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1.

001-es BibID:BIBFORM030268
Első szerző:Jednákovits Andrea
Cím:Effect of subchronic bimoclomol treatment on vascular responsiveness and heat shock protein production in spontaneously hypertensive rats / Andrea Jednákovits, István Kurucz, Péter P. Nánási
Dátum:2000
ISSN:0024-3205
Megjegyzések:This study was designed to investigate the effects of subchronic bimoclomol treatment on endothelial function and expression of 72 kD heat shock protein (HSP-72) in spontaneously hypertensive rats. Endothelial function was tested by monitoring vascular responses to acetylcholine in isolated aortic ring preparations. Polymerase chain reaction was applied to determine HSP-72 mRNA content in the tissue samples. Significant age-dependent declines in relaxation to acetylcholine and vascular HSP-72 mRNA levels were observed in the spontaneously hypertensive animals. Both changes were prevented by subchronic application of bimoclomol suggesting that preservation of endothelial function might be related to sustained levels of HSP-72. (C) 2000 Elsevier Science Inc. All rights reserved.
Tárgyszavak:idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Life Sciences. - 67 : 14 (2000), p. 1791-1797. -
További szerzők:Kurucz István Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM030263
035-os BibID:WOS:000168774300010
Első szerző:Jednákovits Andrea
Cím:In vivo and in vitro acute cardiovascular effects of bimoclomol / Andrea Jednákovits, Péter Ferdinándy, László Jaszlits, Tamás Bányász, János Magyar, Péter Szigligeti, Ágnes Körtvély, József A. Szentmiklósi, Péter P. Nánási
Dátum:2000
ISSN:0306-3623
Megjegyzések:Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was studied in various mammalian cardiac and rabbit aortic preparations. Bimoclomol decreased the ST-segment elevation induced by coronary occlusion in anesthetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary now (CF), decreased the reduction of cardiac output (CO) and left ventricular developed pressure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, precontracted with phenylephrine, bimoclomol induced relaxation (EC50=214 muM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclomol failed to relax preparations precontracted with serotonin, PGF(2) or angiotensin II. All these effects were evident within a few minutes after application of bimoclomol. A rapid bimoclomol-induced compartmental translocation of the already preformed HSPs may explain the protective action of the compound. (C) 2001 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology-the Vascular System. - 34 : 5 (2000), p. 363-369. -
További szerzők:Ferdinándy Péter Jaszlits László Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Körtvély Ágnes Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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3.

001-es BibID:BIBFORM030267
Első szerző:Körtvély Ágnes
Cím:Cardiovascular effects of BRX-005 comparison to bimoclomol / Ágnes Körtvély, Gyula Szigeti, Rudolf Gesztelyi, Judit Zsuga, Tamás Bányász, János Magyar, Péter Szigligeti, László Kovács, Andrea Jednákovits, A. József Szentmiklósi, Péter P. Nánási
Dátum:2000
ISSN:0024-3205
Megjegyzések:Concentration-dependent effects of BRX-005, the novel heat shock protein coinducer, cardioprotective and vasoprotective agent, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea pig hearts loaded with the fluorescent calcium indicator dye Fura-2. BRX-005 increased peak left ventricular pressure, the rate of force development and relaxation significantly in a concentration-dependent manner. The amplitude of [Ca2+](i) transients was left unaltered by the drug, in contrast to BRX-005, bimoclomol increased both contractility and the amplitude of [Ca2+](i) transients, In canine ventricular cardiomyocytes high concentrations of BRX-005 had no effect on depolarization, whereas bimoclomol suppressed action potential upstroke markedly. In guinea pig pulmonary artery preparations precontracted with phenylephrine, BRX-005 induced concentration-dependent relaxation. This effect of BRX-005 was independent of the integrity of endothelium indicating that vasorelaxant effect of the drug develops directly on vascular smooth muscle, (C) 2000 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Life Sciences. - 67 : 14 (2000), p. 1783-1789. -
További szerzők:Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Kovács László (1939-) (élettanász) Jednákovits Andrea Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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4.

