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At least 19 recordsLinked to original sources
PubMed1979

[Action mechanism and clinical indications for thrombocyte aggregation inhibitors].

The mechanisms of action of three most commonly used antiplatelet agents (aspirin, sulfinpyrazone, dipyridamole) are briefly discussed. Aspirin inhibits the prostaglandin synthetase of platelets irreversibly and thereby blocks the production of prostaglandin endoperoxides and thromboxane A2, which stimulate platelet aggregation. A daily aspirin dose of 200--300 mg is sufficient to achieve this effect. Sulfinpyrazone appears to interfere with the adhesion of platelets to subendothelial structures and atherosclerotic plaques. Dipyridamole increases cyclic AMP in platelets and thus reduces platelet response to aggregating agents. A few of the satisfactorily performed studies on the clinical effectiveness of antiplatelet agents are mentioned. Sulfinpyrazone treatment of patients with myocardial infarction (Killip--classification I and II), starting 25--35 days after the acute myocardial infarction, reduces cardiac mortality and incidence of sudden death for a period of two years. The efficacy of aspirin treatment in coronary artery disease is not yet definitely established. In patients with transient ischemic attacks, particularly males with appropriate carotid lesions, aspirin therapy reduces the frequency of transient ischemic attacks and possibly the incidence of stroke and death. Sulfinpyrazone is ineffective in these patients. Sulfinpyrazone and aspirin are of value in the prevention of thrombosis in straight arterio-venous shunts. Aspirin reduces the frequency of deep venous thrombosis after total hip replacement in males but not in females. In patients with recurrent venous thrombosis, sulfinpyrazone treatment is effective in preventing thrombosis.

Anticoagulants↗
PubMed1979

The action mechanism of the purified platelet aggregation principle of Trimeresurus mucrosquamatus venom.

The minimal concentration of the platelet aggregation principle (Platelet Aggregoserpentin, PAS) necessary to induce platelet aggregation was 10 ng/ml, about one-hundredth of that of the crude venom. PAS induced the release of platelet factors 3 and 4 from platelets, but the released platelet factor 3 was easily inactivated by the anti-phospholipid effect of PAS. Pretreatment of platelets with neuraminidase potentiated PAS-induced platelet aggregation. PAS-induced platelet aggregation was independent on released ADP; it could occur in the ADP-removing systems, such as apyrase or a combination of phosphoenolpyruvate and pyruvate kinase. However, PAS-induced platelet aggregation could be inhibited by adenine nucleotides and adenosine. PAS-induced platelet aggregation was inhibited by some anti-inflammatory agents, antimalarial drugs, local anesthetics, antihistamine and smooth muscle relaxants. After deaggregation of PAS-treated platelets, thrombin and sodium arachidonate could further induce platelet aggregation, but ADP and second dose of PAS could not. It is concluded that PAS-induced platelet aggregation is due to prostaglandin synthesis. Recent literatures on the mechanism of platelet aggregation were surveyed and the actions of PAS were discussed.

Animals↗
PubMed1978

[Mechanism of action of antibiotics:some examples].

Antibiotics are very commonly used substances to eradicate bacterial infections by bacteriostatic or even bactericid effect. They act at a very specific stage (target), although other less important or secondary interactions can occur. We studied the interaction of three antibiotic families (beta-lactamins, aminosides, rifampicin) with bacterial cell. Penicillin disturbs the cell wall synthesis and more accurately the glycopeptide (or murein) formation, a substance giving rigidity or shape to bacteria. It acts in the late phase of murein-biosynthesis, when N-acetyl glucosamin -- N-acetyl muramic acid L ala -D glu M-DAP (L lys) -D ala -D ala are linked together by the peptide part, under the effect of several enzymes, particularly transpeptidase and DD-carboxy-peptidase. It would appear that beta-lactame-thiazolidine rings have a steric analogy with dipeptide D-alanyl D-alanine. The result would be that the enzyme would act on the antibiotic instead of peptide: the consequence would be inhibition of the peptidic link, giving an abnormal murein, and an incomplete cell wall i.e. fragile bacteria. Aminosides, particularly Streptomycin, link themselves to 30 S subunit of bacterial ribosome. In this case, it seems that it is a 3''OH function which reacts with lysine (from S 12 protein part of 30 S subunit). The consequence is an alteration in the RNA messager lecture, and a false traduction and consequently protein biosynthesis stops with a decrease of polyribosomes and of the formation of inert 70 S ribosome. Rifamycins, and particularly Rifampicin act by inhibition of RNA messager synthesis. One molecule of antibiotic links itself to one molecule of RNA messager : hydroxyl and cetone function in C1 Cs C21 C23 and "ansa" bridge link to beta subunit of RNA polymerase. This linkage gives a conformational change to the RNA polymerase-DNA complex, inhibiting the catalytic action of this enzyme, and consequently stopping RNA messager and protein synthesis. The study of the action mechanism of these antibiotics enables us to show the action specificity of these products in the bacteria. This specificity is more accurate when the target is not to be found in the eucaryotic cells : in this case the antibiotic may be considered as entirely atoxic. If the study of the action mechanism of antibiotics gives a better understanding of the use of these drugs, their action at a definite stage in bacterial metabolism is a valuable tool for scientists in their approach to cell functioning.

