@article{MTMT:2803767,
	title = {Progressive chromogenic anti-factor Xa assay and its use in the classification of antithrombin deficiencies},
	url = {https://m2.mtmt.hu/api/publication/2803767},
	author = {Kovács, Bettina Erzsébet and Bereczky, Zsuzsanna and Selmeczi, Anna and Gindele, Réka and Oláh, Zsolt and Kerenyi, Adrienne and Boda, Zoltán and Muszbek, László},
	doi = {10.1515/cclm-2014-0246},
	journal-iso = {CLIN CHEM LAB MED},
	journal = {CLINICAL CHEMISTRY AND LABORATORY MEDICINE},
	volume = {52},
	unique-id = {2803767},
	issn = {1434-6621},
	year = {2014},
	eissn = {1437-4331},
	pages = {1797-1806},
	orcid-numbers = {Bereczky, Zsuzsanna/0000-0002-1483-3703; Gindele, Réka/0000-0002-4145-3335; Muszbek, László/0000-0002-3798-9962}
}

@article{MTMT:2515572,
	title = {Factor XIII deficiency: complete phenotypic characterization of two cases with novel causative mutations},
	url = {https://m2.mtmt.hu/api/publication/2515572},
	author = {Katona, Éva and Muszbek, László and Devreese, K and Kovács, Kitti Bernadett and Bereczky, Zsuzsanna and Jonkers, M and Shemirani, Amir Houshang and Mondelaers, V and Ermens, AAM},
	doi = {10.1111/hae.12267},
	journal-iso = {HAEMOPHILIA},
	journal = {HAEMOPHILIA},
	volume = {20},
	unique-id = {2515572},
	issn = {1351-8216},
	abstract = {Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A(2)B(2)) in the plasma and as dimer (FXIII-A(2)) in cells. Activated FXIII mechanically stabilizes fibrin and protects it from fibrinolysis by cross-linking fibrin chains and (2)-plasmin inhibitor to fibrin. FXIII is essential to maintaining haemostasis, and its deficiency causes severe bleeding diathesis. Due to improper laboratory practices, FXIII deficiency is considered the most under-diagnosed bleeding disorder. The aim of this study was to demonstrate in two cases how FXIII deficiency is properly diagnosed and classified, and to compare results of laboratory analysis and clinical symptoms. FXIII activity from plasma and platelets was measured by a modified ammonia release assay, while FXIII-A(2)B(2), FXIII-A and FXIII-B antigens were determined by ELISA. The exon-intron boundaries and the promoter region of F13A1 gene were amplified by PCR and the amplified products were analysed by direct fluorescent sequencing. FXIII-A mRNA in platelets was determined by RT-qPCR. Two children with severe bleeding symptoms were investigated. In both cases FXIII activity and FXIII-A antigen were undetectable in the plasma and platelet lysate. In the plasma no FXIII-A(2)B(2) antigen was found, while FXIII-B antigen was >30% in both cases. Proband1 was a compound heterozygote possessing a known missense mutation (c.980G>A, p.Arg326Gln) and a novel splice-site mutation (c.1112+2T>C). Proband2 was homozygote for a novel single nucleotide deletion (c.212delA) leading to early stop codon. The discovered mutations explain the severity of clinical symptoms and the laboratory data. Methods precise in the low activity/antigen range are required to draw valid conclusion on phenotype-genotype relationship.},
	keywords = {EXPRESSION; ASSAY; PLASMA; FIBRIN; A-SUBUNIT; Factor XIII; COAGULATION-FACTOR; splice-site mutation; single nucleotide deletion; rare bleeding disorder; factor XIII-A deficiency; factor XIII determination},
	year = {2014},
	eissn = {1365-2516},
	pages = {114-120},
	orcid-numbers = {Katona, Éva/0000-0003-3476-794X; Muszbek, László/0000-0002-3798-9962; Kovács, Kitti Bernadett/0000-0003-1781-2390; Bereczky, Zsuzsanna/0000-0002-1483-3703}
}

