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001-es BibID:BIBFORM074794
035-os BibID:(WoS)000447365100097 (Scopus)85052651287
Első szerző:Erdei Tamás Dániel (kísérletes farmakológus)
Cím:FSCPX, a chemical widely used as an irreversible A1 adenosine receptor antagonist, modifies the effect of NBTI, a nucleoside transport inhibitor, by reducing the interstitial adenosine level in the guinea pig atrium / Tamas Erdei, Adrienn Monika Szabo, Nora Lampe, Katalin Szabo, Rita Kiss, Judit Zsuga, Csaba Papp, Akos Pinter, Andras Jozsef Szentmiklosi, Zoltan Szilvassy, Bela Juhasz, Rudolf Gesztelyi
Dátum:2018
ISSN:1420-3049
Megjegyzések:Based on in silico results, recently we have assumed that FSCPX, an irreversible A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on E/c curves of adenosine receptor agonists. As a mechanism for this unexpected effect, we hypothesized that FSCPX might modify the equilibrative and NBTI-sensitive nucleoside transporter (ENT1) in a way that it allows ENT1 to transport adenosine but impedes NBTI to inhibit this transport. This assumption implies that our method developed to estimate receptor reserve for agonists with short half-life such as adenosine, in its original form, overestimates the receptor reserve. In this study, therefore, our goals were to experimentally test our assumption on this effect of FSCPX, to improve our receptor reserve-estimating method, and then to compare the original and improved forms of this method. Thus, we improved our method and assessed the receptor reserve for the direct negative inotropic effect of adenosine with both forms of this method in guinea pig atria. We have found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes participating in the interstitial adenosine production can be hypothesized, while modification of ENT1 can be excluded. Furthermore, we have shown that, in comparison with the improved form, the original version of our method overestimates receptor reserve, but only to a small extent. Nevertheless, use of the improved form is recommended in the future.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adenosine
CPA
FSCPX
NBTI
A1 adenosine receptor
receptorial responsiveness method
atrium
Megjelenés:Molecules. - 23 : 9 (2018), p. 1-17. -
További szerzők:Szabó Adrienn Mónika (1982-) (orvos) Lampé Nóra Szabó Katalin (1989-) (táplálkozástudományi szakember) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Pintér Ákos (1967-) (matematikus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
EFOP
GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Szerző által megadott URL
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2.

001-es BibID:BIBFORM068219
Első szerző:Papp Csaba (aneszteziológus és intenzív terápiás szakorvos)
Cím:Alteration of the irisin-brain-derived neurotrophic factor axis contributes to disturbance of mood in COPD patients / Csaba Papp, Krisztian Pak, Tamas Erdei, Bela Juhasz, Ildiko Seres, Anita Szentpéteri, Laszlo Kardos, Maria Szilasi, Rudolf Gesztelyi, Judit Zsuga
Dátum:2017
ISSN:1176-9106 1178-2005
Megjegyzések:Chronic inflammatory pulmonary disease (COPD) is accompanied by limited physical activity, worse quality of life and increased prevalence of depression. A possible link between COPD and depression may be irisin, a myokine, expression of which in the skeletal muscle and brain positively correlates with physical activity. Irisin enhances the synthesis of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in reward-related processes. Thus, we hypothesized that mood disturbances accompanying COPD are reflected by the changes of the irisin/BDNF axis.Case history, routine laboratory parameters, serum irisin and BDNF levels, pulmonary function and disease-specific quality of life (SGRQ) were determined in a cohort of COPD patients (n=74). Simple and then multiple linear regression was used to evaluate data.We found that mood disturbances is associated with lower serum irisin levels (SGRQ's Impacts score and reciprocal of irisin showed a strong positive association; ?: 419.97; CI: 204.31, 635.63; p<0.001). This association was even stronger among patients in the lower 50% of BDNF levels (?: 434.11; CI: 166.17, 702.05; p=0.002), while it became weaker for patients in the higher 50% of BDNF concentrations (?: 373.49; CI: -74.91, 821.88; p=0.1). These results suggest that irisin exerts beneficial effect on mood in COPD patients, possibly by inducing the expression of BDNF in brain areas associated with reward-related processes involved in by depression. Future interventional studies targeting the irisin-BDNF axis (eg, endurance training) are needed to further support this notion.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
irisin
BDNF
SGRQ
whole-body plethysmography
Megjelenés:International Journal of Chronic Obstructive Pulmonary Disease. - 12 (2017), p. 2023-2033. -
További szerzők:Pák Krisztián (1987-) (gyógyszerész) Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Seres Ildikó (1954-) (biokémikus) Szentpéteri Anita (1988-) (biológus) Kardos László (1970-) (megelőző orvostan és népegészségtan szakorvos) Szilasi Mária (1953-) (tüdőgyógyász, klinikai immunológus, allergológus, belgyógyász) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager)