001-es BibID:BIBFORM030265
035-os BibID:WOS:000085470500011
Első szerző:Magyar János (élettanász)
Cím:Electrophysiological effects of bimoclomol in canine ventricular myocytes / János Magyar, Tamás Bányász, Péter Szigligeti, Ágnes Körtvély, Andrea Jednákovits, Péter P. Nánási
Dátum:2000
ISSN:0028-1298
Megjegyzések:Concentration-dependent effects of bimoclomol, a novel heat shack protein (HSP) coinducer, were studied on the parameters of action potential and transmembrane ionic currents in enzymatically dispersed canine ventricular cardiomyocytes using conventional microelectrode and whole cell voltage clamp techniques. Bimoclomol (10-100 mu M) decreased the maximum velocity of depolarization ((V) over dot(max)) and amplitude of action potentials in a concentration-dependent manner. These effects were fully reversible after a 5-min period of washout in drug-free medium. Action potential duration measured at 50% or 90% level of repolarization (APD-50 and APD-90, respectively) was markedly shortened by bimoclomol. Both APD-50 and APD-90 were decreased, but the reduction in APD-50 was more pronounced. The APD-shortening effect of bimoclomol was significantly reduced in the presence of 20 nM charybdotoxin (inhibitor of the Ca-dependent K current) or 0.5 mM anthracene-9-carboxylic acid (inhibitor of the Ca-dependent Cl current) or 1 mu M glibenclamide (inhibitor of the ATP-sensitive K current). In the presence of anthracene-9-carboxylic acid, APD-90 was lengthened by bimoclomol. The APD-shortening effect of bimoclomol was also partially antagonized by chelation of intracellular Ca2+ by application of the cell permeant form of BAPTA, or when using 10 mM EGTA-containing patch pipettes to record action potentials. The (V) over dot(max)-depressant effect of bimoclomol was not affected by charybdotoxin, anthracene-9-carboxylic acid, glibenclamide, or BAPTA load. In voltage clamped cardiomyocytes bimoclomol (100 mu M) had no effect all the amplitude of I-Ca, but decreased significantly the inactivation time constant of I-Ca (from 19.8+/-1.6 ms to 16.8+/-1.2 ms at 0 mV). Bimoclomol also decreased significantly the amplitude of I-K1 (from -20.5+/-1.1 pA/pF to -16.6+/-0.8 pA/pF at -135 mV), causing reduction in slope of the negative branch of the I-V curve. At positive potentials, however, bimoclomol increased outward current. The bimoclomol-induced current, therefore, was studied in the presence of BaCl2, when I-K1 current was blocked. The bimoclomol-induced current had a reversal potential close to -90 mV. Bimoclomol (100 mu M) had no effect on the amplitude or kinetic properties of the transient outward K current (I-to) and the delayed rectifier K current (I-K). It is concluded that bimoclomol exerts both Ca-independent (inhibition of I-Na and I-K1, activation of the ATP-sensitive K current) and Ca-dependent effects (mediated by Ca-activated Cl and probably K currents) in canine ventricular myocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 361 : 3 (2000), p. 303-310. -
További szerzők:Bányász Tamás (1960-) (élettanász) Szigligeti Péter Körtvély Ágnes Jednákovits Andrea Nánási Péter Pál (1956-) (élettanász)
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5.

001-es BibID:BIBFORM120391
035-os BibID:(WoS)000089136601707
Első szerző:Nánási Péter Pál (élettanász)
Cím:Biphasic effect of bimoclomol, a new heat shock protein coinducer, on calcium handling in mammalian ventricular myocardium / Nánási P. P., Jóna I., Szigeti G., Jednákovits A.
Dátum:2000
ISSN:0195-668X
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:European Heart Journal. - 21 : Suppl_1 (2000), p. 439. -
További szerzők:Jóna István (1948-) (élettanász, fizikus) Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Jednákovits Andrea
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6.