@article{MTMT:2515610,
	title = {The Superiority of Anti-FXa Assay Over Anti-FIIa Assay in Detecting Heparin-Binding Site Antithrombin Deficiency},
	url = {https://m2.mtmt.hu/api/publication/2515610},
	author = {Kovács, Bettina Erzsébet and Bereczky, Zsuzsanna and Oláh, Zsolt and Gindele, Réka and Kerenyi, Adrienne and Selmeczi, A and Boda, Zoltán and Muszbek, László},
	doi = {10.1309/AJCPVY4Z9XZMFOTH},
	journal-iso = {AM J CLIN PATHOL},
	journal = {AMERICAN JOURNAL OF CLINICAL PATHOLOGY},
	volume = {140},
	unique-id = {2515610},
	issn = {0002-9173},
	abstract = {Objectives: Antithrombin is a progressive inhibitor of active factor X (FXa) and thrombin (FIIa). Its effect is 500- to 1,000-fold accelerated by heparin or heparan sulfate. Heterozygous type I (quantitative) and most type II (qualitative) antithrombin deficiencies highly increase the risk of venous thromboembolism (VTE), while homozygous mutations are lethal. The functional defect affecting the heparin-binding site confers moderate risk of VTE to heterozygous and high risk of VTE to homozygous individuals. Methods: Antithrombin activity assays based on the inhibition of FIIa and FXa were compared for their efficiency in detecting heparin-binding site defects. Results: With a single exception, in heterozygotes for heparin-binding site defects (n = 20), anti-FIIa activities remained in the reference interval, while anti-FXa activities were uniformly decreased. In individuals who were homozygous for heparin-binding site mutations (n = 9), anti-FIIa activities were in the range of 48% to 80%; the range of anti-FXa activities was 9% to 25%. Anti-FIIa and anti-FXa activities in type I deficiencies and type II pleiotropic deficiency did not differ significantly. Conclusions: Anti-FXa antithrombin assay is recommended as a first-line test to detect type II heparin-binding site antithrombin deficiency.},
	keywords = {MECHANISM; RISK; PREVALENCE; THROMBOSIS; VARIANT; THROMBOPHILIA; Ternary complex; venous thromboembolism; antithrombin; REVEALS; Antithrombin deficiency; Heparin-binding site defect},
	year = {2013},
	eissn = {1943-7722},
	pages = {675-679},
	orcid-numbers = {Bereczky, Zsuzsanna/0000-0002-1483-3703; Gindele, Réka/0000-0002-4145-3335; Muszbek, László/0000-0002-3798-9962}
}

@article{MTMT:2448651,
	title = {C-(β-D-Glucopyranosyl)formamidrazones, formic acid hydrazides and their transformations into 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles: a synthetic and computational study.},
	url = {https://m2.mtmt.hu/api/publication/2448651},
	author = {Bokor, Éva and Fekete, Attila and Varga, Gergely and Szőcs, Béla and Czifrák, Katalin and Komáromi, István and Somsák, László},
	doi = {10.1016/j.tet.2013.09.099},
	journal-iso = {TETRAHEDRON},
	journal = {TETRAHEDRON},
	volume = {69},
	unique-id = {2448651},
	issn = {0040-4020},
	abstract = {Synthesis of O-perbenzoylated 3-(β-d-glucopyranosyl)-5-substituted-1,2,4-triazoles, precursors of potent inhibitors of glycogen phosphorylase, was studied by ring closures of N1-acyl-carboxamidrazone type intermediates. Reactions of C-(β-d-glucopyranosyl)formimidate or C-(β-d-glucopyranosyl)formamidine with acid hydrazides as well as acylation of C-(β-d-glucopyranosyl)formamidrazone by acid chlorides unexpectedly gave the corresponding 1,3,4-oxadiazoles instead of 1,2,4-triazoles. The desired triazoles were obtained in reactions of C-(β-d-glucopyranosyl)formamidine or C-(β-d-glucopyranosyl)formyl chloride with arenecarboxamidrazones, and also in acylations of N1-tosyl-C-(β-d-glucopyranosyl)formamidrazone with acid chlorides. Theor. calcns. (B3LYP and M06-2X DFT with the std. 6-31G(d,p) basis set) on simple model compds. with Me and Ph substituents to understand the bifurcation of the ring closure of N1-acyl-carboxamidrazones indicated that in general the reaction led to 1,2,4-triazoles. However, the probability of the 1,3,4-oxadiazole forming pathway was shown to be significantly higher with N1-benzoyl-acetamidrazones, which were closest analogs of the intermediates resulting in C-glucosyl-1,3,4-oxadiazoles. It was thereby demonstrated that the substitution pattern of the N1-acyl-carboxamidrazones played a fundamental role in detg. the direction of the ring closing reaction. [on SciFinder(R)]},
	keywords = {ring closure; DFT calculation; 1,3,4-Oxadiazole; C-glucopyranosyl derivative; 1,2,4-Triazole; Molekulatudomány; N1-Acyl-carboxamidrazone},
	year = {2013},
	eissn = {1464-5416},
	pages = {10391-10404},
	orcid-numbers = {Somsák, László/0000-0002-9103-9845}
}

