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Biomedical subjects

D Pawlak

Publications and source records attributed to D Pawlak.

At least 55 records · Page 3Linked to original sources

[Fibrinolytic and peripheral serotonergic system in patients with glomerulonephritis].

Some fibrinolytic parameters, whole blood and plasma serotonin were studied in normotensive and hypertensive patients with glomerulonephritis. Diminished activity of tissue plasminogen activator (tPA) and a significant prolongation of the euglobulin clot lysis time was observed in hypertensive and normotensive patients with glomerulonephritis when compared to healthy volunteers. Antigen and activity of inhibitor of tissue plasminogen activator (PAI) was found to be higher in hypertensive patients relative to control group. Whole blood serotonin was significantly lower, whereas plasma serotonin was higher in normotensive and hypertensive patients with glomerulonephritis when compared to healthy subjects. Impairment in fibrinolysis and elevated plasma serotonin levels may contribute to the increased risk of thromboembolic complications and accelerated atherosclerosis in these patients.

Adult↗

Influence of Tołpa Peat Preparation on haemostasis in rats.

The influence of Tołpa Peat Preparation (TPP) on certain parameters of haemostasis was studied. The present results indicate that TPP (100, 200 and 300 mg/kg p.o.) had no influence on the bleeding time, clotting time, thrombin time, prothrombin time, kaolin-kephalin time, euglobulin lysis time, the concentration of fibrinogen, the platelet count and ADP-induced platelet aggregation. No changes in animals after long-term treatment with TPP (100 mg/kg for two weeks) were found either. In in vitro studies TPP given in concentrations 10(-5), 10(-4), 10(-3) and 10(-2) g/cm3 was used and certain changes of the studied parameters, probably caused by the presence of high salt content in this substance, were observed.

Amino Acids↗

Lack of effect of acetaldehyde on the cardiovascular system in rats.

The present study was designed to evaluate the kinetics of acetaldehyde (ACT) and and its action on the cardiovascular system in rats. ACT (3, 6, 12 mg/kg i.p.) causes accumulation of this metabolite in the blood, at a concentration corresponding to that obtained from ethanol metabolism after its administration in doses of 1, 2, 4 g/kg p.o., respectively. After intraperitoneal injection of ACT there were no significant changes in blood pressure and heart rate in comparison to the control group. It appears that, in rats, ACT has no influence on the function of the cardiovascular system after the ingestion of ethanol.

Acetaldehyde↗

Cardiovascular effects of acetaldehyde in pithed rats.

The influence of acetaldehyde (30 mg/kg i.v.) on blood pressure and heart rate in anesthetized and pithed rats was studied. In anesthetized rats we observed a small increase, and a subsequent considerable decrease in mean blood pressure. The latter did not occur in pithed rats. Stimulation of the circulatory system in anesthetized and in pithed rats was completely abolished by administration of phentolamine or reserpine. Both in anesthetized and in pithed rats acetaldehyde caused an increase in heart rate which was inhibited in animals treated earlier with propranolol or reserpine. Our results demonstrated that besides its peripheral action, acetaldehyde exerts central effects which cause severe hypotension.

Acetaldehyde↗

Influence of acetaldehyde on the vasopressor effect of serotonin in pithed rats.

In pithed rats, the intravenous (i.v.) administration of serotonin (3, 10, 30, 100, 300 and 1000 micrograms/kg) produced a dose-dependent increase in blood pressure. The pressor response to serotonin was reduced by acute acetaldehyde administration in a dose of 30 mg/kg i.v. and by 5-HT2 antagonist ketanserin (0.03 mg/kg i.v.). However, the lowest doses of acetaldehyde (10 and 20 mg/kg) were ineffective. In in vitro studies we also demonstrated that acetaldehyde (0.43 mM/l) and ketanserin (0.1 microM/l) inhibited the serotonin-induced vasoconstriction of isolated rat tail artery. In both experimental models the combination of acetaldehyde with ketanserin decreased the action of serotonin to the same extent as did ketanserin alone. In pithed rats pretreated with a high dose of ketanserin (3 mg/kg i.v.) serotonin produced hypotension by stimulation of 5-HT1 receptors. This effect was not enhanced by acetaldehyde (30 mg/kg) injection. Our data suggested that the action of acetaldehyde on the effects of serotonin in pithed rats was non-specific and independent of its interaction with serotonergic 5-HT1 and 5-HT2 receptors in blood vessels.

Acetaldehyde↗

Influence of DAU 6215, a novel 5-HT3 receptor antagonist, on the cardiovascular system in anaesthetized and pithed rats.

The cardiovascular effects of DAU 6215, a novel 5-HT3 receptor antagonist were studied. DAU 6215 (20 micrograms/kg) inhibited the serotonin-induced Bezold-Jarisch reflex in anaesthetized rats, but did not affect the mean blood pressure and heart rate in anaesthetized rats, in anaesthetized animals after bilateral vagotomy and in pithed rats. This substance also did not affect the serotonin-induced rise in blood pressure in pithed rats and did not influence the response of the isolated rat tail artery to 5-HT. Moreover, DAU 6215 did not change the cardiovascular effects of noradrenaline- and angiotensin-II-stimulated constriction of rat tail artery. Our data suggest that DAU 6215 is rather a selective antagonist, without an affinity to 5-HT2, alpha-adrenoceptors, beta-adrenoceptors and angiotensin II receptors.