001-es BibID:BIBFORM030264
035-os BibID:WOS:000086138300017
Első szerző:Nánási Péter Pál (élettanász)
Cím:Biphasic effect of bimoclomol on calcium handling in mammalian ventricular myocardium / Péter P. Nánási, Sándor Sárközi, Gyula Szigeti, István Jóna, Csaba Szegedi, Ágnes Szabó, Tamás Bányász, János Magyar, Péter Szigligeti, Ágnes Körtvély, László Csernoch, László Kovács, Andrea Jednákovits
Dátum:2000
ISSN:0007-1188
Megjegyzések:1 Concentration-dependent effects of bimoclomol, the novel heat shock protein coinducer, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea-pig hearts loaded with the fluorescent calcium indicator dye Fura-2. Bimoclomol had a biphasic effect on contractility: both peak left ventricular pressure and the rate of force development significantly increased at a concentration of 10 nM or higher. The maximal effect was observed between 0.1 and 1 mu M, and the positive inotropic action disappeared by further increasing the concentration of bimoclomol. The drug increased systolic calcium concentration with a similar concentration-dependence. In contrast, diastolic calcium concentration increased monotonically in the presence of bimoclomol. Thus low concentrations of the drug (10-100 nM) increased, whereas high concentrations (10 mu M) decreased the amplitude of intracellular calcium transients. 2 Effects of bimoclomol on action potential configuration was studied in isolated canine ventricular myocytes. Action potential duration was increased at low (10 nM), unaffected at intermediate (0.1-1 mu M) and decreased at high (10-100 mu M) concentrations of the drug. 3 In single canine sarcoplasmic calcium release channels (ryanodine receptor), incorporated into artificial lipid bilayer, bimoclomol significantly increased the open probability of the channel in the concentration range of 1-10 mu M. The increased open probability was associated with increased mean open time. The effect of bimoclomol was again biphasic: the open probability decreased below the control level in the presence of 1 mM bimoclomol. 4 Bimoclomol (10 mu M-1 mM) had no significant effect on the rate of calcium uptake into sarcoplasmic reticulum vesicles of the dog, indicating that in vivo calcium reuptake might not substantially be affected by the drug. 5 In conclusion, the positive inotropic action of bimoclomol is likely due to the activation of the sarcoplasmic reticulum calcium release channel in mammalian ventricular myocardium.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:British Journal of Pharmacology. - 129 : 7 (2000), p. 1405-1412. -
További szerzők:Sárközi Sándor (1966-) (élettanász) Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Jóna István (1948-) (élettanász, fizikus) Szegedi Csaba Szabó Ágnes Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Körtvély Ágnes Csernoch László (1961-) (élettanász) Kovács László (1939-) (élettanász) Jednákovits Andrea
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7.

