Browsing by Author "Prostran, M. (7004009031)"

OBJECTIVE: Magnesium is an endogenous voltage-dependent NMDA receptorchannel blocker and ketamine is a non-competitive NMDA receptor antagonist. Magnesium may potentiate the effect of ketamine in analgesia and anaesthesia, but may also interact in an opposing manner.This study aimed at evaluating type of the interaction between magnesium sulphate and ketamine administered systemically in rats with an acute nociceptive pain (tail-immersion test). MATERIALS AND METHODS: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 ± 0.5°C) and the time for tail-withdrawal was measured as response latency. RESULTS: Magnesium sulphate (2.5-30 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) administered alone did not produce any effect. However, significant antinociception (synergistic interaction) was revealed at the following doses of ketamine: magnesium sulphate of 5:5 mg/kg, 2.5:5 mg/kg and 10:5 mg/kg. The effect was not dose-dependent, and a greater response was obtained when ketamine was administered before magnesium sulphate. CONCLUSIONS: This study revealed that (1) magnesium sulphate and ketamine given alone were not effective against acute nociceptive pain in rats, but (2) a combination of both drugs resulted in synergistically inhibited nociception, (3) which occurred only at selected low doses and proportions of the medications in a combination and (4) suggested the importance of the order of drug administration.

Atrial fibrillation (AF) currently affects approximately 2% of the general adult population, and the number of patients suffering from AF constantly increases. Although the occurrence of AF rarely poses an immediate threat to patient's survival, the arrhythmia is associated with significant cardiovascular morbidity and mortality mostly resulting from ischemic stroke or systemic thromboembolism, or heart failure. Overall, patients with AF have a 5-fold greater risk of stroke compared to individuals in sinus rhythm, but individual stroke risk depends on the presence of various stroke risk factors, and optimal stroke prevention is essential for AF patients. Several major advances in AF-related stroke prevention have been achieved recently, including the refinements in stroke and bleeding risk assessment with an essential shift in the recognition of AF patients who should be offered oral anticoagulant (OAC) therapy, the advent of non-Vitamin K antagonist oral anticoagulants (NOACs) which are increasingly used in the "real-world" setting, as well as the development of non-pharmacological means of thromboprophylaxis in AF patients (e.g., left atrial appendage [LAA] occluding devices). In this review article, we summarize these recent developments in stroke risk reduction strategies and discuss the main principles of decision-making regarding OAC therapy in AF patients.

Tourniquet trauma produced a decrease in the noradrenaline content in the heart of the rats through the period of tourniquet application (up to 4 hr). In the same period, the content of adrenaline was significantly increased. This relationship between noradrenaline and adrenaline remained the same in the posttraumatic period. Parallel to the observed changes in the catecholamine content of the heart, a significant decrease in the number of the beta-adrenergic receptors (B(max)) and an increase in their affinity (a decrease in K(D)) was also found in the hearts of rats exposed to tourniquet trauma. These changes remained throughout the posttraumatic period, with one exception: no change 30 min after trauma has been observed. Reapplication of tourniquet was associated with a restoration of the beta-adrenergic receptors and complete survival of the animals. The decrease in the beta-receptors density after trauma might be due to down-regulation produced by increased concentration of adrenaline, a beta-receptor agonist. Meanwhile, some other factors, particularly ischaemia, might also contribute to the observed changes in the beta-adrenergic binding sites.

Aim: This study analyzed the prevalence of hypertension and the pattern of antihypertensive treatment before and after kidney transplantation. Patients and methods: The prevalence of hypertension and the class and daily dosage load of antihypertensive medications were analyzed in 116 patients before kidney transplantation and 1, 6, and 12 months after transplantation (67.2 % males, mean age 45.9 ± 11.4 years). Two patients died and eight had the allograft explanted, leaving 106 patients in the final analysis. Blood pressure (BP) was recorded on the day of transplantation and at every follow-up; it was considered uncontrolled at values > 130/80 mmHg. Results: The prevalence of uncontrolled BP was significantly reduced after kidney transplantation (63.2 % before transplantation vs. 54.7, 41.5, and 25.5 % at the 1‑, 6‑, and 12-month follow-up, respectively, p < 0.001 for all). The number of prescribed antihypertensives did not change significantly during the follow-up (1.96 ± 1.03 before transplantation vs. 2.01 ± 0.88, 1.71 ± 0.78, and 1.73 ± 0.73 at the 1‑, 6‑, and 12-month follow-up, respectively, p > 0.05 for all). There was a significant decrease in antihypertensive drug load during the follow-up (1.08 ± 1.3 end of the study vs. 2.05 ± 2.32 before transplantation, p < 0.008). Before kidney transplantation, angiotensin-converting enzyme (ACE) inhibitors were most commonly prescribed (52.8 %), while after surgery β‑blockers gained prevalence (59.4–63.2 %). Mean arterial pressure decline correlated with an improvement of graft function. Conclusion: The prevalence of uncontrolled BP and the antihypertensive drug dosage load reduced significantly after kidney transplantation. β‑blockers were used more frequently than ACE inhibitors after kidney transplantation. © 2016, Springer Medizin Verlag.

The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether α2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an α2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an α2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (1/4, 1/2 and 3/4) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that α2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect. © 2007 Prous Science. All rights reserved.

