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Biomedical subjects

W Buczko

Publications and source records attributed to W Buczko.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Altered circadian rhythm of platelet aggregation in patients on longterm hemodialysis].

Chronic uremia is associated with a bleeding tendency, and paradoxically with propensity for thrombotic complications. Several physiological systems are subject to circadian rhythm, including among others hemostasis, platelet aggregability and fibrinolysis. Alterations in these rhythms were suggested to be involved in the pathogenesis of sudden cardiac and cardiovascular complications of diabetes mellitus. As cardiovascular events are the most frequent cause of death in dialyzed patients, we studied circadian rhythm of platelet function in chronically hemodialyzed patients in relation to blood and plasma serotonin. We investigated 16 patients (mean age 49.7 +/- 12.2 years, 10 females, 6 males) who had been maintained on chronic hemodialysis. Control group consisted of 8 age matched healthy volunteers. Blood was collected after 15 min. rest at 8:00, 11:00, 17:30, and 23:00 from antecubital veins. Platelet aggregation was measured according to the method of Born. Following concentrations of aggregating agents were used: ADP 5 microM; collagen, 2 micrograms/ml; arachidonic acid 0.75 microM, serotonin 1 microM; and ristocetin 1.5 micrograms/ml. Serotonin was measured in whole blood and plasma by HPLC method. In PRP from healthy subjects aggregatory responses to ADP and arachidonic acid were significantly higher at 17:30 than at 8:00. In uremic patients aggregatory response to ADP and ristocetin was more intensive at 11:30 and 23:00 in comparison to 8:00. Whole blood 5-HT did not change during the day, while plasma 5-HT concentration increased significantly in uremics at 11:30 in comparison to initial value. In conclusion, our study demonstrates that in chronically dialyzed patients circadian changes in platelet aggregation are different from normal persons.

Adult↗
PubMed1996

Facilitation by substance P and inhibition by (+)-tubocurarine of the 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats.

The influence of substance P 3 (microgram/kg) and (+)-tubocurarine (850 micrograms/kg) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. The Bezold-Jarisch reflex was induced by the 5-HT3 receptor agonist phenylbiguanide (0.3, 1, 3 and 10 micrograms/kg i.v.) and by capsaicin (10 micrograms/kg i.v.). The 5-HT3 receptor antagonist ondansetron (10 micrograms/kg) abolished the phenylbiguanide- but not the capsaicin-stimulated bradycardia, indicating that phenylbiguanide and capsaicin act via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Substance P significantly potentiated the phenylbiguanide- but not the capsaicin-induced decrease in heart rate. Also, when the phenylbiguanide-induced response was amplified by substance P, it was abolished by ondansetron. (+)-Tubocurarine inhibited the phenylbiguanide-induced bradycardia, but did not affect the capsaicin-stimulated decrease in heart rate. Our results demonstrate that substance P potentiates but (+)-tubocurarine inhibits the 5-HT3 receptor-mediated Bezold-Jarisch reflex. Both effects are probably due to direct influences of the drugs on the 5-HT3 receptors on sensory vagal nerves in the heart.

Animals↗
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

The effect of tacrolimus (FK506) and cyclosporin A (CyA) on peripheral serotonergic mechanisms in uremic rats.

The aim of this study was to investigate the mechanism of hypertension and thromboembolic events induced by cyclosporin (CyA) and tacrolimus (FK506) in respect to their action on the serotonergic blood system. The study was carried out on healthy rats and those with experimental chronic renal failure. CyA injected into healthy and uremic rats caused an increase in serotonin (5-HT) concentration levels in whole blood and platelets. Concomitantly a rise in systolic blood pressure was observed. Platelet aggregation values were significantly higher in uremic rats given CyA. FK506 had no influence on 5-HT blood content, blood pressure or platelet aggregation values. It is concluded that 5-HT may play a role in the development of hypertension and thrombotic events caused by CyA. Furthermore, lower incidence of these complications during FK506 treatment could be the result of this drug's limited effect on the serotonergic blood system.

Animals↗
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

Morphological and hemostatic changes in rats with abdominal arterial prosthesis.

