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  • Title: Pharmacological modification of oxygen affinity improves deformability of deoxygenated sickle erythrocytes: a possible therapeutic approach to sickle cell disease.
    Author: Keidan AJ, Sowter MC, Johnson CS, Marwah SS, Stuart J.
    Journal: Clin Sci (Lond); 1989 Apr; 76(4):357-62. PubMed ID: 2714049.
    Abstract:
    1. The formation of polymerized haemoglobin S in sickle cells is critically dependent on the concentration of deoxygenated haemoglobin so that compounds which increase the oxygen affinity of haemoglobin S are potential anti-sickling agents. 2. BW12C [5-(2-formyl-3-hydroxyphenoxy)pentanoic acid] and BWA589C [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid] are aromatic benzaldehydes that cause a dose-dependent left-shift of the oxygen saturation curve of haemoglobin S by stabilization of its oxy-(R)-conformation. 3. A 5 micron pore filtration method, which is highly sensitive to polymerization of haemoglobin S, was used to demonstrate a significant improvement in the deformability of deoxygenated sickle erythrocytes at concentrations (0.75-1.5 mmol/l] of BW12C and BWA589C that are achievable in vivo. Both compounds may therefore be of value for the treatment of sickle cell disease. 4. Filtration of sickle cells through pores of 5 microns diameter is a sensitive technique for evaluating the rheological effects of potential anti-sickling compounds.
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