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1.

001-es BibID:BIBFORM030274
035-os BibID:WOS:000079560700007
Első szerző:Bányász Tamás (élettanász)
Cím:EGIS-7229, the new combined class III antiarrhythmic agent : lack of EAD inducing effect / Tamás Bányász, János Magyar, András Varró, Anikó Kovács, Ildikó Gyönös, Gábor Szénási, Péter P. Nánási
Dátum:1999
ISSN:0306-3623
Megjegyzések:EGIS-7229 is a novel antiarrhythmic candidate having multiple mechanisms of action with class III predominance. In this study, the effects of EGIS-7229 and sotalol on action potential duration (APD) and incidence of early afterdepolarizations (EADs) were studied and compared in rabbit papillary muscle by using conventional microelectrode techniques. In control bathing solution, both drugs increased APD in a concentration-dependent manner; however, the prolongation of APD was greater with sotalol than with EGIS-7229 when the same drug concentrations were compared. EAD developed in 3 of the 11 preparations (27%) bathed with a solution containing 3.6 mmol/l CsCl + 2 mmol/l KCl within the first 120 min of superfusion. The addition of 100 mu mol/l sotalol to this superfusate increased the incidence of EAD to 83% (10 from 12), whereas the addition of the same concentration of EGIS-7229 prevented the development of EAD in all of the 9 preparations studied. These differences in incidence of EAD are likely attributable to differences in drug-induced increases of APD-50 in the presence of CsCl. Prolongation of APD-90 showed less correlation with incidence of EAD than changes in APD-50. On the basis of these in vitro results, high concentrations of EGIS-7229 cannot be expected to be torsadogenic in vivo-in contrast with sotalol-presumably owing to the combined class III + IV activity of the compound. (C) 1999 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology. - 32 : 3 (1999), p. 329-333. -
További szerzők:Magyar János (1961-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Kovács Anikó Gyönös Ildikó Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM030250
035-os BibID:WOS:000182475600002
Első szerző:Fülöp László (kardiológus)
Cím:Differences in electrophysiological and contractile properties of mammalian cardiac tissues bathed in bicarbonate - and HEPES-buffered solutions / L. Fülöp, G. Szigeti, J. Magyar, N. Szentandrássy, T. Ivanics, Z. Miklós, L. Ligeti, A. Kovács, G. Szénási, L. Csernoch, P. P. Nánási, T. Bányász
Dátum:2003
ISSN:0001-6772
Megjegyzések:Aim: The aim of this study was to compare the action potential configuration, contractility, intracellular Ca2+ and H+ concentrations in mammalian cardiac tissues bathed with Krebs and Tyrode solutions at 37 degreesC. Results: In Langendorff-perfused guinea-pig hearts, loaded with the fluorescent Ca2+ -indicator Fura-2, or H+ -sensitive dye carboxy-SNARF, shifts from Krebs to Tyrode solution caused intra-cellular acidification, increased diastolic pressure and [Ca2+ ](i) , decreased systolic pressure and [Ca2+ ](i) , leading to a reduction in the amplitude of [Ca2+ ](i) transients and pulse pressure. Contractility was also depressed in canine ventricular trabeculae when transferred from Krebs to Tyrode solution. Shifts from Krebs to Tyrode solution increased the duration of action potentials in multicellular cardiac preparations excised from canine and rabbit hearts but not in isolated cardiomyocytes. All these changes in action potential morphology, contractility, [Ca2+ ](i) and [H+ ](i) were readily reversible by addition of 26 mmol L-1 bicarbonate to Tyrode solution. Effects of dofetilide and CsCl, both blockers of the delayed rectifier K current, on action potential duration were compared in Krebs and Tyrode solutions. Dofetilide lengthened rabbit ventricular action potentials in a significantly greater extent in Tyrode than in Krebs solution. Exposure of canine Purkinje fibres to CsCl evoked early after depolarizations within 40 min in all preparations incubated with Tyrode solution, but not in those bathed with Krebs solution. Conclusion: It is concluded that the marked differences in action potential morphology, [Ca2+ ](i) , [H+ ](i) and contractility observed between preparations bathed with Krebs and Tyrode solutions are more likely attributable to differences in the intracellular buffering capacities of the two media.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Acta Physiologica Scandinavica. - 178 : 1 (2003), p. 11-18. -
További szerzők:Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Magyar János (1961-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Ivanics Tamás Miklós Zsuzsanna Ligeti László Kovács A. Szénási Gábor Csernoch László (1961-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Bányász Tamás (1960-) (élettanász)
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3.

