98 CHOLINE 



as appears to be the case in the rat. Fouts produced a severe deficiency in 

 dogs which was characterized by loss of weight, anemia, dermal and peptic 

 ulcers, fatty cirrhotic livers, and death, and which responded to the com- 

 bined administration of choline and liver extract. ^^^ It was also apparent 

 that choline is one of the nutrients essential for growth and for hemoglobin 

 production in young dogs.^^'*- '" Hough et al. observed a decrease in hepatic 

 dye clearance and an elevation of serum phosphatase in puppies and in 

 adult dogs on choline-deficient diets.^^^ Both manifestations of impaired 

 liver function were prevented or reversed by choline. McKibbin et al. de- 

 veloped a ration which produced fatal choline deficiency in 3 weeks or less 

 in puppies.^" ■ ^^* In addition to decreased bromosulfalein elimination and 

 increased plasma phosphatase, a fall in plasma cholesterol and in its ester, 

 and increase in prothrombin time, and decreases in hemoglobin, hemato- 

 crit, and plasma proteins were noted. Total lipids in the liver increased 

 markedly. In an extensive analysis of the tissues of normal and choline- 

 deficient puppies,'^^ little or no change was found in the lipids of the cere- 

 brum, spleen, pancreas, kidney, heart, and lungs, but a marked shift in 

 the pattern of the liver and plasma lipids was evident. In the liver this was 

 characterized by a decrease in choline and by an increase in sphingosine and 

 in other undetermined nitrogenous components of lipids, although the total 

 phospholipids were unchanged. In the plasma there was a marked decrease 

 in total phospholipids. The data suggested that sphingomyelins were re- 

 placing lecithins, but the percentage of choline phospholipids in the plasma 

 remained the same. Schaefer et al. were able to produce chronic choline de- 

 ficiency in dogs which was characterized by cirrhotic livers, edema, and 

 duodenal ulcers. ^^° The protective level of choline was halved by adminis- 

 tration of Bi2. Burns and McKibbin also observed this effect of B12 and 

 noted that liver impairment in some puppies was prevented completely 

 by B12 alone. ^^^ 



Chaikoff and coworkers have studied the mechanisms by which choline 

 exerts its lipotropic activity in dogs by means of determinations of the 



353 p. J. Fouts, J. Nutrition 25, 217 (1943). 



354 W. R. Ruegamer, L. Michaud, C. A. Elvehjem, and E. B. Hart, Aw. J. Physiol. 

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355 A. E. Schaefer, J. M. McKibbin, and C. A. Elvehjem, Proc. Soc. Exptl. Biol. Med. 

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356 V. H. Hough, E. P. Monahan, T. W. Li, and S. Freeman, Am. J. Physiol. 139, 642 

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357 J. M. McKibbin, S. Thayer, and F. J. Stare, J. Lab. Clin. Med. 29, 1109 (1944). 



358 J. M. McKibbin, R. M. Ferry, Jr., S. Thayer, E. G. Patterson, and F. J. Stare, 

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359 J. M. McKibbin and W. E. Taylor, J. Biol. Cheni. 185, 357 (1950). 



360 A. E. Schaefer, D. H. Copeland, and W. D. Salmon, J. Nutrition 43, 201 (1951). 



361 M. M. Burns and J. M. McKibbin, /. Nutrition 44, 487 (1951). 



