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Biomedical subjects

J Malyszko

Publications and source records attributed to J Malyszko.

At least 37 records · Page 2Linked to original sources
PubMed1998

Vascular and cardiac effects of DV-7028, a selective, 5-HT2-receptor antagonist in rats.

The effect of 5HT2A-receptor antagonist DV-7028 (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6,7,8,9-tetrahydro - 2H-pyrido[1,2,-a]-1,3,5-triazine-2,4(3H)-dione maleate on the rat cardiovascular system was evaluated. DV-7028 (0.1 and 1.0 mg/kg), given intravenously, caused a significant, dose-dependent decrease in mean arterial blood pressure in anesthetized normotensive rats. In vagotomized rats, administration of DV-7028 resulted in a reduction of mean blood pressure, but this effect was less prominent than that seen in nonvagotomized rats. Intravenous administration of DV-7028 induced bradycardia, which was almost completely abolished by vagotomy. In pithed rats, bradycardia and hypotension were not demonstrated after DV-7028 administration. In pithed rats, serotonin administered intravenously caused a dose-dependent increase in blood pressure. In this experimental model, DV-7028 inhibited the pressor effects of serotonin at doses of 0.01 and 0.1 mg/kg, which caused neither hypotension nor bradycardia in anesthetized rats. DV-7028 strongly inhibited the pressor effects of serotonin in the isolated perfused hindlegs of the rat (IC50 = 0.032 +/- 0.004 microM) and caused a concentration-dependent, almost parallel shift to the right of the concentration-response curve to serotonin for its pressor effect in the rat perfused tail artery (pA2 value for DV-7028 was 7.92, a slope 0.94). These data demonstrate that DV-7028 exhibits 5-HT2A-receptor antagonistic property in the rat cardiovascular system. Besides this peripheral action, DV-7028, when applied in high doses, exerts hypotension and bradycardia via an unknown site and mechanism.

Animals↗
PubMed1996

The coagulo-lytic system and endothelial function in cyclosporine-treated kidney allograft recipients.

Since thromboembolic complications in transplanted patients are generally attributed to combined abnormalities in platelets and coagulo-lytic system, some hemostatic parameters tPA (tissue plasmogin activator):Ag and activity, its inhibitor-PAIAg and activity, tPA/PAI, thrombin-antithrombin (TAT) and plasmin-antiplasmin complexes (PAP), urokinase-uPA, euglobulin clot lysis time-ECLT, fibrinogen, plasminogen, protein C activity, D-dimer, prothrombin fragments1+2 (F1+2), fibrin monomers, fibronectin, lipoprotein-a, and von Willebrand factor(vWF), were evaluated using commercially available kits. The studies were performed on kidney transplant recipients treated with CsA, azathioprine and prednisone (n=21), and healthy volunteers (n=21). ECLT was significantly prolonged in kidney transplant recipients together with a rise in F1+2,lipoprotein-a, fibrinogen, fibronectin, and vWF when compared with controls. The TPA level was lower, whereas the PAI level was higher in kidney transplant recipients when compared with controls. In conclusion, CsA-treated kidney transplant recipients show evidence of pronounced impairment in fibrinolysis and endothelial damage in comparison with healthy volunteers.

Adult↗
PubMed1996

Hemostasis, platelet function and serotonin in acute and chronic renal failure.

A pathogenetic role for fibrin deposition and platelet activation in the kidney is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus, some fibrinolytic parameters and platelet function have been studied in 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF). Since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Increased levels of lipoprotein (a), von Willebrand factor (vWF) and fibronectin were found in ARF relative to controls. Protein C activity was significantly lower in patients with ARF. Euglobulin clot lysis time was prolonged in ARF and CRF, reflecting a decreased overall fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP) complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were found, whereas concentration of fibronectin was lowered when compared to controls. In both groups of renal failure patients increased levels of fibrin monomers and d-dimer were found relative to healthy volunteers. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in patients with ARF and CRF relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure.

Acute Kidney Injury↗
PubMed1996

Peripheral serotonergic system in uremia.

