Comenius University in Bratislava, Slovakia...• Surgical microscopes (module for 5ALA, module for...

FACULTY OF MEDICINEComenius University in Bratislava, Slovakia

MAIN RESEARCH AREAS

FACULTY OF MEDICINEComenius University in Bratislava, Slovakia

MAIN RESEARCH AREAS

As for February 2019

Research at the Faculty of Medicineof the Comenius University in Bratislava

The Faculty of Medicine, which has been developing since 1919, is the first and founding faculty of the Comenius University in Bratislava. The Faculty of Medicine in Bratislava is the largest and oldest medical faculty in Slovakia.

From the beginning, the Faculty of Medicine was focused on two tightly interconnected activities, education and research. In 1921 there was established a scientific medical journal Bratislava Medical Journal (Bratisl Lek Listy), which has been published so far as the oldest medical journal in Slovakia.

In the last decade, the research at the Faculty of Medicine is focused on four main research areas:• Neuroscience• Cardiovascular diseases• Oncological diseases• Metabolic, endocrine, and inflammatory diseases

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Contents

Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1A. Central nervous system tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4B. Neuroanatomy, deep brain stimulation, brain mapping, neuromonitoring . . . . . . . . . . . . . . . . 7C1. Neurodegenerative diseases - dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9C2. Neurodegenerative diseases - Parkinson’s disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11D1. Multiple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14D2. Multiple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16D3. Multiple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17E. Cerebrovascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19F. Sensory diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21G1. Sleep disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23G2. Sleep disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24H1. Depression in adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25H2. Depression in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26I. Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28J. Autism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29K. Neurobiology of cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35A. Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38B. Heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39C. Remodeling in cardiovascular system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41D. Cardiotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44E. Inherited heart defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46F1. Vascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47F2. Vascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49G. Pharmacoepidemiology of cardiovascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51H. Drugs for hypertension therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

Oncological Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55A1. Mammary carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58A2. Mammary carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61B. Testicular cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62C. Tumors of head and neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65D. Innovative clinical applications of diagnostic radiopharmaceuticals . . . . . . . . . . . . . . . . . . . 66E. Late toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67F. Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Metabolic, Endocrine, and Inflammatory Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . 71A1. Diabetes mellitus - diabetic foot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74A2. Diabetes mellitus - monogenic disorders of insulin secretion and action . . . . . . . . . . . . . . . . . 76B. Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79C. Short stature in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81D. Disorders of sexual development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82E. Metabolic syndrome in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84F. Inborn errors of metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86G. Thyroid gland and ORL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88H. Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89I. Autoimmunity and autoinflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92J. Inflammation in cardiovascular diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94K. Rheumatoid arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96L. Inflammatory bowel diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98M. Legionnaires´disease, Leptospirosis, Tularemia, nosocomial infections . . . . . . . . . . . . . . . . . 100N. Sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102O1. Microscopic structure, development and evolution of thymus . . . . . . . . . . . . . . . . . . . . . . 104O2. Microscopic structure and blood microcirculation of spleen . . . . . . . . . . . . . . . . . . . . . . . 106P. Hereditary ciliopathies, RASopathies and tubulopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . 108Q. Extracellular DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110R. Novel biomarkers in chronic kidney disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112S. Bioenergetics and anti-oxidative systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114T. Epidemiology of non-communicable diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117

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Research area Topic Specification

Neurological diseases

Central nervous system tumors

Glioma Optimization of cerebral glioma therapy

Hypophyseal tumors Correlation of expression of cell proliferation markers, immunohistochemical profile, growth features of tumors and patients age with biological features of hormonally active adenoma of hypophysis

Neuroanatomy Brain mapping, neuromonitoring

Per-operative identification of small arterioles reaching deep brain structures

Neurodegenerative diseases

Dementias, Parkinson’s disease, multiple sclerosis

Clinical and therapeutical aspects (role of free radicals and antioxidants)

Multiple sclerosis

Markers of therapeutic outcome

Relation between changes in liquor in patients and clinical and therapeutic outcomes

Genetic polymorphisms Role of polymorphisms and other genetic variations in genes for cytokines and membrane signalization molecules of immune cells in predisposition and progression of multiple sclerosis

