem. 145, 137 

 (1942)]. 



36 Z. A. Lewitus and A. Aschireli, Harefuah 35, 13 (1948); W. K. Rieben, Helv. Med. 

 Acta 13, 295 (1946); C. M. Thompson and D. J. Hilferty, Med. Clin. N. Amer. 33, 

 1685 (1949). The coagulation changes resulting from prolonged treatment with anti- 

 biotic substances are to be distinguished from their clot-accelerating activities 

 during the first hour or two after administration [L. F. Moldavsky, W. B. Hassel- 

 l)rock, C. Cateno, and D. Goodwin, Science [N. S.J 102, 38 (1945); D. I. Macht, 

 ibid. 105, 313 (1947); Editorial, J. Am. Med. Assoc. 141, 924 (1949)]. 



37 A. Kornberg, F. S. Daft, and W. H. Sebrell, J. Biol. Chem. 155, 193 (1944). 



