Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A machine for the extracorporeal delivery of covalent anti-sickling agents has been described by Babb and coworkers and this therapeutic modality has been found feasible by others. We report here, further evaluation of nitrogen mustard (HN2), for possible use in the extracorporeal therapy of sickle cell anemia. Heparinized aliquots of whole blood from three patients with sickle cell disease were treated extra-corporeally with HN2 (0.65 mg/ml); the excess HN2 was neutralized with thiosulfate, and the blood was returned to the donor after labelling with 51Cr. HN2 produced an average 51Cr T1/2 which was 160% of control values. Fractionation of labelled red cells into different densities (ages) revealed that the main effect of HN2 was on the younger cell population which was characterized by a 51Cr T1/2 increase of 300% over the untreated blood. Further, "in vitro" studies were conducted to establish the effects on the SS red cells that could be expected from the treatment with HN2 at the concentrations used. Solubility determination (Csat) of deoxy hemoglobin S gels demonstrated that HN2 markedly inhibited the polymerization of HbS, was significantly more effective than potassium cyanate, and is among the most potent anti-sickling agents thus far reported. The viscosity of deoxygenated sickle red cells in a cone plate viscometer was markedly reduced by HN2, and hemodynamic studies using the microvasculature of an isolated rat mesoappendix demonstrated a reduction of peripheral resistance and an increase in flow rate when deoxygenated sickle cells pre-treated with HN2 were tested. At the highest concentration of HN2 (2 mg/ml), the peripheral resistance and the flow rates of deoxygenated cells attained levels found with oxygenated sickle blood. O2 affinity was partially corrected in the HN2 treated HbSS red cells. -SH reactivity of the red cell membrane was not affected by HN2. Among the added advantages of HN2 for extra-corporeal use is its rapid reaction rate, the lack of significant change of the O2 equilibrium at the concentration tested and the fact that the unreacted compound can be readily detected and neutralized. For these reasons HN2 is well suited for extra-corporeal treatment of sickle cell anemia for those patients with a severe form of the disease.
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PMID:Survival rates and properties of sickle cell anemia red cells treated with nitrogen mustard. 361 91