vitamin-k-semiquinone-radical and Thalassemia

We have attempted to determine the cellular mechanism by which alpha-thalassaemia may protect against Plasmodium falciparum malaria. Invasion and development of P. falciparum in the microcytic red cells of two-gene deletion forms of alpha-thalassaemia when measured morphologically or by [3H]hypoxanthine incorporation were normal compared to controls. Normal invasion rates were also observed following schizogony in thalassaemic red cells. Neither the addition of the oxidant menadione, 30% oxygen, nor modified medium, produced differential damage to parasites within thalassaemic cells. Furthermore, there were no significant differences in the binding of P. falciparum-parasitized alpha-thalassaemic and normal cells to C32 melanoma cells in vitro. However, when neoantigen expression on the surface of infected thalassaemic cells was estimated using a quantitative radiometric antiglobulin assay, clear differences were observed. It was found that alpha-thalassaemic cells bound higher levels of antibody from serum obtained from individuals living in a malaria endemic area than control normal red cells. The binding ratio for thalassaemic compared with controls was 1.69 on a cell-for-cell basis, and 1.97 when related to surface area. The binding of antibody from immune serum increased exponentially during parasite maturation. We also found increased binding of naturally occurring antibody present in non-immune serum to parasitized thalassaemic red cells which also increased during parasite maturation. We conclude that the protection afforded by thalassaemia against malaria may not reside in the ability of parasites to enter, grow or cytoadhere to endothelium in such cells, but may be related to immune recognition and subsequent clearance of parasitized red cells.

Topics: Animals; Antigens, Protozoan; Antigens, Surface; Erythrocytes; Humans; Immunoglobulin G; Malaria, Falciparum; Oxygen Consumption; Plasmodium falciparum; Thalassemia; Vitamin K

Coagulation studies were carried out in 20 beta-thal children (five splenectomized) and 16 control children. It was found that the activities of factors II, VII, IX, and X (prothrombin complex group), V, and possibly I that are produced by hepatic parenchymal cells were uniformly depressed. Factor VIII activity was normal. There was no statistically significant difference in the prothrombin complex activity between the splenectomized and nonsplenectomized group, or those with and without parenteral vitamin K administration. The absence of "cold-activation" of factor VII in thal plasma, probably secondary to depressed activities of plasma kallikrein and HMW kininogen, further implicates liver involvement in these children.

Topics: Adolescent; Blood Coagulation Factors; Child; Child, Preschool; Female; Humans; Liver; Male; Nutritional Status; Splenectomy; Thalassemia; Vitamin K

Topics: Adult; Cells, Cultured; Erythrocytes; Fetal Hemoglobin; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Humans; Malaria; Oxidation-Reduction; Oxygen; Plasmodium falciparum; Riboflavin; Thalassemia; Vitamin K

The effects of dipyridamole on potassium and sodium content of human red blood cells from normals or from patients with hypochromic anaemia, and of normal red cells pretreated with menadione, have been studied. Dipyridamole added to the incubation medium decreases the loss of potassium and the accumulation of sodium in all three types of red cells incubated at 37 degrees C for 24 h, either with or without calcium. The possible mechanism underlying these effects of dipyridamole is discussed.

Topics: Anemia, Hypochromic; Dipyridamole; Erythrocytes; Humans; Potassium; Sodium; Thalassemia; Vitamin K