@article{MTMT:2377730,
	title = {Comparison of a New P2Y12 Receptor Specific Platelet Aggregation Test with Other Laboratory Methods in Stroke Patients on Clopidogrel Monotherapy},
	url = {https://m2.mtmt.hu/api/publication/2377730},
	author = {Bagoly, Zsuzsa and Sarkady, F and Magyar, Mária Tünde and Kappelmayer, János and Pongracz, E and Csiba, László and Muszbek, László},
	doi = {10.1371/journal.pone.0069417},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {8},
	unique-id = {2377730},
	issn = {1932-6203},
	abstract = {Background: Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. Objectives: To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy. Patients/Methods: Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute. Results: The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3',5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency. Conclusion: The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.},
	keywords = {INHIBITION; RESISTANCE; PREVALENCE; RESPONSIVENESS; REACTIVITY; ANTIPLATELET THERAPY; STENT IMPLANTATION; VASP-PHOSPHORYLATION; RESPONSE VARIABILITY},
	year = {2013},
	eissn = {1932-6203},
	orcid-numbers = {Bagoly, Zsuzsa/0000-0001-5314-5607; Muszbek, László/0000-0002-3798-9962}
}

@article{MTMT:2363968,
	title = {Direct thrombin inhibitors and factor xa inhibitors can influence the diluted prothrombin time used as the initial screen for lupus anticoagulant},
	url = {https://m2.mtmt.hu/api/publication/2363968},
	author = {Oláh, Zsolt and Szarvas, M and Bereczky, Zsuzsanna and Kerenyi, Adrienne and Kappelmayer, János and Boda, Zoltán},
	doi = {10.5858/arpa.2012-0236-OA},
	journal-iso = {ARCH PATHOL LAB MED},
	journal = {ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE},
	volume = {137},
	unique-id = {2363968},
	issn = {0003-9985},
	abstract = {Context.-Lupus anticoagulant (LA) is a heterogeneous group of antiphospholipid antibodies. Among others, diluted prothrombin time (dPT) is a sensitive screening test for LA; however, the interpretation of LA tests is difficult in patients treated with anticoagulants. The effect of different types of anticoagulants on the result of LA tests, particularly on dPT, has not been studied extensively. Objective.-To determine whether the direct thrombin inhibitors lepirudin and argatroban and the predominantly factor Xa inhibitors enoxaparin, danaparoid, and fondaparinux could interfere with LA screening based on dPT. Design.-Each drug was added to normal and LA-positive plasmas in clinically relevant concentrations. Each sample was tested for dPT. Samples with factor Xa inhibitors were investigated before and after addition of heparinase. Mixing and confirmatory tests for LA were not performed. Results.-In the presence of lepirudin or argatroban, dPT increased notably and the dPT ratio exceeded the cutoff value even at subtherapeutic concentrations resulting in false positivity. With increasing factor Xa inhibitor concentrations, a linear increase of dPT ratios and false-positive results were also demonstrated. Although heparinase could almost completely neutralize the anti-Xa effect of all investigated factor Xa inhibitors, dPT ratio returned to the basal level only in case of enoxaparin. Conclusions.-Here we provide evidence that both the direct thrombin and indirect factor Xa inhibitors influence dPT assay for LA, causing false positivity. This should be considered when interpreting LA results during anticoagulant therapy. However, dPT seems to be a reliable test for LA screening under enoxaparin therapy after neutralization by heparinase.},
	year = {2013},
	eissn = {1543-2165},
	pages = {967-973},
	orcid-numbers = {Bereczky, Zsuzsanna/0000-0002-1483-3703}
}

