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Biomedical subjects

J Malyszko

Publications and source records attributed to J Malyszko.

At least 55 records · Page 3Linked to original sources
PubMed1995

A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy.

Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, beta-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.

Adenosine Diphosphate↗
PubMed1995

In vitro effect of endothelin-1 on collagen, and ADP-induced aggregation in human whole blood and platelet rich plasma.

The effect of ET-1 on ADP- and collagen-induced platelet aggregation in whole blood and platelet rich plasma (PRP) was studied in 39 healthy volunteers. Although ET-1 itself did not cause platelet aggregation, a marked enhancement of ADP-induced aggregation after the preincubation with ET-1 for 5 min was observed in whole blood, but not in PRP. This ET-1 concentration and preincubation time-dependent phenomenon could be demonstrated only at threshold concentrations (5 and 7.5 microM) of ADP and is probably due to an interaction of ET-1 with cells which are involved in the whole blood aggregation, such as polymorphonuclear neutrophils. In whole blood and PRP an inhibition of collagen-induced aggregation after the preincubation with ET-1 was detected. In contrast to ADP, a direct influence of ET-1 on platelet activation after the addition of collagen is therefore more likely. These results suggest that human platelets may possess ET-1 receptor(s) and that ET-1 may also interact with other blood cells.

Adenosine Diphosphate↗
PubMed1995

Gastric and pancreatic functions in haemodialyzed patients.

The aim of this work was to assess gastric acid secretion in relation to morphological and histological changes in the gastric mucosa as well as prevalence of Helicobacter pylori in chronically haemodialyzed uraemic patients. Exocrine pancreatic functions after secretin-cerulein test were also studied. In haemodialyzed patients low basal gastric acid output was found, whereas peak output after pentagastrin stimulation did not differ significantly when compared to controls. Endoscopy of gastric and duodenal mucosa revealed inflammatory changes in the majority of patients, described histologically as chronic gastritis with duodenitis. Helicobacter pylori antigen was detected in the serum of 45% of uraemic patients. Serum amylase activity was elevated in haemodialyzed patients relative to controls. Although clinically asymptomatic, haemodialyzed patients exhibited various degrees of gastrointestinal mucosal abnormalities and impairment in exocrine pancreatic functions, mainly low stimulated bicarbonate and protein output as well as low electrolyte concentrations in duodenal content.

Adult↗
PubMed1995

Amino acids, serotonin, and 5-hydroxyindoleacetic acid following foot shock in rats.

Concentrations of tryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in brain and plasma, as well as plasma amino acid composition, were measured after 1-h foot shock. Stress induced a rise in both plasma and brain 5-HIAA, whereas 5-HT concentration was found to be increased only in plasma. A prominent rise in brain tryptophan was observed, whereas in plasma, foot shock caused a significant increase only in tryptophan level. Concentrations of other amino acids were found to be either decreased or unchanged. Ratio of tryptophan to the other long-chain neutral amino acids increased significantly following foot shock. It is possible that stress-related changes in 5-HT turnover are due to increased plasma tryptophan, in turn causing a rise in brain tryprophan, necessary to cope with enhanced 5-HT metabolism, reflected as a rise in 5-HIAA levels.

Amino Acids↗
PubMed1994

Serotonergic measures in cyclosporine A treated rats.

Whole blood and plasma serotonin (5-HT), its major metabolite--5-hydroxyindoleacetic acid (5-HIAA), renal cortical blood flow, serum creatinine and whole blood cyclosporine A (CyA) levels were investigated in rats administered with CyA at a dose of 5 mg/kg b.w. or 10 mg/kg b.w. for 14 consecutive days. Serum creatinine remained unaltered during CyA treatment and no apparent changes in excised kidneys were found. Dose-dependent increases in whole blood and plasma 5-HT as well as whole blood 5-HIAA levels were observed. Renal cortical blood flow declined significantly and correlated inversely with whole blood 5-HT and 5-HIAA as well as with plasma 5-HT. Whole blood 5-HT was positively related to whole blood CyA levels. Taking all these data into account and considering the fact that 5-HT is a potent vasoconstrictor, a possible role of this amine in the pathogenesis of renal ischemia during CyA administration is suggested.

Animals↗
PubMed1994

Fibrinolysis and serotonin under cyclosporine A treatment in renal transplant recipients.