The anticonvulsant carbamazepine was recently shown to possess local peripheral antinociceptive properties. In this study, we investigated whether α2-adrenergic receptors are involved in the local peripheral antihyperalgesic effects of carbamazepine and determined the type of interaction between carbamazepine and clonidine, an α2-adrenoceptor agonist. Intraplantar (i.pl.) coadministration of either carbamazepine (100-1000 nmol/paw) or clonidine (1.9-3.7 nmol/paw) with the proinflammatory compound concanavalin A (Con A; 0.8 mg/paw) caused a significant dose- and time-dependent reduction of the difference between the forces exerted by a rat's hind paws in a modified paw-pressure test. The coadministration of 260 and 520 nmol/paw (i.pl.) yohimbine, an α2-adrenoceptor antagonist, with carbamazepine, significantly depressed the local antihyperalgesic effect in a dose- and time-dependent manner whereas yohimbine by itself did not have any effect. The administration of a mixture of carbamazepine and clonidine at fixed dose fractions (1/4, 1/2 and 3/4) of ED50 caused a significant and dose-dependent reduction of Con A-induced hyperalgesia. Isobolographic analysis revealed an additive interaction. These results suggest that α2-adrenoceptors play a role in the local peripheral antihyperalgesic effects of carbamazepine and that local peripheral coadministration of carbamazepine with clonidine results in an additive antihyperalgesic effect. © 2007 Prous Science. All rights reserved.

The present study was undertaken in order to examine transduction mechanism involved in the single application of 100 μM homocysteine (Hcy) on isolated rat femoral artery (RFA) rings equilibrated on the basal tone; to establish if a single application of 100 μM Hcy alters contractile effect of phenylephrine (Phe), or oppositely the relaxant effect of acetylcholine (ACh) or bradykinin (BK) after 60-min-long incubation of 100 μM Hcy; and finally to identify morphological changes on the vascular wall after a 24-h-long incubation of 100 μM Hcy. Hcy produced contractile response of intact RFA, which was increased after endothelial denudation, while decreased by urapidil (an α1 receptor blocker), nifedipine (a voltage-gated L-type Ca++ channel blocker) or indomethacin (a cyclooxygenase inhibitor). The initial RFA contraction evoked by Phe was further increased by the single addition of Hcy, which was not the case when ouabain (an inhibitor of Na+/K+-ATPase) was preincubated. After 60-min-long incubation of Hcy relaxant actions of ACh and BK were unaltered, equieffective and equipotent. A 24-h-long incubation of RFA rings with Hcy produced an impairment of vascular endothelium, expressed as a minor or more pronounced interruption of endothelial cells. © 2014 Akadémiai Kiadó, Budapest.

1. The effect of L-N6-phenylisopropyladenosine (L-PIA) on the maximum tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of the isolated hemidiaphragm of the rat was investigated during direct electrical stimulation. 2. L-PIA itself (0.07-5.5 μmol l-1) did not produce significant changes in either Td or dT/dt max. 3. In the presence of a standard concentration of dipyridamole (26.4 μmol l-1), L-PIA produced a significant and concentration-dependent increase in both Td and dT/dt max. 4. In the presence of a standard concentration of aminophylline (640 μmol l-1), L-PIA produced a small and insignificant, but concentration-dependent decrease of both Td and dT/dt max. 5. In the presence of both dipyridamole (26.4 μmol l-1) and of aminophylline (640 μmol l-1), L-PIA (0.07-5.5 μmol l-1) produced a small and insignificant potentiation of the isometric contraction of the isolated hemidiaphragm. 6. It is concluded that antagonistic action between L-PIA and aminophylline probably takes place at A1-receptors. The inhibitory action of L-PIA, observed after blockade of adenosine receptors by aminophylline, is presumably realized through some other mechanism(s) independent of adenosine receptor sites.

1. The effect of L-N6-phenylisopropyladenosine (L-PIA) on the maximum tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of the isolated hemidiaphragm of the rat was investigated during direct electrical stimulation. 2. L-PIA itself (0.07-5.5 μmol l-1) did not produce significant changes in either Td or dT/dt max. 3. In the presence of a standard concentration of dipyridamole (26.4 μmol l-1), L-PIA produced a significant and concentration-dependent increase in both Td and dT/dt max. 4. In the presence of a standard concentration of aminophylline (640 μmol l-1), L-PIA produced a small and insignificant, but concentration-dependent decrease of both Td and dT/dt max. 5. In the presence of both dipyridamole (26.4 μmol l-1) and of aminophylline (640 μmol l-1), L-PIA (0.07-5.5 μmol l-1) produced a small and insignificant potentiation of the isometric contraction of the isolated hemidiaphragm. 6. It is concluded that antagonistic action between L-PIA and aminophylline probably takes place at A1-receptors. The inhibitory action of L-PIA, observed after blockade of adenosine receptors by aminophylline, is presumably realized through some other mechanism(s) independent of adenosine receptor sites.

The intravenous injection of physostigmine (70 μg kg1) produces a life-saving effect in acute haemorrhagic shock in non-anaesthetized rabbits. This effect is most probably due to a transfer of tissue fluids into circulation. The crucial beneficial effect of physostigmine might be a decrease of the capillary hydrostatic pressure due to changes in pre- to postcapillary resistance ratio. Both lines of defence comprise a normalization of blood pressure and normalization of blood volume, thus saving the life of the animal. © 1991.

The intravenous injection of physostigmine (70 μg kg1) produces a life-saving effect in acute haemorrhagic shock in non-anaesthetized rabbits. This effect is most probably due to a transfer of tissue fluids into circulation. The crucial beneficial effect of physostigmine might be a decrease of the capillary hydrostatic pressure due to changes in pre- to postcapillary resistance ratio. Both lines of defence comprise a normalization of blood pressure and normalization of blood volume, thus saving the life of the animal. © 1991.