Carvedilol--a beta-blocker with considerable antiaggregatory effect on human blood platelets.

BACKGROUND: Activated blood platelets play a key role in the genesis of many pathological states. Several studies have documented that beta-blockers can influence platelet aggregation. Carvedilol, a third generation non-selective agent with vasodilatory properties, is successfully used in pathological states accompanied with platelet hyperreactivity, however information on its antiplatelet activity is lacking. OBJECTIVES: The aim of this study was to analyse the in vitro effect of carvedilol on aggregation of human blood platelets, to compare this effect with the effect of propranolol and atenolol, and to determine whether its suggested antiaggregatory effect was accompanied with reduced thromboxane B2 formation. Moreover, some physico-chemical parameters of the drugs tested were calculated and compared. METHODS: Platelets were isolated by differential centrifugation and platelet aggregation was measured by the turbidimetric method. The amount of thromboxane B2 was measured by the radioimmunoassay method. Physico-chemical parameters of the drugs tested were calculated using the computer programme Hyperchem. RESULTS: Carvedilol and propranolol inhibited platelet aggregation in the rank order of stimuli: PMA > thrombin > A23187 > epinephrine. The reduction was accompanied by inhibition of thromboxane B2 formation. In comparison to propranolol, carvedilol was more effective, with the exception for aggregation stimulated with ADP. Atenolol did not affect any platelet function tested. From the drugs studied, the molecule of carvedilol was found to possess the highest partition coefficient, the highest index of molar refractivity, and the lowest dipole moment. CONCLUSION: Our study found carvedilol to be more potent than propranolol and atenolol in inhibiting platelet aggregation and thromboxane B2 production. This may be due to the different structure and more convenient physico-chemical parameters of the carvedilol molecule.

Inhibition of chemiluminescence by carvedilol in the cell-free system, whole human blood and blood cells.

Carvedilol inhibits luminol-enhanced chemiluminescence of reactive oxygen metabolites in vitro. In this study it was found that, in the cell-free system, carvedilol dose-dependently decreased chemiluminescence in the following ranking order of radicals: hydroxyl radical > hydrogen peroxide > superoxide radical. The inhibition of myeloperoxidase was significant with carvedilol concentrations of 10 and 100 micromol/l and manifested in the concentration-dependent shift of chemiluminescence peaks to the right. In whole blood, carvedilol in concentrations of 10 and 100 micromol/l significantly inhibited chemiluminescence induced by both receptor-bypassing stimuli (A23187, PMA) and receptor-operating stimuli (fMLP, OpZ). Carvedilol dose-dependently inhibited chemiluminescence of isolated human polymorphonuclear leucocytes in the ranking order of stimuli: A23187 > OpZ > fMLP. In the presence of blood platelets, carvedilol did not substantially change chemiluminescence induced by fMLP and OpZ, while it was much more effective on chemiluminescence stimulated with calcium ionophore A23187. This could be the result of the supportive effect of serotonin liberated from platelets by A23187.

Stobadine-modulated human neutrophil functional responsiveness: effect on particular and soluble stimulation.

The effect of stobadine on degranulation (myeloperoxidase release) and on oxidative burst, measured as superoxide anion production, was investigated in human neutrophils activated with receptor-specific (fMLP, opsonized zymosan) and nonreceptor stimuli (PMA, A 23187). Wortmannin, a specific inhibitor of 1-phosphatidylinositol 3-kinase, significantly inhibited fMLP-stimulated generation only. This effect was pronounced by stobadine. Stobadine dose-dependently decreased superoxide generation and myeloperoxidase release after receptor-specific stimuli, with the highest effect on fMLP stimulation of superoxide generation and on opsonized zymosan stimulation of myeloperoxidase release.

[New views on the etiopathogenesis of beta-thalassemia]. / Niektoré nové aspekty v etiopatogenéze beta-talasémií.

In the submitted paper the author deals with recent findings on damage of erythrocyte membranes and enzymes in beta-thalassemia. The primary disorder in the formation of beta chains leads to the formation of haemichromes and free oxygen radicals which leads to peroxidative damage of the lipid membrane. The thus generated aldehydes damage important thiol groups of enzymes. Haemichromes interfere with the structure of the protein membrane and the cytoskeleton of the cell. There are differences in membrane damage between alpha and beta thalassaemia. Beta-thalassaemia must be conceived as a comprehensive disease of red blood cells not only as a haemoglobinopathy.

[New views on the therapy of beta-thalassemia]. / Niektoré nové aspekty v liecbe beta-talasémií.

The author describes the present situation as regards treatment of beta-thalassaemias. Most frequently the classical combination of transfusions and desferrioxamine is used. Other possibilities are total or partial splenectomy, as well as transplantation of the bone marrow. The mentions also perspective causal therapy by genetic engineering. Systematic and planned prevention still remains most successful.

[Platelet satellitosis]. / Dostickový satelitizmus.

Platelet satellitism (PS) is a rare phenomenon described sporadically in the literature. It involves adhesion of thrombocytes sensitized by antibodies to leucocytes and is observed in vitro in EDTA anticoagulated blood. The authors' contribution to the problem is the observation of special thrombocyte aggregates surrounding neutrophils resembling comet tails, as well as the fact that the authors observed the formation of aggregates surrounding also lymphocytes and eosinophil cells.

[Use of nuclear magnetic resonance in the study of hemolytic anemia. Preliminary report]. / Vyuzitie nukleárnej magnetickej rezonancie pri stúdiu hemolytických anémií. Predbezné zdelenie.

Nuclear magnetic resonance is a method which contributes nowadays to further investigations of the phosphate metabolism in red blood cells. By means of 31P nuclear magnetic resonance it is possible to record in intact red cells signals of phosphate compounds as well as changes in their concentrations. In the submitted work the authors followed up the important phosphate compounds in red cells--adenosine triphosphate, adenosine diphosphate and inorganic phosphate. They assessed and evaluated by statistical methods spectra of 10 healthy blood donors of different age and sex. The same procedure was used in 6 patients with hereditary spherocytosis, in 6 patients with G-6-PD deficiency and in 4 patients with pyruvate kinase deficiency. The most important changes were recorded in the latter pathological entity, the results being consistent with those obtained by other methods.

Preservation surgery of the spleen.

Authors point out possibilities of preservation of the spleen or its parts in injuries and some diseases, especially non-parasitic cysts. Review is completed by a case report of successful management of a splenic pseudocyst by partial resection.