Pályázati támogatás:GINOP-2.3.2-15-2016-00062
GINOP
AGR-PIAC-13-1- 2013-0008
Egyéb
KTIA_13_NAP-A-V/2
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM082554
035-os BibID:(PMID)31842299 (cikkazonosító)6264 (scopus)85076680797 (wos)000506840100158
Első szerző:Szabó Adrienn Mónika (orvos)
Cím:Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists / Adrienn Monika Szabo, Gabor Viczjan, Tamas Erdei, Ildiko Simon, Rita Kiss, Andras Jozsef Szentmiklosi, Bela Juhasz, Csaba Papp, Judit Zsuga, Akos Pinter, Zoltan Szilvassy, Rudolf Gesztelyi
Dátum:2019
ISSN:1661-6596 1422-0067
Megjegyzések:The receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (cx). The model of RRM describes the co-action of two agonists that consume the same response capacity (due to the use of the same postreceptorial signaling in a biological system). While using RRM, uniquely, an acute increase in the concentration of an agonist (near the receptors) can be quantified (as cx), via evaluating E/c curves that were constructed with the same or another agonist in the same system. As this measurement is sensitive to the implementation of the curve fitting, the goal of the present study was to test RRM by combining di erent ways and setting options, namely: individual vs. global fitting, ordinary vs. robust fitting, and three weighting options (no weighting vs. weighting by 1/Y2 vs. weighting by 1/SD2). During the testing, RRM was used to estimate the known concentrations of stable synthetic A1 adenosine receptor agonists in isolated, paced guinea pig left atria. The estimates were then compared to the known agonist concentrations (to assess the accuracy of RRM); furthermore, the 95% confidence limits of the best-fit values were also considered (to evaluate the precision of RRM). It was found that, although the global fitting o ered the most convenient way to perform RRM, the best estimates were provided by the individual fitting without any weighting, almost irrespective of the fact whether ordinary or robust fitting was chosen.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
A1 adenosine receptor
atrium
heart
receptorial responsiveness method
RRM
Megjelenés:International Journal Of Molecular Sciences. - 20 : 24 (2019), p. 1-14. -
További szerzők:Viczján Gábor (1993-) (kísérletes farmakológus) Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Simon Ildikó (1987-) (radiográfus (BSc) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Juhász Béla (1978-) (kísérletes farmakológus) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Pintér Ákos (1967-) (matematikus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
EFOP
GINOP-2.3.4-15-2016-00002
GINOP
NKFIH-1150-6/2019
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM079164
035-os BibID:(cikkazonosító)2207 (Wos)000473816900013 (Scopus)85067308414
Első szerző:Szabó Adrienn Mónika (orvos)
Cím:An Advanced in silico Modelling of the Interaction between FSCPX, an Irreversible A1 Adenosine Receptor Antagonist, and NBTI, a Nucleoside Transport Inhibitor, in the Guinea Pig Atrium / Adrienn Monika Szabo, Tamas Erdei, Gabor Viczjan, Rita Kiss, Judit Zsuga, Csaba Papp, Akos Pinter, Bela Juhasz, Zoltan Szilvassy, Rudolf Gesztelyi
Dátum:2019
ISSN:1420-3049
Megjegyzések:In earlier studies, we generated concentration-response (E/c) curves with CPA (N6- cyclopentyladenosine; a selective A1 adenosine receptor agonist) and adenosine, in the presence or absence of S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)- benzoyloxy)propyl]-N1-propylxanthine (FSCPX, a chemical known as a selective, irreversible A1 adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e. the co-treatment with FSCPX and NBTI appeared to enhance the direct negative inotropic response to adenosine. In the present in silico study, we aimed to reproduce eight of these E/c curves. Four models (and two additional variants of the last model) were constructed, each one representing a set of assumptions, in order to find the model exhibiting the best fit to the ex vivo data, and to gain insight into the paradoxical phenomenon in question. We have obtained in silico evidence for an interference between effects of FSCPX and NBTI upon our ex vivo experimental setting. Regarding the mechanism of this interference, in silico evidence has been gained for the assumption that FSCPX inhibits the effect of NBTI on the level of endogenous (but not exogenous) adenosine. As an explanation, it may be hypothesized that FSCPX inhibits an enzyme participating in the interstitial adenosine formation. In addition, our results suggest that NBTI does not stop the inward adenosine flux in the guinea pig atrium completely.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
receptorial responsiveness method
RRM
computer simulation
FSCPX
NBTI
adenosine
Megjelenés:Molecules. - 24 : 12 (2019), p. 1-16. -
További szerzők:Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Viczján Gábor (1993-) (kísérletes farmakológus) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Pintér Ákos (1967-) (matematikus) Juhász Béla (1978-) (kísérletes farmakológus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
EFOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

5.