Aminoglycosides↗
PubMed1976

Studies on the action mechanism of the antihemostatic effect of lodopeptides.

A synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9% NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl. Studies with Russell's viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation.

Animals↗
PubMed1976

[Action mechanisms of the contracting drugs, K, acetylcholine, histamine and Ba and of the antispasmodics, isoproterenol and papaverine in the isolated guinea pig ileum, particularly in relation to Ca].

Shapes of the contractions induced by K, acetylcholine (AHc), histamine and Ba consisted of the phasic contraction (PC) and the subsequent tonic contraction (TC). PCs by K, ACh and histamine are initiated by the release and the passive influx of Ca, whereas that by Ba is only initiated by the release of Ca. TCs by K, ACh and histamine are maintained by the active influx of Ca, whereas that by Ba is maintained by the active influx and the release of Ca. Storage sites of Ca in the cell membrane of this preparation can be divided into three; the first, the second and the third, which contain the loosely, the less loosely-, and the tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh or histamine does so from the first and second divisions, and Ba does so from all of the three divisions. Based on the influence of high K-depolarizing bath solution on the relaxations by isoproterenol (Iso) and papaverine (Pap) and the effects of Iso and Pap on the shapes of contractions by K, ACh, Ba and exogenous Ca, the following assumptions were made: antispasmodic action of Iso is produced by inhibition of cell membrane (inhibition of release and influx of Ca), whereas that by Pap is due to this inhibition followed by inhibition of the muscle contractile system with the increase of concentrations. The effects of Iso and Pap on the concentration-action curves of the contractions by K, ACh, Ba and exogenous Ca(Table II) suggest that the parallel shift to the right of the curves of K, ACh and Ba is due to the functional antagonism between the antispasmodics and the mobilization of Ca produced by the contracting agents.

Acetylcholine↗
PubMed1976

[Action mechanism of dibenamine on the tonus and inhibition of drug-induced contraction of the isolated guinea pig ileum, with special reference to its relationship to Ca].

Dibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction(PC) and tonic contraction(TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine-induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentration-action curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site.

Acetylcholine↗
PubMed1978

Properties and action mechanism of the toxic lectin modeccin: interaction with cell lines resistant to modeccin, abrin, and ricin.

The toxic lectin modeccin, which inhibits protein synthesis in eukaryotic cells, is cleaved upon treatment with 2-mercaptoethanol into two peptide chains which move in polyacrylamide gels at rates corresponding to molecular weights 28,000 and 38,000. After reduction, the toxin loses its effect on cells, while its ability to inhibit cell-free protein synthesis increases. Like abrin and ricin it inhibits protein synthesis by inactivating the 60S ribosomal subunits. Modeccin binds to surface receptors containing terminal galactose residues. Competition experiments with various glycoproteins indicate that the modeccin receptors are different from the abrin receptors. In addition, they were present on HeLa cells in much smaller numbers. Moreover, mutant lines resistant to abrin and ricin were not resistant to modeccin and vice-versa. The toxin resistance of various mutant cell lines could not be accounted for by a reduced number of binding sites on cells. The data are consistent with the view that the cells possess different populations of binding sites with differences in ability to facilitate the uptake of the toxins and that in the resistant lines the most active receptors have been reduced or eliminated.