Role of inflammation Clinical and therapeutic aspects

Sensory deficits Genetically determined hearing disorders

Genotype of patients with hearing diseases as predictor of success of cochlear implantation

Sleep diseasesCerebral ischemia and sleep disorders

Changes of sleep architecture in patients with focal brain ischemia

Restless legs syndrome Predictors of therapeutic response

Psychiatric diseases

Affective diseasesDepression in adults Neurobiological mechanisms

Depression in children Impact of omega 3 fatty acids on depressive symptoms in children and adolescence

Schizophrenia Psychopathology and pharmacology

Social cognition, psychopharmacology

Neurodevelopmental Autism Etiology of autism, the effect of hormones on cognitive functions

Somatic diseases

Brain and somatic cancer

Neurobiology of cancer Modulatory effect of the brain on development and progression of somatic cancer

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Neuroscience research has a long tradition at the Faculty of Medicine. Whereas in the past research was focused mainly on investigation of axonal transport and morphological features of nerve tissue, recently is represented by investigation of optimal therapy of cerebral gliomas, etiopathogenesis of neurodegenerative diseases, multiple sclerosis, depression and other disease.

Principal investigatorsDr. h. c. Prof. Juraj Šteňo, MD, DSc, IFAANSProf. Peter Valkovič, MD, PhDProf. Viktor Matejčík, MD, PhDAssoc. Prof. Mária Bucová, MD, PhDProf. Boris Mravec, MD, PhDProf. Daniela Ostatníková, MD, PhDProf. Ján Pečeňák, MD, PhDAssoc. Prof. Andrej Šteňo, MD, PhD, MPHProf. Milan Profant, MD, PhDProf. Peter Turčáni, MD, PhD

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A. Central nervous system tumors

InvestigatorsProf. Juraj Šteňo, MD, DSc ([email protected])Assoc. Prof. Gabriela Timárová, MD, PhDAssoc. Prof. Andrej Šteňo, MD, PhDVladimír Hollý, MDProf. Viktor Matejčík, MD, PhDVíťazoslav Belan, MD, PhDPeter Matejička, MDĽubica Pružincová, MDMartin Fabian, MDAnna Peržeľová, MDIvana Siváková, RNDr, PhDIvan Bízik, MD

TopicThe main goals of research of the team:• Improving the treatment of cerebral gliomas: - the possibilities of intraoperative visualization of the lenticulostriate arteries - methods of improvememnt of the intraoperative 3D ultrasound image - the MRI features of initial regrowth of the cerebral gliomas• Study of the variations of the peripheral nerves: - intradural and extradural variations of the spinal nerves - variation of the peripheral nerves are relevant to surgery

Plans for future research• Optimization of cerebral glioma therapy based on results of: - their genotyping, biomarkers determinations, by more precise investigation of their growth dynamics by

employing of serial MRI, - morphological and radiological study of the lenticulostriate arteries.

Devices and methods• Device for pre- and peri-operative stimulation of brain structures and for neuroimaging• 3D navigated sonograph• fMRI, DTI (MR) tractography (imaging of nervous pathways)• Surgical microscopes (module for 5ALA, module for ICG angiography)• Endoscope

Grants and Funding (in the last 10 years)• VEGA 1/3430/06: Dynamics of changes of selected metabolic parameters of gliomas and surrounding brain

tissue after different therapeutic modalities (2006-2008)• VEGA 1/3439/06: Immunocytochemical analysis of glia precursor cells in adult brain tissue an in tissue cultures

(2006-2008)• VEGA 1/1166/10: Correlation between expression of cell proliferation markers, immunohistochemical profile,

growth features of tumor and patient age with biological features of hormonally active hypophyseal adenoma (2011-2014)

mailto:juraj.steno%40fmed.uniba.sk?subject=

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• VEGA 1/0959/16: Correlation of the accuracy of imaging the lenticulostriate arteries in patients with infiltrative gliomas of the insula by means of the intraoperative 3D sonography and the -Tesla MRI (2016-2018)

• VEGA 1/0719/18: Analysis of the influence of the growth activity and the extent of the microsurgical resection of supratentorial infiltrative WHO grade II gliomas on their malignant transformation (2018-2020)

Selected publications• Šteňo J. Craniopharyngiomas. In: M Sindou (ed.): Practical handbook of neurosurgery. From leading neurosurgeons. Wien:

Springer 2009; 235-53.• Šteňo J. Craniopharyngiomas and suprasellar tumors. In: RG Ellenbogen, I Abdulrauf, LN Sekhar (eds.): Principles of

Neurological Surgery. Philadelphia: Elsevier Saunders 2012; 597-620.• Šteňo J, Najjar J, Aboud ET, Elbabaa SK, Knosp E, Aygül M. Approaches to a colloid cyst: Transcranial vs. endoscopic.

