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  • Title: Sickling reversed and blocked by urea in invert sugar.
    Author: Nalbandian RM, Henry RL, Barnhart MI, Nichols BM, Camp FR, Wolf PL.
    Journal: Am J Pathol; 1971 Aug; 64(2):405-22. PubMed ID: 5142273.
    Abstract:
    Optical and electron microscopic evidence is presented to support the finding that sickling of hemoglobin S can be reversed and blocked by urea in invert sugar (UIS). Erythrocytes from subjects having hemoglobin SS, AS or AA were treated with the UIS either before or after deoxygenation with Na(2)S(2)O(5). Light microscopic studies indicated that approximately one-fifth as much urea is required to block sickling as is necessary to reverse sickled poikilocytes to normal forms. Intracellular microfilaments apparent in transmission electron micrographs of sickled erythrocytes were eliminated by treating aliquots of the same deoxygenated erythrocytes with UIS. Scanning electron micrographs showed a reversion of sickled poikilocytes to a normal erythrocyte population of biconcave discs. The use of UIS was deduced from Murayama's hypothesis that the molecular mechanism of sickling clearly involves hydrophobic bonds formed between the number-6 valine substitution of the beta-chain S globins and the alpha-chain globins of interacting hemoglobin molecules. The use of UIS to arrest the formation of such hydrophobic bonds is advocated as an evident and effective therapeutic strategy to treat sickle cell crisis.
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