Cyclosporine A (CyA), a potent immunosuppressive drug, has been used in renal transplant recipients with increasing frequency since 1982. Despite its efficacy, CyA therapy has been associated with an increased incidence of thromboembolic complications. This has been attributed to increased thromboxane production, reduced prostacyclin synthesis and increased platelet aggregability. The coagulation system is also altered in CyA-treated patients and some of these changes would favor thrombosis. Increased fibrinogen and FVII:C levels have also been associated with an enhanced risk of thrombosis. In contrast, CyA therapy was reported to increase the levels of antithrombin III and protein C, two proteins known to protect against venous thromboembolism. However, the possible effect of CyA on the fibrinolytic system has not been thoroughly investigated and rather confusing data have been reported concerning both enhancement and suppression of fibrinolysis. Serotonin (5-hydroxytryptamine, 5-HT) may play a role in hemostasis and platelet/vessel wall interactions. It may facilitate platelet thrombus formation by potentiating the aggregatory response to other agents such as ADP, collagen or epinephrine and by causing vasoconstriction. Taking all these data into consideration we have measured some fibrinolytic parameters, whole blood and plasma serotonin concentration in cyclosporine A- and non-cyclosporine A-treated kidney transplant recipients.

Creatinine↗
PubMed1994

Correlations between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates.

We have studied the relationships between whole blood and plasma serotonin (5-hydroxytryptamine, 5-HT), its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) and serum lipids, platelet aggregation in the whole blood and in the platelet-rich plasma (PRP), and some fibrinolytic parameters in monkeys. Plasma 5-HT was found to be positively related to 5-HT- and ADP-induced platelet aggregation, tissue plasminogen activator (tPA) activity, serum cholesterol and LDL-cholesterol, whereas 5-HT in cerebrospinal fluid correlated inversely with serum cholesterol. Plasminogen activator inhibitor (PAI) activity was positively related to LDL. Euglobulin clot lysis time was related to both tPA and PAI activities. The significance of these findings and the possible role of 5-HT in atherogenesis and hemostasis are discussed.

Animals↗
PubMed1994

Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes.

The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n = 10) and diabetic patients (type II diabetes mellitus n = 12). Platelet aggregation in the whole blood induced by collagen (2 micrograms/ml), ADP (10 microM), arachidonic acid (0.5 mM) and epinephrine (10 microM), and in PRP induced by collagen (2 micrograms/ml), ADP (5 microM), arachidonic acid (250 microM), epinephrine (10 microM) and serotonin-5-HT (1 microM) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5-HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT2 receptor blockers may be of value in DM patients.

Adenosine Diphosphate↗
PubMed1994

Electric-foot-shock induced the suppression of fibrinolytic activity in rats.

Electric-foot-shock was given to rats to initiate constant mental stress and its effect on fibrinolytic activity was analyzed. After the termination of electric-foot-shock which was given for an hour, euglobulin clot lysis time in the stressed group significantly prolonged than those in the control group. tissue plasminogen activator activity was also significantly lower in the stressed group. These effects lasted at least for an hour and returned to the control values 24 hours after the stress. Whole blood serotonin levels, which mainly show serotonin contents in platelets, were higher in the stressed group. A negative correlation between whole blood serotonin and tPA activity in the stressed group was obtained. These results suggest that prolonged mental stress impairs fibrinolysis by decreasing tPA activity with a concomitant increase of serotonin contents in platelets.

Animals↗
PubMed1994

Relationships between serum lipids, serotonin, platelet aggregation and some fibrinolytic parameters in humans.

We have studied relationships between serum lipids, plasma serotonin (5-hydroxytryptamine, 5-HT), platelet aggregation in the platelet-rich plasma (PRP), and some fibrinolytic parameters in healthy volunteers. LDL was positively related to 5-HT-induced platelet aggregation. Higher serum HDL levels were related to higher fibrinolytic activity expressed by shorter euglobulin clot lysis time (ECLT). No correlation existed between serum lipids and plasma 5-HT. Plasma 5-HT was found to be related to tissue plasminogen activator (t-PA), suggesting some link between plasma serotonin and the release of t-PA from endothelial cells. There were mutual relations among fibrinolytic parameters such as tissue plasminogen activator (t-PA) antigens, total plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI-1 complex, free PAI-1, and ECLT. In conclusion higher LDL may be more thrombogenic due to enhanced 5-HT induced platelet aggregation whereas high HDL may be more protective against thrombosis due to enhancement of fibrinolysis.

Adult↗
PubMed1994

Stress-dependent changes in fibrinolysis, serotonin and platelet aggregation in rats.