Anesthesia↗

Influence of acute and chronic ethanol administration on the vasopressor effect of serotonin in pithed rats.

In pithed rats, the intravenous administration of serotonin (3, 10, 30, 100, 300 and 1,000 micrograms/kg) produced a dose-dependent increase in blood pressure. This action of 5-HT was not changed by chronic ethanol intoxication (6.0 g/kg/day for 2 weeks). The pressor responses to serotonin were, in a dose-dependent manner, significantly reduced by acute ethanol administration (0.5, 1.0, 2.0 and 4.0 g/kg p.o.) and by ketanserin injection (0.03 mg/kg i.v.). However, ethanol (2.0 g/kg) did not amplify the dilator effect of serotonin in pithed rats pretreated with ketanserin (3.0 mg/kg i.v.). We also demonstrated that, in contrast to ketanserin (10(-7) mol/l), ethanol (0.05 mol/l) potentiated the serotonin-induced vasoconstriction of isolated rat tail arteries. These data suggest that the action of ethanol on the vasopressor effect of serotonin in pithed rats does not depend on its influence on serotonergic receptors in blood vessels.

Animals↗

Cardiovascular effects of ethanol in anaesthetized, conscious and pithed rats.

The influence of ethanol (2.0 g/kg p.o.) on heart rate and blood pressure in anaesthetized, conscious and pithed rats was studied. In anaesthetized rats we observed an increase in heart rate and a marked and very sudden decrease in blood pressure. In pithed rats blood pressure decreased more slowly than in anaesthetized and conscious animals and there were no changes in heart rate. These results show that the central nervous system may be responsible for the increase in heart rate and early phase of hypotension caused by acute ethanol administration. The slower decrease (up to 1 h) in blood pressure may be caused by central and different indirect peripheral mechanisms.

Anesthesia↗

Synthesis of a novel side-chain to side-chain cyclized enkephalin analogue containing a carbonyl bridge.

A novel type of cyclic opioid peptide analogue, cyclo[N epsilon,N epsilon'-carbonyl-D-Lys2,Lys5]enkephalinamide, was prepared from a linear precursor peptide. The peptide was synthesized on the Merrified resin and also by a combination of the solid-phase technique and the classical method in solution. In both cases the cyclization was performed by reaction of bis(4-nitrophenyl)carbonate with the free side-chain amino groups of the two lysine residues. The described method permits the convenient preparation of novel peptide analogues cyclized via a ureido group incorporating the side-chain amino groups of two alpha, omega-diamino acid residues. The cyclic enkephalin analogue containing a 21-membered ring structure showed preference for mu over delta opioid receptors in opioid bioassays in vitro.

Animals↗

Possible involvement of kynurenamines in the pathogenesis of cataract in diabetic patients.

BACKGROUND: It has been demonstrated that the products of tryptophan degradation, kynurenamines, play an important role in senile cataract formation. However, the involvement of these compounds in the development of diabetic cataract has not been studied. The aim of the present study was to compare the concentration of tryptophan and kynurenamines in the aqueous humor and lenses obtained from non-diabetic and diabetic patients with cataract. MATERIAL AND METHODS: The concentration of tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid and anthranilic acid was measured using high-performance liquid chromatography (HPLC) with appropriate detection in aqueous humor and lenses obtained from 38 non-diabetic subjects and 20 patients with type II diabetes in course of surgical cataract extraction. RESULTS: In diabetic patients the concentration of kynurenine, 3-hydroxykynurenine and anthranilic acid in the aqueous humor was increased in comparison with non - diabetic subjects, while the concentration of tryptophan and kynurenic acid was similar in both groups. In the lenses obtained from patients with diabetes accumulation of tryptophan and all of its assayed metabolites was observed. CONCLUSIONS: Concentrations of the products of kynurenine pathway of tryptophan degradation in the aqueous humor and the lenses of diabetic patients are increased. We suggest that these compounds could play an important role in the development of diabetic cataract.

Aqueous Humor↗

Behavioral changes in the course of chronic renal insufficiency in rats.

In addition to the changes in various biochemical parameters chronic renal insufficiency (CRI) leads to progressive behavioral disturbances both in humans and rats. To further characterize these changes, the present study aimed to investigate locomotor, exploratory and emotional activity of rats with experimental CRI. Our experiments with the open field test have shown a marked decrease in locomotor, exploratory and emotional activity of the animals suffering from CRI. These changes were parallel with an increased water intake, reduced food intake and body weight. Thus, behavioral disturbances accompanying CRI in rats are similar to those occurring in human patients. The experimental model of CRI described by us seems to be a good tool for pharmacological studies.

Animals↗

Effect of captopril on serotonergic mechanisms in two-kidney, one-clip renal hypertensive rats.

