VIII. PHARMACOLOGY 437 



alcohol, which was then slowly mixed with 1 to 1.5 1. of 5 to 10% sterile 

 glucose solution (the alcohol may lead to transient euphoria). Phelps and 

 Jones^ employed a similar technique but increased the dose of phytyl 

 menadione or its oxide to 1 g. Blood transfusions Avere reported l)y Kinsey^^ 

 to be more effective in the treatment of the bleeding of hepatic failure if 

 the blood donor w^as pretreated wdth vitamin K; confirmation is lacking. ^- 



D. ACTION OF VITAMIN K 



As has already been suggested, prothrombin production is believed to 

 be intimately related to the liver, for a constant level of prothrombin in 

 the blood is found only if hepatic function is approximately normal. Assays 

 of prothrombin in portal lymph demonstrated a concentration near that of 

 the blood, whereas lymph from other sources had lesser concentrations.^^ 

 These facts suggest either that the plasma prothrombin is synthesized in 

 the liver or that the finishing touches of proteins made elsewhere are ac- 

 complished by the liver. Furthermore, the action of vitamin K is demonstra- 

 ble only if hepatic function is adequate. The work of Jaques' group^^ 

 indicates that vitamin K displaces dicoumarol from the liver and so ap- 

 parently acts on that organ. There is other evidence that may link vitamin 

 K with the liver: Nassi and Ragazzini^^ found that relatively large doses of 

 vitamin K (60 to 500 mg.) depressed hepatic glycogen. Dogs on normal diets 

 when given cinchophen did not show clotting changes, according to Hue- 

 per,^^ but did show changes when they were given a vitamin K-free diet. 

 Honorato's group'^ has reported that on either a choline-free or vitamin 

 K-free diet rats developed fatty livers; administration of choline or vitamin 

 K in either case reduced the hepatic defect. Field and Dam^^ were unable to 

 detect any change in hepatic lipids of vitamin K-deficient chicks, however, 

 and the results of the common clinical tests of hepatic function are normal 

 in uncomplicated vitamin K deficiency states. ^^ 



Whether vitamin K acts as a coenzyme for a prothrombin-synthesizing 

 enzyme in the liver or whether a part or all of the vitamin is-incorporated 

 in the prothrombin molecule is not known. The latter might be suspected, 



'» R. E. Kinsey, Arch. Internal Med. 73, 131 (1944). 



'2 H. R. Butt, T. B. Magath, and T. H. Seldon, Arch. Internal Med. 81, 131 (1948). 



'3 K. M. Brinkhous and S. A. Walker, Am. J. Physiol. 132, 666 (1941). 



'" C. C. Lee, L. W. Trevoy, J. W. T. Spinks, and L. B. Jaques, Proc. Soc. Exptl. Biol. 



Med. 74, 151 (1950); J. W. T. Spinks and L. B. Jaques, Nature 166, 184 (1950). 

 '^ L. Nassi and F. Ragazzini, Boll. soc. ital. biol. sper. 24, 703 (1948). 

 '6 W. C. Hueper, Arch. Pathol. 41, 592 (1946). 

 '^ C. R. Honorato and H. Molina, Rev. soc. argentina biol. 18, 431 (1942) ; G. S. Topel- 



herg and C. R. Honorato, ibid. 19, 409 (1943). 

 '8 J. B. Field and H. Dam, Proc. Soc. Exptl. Biol. Med. 60, 146 (1945). 

 I'M. A. Pessagno Espora, Dia med. 22, 1264 (1950). 



