Sickling-induced cation fluxes contribute to cellular dehydration of sickle red blood cells (SS RBCs), which in turn potentiates sickling. This study examined the inhibition by dipyridamole of the sickling-induced fluxes of Na(+), K(+), and Ca(++) in vitro. At 2% hematocrit, 10 microM dipyridamole inhibited 65% of the increase in net fluxes of Na(+) and K(+) produced by deoxygenation of SS RBCs...

A rapid-reaction parallel-plate flow channel was used to study the kinetics of erythrocyte sickling upon sudden deoxygenation with sodium dithionite. The erythrocytes were recorded on 16-mm film or video tape and visually tracked in time. Sickling was identified by morphologic criteria. At the flow rate used in these studies, the rate of sickling was a reaction-limited process. There was no los...

The ultimate goal of gene therapy for sickle cell anemia (SCA) is an improved phenotype for the patient. In this study, we utilized bone marrow from a sickle cell patient as a model of disease in an in vitro setting for the hyperactive Sleeping Beauty transposon gene therapy system. We demonstrated that mature sickle red blood cells containing hemoglobin-S and sickling in response to metabisulf...

Haemoglobin concentrations in vertebrate red blood cells are so high that in human sickle cell disease a single surface amino acid mutation can result in formation of large insoluble haemoglobin aggregates at low oxygen levels, causing peculiar cell deformations or 'sickling'. This may cause vascular occlusion and thereby severe pain, organ failure and death. Here, using light and transmission ...

Urea inglucose solutions has been advanced as a chemotherapeutic agent in sickle cell disease because it has been found effective both in reversing and in blocking sickling. It has been suggested recently that this beneficial action of urea may be the result of formation of cyanate from urea and subsequent carbamylation of beta S globin chains in the hemoglobin S molecule. In this paper, we sho...

By William A. Eaton, James Hofrichter, and Philip D. Ross T HE FACTORS which determine the frequency of crises and overall severity in sickle cell disease are still not clear. Although Allison,’ Charache and Conley,2 and others3’4 have considered that the kinetics of sickling may be important clinically, accurate measurements of the rates of hemoglobin S gelation and cell sickling have only bee...

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were...

Sickle cell trait can pose a grave risk for some athletes. In the past few years, exertional sickling has killed nine athletes, including five college football players in training. Exercise-physiology research shows how and why sickle red cells can accumulate in the bloodstream during intense exercise bouts. Sickle cells can "logjam" blood vessels and lead to collapse from ischemic rhabdomyolys...

In sickle cell disease (SCD), the events originating from hemoglobin S polymerization and intravascular sickling lead to reperfusion injury, hemolysis, decreased nitric oxide (NO) bioavailability, and oxidative stress. Oxidative stress is implicated as a contributing factor to multiple organ damage in SCD. We hypothesize that inhibition of sickling by genetic manipulation to enhance antisicklin...

Fifteen compounds reported to be inhibitors of gelation or sickling were studied by standard methods. These tests included (1) the determination of the solubility of deoxyhemoglobin S or Csat, (2) evaluation of sickling in whole SS blood at various pO2s, (3) measurement of the oxygen affinity of hemoglobin and blood, and (4) examination of red cell indices and morphology. Among the 4 noncovalen...