001-es BibID:BIBFORM075286
035-os BibID:(cikkazonosító)818
Első szerző:Zsuga Judit (neurológus, pszichoterapeuta, egészségügyi szakmanager)
Cím:Blind spot for sedentarism : redefining the diseasome of physical inactivity in view of circadian system and the irisin/BDNF axis / Judit Zsuga, Csaba E. More, Tamas Erdei, Csaba Papp, Szilvia Harsanyi, Rudolf Gesztelyi
Dátum:2018
ISSN:1664-2295
Megjegyzések:Introduction: The term "diseasome of physical inactivity" was coined by Pedersen to explain clustering of chronic diseases linked to physical inactivity. Accordingly, physical inactivity per se contributes to the accumulation of visceral fat, which, generates chronic low-grade systemic inflammation, contributes to emergence of chronic, non-communicable diseases. Diversity of these disorders posits the possible involvement of a supraphysiological system. Methods: Hypothesis driven literature search and deductive reasoning was used to review relevant literature and formulate a novel theory. Results: We have identified the circadian system, omnipresent in virtually every cell, as a possible vehicle for brain muscle crosstalk, explaining some aspects of the diseasome of physical inactivity This system is hierarchically organized, with the suprachiasmatic nucleus (SCN) being the master clock that entrains to the dark/light cycle and synchronizes subsidiary molecular clocks in the periphery. Insufficient photic entrainment also causes chronic disease evolution. The recently identified irisin, was shown to induce brain-derived neurotrophic factor (BDNF) production in several brain areas. BDNF assumes significant role in gating light's influence in the retinohypothalamic synapse, by having a permissive effect on glutamate signal transduction underlying photic entrainment. Conclusions: Here we provide theoretical evidence to support the hypothesis that irisin may facilitate photic entrainment of the SCN, via BDNF. By this irisin opens up possible pathways for peripheral non-photic entrainment signals to exert influence on the master clock that is otherwise resistant to these. Furthermore, we suggest that intertwining processes of circadian, redox, inflammatory and myokine systems lay underneath the diseasome of physical inactivity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
cirkadián ritmus
circadian rhythm
irisin
BDNF
Megjelenés:Frontiers in Neurology. - 9 (2018), p. 1-13. -
További szerzők:Móré Elek Csaba (1966-) (pszichiáter szakorvos) Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Kolozsváriné Harsányi Szilvia (1983-) (okleveles egészségpolitikai szakértő) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00009
EFOP
Establishing Thematic Scientific and Cooperation Network for Clinical Research
GINOP-2.3.2-15-2016-00005
GINOP
2017-1.2.1-NKP-2017-00002
egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM069057
035-os BibID:(cikkazonosító)839 (WoS)000404522900156 (Scopus)85020236730
Első szerző:Zsuga Judit (neurológus, pszichoterapeuta, egészségügyi szakmanager)
Cím:Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life / Judit Zsuga, Tamas Erdei, Katalin Szabó, Nora Lampe, Csaba Papp, Akos Pinter, Andras Jozsef Szentmiklosi, Bela Juhasz, Zoltán Szilvássy, Rudolf Gesztelyi
Dátum:2017
ISSN:1420-3049
Megjegyzések:The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration?effect (E/c) curves for the determination), the consequent accumulationof endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditionalreceptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidlyeliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N1-propylxanthine), an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adenozin
szív
A1 adenozin receptor
pitvar
RRM
receptor rezerv
Megjelenés:Molecules. - 22 : 5 (2017), p. 1-17. -
További szerzők:Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Szabó Katalin (1989-) (táplálkozástudományi szakember) Lampé Nóra Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Pintér Ákos (1967-) (matematikus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Juhász Béla (szülész-nőgyógyász) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
Egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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