@article{MTMT:2360113,
	title = {Vitamin B12 level in peripheral arterial disease},
	url = {https://m2.mtmt.hu/api/publication/2360113},
	author = {Zsóri, KS and Csiki, Zoltán and Katona, Éva and Bereczky, Zsuzsanna and Shemirani, Amir Houshang},
	doi = {10.1007/s11239-012-0807-6},
	journal-iso = {J THROMB THROMBOLYS},
	journal = {JOURNAL OF THROMBOSIS AND THROMBOLYSIS},
	volume = {36},
	unique-id = {2360113},
	issn = {0929-5305},
	abstract = {Hyperhomocysteinemia is considered a risk factor for atherosclerosis. Methyltetrahydrofolate reductase (MTHFR) gene mutation and low level of plasma vitamin B12 and folate could take part in the etiology of peripheral arterial disease (PAD). We examined whether plasma vitamin B12 and folate levels and MTHFR-C677T polymorphism are associated with the risk of PAD. The study comprised 293 patients (107 females, 186 males, mean age of 66 ± SEM0.7 years) and 293 sex-matched control subjects (mean age of 62 ± SEM0.8 years). We also determined plasma lipid profile, hs-CRP, creatinine, vitamin B12, folate and total homocysteine (tHcy) for all patients and controls. Odds ratios were non-significant for different genotypes of MTHFR-C677T polymorphism. There was a significant lower level of vitamin B12 in PAD patients. 43 and 25 % of patient and control populations were in the lowest quartile of vitamin B12 (<188 pmol/L), respectively. Plasma level of vitamin B12 in the lowest quartile significantly increased tHcy level in PAD patients, and it was independent of plasma folate level. Low level of plasma vitamin B12 was independently associated with hyperhomocysteinemia in PAD patients. The prevalence of the MTHFR-C677T mutation was not significantly different in patients with PAD compared with controls. © 2012 Springer Science+Business Media, LLC.},
	year = {2013},
	eissn = {1573-742X},
	pages = {77-83},
	orcid-numbers = {Katona, Éva/0000-0003-3476-794X; Bereczky, Zsuzsanna/0000-0002-1483-3703}
}

@article{MTMT:2350429,
	title = {Tetrodotoxin Blockade on Canine Cardiac L-Type Ca2+ Channels Depends on pH and Redox Potential.},
	url = {https://m2.mtmt.hu/api/publication/2350429},
	author = {Hegyi, Bence and Komáromi, István and Kistamás, Kornél and Ruzsnavszky, Ferenc and Váczi, Krisztina and Horváth, Balázs and Magyar, János and Bányász, Tamás and Nánási, Péter Pál and Szentandrássy, Norbert},
	doi = {10.3390/md11062140},
	journal-iso = {MAR DRUGS},
	journal = {MARINE DRUGS},
	volume = {11},
	unique-id = {2350429},
	issn = {1660-3397},
	abstract = {Tetrodotoxin (TTX) is believed to be one of the most selective inhibitors of voltage-gated fast Na+ channels in excitable tissues. Recently, however, TTX has been shown to block L-type Ca2+ current (ICa) in canine cardiac cells. In the present study, the TTX-sensitivity of ICa was studied in isolated canine ventricular myocytes as a function of (1) channel phosphorylation, (2) extracellular pH and (3) the redox potential of the bathing medium using the whole cell voltage clamp technique. Fifty-five micromoles of TTX (IC50 value obtained under physiological conditions) caused 60% +/- 2% inhibition of ICa in acidic (pH = 6.4), while only a 26% +/- 2% block in alkaline (pH = 8.4) milieu. Similarly, the same concentration of TTX induced 62% +/- 6% suppression of ICa in a reductant milieu (containing glutathione + ascorbic acid + dithiothreitol, 1 mM each), in contrast to the 31% +/- 3% blockade obtained in the presence of a strong oxidant (100 muM H2O2). Phosphorylation of the channel protein (induced by 3 muM forskolin) failed to modify the inhibiting potency of TTX; an IC50 value of 50 +/- 4 muM was found in forskolin. The results are in a good accordance with the predictions of our model, indicating that TTX binds, in fact, to the selectivity filter of cardiac L-type Ca channels.},
	keywords = {tetrodotoxin; calcium current; pH dependence; redox potential; DOG HEART},
	year = {2013},
	eissn = {1660-3397},
	pages = {2140-2153},
	orcid-numbers = {Horváth, Balázs/0000-0003-2562-8446; Szentandrássy, Norbert/0000-0003-0197-9567}
}