In 2K,1C-RHR (two-kidney, one-clip hypertensive rats) serotonergic mechanisms in blood platelets were studied. The endogenous serotonin (5-HT) concentration in whole blood and in platelets remained unchanged in relation to the sham operated rats. Also the uptake of labelled 5-HT in rats with renal hypertension was not altered. However platelets aggregability was increased in 2K,1C-RHR. Acute administration of captopril (10 mg/kg and 100 mg/kg po) diminished blood pressure but did not change either the concentration of 5-HT in whole blood and in platelets of hypertensive rats or the uptake of this amine. Platelets aggregation and the amplifying effect of 5-HT in hypertensive rats were also unchanged after acute captopril administration. Similar results were observed after its administration in a dose of 30 mg/kg for one week. Our results indicate that captopril did not affect the platelets serotonergic mechanisms in 2K,1C-RHR.

Animals↗

The effect of ethanol and serotonin on blood vessels of the rat.

In in vitro conditions ethanol dose-dependently contracts the isolated tail artery and aorta of the rat. In concentration 0.03 M ethanol did not change the perfusing pressure in isolated vessels, but potentiated the contracting action of serotonin. In concentration of 0.1 M ethanol did not change the sensitivity of blood vessels to serotonin, and in concentration of 0.3 M inhibited it. Statistically significant changes were observed only in tail artery. The tail artery isolated from the rat receiving a single dose of ethanol (2 g/kg) displayed decreased sensitivity to action of serotonin. Chronic administration of ethanol (6 g/kg/day for 14 days) did not change the serotonin-induced contraction of the isolated tail artery of the rat. The present data indicate that ethanol modifies the sensitivity of rat blood vessels to serotonin.

Animals↗

Influence of acetaldehyde on some serotonergic mechanisms in rat blood platelets.

Acetaldehyde (ACT), both, ex vivo and in vitro did not change the ADP-induced rat platelet aggregation and the potentiating action of serotonin. The whole blood serotonin content was decreased only when ACT was used in doses of 20 and 30 mg/kg, i.v. and the platelet serotonin content remained unchanged. Ex vivo, ACT had no influence on the labeled serotonin uptake, whereas in experiments in vitro it inhibited the amine uptake and augmented the serotonin release from blood platelets in a dose dependent manner. The results indicate that all the changes in the platelet serotonergic mechanisms appear only after high concentrations of ACT. They may be of significant importance in the circulatory system or hemostasis only during disulfiram or calcium carbamide therapy.

Acetaldehyde↗

Influence of captopril on the serotonin-induced vasopressor effect in tail artery isolated from two-kidney, one-clip renal hypertensive rats.

The influence of captopril and ritanserin (5-HT2 receptor antagonist) on the serotonin-induced contraction of isolated tail artery of two-kidney, one clip hypertensive (2K, 1C-RHR) and normotensive rats was studied. Captopril, administrated in a single dose of 100 mg/kg, po or in a dose of 30 mg/kg/day, po for one week, diminished the systolic blood pressure in both groups of rats. Ritanserin (0.01 mg/kg/day, sc for one week) administrated alone or in combination with captopril (30 mg/kg/day) evoked such effect only in 2K, 1C-RHR. The reactivity of rat tail artery isolated from 2K, 1C-RHR to serotonin was significantly higher than that obtained from normotensive ones. Captopril given in a single dose or chronically did not change the serotonin-induced contraction of rat tail artery in normotensive rats. The attenuation of serotonin contractile effect was registered in hypertensive rats pre-treated with captopril. Administration ritanserin with or without captopril also inhibited the response to serotonin in both groups. The stronger effect was observed after administration of ritanserin with captopril in 2K, 1C-RHR than in control group. Our results indicate, that in 2K, 1C-RHR the reactivity of rat tail arteries to serotonin is enhanced and this effect can be reduced by chronic captopril administration.

Angiotensin-Converting Enzyme Inhibitors↗

Comprehensive study on platelet function, hemostasis, fibrinolysis, peripheral serotonergic system and serum lipids in nephrotic syndrome.

A comprehensive study on platelet aggregation, hemostasis, fibrinolysis and serum lipids in relation to peripheral serotonergic system has been performed on 41 nephrotic patients. Enhanced platelet aggregatory responses in both whole blood and in platelet rich plasma (PRP) were found upon stimulation with different agonists when compared to healthy volunteers. Increased levels of fibrinogen, fibrin monomers, and protein C activity were observed in nephrotic patients. Euglobulin clot lysis time was significantly prolonged in nephrotic patients. Activity of tissue plasminogen activator (tPA) inhibitor was higher in nephrotic syndrome, whereas tPA activity was significantly lower in these patients when compared to controls. Urokinase concentration, lipoprotein (a), cholesterol, LDL and VLDL levels were significantly higher in nephrotic patients over controls. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in nephrotic patients relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with nephrotic syndrome. Disequilibrium in the coagulolytic system, platelet hyperactivity, hyperfibrinogenemia, disturbances in peripheral serotonergic system together with lipid abnormalities may contribute to the progression and development of atherosclerosis and an enhanced risk of thromboembolic complications in nephrotic syndrome.

Adenosine Diphosphate↗