Subject(s)
Anemia, Sickle Cell/drug therapy , Calcium-Binding Proteins/metabolism , Calmodulin/metabolism , Erythrocyte Membrane/physiology , Erythrocytes/physiology , Anemia, Sickle Cell/blood , Anesthetics, Local/therapeutic use , Antipsychotic Agents/therapeutic use , Calmodulin/antagonists & inhibitors , Erythrocyte Membrane/drug effects , Humans , Models, Biological , Phenothiazines , Zinc/therapeutic useABSTRACT
The ability of phosphate alone and in combination with sodium bicarbonate, vitamin C and pyruvate to elevate 2,3-diphosphoglycerate (DPG) levels was examined in normal human subjects in vivo. Statistically significant increases in DPG levels were noted (P less than .001) for all regimens pooled. Average rise in DPG levels reached 6% above pretreatment levels after 2 to 3 days of treatment. No changes in DPG levels were detectable in a group of control subjects over the same time period. Variation among pharmacologic trials and among subjects within trials in the actual magnitude of DPG build-up was marked. Significant differences could not be detected among the pharmacologic regimens in their ability to produce DPG increases. Previous reports suggested the use of these agents to stimulate red cell glycolysis but it seems that their effects and the mechanisms of glycolytic control in vivo are considerably more complex than has been previously suggested.
Subject(s)
Diphosphoglyceric Acids/blood , Erythrocytes/drug effects , Ascorbic Acid/pharmacology , Bicarbonates/pharmacology , Erythrocytes/metabolism , Female , Humans , Male , Phosphates/pharmacology , Pyruvates/pharmacology , Stimulation, Chemical , Time FactorsABSTRACT
Zinc administered orally to 12 patients with SCA decreased the mean number of circulating ISC's from 28.0% before treatment to 18.6% during treatment. Seven of the 12 patients had statistically significant individual decreases in ISC counts, and two others had moderate reduction in ISC's of borderline significance. Patients who did not have a significant decrease in ISC count while on zinc therapy had low counts initially. The decrease in ISC's may mean improved oxygenation. The decrease in ISC's provides objective evidence of an in vivo effect of oral zinc treatment in SCA. The role of ISC's in the pathology and symptomatology of SCA is unknown, but some evidence suggests that ISC's may be related to vascular and organ damage. If so, therapies which decrease ISC counts, such as zinc, have the potential of reducing organ damage.