001-es BibID:BIBFORM013054
Első szerző:Harmati Gábor (élettanász)
Cím:Effects of β-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes / Harmati G., Bányász T., Bárándi L., Szentandrássy N., Horváth B., Szabó G., Szentmiklósi J., Szénási G., Nánási P., Magyar J.
Dátum:2011
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
isoproterenol
beta adrenerg
canine
cardiomyocyte
ionic current
Megjelenés:British Journal of Pharmacology. - 162 : 4 (2011), p. 890-896. -
További szerzők:Bányász Tamás (1960-) (élettanász) Bárándi László (1984-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Horváth Balázs (1981-) (élettanász) Szabó G. (orvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Szénási Gábor Nánási Péter Pál (1956-) (élettanász) Magyar János (1961-) (élettanász)
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4.

001-es BibID:BIBFORM030261
035-os BibID:WOS:000184795700023
Első szerző:Kovács Anikó
Cím:Beta-adrenoceptor activation plays a role in the reverse rate-dependency of effective refractory period lengthening by dofetilide in the guinea-pig atrium, in vitro / Anikó Kovács, János Magyar, Tamás Bányász, Péter P. Nánási, Gábor Szénási
Dátum:2003
ISSN:0007-1188
Megjegyzések:1 Blockers of the rapid component of the delayed rectifier potassium current (I-Kr) prolong cardiac action potential duration (APD) and effective refractory period (ERP) in a reverse rate-dependent manner. Since activation of beta-adrenoceptors attenuates prolongation of APD evoked by I-Kr blockers, rate-dependent neuronal noradrenaline liberation in the myocardium may contribute to the reverse rate-dependent nature of the effects of I-Kr blockers. In order to test this hypothesis, we studied the effects of dofetilide, a pure I-Kr blocker, on ERP after activation or blockade of beta-adrenoceptors and after catecholamine depletion in guinea-pig left atrial myocardium paced at 3, 2 and 1 Hz, in vitro. 2 Dofetilide (100 nM) lengthened ERP in a reverse rate-dependent manner in the left atrial myocardium of guinea-pigs. Strong activation of beta-adrenoceptors using 10 nM isoproterenol abolished the dofetilide-induced lengthening of ERP at all pacing rates. 3 Blockade of the beta-adrenoceptors with metoprolol (1 muM), atenolol (3 muM) or propranolol (300 nM) increased the dofetilide-evoked prolongation of ERP at 3 and 2 Hz, but not at 1 Hz. As a consequence, metoprolol attenuated while propranolol and atenolol fully eliminated the reverse rate-dependent nature of the dofetilide-induced ERP lengthening. In catecholamine-depleted atrial preparations of the guinea-pig (24 h pretreatment with 5 mg kg(-1) reserpine i.p.), the effect of dofetilide on ERP was not frequency dependent, and propranolol did not alter the effects of dofetilide. 4 In contrast to results obtained in guinea-pig atrial preparations, propranolol failed to change the reverse rate-dependent effect of dofetilide on ERP in the right ventricular papillary muscles of rabbits and guinea-pigs. 5 As an indication of the functional consequences of rate-dependent noradrenaline liberation, propranolol decreased twitch tension at 3 and 2 Hz but not at 1 Hz in the atrial myocardium of control guinea-pigs, whereas no such effect was detected in catecholamine-depleted atrial preparations. Propranolol failed to change contractility of ventricular myocardium in guinea-pigs and rabbits. 6 It is concluded that rate-dependent noradrenaline release and the ensuing beta-adrenoceptor activation contributed to the reverse rate-dependent nature of ERP prolongation caused by I-Kr blockers in isolated guinea-pig atrial myocardium.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:British Journal of Pharmacology. - 139 : 8 (2003), p. 1555-1563. -
További szerzők:Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Szénási Gábor
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5.

