Biomedical subjects

V Jancinova

Publications and source records attributed to V Jancinova.

3 recordsLinked to original sources

PubMed2005

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.

Adrenergic beta-Antagonists↗

PubMed2004

Blood platelets decrease concentration of reactive oxygen species produced by polymorphonuclear leukocytes.

BACKGROUND: Reactive oxygen species produced by polymorphonuclear leukocytes (PMNL) participate substantially in vascular injury induced by ischaemia and reperfusion. Blood platelets, accumulated simultaneously with PMNL may modulate this process. OBJECTIVE: To compare effects of resting and completely stimulated platelets on PMNL-derived oxidants. METHODS: Autologous human platelets and PMNL were co-incubated in the physiological cell ratio 50:1, and the formation of reactive oxygen species was detected by luminol- and isoluminol-enhanced chemiluminescence methods. To compare effects of platelets at different degrees of their activation, FMLP (selective PMNL stimulus) and Ca2+-ionophore A23187 (activates both PMNL and platelets) were used as chemiluminescence stimuli. The liberation of serotonin from platelets was estimated fluorometrically. RESULTS: Both stimulated and non-stimulated platelets inhibited PMNL chemiluminescence. However, while the decreasing effect of resting platelets disappeared at increased extracellular peroxidase concentration, the inhibition of chemiluminescence by activated platelets became even more pronounced after the addition of peroxidase and was accompanied by liberation of serotonin. The concentrations of serotonin released from platelets were sufficiently high to inhibit PMNL chemiluminescence. CONCLUSION: The obtained data indicate that by interference of platelets with peroxidase liberation from PMNL and the scavenging effect of platelet serotonin, resting and stimulated platelets might be respectively operative in inhibiting chemiluminescence. Since the presence of blood platelets in the proximity of PMNL effectively decreased the concentration of reactive oxygen species, platelets may represent a unique protective mechanism, active only in case of emergency and selectively at sites exposed to toxic effects of reactive oxygen species. (Tab. 1, Fig. 4, Ref. 42.).

Blood Platelets↗

PubMed2001

Pharmacological intervention with platelet phospholipase A2.

BACKGROUND: Metabolites of arachidonic acid are important regulatory substances in blood platelets. They participate in platelet adhesion and aggregation, and pharmacological intervention with arachidonate cascade is widely used in therapy of hyperactive platelets and in the prevention of thromboembolic complications. AIM OF THE STUDY: To verify and compare the effect of cationic amphiphilic drugs (CAD) from different pharmacological groups on activation of platelet phospholipase A2--the essential enzyme of arachidonic pathway in blood platelets. METHODS: Blood platelets were isolated from human and rat blood by differential centrifugation and aggregation was measured in pretreated and subsequently stimulated platelets in a dual channel aggregometer and recorded on a linear recorder. Activity of cytosolic phospholipase A2 (cPLA2) was determined by means of arachidonic acid liberation from platelet membrane phospholipids incorporated as triciated radionuclide. The radioactivity was determined by liquid scintillation method in Packard TriCarb 2500T. RESULTS: Cationic amphiphilic drugs of the beta-adrenoceptor blocking group inhibited platelet aggregation in the rank order of potency: propranolol > alprenolol > metipranolol > atenolol. Similarly did the H1-histamine antagonists bromadryl and dithiaden as well as the antimalarial chloroquine show antiplatelet effect in vitro in the rank order of potency: dithiaden > or = bromadryl > or = chloroquine. Dose-dependent inhibition of aggregation was followed by inhibition of arachidonic acid liberation from membrane phospholipids of platelets stimulated at receptor site (thrombin) or by a stimulus bypassing membrane receptors (Ca2+ ionophore A23187). The rank order potency for inhibition of stimulated 3H-AA liberation from membrane phospholipids was: a) for BAB drugs: propranolol > or = alprenolol > metipranolol, b) for other drugs: dithiaden > bromadryl > chloroquine. CONCLUSION: The drugs investigated interference with liberation of stimulated arachidonic acid showed nonspecific inhibition of platelet cytosolic phospholipase A2 by these drugs at intracellular level. The results revealed that besides inhibition of cyclooxygenase pathway, and of receptors for ADP and glycoproteins Gp IIb/IIIa, interaction of drugs with cPLA2 may represent a further site for antiplatelet action. (Fig. 5, Ref. 39.)

Adrenergic beta-Antagonists↗