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Biomedical subjects

R Nosál'

Publications and source records attributed to R Nosál'.

18 recordsLinked to original sources
PubMed2000

Chloroquine: a multipotent inhibitor of human platelets in vitro.

Chloroquine inhibited human platelet aggregation in vitro both at receptor- and nonreceptor-operated stimuli. The inhibition was dose-dependent, recorded on isolated platelets as well as in platelet-rich plasma, and followed the rank order of stimuli: adrenaline (second phase)>phorbol 12-myristate 13 acetate>adenosine diphosphate>adrenaline (first phase)>thrombin>calcium ionophore A23187. In thrombin-activated platelets, chloroquine decreased in a dose-dependent manner phospholipase A(2)-induced arachidonic acid liberation from membrane phospholipids, malondialdehyde formation (a marker of membrane phospholipid peroxidation), and thromboxane generation, considered the most potent autoaggregatory agent. Chloroquine only slightly altered the arachidonic acid cascade of platelets stimulated with A23187 and phorbol 12-myristate 13 acetate. Histamine formation and liberation induced with thrombin and A23187 were not affected by chloroquine. On the other hand, thrombin-stimulated serotonin secretion was significantly decreased with chloroquine in the concentration of 10 micromol/L. This indicated that chloroquine might interfere with stimulated secretion from platelets. The results suggest that chloroquine inhibited activated platelets: first, intracellularly; second, in a close relationship to the intraplatelet Ca(2+) mobile pool; and third, most probably at the site of platelet phospholipase A(2) activation.

Adult↗
PubMed1991

[Pharmacotoxicologic characteristics of pentacaine].

Long-term administration of pentacaine to experimental animals in investigations of chronic toxicities confirmed that this substance is relatively safe in amounts of 10 mg/kg/day. Larger doses caused ECG changes, as well as changes of some clinical and biochemical indicators and histopathological findings which were independent on the dose and sex. The embryotoxic and teratogenic action of pentacaine was manifested only after large doses in mice (more than 20 mg/kg). Doses under 10 mg/kg per day did not produce toxic effects in mother and foetus, whereby the substance penetrates through the placenta and is distributed in the maternal and foetal organs of rabbits in a proportionate way. From the in vitro action of pentacaine ensues that it has a strong stimulating action on isolated cells which gradually changes into cytotoxic action. The results support the decision not to use pentacaine for intravenous, infiltration and conduction anaesthesia and to recommend only its oral administration.

Anesthetics, Local↗
PubMed1991

[The role of prostaglandins in the effect of beta-blockers on stimulated blood platelets].

Atenolol, a selective beta-blocker, slightly potentiates the stimulated aggregation of platelets against dose-dependence. The drug potentiates similarly stimulated release of arachidonic acid, it does not influence the formation of malondialdehyde and the thromboxane B2 production in stimulated platelets. The non-selective beta-blocker propranolol inhibits in a dose-dependent way stimulated aggregation, the release of arachidonic acid, it reduces thromboxane B2 production in stimulated platelets. The authors revealed that the anti-aggregating action of beta-blockers is closely related to their ability to influence prostaglandin synthesis in stimulated platelets.

Adrenergic beta-Antagonists↗
PubMed1990

[Analysis of the adverse effects of drugs at the cellular and subcellular levels].

A release of histamine after the lipophilic betablockers exaprolol and propranolol correlates with their capability of displacing the bound membrane Ca2+ and increasing the disorder of phospholipidic membranes of the isolated mast cells. Electron microscopy confirmed intracellular displacement of histamine from granules of mast cells after exaprolol without marked structural changes on the plasmatic membrane. Hydrophilic and selective atenolol, which does not possess a histamine-liberating effect, decreases spontaneous transfer of the intracellular calcium, decreases the disorder of the mast-cell membranes, and together with exaprolol and propranolol inhibits, in dose-dependence way, the gain of extracellular histamine in cells. The inhibitory effect of EDTA, tetrodotoxine and suramine on histamine release after exaprolol explains the non-receptor mechanism of exaprolol effect, which confirms a possibility of induction of adverse effects of blockers of the beta-adrenergic receptor in the development of a bronchospasm.

Adrenergic beta-Antagonists↗
PubMed1990

[The effect of adrenergic beta receptor blockers on phospholipid metabolism in mast cells].

The aim of this study was to determine whether beta adrenergic receptor blocking drugs exaprolol, metipranolol and propranolol effect the metabolism of phospholipids in isolated rat mast cells. The phospholipids were labelled by 3H-arachidonic acid (3H-AA) and 32P. Exaprolol, metipranolol and propranolol significantly modulated 32P incorporation into phospholipids of resting and 48/80 stimulated cells. Atenolol had no effect. Studies with 3H-AA Labelled mast cells showed an enhanced liberation of arachidonate related radioactivity on exaprolol and propranolol treatment. The results indicated that 3H-activity was lost mainly from phosphatidylethanolamine. Atenolol and metipranolol significantly decreased the 48/80 stimulated 3H-AA release.

Adrenergic beta-Antagonists↗
PubMed1990

[Characteristics of new approaches for evaluation of embryotoxic effects of chemical substances].

New approaches to the evaluation of embryotoxic effects of xenobiotics are characterized in the light of mother--fetus interrelationship. The first part of the paper analyzes problems of evaluating maternal and embryofetal toxicity and substantiates the necessity of sensitive selection and precise evaluation of individual parameters of toxicity. The second part presents a survey of classical testing procedures and of alternative methods used in assessing the safety of new drugs. The third part characterizes methods of quantitative determination of risks inherent to chemical substances. A detailed description of the principles of the new method is presented which is based on the interrelationship of maternal and embryofetal toxicity (adult/developmental--A/D). The acceptability of the new method has been verified experimentally on evaluating some new prospective drugs according to standard teratological studies.

Abnormalities, Drug-Induced↗
PubMed1990

[Transplacental transfer, tissue localization and morphological study of the rabbit placenta after the administration of pentacaine].

On day 29 of gravidity, the New Zealand white breed rabbits were intravenously administered 3H-pentacaine (0.5 mg.kg-1), a new local anaesthetic agent with anti-ulcerous effect in order to study the distribution in pregnant females. Transplacental passage and a relatively homogenous distribution of unchanged pentacaine were found in the organs of females with the largest accumulation in the lungs. Pentacaine is distributed in the same manner in the fetal organs as in the organs of the mother, but the levels in the foetuses were significantly lower. A morphological study of the rabbit placenta on day 29 of gravidity after the doses of 1, 10 and 50 mg.kg-1 of pentacaine did not show any pathological changes.

Anesthetics, Local↗
PubMed1986

Interaction of local anaesthetics with blood platelet aggregation.

The effect of three newly synthesized local anaesthetics on platelet aggregation, serotonin release and integrity of platelets was investigated. Pentacaine, heptacaine and carbisocaine were found to be about 10 times more active than "classic" local anaesthetics. They inhibited platelet aggregation stimulated by collagen, thrombin and ADP at the concentrations of 0.01, 0.1 and 1 mmol/l respectively. At millimolar concentrations the test local anaesthetics liberated serotonin from platelets and disintegrated platelet membranes. Pentacaine was the most effective, followed by heptacaine and carbisocaine. The authors suppose that the perturbation induced in platelet membranes by local anaesthetics could be responsible for inhibition of platelet aggregation and release of serotonin.

Anesthetics, Local↗
PubMedDate not supplied

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.

Carbolines↗