001-es BibID:BIBFORM030254
Első szerző:Kovács Anikó
Cím:Effects of EGIS-7229 (S 21407), a novel class III antiarrhythmic drug, on myocardial refractoriness to electrical stimulation in vivo and in vitro / Anikó Kovács, Ildikó Gyönös, János Magyar, Tamás Bányász, Péter P. Nánási, Michael Spedding, Gábor Szénási
Dátum:2001
ISSN:0160-2446
Megjegyzések:The I-Kr blocker EGIS-7229 (S-21407), displays class Ib and class IV effects that may alter its pharmacologic profile compared with those of pure I-Kr blockers. Therefore, the concentration- and frequency-dependent effects of EGIS-7229, and of the I-Kr blockers d,l-sotalol and dofetilide, on the effective refractory period (ERP) were measured in isolated right ventricular papillary muscle of the rabbit in vitro. The effects of these drugs on right ventricular fibrillation threshold (RVFT) at increasing intravenous doses were also determined in anesthetized cats. Dofetilide and d,l-sotalol increased ERP in a concentration-dependent manner (dofetilide: 3-100 nM; d,l-sotalol: 3-100 muM) with strong reverse frequency dependence at high concentrations. EGIS-7229 concentration dependently lengthened ERP at 1-30 muM. Its effect on ERP was clearly reverse frequency dependent at 3 muM, but this feature of the drug diminished at 10 muM and was not apparent at 30 muM The effect of EGIS-7229 (30 muM) on ERP was devoid of reverse frequency dependence as it was more effective (31%) than dofetilide (16 %) at high-pacing rate (3 Hz), whereas it was less effective (50%) than dofetilide (70%) at slow-pacing rate (1 Hz). Reverse frequency-dependent ERP effect of dofetilide (100 nM) was similarly abolished by the addition of lidocaine (30 muM). EGIS-7229 (1-8 mg/kg iv), d,l-sotalol (1-8 mg/kg iv), and dofetilide (10-80 mug/kg iv) caused a dose-dependent increase in RVFT. The minimum effective dose of d,l-sotalol and EGIS-7229 was 1 and 2 mg/kg, respectively. whereas that of dofetilide was 10 mug/kg. EGIS-7229 induced a smaller peak effect in RVFT than sotalol or dofetilide. In conclusion, EGIS-7229 markedly increased refractoriness to electrical stimulation in vitro and in vivo. Compared with pure I-Kr blockers, the benefits of EGIS-7229 seem to be a greater lengthening of effective refractory period at rapid stimulation rates, suggesting a strong antiarrhythmic action, and a smaller effect at slow stimulation rates, suggesting low potential to induce early afterdepolarizations.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Journal of Cardiovascular Pharmacology. - 37 : 1 (2001), p. 78-88. -
További szerzők:Gyönös Ildikó Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Spedding, Michael Szénási Gábor
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6.