We evaluated the changes over time in hemostatic factors during ongoing arterial thrombosis in rats, as induced by a loop-shaped aortic prosthesis. Moreover, we investigated this condition by inspecting in parallel local thrombus growth, systemic vascular prostacyclin and t-PA production. One minute after loop insertion, activated platelets spread on the internal surface of the prosthesis and 24 hrs later numerous platelet aggregates supported by a fibrin network could be observed. However, no evidence for platelet activation could be concomitantly found in peripheral blood. A sustained increased in PGI2 formation was detected together with a progressive increase in plasma fibrinolytic activity during thrombus growth. The levels of fibrinogen as well as antithrombin III (ATIII) and heparin cofactor II (HCII) activities were steadily increased in loop-bearing animals. In conclusion, the dynamic phases of thrombus formation, in an aortic prosthesis, produce changes in vascular function and in hemostatic factors at the level of systemic blood.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Antithrombotic activity of dermatan sulphates, heparins and their combination in an animal model of arterial thrombosis.

Dermatan sulphates have been shown to inhibit thrombus formation and thrombus growth in different experimental model of venous thrombosis. At variance with heparins, they show a remarkably low haemorrhagic potential. On the other hand, very few data are available on the effect of dermatan sulphates on arterial thrombus formation. We evaluated the effects of a low molecular weight (LMW)-dermatan sulphate, a high molecular weight (HMW)-dermatan sulphate and sulodexide (a mixture of fast-moving heparin fraction and dermatan sulphate) in comparison with LMW- and HMW-heparin, in a model of arterial thrombosis in rats. The insertion of an artificial prosthesis into the abdominal aorta of the animals induced the formation of an occluding thrombus within 2-5 days. The time in which 50% of the loops became occluded (OT50) was also calculated and used to compare the efficacy of the different drug treatments. This was 2.84 days for control animals and 4.25 and 5.80 days for HMW- and LMW-dermatan sulphate, respectively. Neither drug changed the "template" bleeding time, even at higher doses. In contrast, HMW-heparin at doses (8 mg/kg, sc, twice a day) inducing an antithrombotic activity comparable to that of dermatan sulphates, dramatically prolonged the bleeding time. LMW-heparin at the same doses was ineffective. Sulodexide (10 mg/Kg, sc, twice a day) prolonged the occlusion time to the same extent as HMW-heparin (OT50 5.10 vs. 4.14 days), with less an effect on the bleeding time (144 +/- 6 s vs. > 300 s, respectively). Histological examination confirms that the prolongation of occlusion time induced by the drugs is really related to thrombus formation inhibition at the site of arterial wall injury. Acetyl salicylic acid (ASA) (100 mg/kg/day in drinking water as lysine acetylsalicylate) did not modify the effect of Desmin 370 and Sulodexide on both occlusion and bleeding time. However, while it did not increase the antithrombotic activity of HMW-heparin, it significantly prolonged its haemorrhagic effect. In conclusion, dermatan sulphates are effective inhibitors of arterial thrombosis in rats, without inducing bleeding complications.

Animals↗
PubMed1996

[Serotonin--its significance in physiology and pathology of the eye].

In this review the basic data concerning metabolism of serotonin, its receptors and effects are presented. The authors have underlined the significance of serotonin in the physiology and pathology of the eye with special regards to the effectiveness of serotonergic system affecting drugs in the disturbances of vision process.

Eye Diseases↗
PubMed1996

Losartan does not influence the blood platelet aggregation in normotensive rats.

Platelet aggregation was studied in PRP upon stimulation with ADP and collagen in normotensive rats treated with losartan (10 mg/kg). The acute and subchronic (5 days) losartan administration did not change the aggregating response of rat platelets. Similarly, in vitro study aggregation of platelets remained unaltered following incubation with losartan and its active metabolite EXP3174. In this study we presented the lack of influence of losartan and its main metabolite on rat platelet aggregation in normotensive rats.

Adenosine Diphosphate↗
PubMed1996

Peripheral serotonergic mechanisms in the cardiovascular system of epidermoid lung cancer patients.

The aim of the work was to evaluate the peripheral serotonergic mechanisms in patients with epidermoid lung cancer. The study was performed on lung cancer patients diagnosed on the basis of histopathological findings. The subjects were treated by radiotherapy. Whole blood 5HT in patients with epidermoid lung cancer was increased, whereas uptake of 3H-5HT by platelets was diminished in these patients when compared to control group. Radiotherapy caused a lowering of serotonin in blood to levels observed in healthy subjects. Platelet aggregation induced by ADP was diminished in patients with epidermoid lung cancer, however radiotherapy resulted in an increased sensitivity of platelets to ADP (an enhanced aggregation). On the other hand, serotonergic amplification of ADP-induced platelet aggregation was higher in these patients. This effect was inhibited by radiotherapy. On the basis of our results, we may suggest that peripheral serotonergic mechanisms play an important role in pathogenesis and course of epidermoid lung cancer in humans.