001-es BibID:BIBFORM030262
Első szerző:Nánási Péter Pál (élettanász)
Cím:Multilateral in vivo and in vitro protective effects of the novel heat shock protein coinducer, bimoclomol : results of preclinical studies / P. P. Nánási, A. Jednákovits
Dátum:2001
ISSN:0897-5957
Megjegyzések:Bimoclomol, the recently developed non-toxic heat shock protein (HSP) coinducer, was shown to display multilateral protective activities against various forms of stress or injuries at the level of the cell, tissue or organism. The compound enhanced the transcription, translation and expression of the 70 kD heat shock protein (HSP-70) in myogenic and HeLa cell lines exposed to heat stress, and increased cell survival on exposure to otherwise lethal thermal injury. Bimoclomol increased contractility of the working mammalian heart, this effect was associated with the increased intracellular calcium transients due to increased probability of opening of ryanodine receptors in the sarcoplasmic reticulum (SR). In healthy tissues these cardiac effects were evident only at relatively high concentrations of the drug, while in the ischemic myocardium bimoclomol exerted significant cardioprotective and antiarrhythmic effects at submicromolar concentrations. It decreased ischemia-induced reduction of contractility and of cardiac output, and dramatically decreased the elevation of the ST-segment during ischemia as well as the occurrence of ventricular fibrillation upon reperfusion. Bimoclomol was also active in various pathological animal models subjected to acute or chronic stress. In the spontaneously hypertensive rats chronic pretreatment with bimoclomol restored sensitivity of aortic rings to acetylcholine; this effect was accompanied by accumulation of HSP-70 in the tissues. Bimoclomol pretreatment significantly diminished the consequences of vascular disorders associated with diabetes mellitus. Diabetic neuropathy, retinopathy, and nephropathy were prevented or diminished, while wound healing was enhanced by bimoclomol. Enhancement of wound healing by bimoclomol was observed after thermal injury as well as following ultraviolet (UV) irradiation. In addition to the beneficial effects on peripheral angiopathies, bimoclomol antagonized the increase in permeability of blood-brain barrier induced by subarachnoid hemorrhage or arachidonic acid. A general and very important feature of the above effects of bimoclomol was that the drug failed to cause alterations under physiological conditions (except the enhanced calcium release from cardiac sarcoplasmic reticulum). Bimoclomol was effective only under conditions of stress. Consistent with its HSP-coinducer property, bimoclomol alone had very little effect on HSP production. Its protective activity became apparent only in the presence of cell damage. Currently, bimoclomol reached the end of the Phase II clinical trial in a group of 410 patients with diabetic complications. Results of this trial will answer the question. whether a compound with promising in vitro and in vivo preclinical findings will produce the anticipated beneficial effects in humans. In the event of a positive outcome of this trial, the indications for bimoclomol will be substantially extended.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cardiovascular Drug Reviews. - 19 : 2 (2001), p. 133-151. -
További szerzők:Jednákovits Andrea
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8.

001-es BibID:BIBFORM030269
Első szerző:Szigeti Gyula (élettanász, elektrofiziológus)
Cím:Effects of bimoclomol, the novel heat shock protein coinducer, in dog ventricular myocardium / Gyula Szigeti, Tamás Bányász, János Magyar, Ágnes Körtvély, Péter Szigligeti, László Kovács, Andrea Jednákovits, Péter P. Nánási
Dátum:2000
ISSN:0024-3205
Megjegyzések:The effects of the novel HSP-coinducer bimoclomol was studied on action potentials, ionic currents and [Ca2+](i) transients in isolated canine ventricular myocytes using conventional microelectrode techniques and whole cell voltage clamp combined with fluorescent [Ca2+](i) measurements. Contractility was studied in right ventricular trabeculae, All preparations were paced with a frequency of 0.2 Hz. Bimoclomol (100 mu M) shortened action potential duration measured at 50% repolarization, but lengthened action potentials at the 90% repolarization level, decreased action potential amplitude and maximum depolarization velocity in a reversible manner. In voltage clamped myocytes, the drug activated a steady-state outward current at positive membrane potentials leaving the peak inward current unaffected, [Ca2+](i) transients, measured under voltage clamp control, were increased in amplitude and had accelerated decay kinetics in the presence of the compound, in addition to reduction of diastolic [Ca2+](i). Bimoclomol significantly decreased the force of contraction in right ventricular trabeculae. Comparison of present data to previous results indicate that the cardiac effects of bimoclomol strongly depend on actual experimental conditions. The reduced contractility in spite of the increased amplitude of [Ca2+](i) transients suggests that 100 mu M bimoclomol may decrease calcium sensitivity of the contractile apparatus. (C) 2000 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Life Sciences. - 67 : 1 (2000), p. 73-79. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Körtvély Ágnes Szigligeti Péter Kovács László (1939-) (élettanász) Jednákovits Andrea Nánási Péter Pál (1956-) (élettanász)
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