001-es BibID:BIBFORM030257
035-os BibID:WOS:000169039300004
Első szerző:Magyar János (élettanász)
Cím:Effects of the antiarrhythmic agent EGIS-7229 (S 21407) on calcium and potassium currents in canine ventricular cardiomyocytes / János Magyar, Tamás Bányász, László Fülöp, Norbert Szentandrássy, Ágnes Körtvély, Anikó Kovács, Gábor Szénási, Péter P. Nánási
Dátum:2001
ISSN:0028-1298
Megjegyzések:Based on earlier pharmacological studies performed using conventional microelectrodes EGIS-7229 (S 21407), the novel antiarrhythmic candidate, was suggested to have a combined mode of action in cardiac tissues isolated from various mammalian species. In order to characterize the electrophysiological effects of the compound, its effects on calcium and potassium currents of isolated canine ventricular cardiomyocytes were studied in the present work using the whole cell configuration of the patch clamp technique. L-type Ca current (I-Ca) was significantly depressed by EGIS-7229 at concentrations of 3 muM or higher with no concomitant changes in the voltage-dependence of activation and time course of inactivation of I-Ca. The drug reversibly suppressed the rapid component of the delayed rectifier K current (I-Kr) in a concentration-dependent manner, having a K-0.5 value of 1.1+/-0.1 muM and a slope factor of close to unity (1.23+/-0.16), indicating that probably one single binding site of high affinity may be involved in binding of EGIS-7229 to the I-Kr channel. In contrast, no changes in the slow component of the delayed rectifier K current (I-Ks,) was observed with the compound up to the concentration of 100 muM, even if the current was fully activated by 8-bromo-cAMP. At a concentration of 10 muM or higher, EGIS-7229 caused also a moderate but significant reduction in the inward rectifier K current (I-K1) and the transient outward K current (I-to) with no change in the voltage-dependence of activation and steady-state inactivation of I-to. Present results indicate that EGIS-7229 can be considered as a selective I-Kr blocker at low (1 muM) concentration; however, its combined (class III + IV) mechanism of action is evident at concentrations of 3 muM or higher. Suppression of I-Ca may explain the lack of development of early afterdepolarizations in the presence of EGIS-7229, predicting a relatively safe clinical application in contrast to pure class III compounds.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 363 : 6 (2001), p. 604-611. -
További szerzők:Bányász Tamás (1960-) (élettanász) Fülöp László (1976-) (kardiológus) Szentandrássy Norbert (1976-) (élettanász) Körtvély Ágnes Kovács Anikó Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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7.

001-es BibID:BIBFORM030278
035-os BibID:WOS:A1997WN91400013
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated mammalian and human cardiac tissues / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, András Varró, Gábor Szénási, Péter P. Nánási
Dátum:1997
ISSN:0028-1298
Megjegyzések:The cellular electrophysiological effects of EGIS-7229 (5-chlor-4-[N-(3,4-dimethoxy-phenyl-ethyl)- amino-propylamino]-3(2H)-pyridazinone fumarate), a novel antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibers and papillary muscle preparations obtained from man, rabbits and guinea pigs. Low concentration of EGIS-7229 (3 mu mol/l) selectively lengthened action potential duration (both APD(50) and APD(90)) in all preparations. The effect of higher concentrations (30-100 mu mol/l) of EGIS-7229 on action potential duration was variable depending on the preparation studied: in rabbit and human papillary muscles both APD(50) and APD(90) were lengthened, in canine Purkinje fibers APD(90) was lengthened but APD(50) was shortened, while in guinea pig papillary muscles both APD(50) and APD(90) were shortened by high concentrations of the drug. At these higher concentrations EGIS-7229 also decreased the maximum velocity of action potential upstroke (V-max) and depressed the plateau of action potentials without affecting the resting membrane potential or action potential amplitude. Both reduction of V-max and lengthening of APD were frequency dependent. The former effect was more prominent at higher pacing frequencies, while the latter was more pronounced at lower driving rates. In guinea pig papillary muscle, the time constant of recovery from V-max block was 719 +/- 33 ms (n = 18) and the rate of onset of the block was 1.81 +/- 0.06 AP(-1) (n = 16) in the presence of 100 mu mol/l EGIS-7229. EGIS-7229 had a complex action on refractoriness in guinea pig papillary muscles: ERP was lengthened at low concentrations (3 to 10 mu mol/l), unchanged at 30 mu mol/l and shortened at 100 mu mol/l. The ratio of ERP/APD(90) however, was significantly increased at concentrations higher than 3 mu mol/l. In canine Purkinje fiber when the delayed rectifier K current (I-K) was blocked by d-sotalol (60 mu mol/l) and APD was shortened back to its control value by additional application of nicorandil (15 mu mol/l), APD was not affected by 3 mu mol/l but was shortened by 30 mu mol/l of EGIS-7229. 100 mu mol/l EGIS-7229 shortened APD in guinea pig papillary muscle. This effect of EGIS-7229 was effectively prevented by nifedipine pretreatment (10 mu mol/l). In this preparation, EGIS-7229 also decreased the V-max of the slow action potential, evoked in the presence of 20 mmol/l external K+ plus 0.5 mmol/l Ba2+. It is likely that EGIS-7229 at low concentrations blocks I-K in human, canine, rabbit and guinea pig cardiac preparations, but at higher concentrations also inhibits Ca and Na currents. Therefore, EGIS-7229 appears to carry mixed class III, IV and IB antiarrhythmic properties.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 355 : 3 (1997), p. 398-405. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Varró András (1954-) (farmakológus, klinikai farmakológus) Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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8.