@article{MTMT:2328210,
	title = {Selectivity problems with drugs acting on cardiac Na+ and Ca2+ channels},
	url = {https://m2.mtmt.hu/api/publication/2328210},
	author = {Hegyi, Bence and Komáromi, István and Nánási, Péter Pál and Szentandrássy, Norbert},
	doi = {10.2174/09298673113209990123},
	journal-iso = {CURR MED CHEM},
	journal = {CURRENT MEDICINAL CHEMISTRY},
	volume = {20},
	unique-id = {2328210},
	issn = {0929-8673},
	abstract = {With the increase of our knowledge on cardioactive agents it comes more and more clear that practically none of the currently used compounds shows absolute selectivity to one or another ion channel type. This is particularly true for Na+ and Ca2+ channel modulators, which are widely applied in the clinical practice and biomedical research. The best example might be probably the marine guanidine poison tetrodotoxin, which has long been considered as a selective Na+ channel blocker, while recently it turned out to effectively inhibit cardiac Ca2+ currents as well. In the present study the cross actions observed between the effects of various blockers of Na+ channels (such as toxin inhibitors, class I antiarrhythmics and local anesthetics) and Ca2+ channels (like phenylalkylamines, dihydropyridine compounds, diltiazem and mibefradil) are overviewed in light of the known details of the respective channel structures. Similarly, activators of Na+ channels, including veratridine and batrachotoxin, are also compared. The binding of tetrodotoxin and saxitoxin to Cav1.2 and Nav1.5 channel proteins is presented by construction of theoretical models to reveal common structures in their pore forming regions to explain cross reactions. Since these four domain channels can be traced back to a common ancestor, a close similarity in their structure can well be demonstrated. Thus, the poor selectivity of agents acting on cardiac Na+ and Ca2+ channels is a consequence of evolution. As a conclusion, since the limited selectivity is an intrinsic property of drug receptors, it has to be taken into account when designing new cardioactive compounds for either medical therapy or experimental research in the future.},
	year = {2013},
	eissn = {1875-533X},
	pages = {2552-2571},
	orcid-numbers = {Szentandrássy, Norbert/0000-0003-0197-9567}
}

@article{MTMT:2323786,
	title = {Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity},
	url = {https://m2.mtmt.hu/api/publication/2323786},
	author = {Lahav, J and Tvito, A and Bagoly, Zsuzsa and Dardik, R and Inbal, A},
	doi = {10.1016/j.thromres.2012.12.003},
	journal-iso = {THROMB RES},
	journal = {THROMBOSIS RESEARCH},
	volume = {131},
	unique-id = {2323786},
	issn = {0049-3848},
	abstract = {Background: Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), and that PDI promotes platelet adhesion and aggregation. Objective: This study sought to examine possible mechanistic effect of FXIII on platelet adhesion to fibrinogen; specifically, the role of its PDI activity. Methods: Ex vivo experiments: Blood platelets derived from five patients with hereditary FXIIIA deficiency before and after treatment with Fibrogammin-P (FXIIIA2B2 concentrate) were washed and incubated on immobilized fibrinogen. Bound platelets were stained and counted by microscopy. In vitro experiments: Platelets derived from patients before treatment and five healthy controls were washed and analyzed for adhesion in the presence or absence of Fibrogammin-P or recombinant FXIII (FXIIIA2 concentrate). Results: In ex vivo experiments, one hour after Fibrogammin-P treatment, mean (+/- SEM) platelet adhesion to fibrinogen increased by 27 +/- 2.32% (p<0.001). In in vitro experiments, treatment with Fibrogammin-P or recombinant FXIII (10 IU/mL each) enhanced platelet adhesion to fibrinogen (in patients, by 29.95 +/- 6.7% and 29.05 +/- 5.3%, respectively; in controls, by 26.06 +/- 3.24% and 26.91 +/- 4.72, respectively; p<0.04 for all). Iodoacetamide-treated FXIII (I-FXIII), where transglutaminase activity is blocked, showed similar enhanced adhesion as untreated FXIII. By contrast, addition of an antibody that specifically blocks FXIIIA-PDI activity inhibited FXIII-mediated platelet adhesion to fibrinogen by 65%. Conclusion: These findings indicate that FXIII-induced enhancement of platelet adhesion is mediated by FXIII-PDI activity. (C) 2012 Elsevier Ltd. All rights reserved.},
	keywords = {EXPRESSION; GENE; OXIDE; PLASMA; TRANSGLUTAMINASE; COAGULATION FACTOR-XIII; ACTIVATION; DEFICIENCY; FAMILIES; EXCHANGE; Factor XIII; Platelet adhesion; PDI},
	year = {2013},
	eissn = {1879-2472},
	pages = {338-341},
	orcid-numbers = {Bagoly, Zsuzsa/0000-0001-5314-5607}
}