Aged↗
PubMed1996

Influence of MCI-9042, a novel 5-HT2 receptor blocker on blood vessels of the rat.

We demonstrated that MCI-9042 potently inhibited the vasoconstrictory effects of serotonin in the isolated perfused hindlegs of the rat. Concentrations of MCI-9042 in the range of 0.01-1 mumol/l caused a dose-dependent inhibition of the vasoconstrictory effect of serotonin (1-30 micrograms/0.1 ml). The maximal inhibitory effect of MCI-9042 was about 97% (1 mumol/l). MCI-9042 caused a concentration-dependent shift to the right of concentration-response curve to serotonin in the rat tail artery. The present data demonstrate MCI-9042 as a potent 5-HT2 receptor antagonist.

Animals↗
PubMed1996

Effect of DV-7028, a novel serotonin 5-HT2 receptor antagonist on the cardiovascular system in rats.

The response of the cardiovascular system to DV-7028 demonstrated the complex action of this substance. In anaesthetized rats DV-7028 decreased the blood pressure and heart rate. These effects did not occur in pithed rats. The hypotensive action and bradycardia was partially reduced in vagotomized animals. DV-7028 potently inhibited the vasoconstrictory effects of serotonin in isolated perfused hindlegs of rat and caused a concentration-dependent shift to the right of response curve to serotonin in the rat tail artery. The present data demonstrate that DV-7028 is a potent 5-HT2 receptor antagonist. Besides its peripheral action, DV-7028 exerts central effects which cause hypotension and bradycardia.

Animals↗
PubMed1996

Influence of captopril on some haemostatic parameters in rats with ongoing process of venous thrombosis.

Recent laboratory findings strongly suggest that renin-angiotensin system plays an important role in regulation of haemostasis and fibrinolysis. In our previous study we showed that captopril exerts antithrombotic effect in venous thrombosis in rats. In this study we demonstrated that this effect is not a result of changes in platelet count, fibrinogen level alterations in blood coagulation pathways and fibrinolytic activity of the plasma. Further investigations are necessary to elucidate the mechanism of antithrombotic action of captopril.

Animals↗
PubMed1996

Effect of endothelin-1 on some hemostatic parameters in normotensive rats.

Some parameters of hemostasis and fibrinolysis were investigated in rats administered with endothelin-1 (ET-1). ET-1 (0.5, 1.0, 5.0 nmol/kg) dose-dependently shortened the bleeding time (BT). Concomitantly significant shortening of the clotting time (CT) was observed. ET-1 produced prolongation of the activated partial thromboplastin time (APTT), whereas prothrombin time (PT) remained unchanged. ET-1 did not influence in vitro platelet aggregation induced by ADP and collagen. The euglobulin clot lysis time (ECLT) was significantly shortened after ET-1 administration. Our results suggest that ET-1 modulates the process of hemostasis and fibrinolysis in the rat.

Animals↗
PubMed1995

Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors.

The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 receptor antagonist ondansetron 10 micrograms/kg i.v. abolished the 5-HT- but not the capsaicin-stimulated bradycardia, indicating that 5-HT and capsaicin acted via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Ethanol at 1.0 and 2.0 g/kg i.p. inhibited in a dose-dependent manner (by 20-45%) the 5-HT- but not the capsaicin-stimulated decrease in heart rate. Our results demonstrate that the inhibitory effect of ethanol on the 5-HT3 receptor-mediated Bezold-Jarisch reflex may be related to the direct effect of ethanol on 5-HT3 receptors on sensory vagal nerves in the heart.

Animals↗
PubMed1995

Serotonin is involved in the pathogenesis of hypertension developing during erythropoietin treatment in uremic rats.

The aim of this study was to investigate the mechanism of erythropoietin-induced hypertension in respect to its action on blood serotonergic system. The experiment was carried out on healthy rats and animals with experimental chronic renal failure. Erythropoietin (rHuEPO) injected into the healthy and uremic rats caused an increase in systolic blood pressure. This effect was completely abolished by ketanserin, an antagonist of 5-HT2 receptors. Concomitantly a rise in blood and platelet serotonin concentration was observed. It is concluded that serotonin may play a role in the development of hypertension caused by rHuEPO. Moreover, ketanserin may serve as a drug for pharmacological protection of rHuEPO-induced rise of blood pressure in uremia.

Anemia↗