001-es BibID:BIBFORM030277
035-os BibID:WOS:A1997XM42500024
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated guinea pig papillary muscle / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, Gábor Szénási, András Varró, Péter P. Nánási
Dátum:1997
ISSN:0306-3623
Megjegyzések:1. The cellular electrophysiological effects of EGIS-7229, a novel antiarrhythmic agent, were studied in guinea pig papillary muscles with the use of conventional microelectrode techniques. 2. The drug had a concentration-dependent biphasic effect on action potential duration (APD). APD was significantly lengthened at low concentration (3 mu mol/l), whereas it was shortened at concentrations higher than 10 mu mol/l. 3. At concentrations higher than 10 mu mol/l, the drug decreased the maximum velocity of action potential upstroke (V-max), the force of contraction, and altered the restitution kinetics of APD. 4. The effect of EGIS-7229 on V-max was frequency dependent; it was most prominent at short pacing cycle lengths (use-dependent block). 5. On the basis of present results, EGIS-7229 appears to carry mixed class I and class III characteristics, Class III properties are present at low concentrations, whereas, at higher concentrations, class I actions may be predominant. GEN PHARMAC 29;2:275-280, 1997. (C) 1997 Elsevier Science Inc.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology 29 : 2 (1997), p. 275-280. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Szénási Gábor Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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9.

001-es BibID:BIBFORM034919
035-os BibID:PMID:21774755 WOS:000294414700012
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Modified cAMP derivatives : powerful tools in heart research / N. Szentandrássy, G. Harmati, V. Farkas, B. Horváth, B. Hegyi, J. Magyar, G. Szénási, I. Márton, P. P. Nánási
Dátum:2011
ISSN:0929-8673
Megjegyzések:Receptor-mediated changes in intracellular cyclic AMP concentration play critical role in the autonomic control of the heart, including regulation of a variety of ion channels via mechanisms involving protein kinase A, EPAC, or direct actions on cyclic nucleotide gated ion channels. In case of any ion channel, the actual signal transduction cascade can be identified by using properly modified cAMP derivatives with altered binding and activating properties. In this study we focus to structural modifications of cAMP resulting in specific activator and blocking effects on PKA or EPAC. Involvement of the cAMP-dependent signal transduction pathway in controlling rapid delayed rectifier K(+ ) current was studied in canine ventricular myocytes using these specific cAMP analogues. Adrenergic stimulation increased the density of I(Kr) in canine ventricular cells, which effect was mediated by a PKA-dependent but EPAC-independent pathway. It was also shown that intracellular application of large concentrations of cAMP failed to fully activate PKA comparing to the effect of isoproterenol, forskolin, or PDE-resistant cAMP derivatives. This difference was fully abolished following inhibition of phosphodiesterase by IBMX. These results are in line with the concept of compartmentalized release, action, and degradation of cAMP within signalosomes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adrenergic stimulation
cAMP analogues
dog myocytes
EPAC
Molekuláris Medicina
intracellular compartmentalization
phosphodiesterase
protein kinase A
rapid delayed rectifier K+ current
cyclic nucleotide
modified cAMP derivatives
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3729-3736. -
További szerzők:Harmati Gábor (1983-) (élettanász) Farkas Viktória Horváth Balázs (1981-) (élettanász) Hegyi Bence (1987-) (élettanász) Magyar János (1961-) (élettanász) Szénási Gábor Márton Ildikó (1954-) (fogszakorvos) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
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