66 CHOLINE 



primary vascular change during the acute stage is congestion of the periph- 

 eral cortical capillaries and capsular blood vessels and, sometimes, of the 

 glomerular blood vessels; hemorrhage, if present, occurs only in the capsule 

 and at the periphery of the cortex; peripheral cortical tubules undergo 

 necrosis or granular or hyaline droplet degeneration; hyaline casts are 

 always abundant in tubules of the inner zone of the cortex and of the outer 

 zone of the medulla; and calcification of degenerated peripheral tubules 

 occurs in the most severely affected kidneys. 



Hartroft and Best^'^" have emphasized the role in this syndrome of small 

 droplets of stainable fat which appear in the epithelial cells of the proximal 

 convoluted tubules of the cortex. Concomitantly, generalized swelling of 

 the affected nephrons occurs, with obstruction of the intervening capillary 

 plexus in the cortex. Tubular ischemia and necrosis are followed by en- 

 gorgement of the proximal cortical vessels which may rupture into and 

 beneath the capsule. Choline feeding has relati\'ely little effect on the total 

 renal lipids. ^^ That the acute renal lesion is an effect of a deficiency of choline 

 has been repeatedly confirmed^^"^^. Conditions for producing a uniformly 

 fatal outcome w^ere described by EngeP'*' ". Handler showed that the lesion 

 occurred in adult rats after unilateral nephrectomy if the animals were 

 placed immediately on the deficient diet.^* The observations of Olsen and 

 Deane^^ included changes in the adrenal cortex which is enlarged during the 

 acute phase with definite evidence of hyperactivity of the zona fasciculata 

 and zona glomerulosa, especially the latter. 



The prevention of hemorrhagic degeneration is relatively specific for 

 choline, although methyl -sparing compounds, such as methionine or beta- 

 ine, and certain other compounds are effective. Substances w^hich resemble 

 choline sufficiently to be built by anabolic processes into lecithin-like mole- 

 cules without obviously serving as inhibitors, such as arsenocholine or 

 triethylcholine, have more or less activity.^*'^" It may be that certain of 

 these compounds will be found later not to be antihemorrhagic. The onset 



' W. S. Hartroft and C. H. Best, Science 105, 315 (1947). 



8W. S. Hartroft, Brit. J. Exptl. Pathol. 29, 483 (1948). 



9 C. H. Best and W. S. Hartroft, Federation Proc. 8, 610 (1949). 



10 W. S. Hartroft, Proc. 1949 Milbank Mem. Fund p. 144 (1950). 



11 G. Gualandi and S. M. Tamburello, Boll. soc. ital. biol. sper. 26, 945 (1950). 



12 P. Gyorgy and H. Goldblatt, J. Exptl. Med. 72, 1 (1940). 



13 R. W. Engel and W. D. Salmon, J. Nutrition 22, 109 (1941). 

 1* P. Handler, J. Nutrition 31, 621 (1946). 



15 F. I. Dessau and J. J. Oleson, Proc. Soc. Exptl. Biol. Med. 64, 278 (1947). 

 '« R. E. Olson and H. W. Deane, J. Nutrition 39, 31 (1949). 

 1' R. W. Engel, Proc. Soc. Exptl. Biol. Med. 50, 193 (1942). 

 ■ 18 A. D. Welch, J. Nutrition 40, 113 (1950). 

 IS A. D. Welch, cited by T. H. Jukes, Proc. Am. Inst. Nutrition, /. Nutrition 21, 



Suppl. 13 (1941). 

 "0 J. M. Patterson and E. W. McHenry, /. Biol. Chem. 145, 207 (1942). 