Carbohydrate Metabolism↗
PubMed2026

Transcriptomic and metabolomic analyses revealed the action mechanism of nesfatin-1 gene on glucolipid metabolism during early development stage of largemouth bass.

Nesfatin-1 has biological roles including the suppression of food intake and the regulation of glucose and lipid metabolism. However, the information available regarding nesfatin-1 in the glycolipid metabolism in the early development stage of fish is still limited. In order to investigate the role of the nesfatin-1 gene in the early development stage of the largemouth bass (Micropterus salmoides), the nesfatin-1 gene was knocked down using siRNA interference technology. Then, we evaluated its mRNA expression levels, transcriptomes and metabolomes. The mRNA expression levels of nesfatin-1 gene were appreciably decreased at 48 h, 72 h and 96 h after injection of nesfatin-1 siRNA in the early development stage. The omics results revealed that knockdown of the nesfatin-1 gene induced 1833 differentially expressed genes (DEGs) and 2370 differentially expressed metabolites (DEMs). Bioinformatic analysis enriched the most affected molecular pathways (sphingolipid metabolism, fatty acid elongation, amino sugar and nucleotide sugar metabolism and biosynthesis of unsaturated fatty acids) and metabolic pathways (biosynthesis of unsaturated fatty acids, sphingolipid metabolism and amino sugar and nucleotide sugar metabolism) in early development stage of largemouth bass. In amino sugar and nucleotide sugar metabolism, increased expression levels of genes such as chic, chs1, and gck genes, alongside decreased expression levels of the chia.1 gene, resulted in significantly elevated concentrations of N-Acetyl-D-glucosamine, β-d-fructose 6-phosphate, β-d-Fructose, D-mannose 6-phosphate, d-glucose, d-glucose 1-phosphate, UDP-glucose, and UDP-glucuronate, whilst the concentration of UDP-N-acetyl-α-D-glucosamine was markedly reduced. Therefore, the nesfatin-1 gene may influence the early development stage of largemouth bass by affecting signaling pathways associated with glycolipid metabolism. Our findings further expand the understanding of molecular mechanisms of the nesfatin-1 gene, and provide further theoretical support for the initial breeding and feed adaptation of largemouth bass.

Animals↗
PubMed1978

Mechanism of action and mechanism of resistance to antineoplastic agents that bind to DNA.

The interaction with DNA of acridines, actinomycins, anthracylines, and bleomycin causes the inactivation of the DNA template in transcription and replication. The lethal effect is probably related to an irreversible damage to the structure of DNA. The acquisition of resistance is a multistep process in which changes in the uptake of the drug, which are related to basic processes such as ion transport, energy production, and regulation of macromolecular synthesis, have crucial importance.

Antibiotics, Antineoplastic↗
PubMed1979

[Thyrotropin-releasing hormone (TRH): action mechanism of an enhanced dopamine release from rat striatal slices (author's transl)].

The enhancing effect of TRH on dopamine(DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10(-5)--10(-3) M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10(-6)--10(-4)M) exhibited a considerable inhibitory effect. TRH (10(-7)--10(--3)M) alone did not increase the DA release into the incubation medium, but it clearly enhanced the DA release in the concomitant presence of desipramine (5 x 10(-5)M). In the superfusion study, TRH (10(-5)--10(-3)M), methamphetamine (10(-6)--10(-4)M) and KCl (2.5--5.0 x 10(-2)M) enhanced the DA release into the perfusion fluid. The DA releasing effect of TRH was completely blocked by cholinergic blockers (scopolamine, hexamethonium and hemicholinium), Ca2+ chelator(EGTA), Ca2+ antagonist(CoCl2) and Ca2+ influx blocker(D-600) or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release, however, was not modified by the above treatments except for a partial decline produced by EGTA coupled with the removal of Ca2+. TRH(10(-4)M) also facilitated the uptake of norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-(6)--10(-4)M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10(-5)--10(-4)M) and methamphetamine (10(-7)--10(-4)M) enhanced the NE release into the perfusion fluid. Therefore, it can be concluded that TRH facilitated the DA release from rat striatal slices by mediating through a cholinergic mechanism and enhancing the influx of Ca2+.

Amino Acids↗