Several data suggest that platelet-derived serotonin (5-HT), previously classified as a trivial modulator of blood-borne cardiovascular disease (1), may play a decisive role in various pathological processes, resulting from abnormal platelet-vessel wall interactions (2). Following platelet activation upon a contact with a damaged vessel wall, 5-HT, released from platelets upon the activation of 5-HT2 receptors, may amplify the action of other agents on vascular smooth muscle cells and platelets (3,4). Platelets play a unique role in 5-HT metabolism: they take it up, store in their dense granules and release upon stimulation. Platelet dysfunction, alteration in platelet count, their consumption and turnover are common in renal diseases (5). Storage pool deficiency regarding 5-HT and ADP was reported in renal failure (6). Previously we reported that 5HT2 receptor blockers may serve as potent antiplatelet drugs in uremic patients, which are prone to thrombotic complications (7,8). Up to date there have been a few reports dealing predominantly with 5-HT levels in renal patients. Thus, we focused on peripheral serotonergic mechanisms including 5-HT uptake and release and kinetics of its uptake in uremic patients.

Adult↗
PubMed1996

Erythropoietin and uremic platelet aggregation in vivo and in vitro.

Erythropoietin treatment is known to correct anemia and to improve hemostasis. Since platelets may contribute to thromboembolic complications, we assessed platelet aggregation in whole blood and platelet-rich plasma from chronically hemodialyzed patients treated with erythropoietin and evaluated in vitro effects of this drug on aggregatory responses of uremic and normal platelets. Recombinant human erythropoietin was given to uremic patients at a dose of 2,000 IU subcutaneously three times a week. Platelet aggregation in whole blood and platelet-rich plasma was induced by collagen, ADP, arachidonic acid, and ristocetin. In uremic patients, erythropoietin therapy resulted in an enhancement of platelet sensitivity to various agonists, particularly in platelet-rich plasma, reaching values comparable to those of healthy volunteers. In vitro studies we were unable to show any direct effect of erythropoietin, used at concentrations that occurred post intravenous administration, on platelet aggregation both in whole blood and in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1996

Changes in serotonergic measures in whole blood and various brain regions of rats administered with the 5-HT1A agonist tandospirone and/or exposed to electric foot-shock.

We studied the effects of foot-shock on tryptophan, serotonin [5-hydroxytryptamine (5-HT)], and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in whole blood and various brain regions of rats pretreated with tandospirone, a novel 5-HT1A receptor agonist. The administration of tandospirone did not result in changes in serotonergic measures, but stress or stress plus the administration of tandospirone resulted in an increase in blood levels of tryptophan, 5-HT, and 5-HIAA. In animals given stress, tryptophan levels rose in every part of the brain, and in animals given stress and tandospirone, tryptophan levels increased in all the brain regions except the medulla. The administration of tandospirone alone did not give rise to changes in tryptophan levels in any part of the brain. The administration of tandospirone resulted in an increase in 5-HT levles in all brain regions except the cerebellum. In rats given stress and tandospirone, 5-HT levels increased in the hypothalamus, midbrain, and cortex relative to controls. In every part of the brain, the administration of tandospirone resulted in a decrease in the turnover rate of serotonin (5-HIAA/5-HT). In the presence of stress, the administration of tandospirone resulted in a decrease in the turnover rate of serotonin in hypothalamus, hippocampus, and midbrain compared with controls and stress alone. These results suggest that tandospirone may stimulate presynaptic receptors in the midbrain and inhibit the activity of monoamine oxidase, resulting in an increase in 5-HT levels in the serotonergic nerve terminals.

Animals↗
PubMed1996

Renal blood flow and serotonin metabolism in tacrolimus treated rats.

BACKGROUND: Serotonin (5-HT) is a potent vasoconstrictor and activator of platelets, endothelial cells and vascular smooth muscle cells. The result of activation by serotonin is platelet aggregation and vasoconstriction. The aim of the present study was to evaluate the role of serotonin metabolism as a mediator of tacrolimus (FK 506) nephrotoxicity. METHODS: The whole blood and plasma levels of serotonin and its major metabolite (5-hydroxyindoleacetic acid: 5-HIAA) as well as renal cortical blood flow were investigated in rats administered FK 506 at doses of 4, 6 or 8 mg/kg b.w. for 14 consecutive days. RESULTS: Renal cortical blood flow declined in a dose-dependent manner in the rats given FK 506, whereas serum creatinine remained unaltered following FK 506 administration. Although there was no significant change in serotonin, the whole blood and plasma 5-HIAA levels increased significantly following FK 506 administration. CONCLUSION: FK 506 may cause acute nephrotoxicity by decreasing renal blood flow and the increase of 5-HIAA suggests some role of serotonin metabolism in the development of FK 506 nephrotoxicity.

Animals↗