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October 29, 1973

Mechanism of Urea Activity in Sickling

JAMA. 1973;226(5):567-568. doi:10.1001/jama.1973.03230050045022

To the Editor.—  The important and stimulating letter by Ratner and Miller (225:313,1973) reported the dissociative effect on polyhydrogel polymers by low concentrations of urea and proposed an alternate molecular mechanism for the desickling action of urea. This information deserves the serious attention of those sicklecell investigators who have a molecular orientation. The observations offered by Ratner and Miller are highly pertinent to the development of new, rational chemotherapeutic approaches to the management of sickle cell disease. Ratner and Miller,1,2 as well as Refojo,3 have each independently shown that urea in low concentrations (0.005 to 0.117 M) breaks down cross-linked bonds (ie, chemical bonds) between microfilaments of polyhydrogels. While Refojo has suggested that hydrophobic bonds are broken in this reaction with urea, Ratner and Miller believe that hydrogen bonds are broken regardless.When these findings are coupled with the recent work of Minton,4 who describes the stages