The effects of different kinds of acute stress on collagen-induced whole blood platelet aggregation and fibrinolysis in relation to blood serotonergic measures were studied. In rats water-immersion restraint stress resulted in a shortening of euglobulin clot lysis time (ECLT), an increase in tissue plasminogen activator (tPA) activity with a concurrent fall in its inhibitor activity. Footshock caused rather a suppression in fibrinolysis with a prolongation of ECLT and a decline in tPA activity as well as a reduction in whole blood platelet aggregation induced by collagen. Serotonin (5-HT) level, a marker of a severity of stress, increased after footshock application with a concomitant rise in its major metabolite-5-hydroxyindoleacetic acid (5-HIAA). This indicates an enhanced 5-HT metabolism. Following water-immersion restraint stress 5-HT and 5-HIAA levels did not differ from controls. In both groups of stressed animals an inverse correlation between tPA activity and blood serotonin was observed. Our data indicate that these types of stress may influence either fibrinolysis or peripheral serotonergic mechanism in different ways. Acute and severe stress such as footshock by causing an impairment in fibrinolysis and a rise in 5-HT may contribute to the pathogenesis of thrombosis and henceforth to the development of atherosclerosis.

Acute Disease↗
PubMed1994

Stress and/or tranylcypromine treatment affects serotonergic measures in blood and brain in rats.

Since stress can alter serotonin (5-hydroxytryptamine, 5-HT) turnover in the brain and the periphery, the effects of different types of acute stress on serotonin and related substances in the whole blood and various brain areas in rats pretreated with tranylcypromine (TCP) were studied. TCP administered alone caused a rise in 5-HT, a fall in its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) in the whole blood and in every part of the brain analyzed relative to controls. In rats given TCP and subjected to footshock or water-immersion restraint stress similar changes, but to a different extent, were observed. 5-HT level remained essentially constant except in the blood and the limbic system, whereas 5-HIAA level was found to be increased in the blood and the brain, mainly in the limbic system and the brainstem following footshock. Water-immersion restraint stress caused an increase in 5-HT only in the limbic system without any changes in 5-HT and 5-HIAA in the blood. Relative to controls, an increase in total tryptophan concentration in the whole blood and in every part of the brain was found only after footshock application with or without pretreatment with TCP. In conclusion, responses to stress in rats may depend upon the type of stimulus applied as well as of a concurrent administration of TCP. Some regional differences may account for an altered in vivo efficacy of this drug.

Animals↗
PubMed1994

Serotonergic systems in brain and blood under stress and tranylcypromine treatment in rats.

The effects of stress on serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), and/or tryptophan in whole blood and various brain areas of rats pretreated with tranylcypromine were studied. In the whole blood, tranylcypromine given alone caused a rise in levels of 5-HT and a fall in levels of its metabolite (5-HIAA) and the ratio of 5-HIAA:5-HT, whereas in stressed rats pretreated with tranylcypromine only the last two findings were observed. We found that animals given tranylcypromine and subjected to water-immersion restraint stress exhibited the greatest rise in 5-HT levels in midbrain, hippocampus, and hypothalamus, together with the lowest 5-HIAA:5-HT ratio relative to controls, whereas in cortex, cerebellum, medulla, and striatum the highest levels of 5-HT together with the lowest ratio of 5-HIAA:5-HT were observed after the administration of tranylcypromine alone. 5-HT levels were found to be higher in medulla and striatum in rats given tranylcypromine alone relative to stressed rats pretreated with this drug. We concluded that regional differences account for variable effects of tranylcypromine on blood and brain serotonergic systems in vivo.

Animals↗
PubMed1994

Foot shock-induced changes in blood and brain serotonin and related substances in rats.

The effects of electric foot shock on peripheral and central serotonergic systems in rats have been studied. We have focused on the time course alterations with particular attention being paid to changes in 5-HT, 5-HIAA, tryptophan concentrations and 5-HIAA/5-HT ratios in blood and various parts of the brain, observed within 1 h following stress application. Blood and brain (7 regions) samples were taken immediately after electric foot shock, 30 min, 1 and 24 h later. In the blood stress induced a rise in tryptophan level as well as rises in 5-HT, 5-HIAA levels and 5-HIAA/5-HT ratio within 1 h following stressful treatment. Tryptophan concentration was found to be increased in every part of the brain within 1 h after electric foot shock application. In striatum it remained higher even after 24 h. 5-HT level showed a significant rise only in medulla, while hypothalamus was the sole region where a fall in 5-HT was found. In other parts of the brain 5-HT level remained unaffected by stress. 5-HIAA content increased in almost every brain area studied except cerebellum and striatum. 5-HIAA/5-HT ratios shared the same pattern of changes. Briefly, foot shock altered 5-HT turnover in various brain regions, in particular within the first hour following stress application, whereas delayed response to stress was rarely observed. Increased brain tryptophan level seems to be necessary to cope with the enhanced 5-HT metabolism caused by stress, reflecting as a rise in 5-HIAA concentration and 5-HIAA/5-HT ratio.

Animals↗