Biomedical subjects
Publications and source records attributed to W Buczko.
The influence of ADP on the central action of catecholamines was investigated. ADP abolished the central action of noradrenaline, amphetamine and nialamide. The peptides decreased apomorphine stereotypy and enhanced haloperidol induced catalepsy. These results support our previous suggestions [10-14] that ADP acts on the CNS by antagonizing the action of central catecholamines.
Cerebrospinal fluid (CSF) serotonin was determined in 38 patients with pyogenic meningitis and tick-borne encephalitis (TBE) before and after treatment. Increase of CSF serotonin concentration was observed in acute phase of pyogenic meningits and normalized after treatment.
Angiotensin-(1-7) [Ang-(1-7)] is a paracrine hormone of the renin-angiotensin system (RAS). It counterbalances the negative actions of angiotensin II (Ang II) acting in the cardiovascular system, kidneys and central nervous system, and is responsible for blood pressure regulation and antiproliferative effects. Current data strongly suggest the existence of a specific receptor for this peptide. The concentration of Ang-(1-7) increases significantly during the administration of RAS blockers. One may suggest the involvement of this peptide in a beneficial effect of these drugs.
BACKGROUND: In our previous experiments we showed that the prototype member of the AT1 receptor antagonists (AT1-As) family, losartan, prevented the development of arterial and venous thrombosis in rats. Recent studies have demonstrated that apart from blocking AT1 receptor, losartan is also a competitive antagonist to thromboxane A2/prostaglandin H2 receptor (TP receptor). Thus, we decided to assess if this feature could contribute to the antithrombotic action of losartan. MATERIAL AND METHODS: We compared the influence losartan, its active metabolite EXP3174 and valsartan on rat platelet adhesion to fibrillar collagen and platelet aggregation in response to thromboxane A2 analogue, U46619. We also assessed the efficacy of these drugs in platelet-dependent pulmonary thrombosis in mice as well as preventive and therapeutic models of venous thrombosis in rats. RESULTS: All the three compounds, given in a single dose, inhibited rat platelet adhesion to fibrillar collagen and platelet aggregation induced with U46619 in vitro and ex vivo, with the action of losartan being much more pronounced than that of EXP3174 or valsartan. Losartan also more effectively protected mice from death in response to the intravenous injection of collagen / epinephrine and it was the only compound which reduced mice mortality after the intravenous injection of U46619. In contrast, all the three AT1 receptor antagonists exerted a similar thrombolytic action and comparably decreased the thrombus weight in the therapeutic and preventive model of venous thrombosis, although in the latter case a high dose of losartan was slightly more effective than a corresponding dose of EXP3174 and valsartan. CONCLUSIONS: Since losartan is endowed with a relatively low affinity towards the AT1 receptor, we conclude that its superiority over EXP 3174 and valsartan in inhibiting thrombocyte function and platelet-dependent thrombosis could result from its stronger action on the TP receptor. This feature seems to be less important in the thrombolytic effect of AT1-As and in the inhibition of the venous thrombosis development, in which platelets play only a minor role.
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.
To clarify if one of the most common antihypertensive drugs, propranolol, can prevent venous thrombotic process, rats were treated with propranolol (PRO; 5 mg/kg i.p.) in an acute or chronic (14 days) manner. Both regimens resulted in a marked reduction of the systolic blood pressure (p < 0.001) and, probably as a consequence, in the shortening of the bleeding time (p < 0.01). After ligation of the vena cava, the incidence of the venous thrombosis and the thrombus weight decreased significantly in both propranolol-treated groups (p < 0.01) when compared to control rats. The antithrombotic effect of PRO was not accompanied by any changes in activated partial thromboplastin time, prothrombin time or euglobulin clot lysis time. However, long-term administfation of PRO resulted in a reduction of the ADP-induced platelet aggregation.
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.
The activity of rat kininforming system and endoxan level in certain organs and in the neoplastic tissue was studied. It was found that trypsin increases markedly the kininforming activity and endoxan level in the Guérin tumor, and slightly in the liver. A direct correlation between the level of endoxan when given with trypsin and the kinin activity were observed. The authors suppose that the selective accumulation of endoxan in the tumor depends on the trypsin -- induced activation of kininforming system within the neoplastic tissue.
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.
Influence of fibrinogen degradation products (FDP) on the ATPase activity in the rat heart. Acta Physiol. Pol., 1978, 29 (2): 185--187. The influence of dialysable fibrinogen degradation products (FDP) on the ATPase activity was studied. It was found that FDP augment the Mg(2+)-- dependent ATPase and slightly decrease the (Na+--K+) dependent ATPase in the rat heart. It is concluded that biological activity of examined peptides depend on other mechanisms than the direct effect on ATPase in the heart.
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.
In normotensive rats the effect of different doses of propranolol (1.0, 5.0 and 10.0 mg/kg i.p.) and ketanserin (10.0 mg/kg p.o.) on mean blood pressure and heart rate and on cardiovascular response to noradrenaline (0.1, 0.3, 0.5, 0.7 and 1.0 micrograms/kg i.v.) was examined. The drugs were given separately or together. Propranolol slightly reduced the hypotensive effect of ketanserin. On the other hand a decrease in heart rate caused by propranolol was not affected by ketanserin. Our results show that propranolol given with ketanserin did not change the effect of the latter on the cardiovascular system.
Verapamil in vitro inhibits the uptake and enhances the release of the labeled serotonin from the rat blood platelets. It also inhibits the facilitating action of serotonin on the aggregation response of platelets stimulated by ADP. The obtained results indicate that verapamil significantly influences serotonergic mechanisms in the blood platelets, at least in the rat.
Under in vitro conditions ethanol inhibits the uptake and enhances release of [14C]-5HT from rat blood platelets. Similar results were obtained in blood platelets isolated from the blood rats receiving 2 g/kg ethanol. Ethanol decreased also the 5-HT content in the blood platelets. It inhibited the aggregation of blood platelets but did not change the potentiating action of 5-HT on ADP-induced aggregation. The results indicate that ethanol by its action on the transport mechanisms in blood platelets may elevate the level of free 5-HT in the blood plasma, in this manner potentiating the action of the amine in the circulatory system.
The participation of prostaglandins (PGs) E2 and F2 alpha administered icv in the action of fibrinopeptides A and B (FAB) on the central dopamine neurons was investigated. PGE2 and PGF2 alpha (0.5 microgram) attenuated the intensity of apomorphine (APO)-induced stereotypy and completely abolished the stimulatory action of FAB. PGE2 given together with FAB attenuated, while PGF2 alpha did not affect the amphetamine-induced stereotypy and haloperidol-induced catalepsy. The investigated PGs did not affect or normalized the level of dopamine depressed by peptides in some parts of the brain. The results indicate that PGE2 alpha and PGF2 alpha do not participate in the mechanism of the central action of FAB.
The effect of kallikrein was studied on the acquisition and extinction of conditioned reactions in rats. It was demonstrated that kallikrein in doses of 50 and 100 mu/kg i.p. accelerated the process of learning in these animals. The observed effect might be connected with a rise in the activity of kininogenic enzymes in the central nervous system.
Fibrinopeptides A and B (FAB) stimulate central dopamine neurons. Inhibition of prostaglandin synthesis by administration of indomethacin potentiated the stimulatory action of FAB on apomorphine stereotypy, while induced inhibitory action of FAB on amphetamine stereotypy. Results of studies on the level and turnover of dopamine do not explain the changes in the stereotyped behavior. The data suggest that prostaglandins may to some extent participate in the mechanism of the central action of FAB.
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