Controversies in Neurosurgery 2. New York: Thieme Medical Publishers 2014; 219-37.• Steno J.Microsurgical topography of craniopharyngiomas. Acta Neurochir Suppl (Wien) 1985; 35: 94-100.• Šteňo J, Bízik I, Matejčík V, Šurkala J. Surgical experience with trigeminal neurinomas. Clin Neurosci 1994; 47: 204-6.• Lombardi V, Valko L, Valko M, Scozzafava A, Morris H, Melnik M, Svitel J, Budesinský M, Pelnár J, Steno J, Liptaj T, Zalibera

L, Budinská J, Zlatos J, Giuliani A, Mascolo L, Leibfritz D, Troncone A, Marzullo F, Mazur M, Klener J, Zverina E. 1H NMR ganglioside ceramide resonance region on the differential diagnosis of low and high malignancy of brain gliomas. Cell Mol Neurobiol 1997; 17: 521-35.

• Steno J, Malácek M, Bízik I. Tumor-third ventricular relationships in supradiaphragmatic craniopharyngiomas: correlation of morphological, magnetic resonance imaging, and operative findings. Neurosurgery 2004; 54: 1051-8.

• Pruzincová L, Steno J, Srbecký M, Kalina P, Rychlý B, Boljesíková E, Chorváth M, Novotný M, Procka V, Makaiová I, Belan V. MR imaging of late radiation therapy- and chemotherapy-induced injury: a pictorial essay. Eur Radiol 2009; 19: 2716-27.

• Steňo J, Bízik I, Steňo A, Matejčík V. Craniopharyngiomas in children: how radical should the surgeon be? Childs Nerv Syst 2011; 27: 41-54.

• Steňo J, Bízik I, Steňo A, Matejčík V. Craniopharyngiomas and the hypothalamus. J Neurosurg 2013; 119: 1646-50.• Chorvath M, Boljesikova E, Pruzincova L, Procka V, Rychly B, Novotny M, Kalina P, Belan V, Makaiova I, Steno J. Post-

therapeutical changes in the brain: novel trends in imaging and their infuence on external beam radiotherapy. Neoplasma 2009; 56: 156-62.

• Steno J, Bízik I, Biksadský P. Pineal region teratomas in children. Ann NY Acad Sci 1997; 824: 241-4.• Šteňo A, Bocko J, Rychlý B, Chorváth M, Celec P, Fabian M, Belan V, Šteňo J. Nonfunctioning pituitary adenomas: association

of Ki-67 and HMGA-1 labeling indices with residual tumor growth. Acta Neurochir (Wien) 2014; 156: 451-61.• Šteňo A, Illéš R, Rychlý B, Fabian M, Šteňo J. Detection of anaplastic foci within infiltrative gliomas with nonsignificant

contrast enhancement using 5-aminolevulic acid- a report of five cases. Cesk Neurol Neurochir 2012; 75: 227-32.• Steno J, Jezová D, Belan V, Tomecková E, Vigas M. Radical and selective removal of hyperfunctional hypophyseal adenomas

using a transsphenoidal approach. Cesk Neurol Neurochir 1991; 54: 107-15.• Fabian M, Jezberová M, Pružincová Ľ, Belan V, Chorváth M, Rzchlý B, Kalina P, Šteňo J, Šteňo A. The Effect of Supratentorial

Grade II GLiomas Growth Rate on their Prognosis. Cesk Neurol Neurochir 2015, 78: 274-81.• Malácek M, Steno J. Does selectivity in radical adenomectomy in invasive hypophyseal adenomas increase the risk of

recurrence? Bratisl Lek Listy 1994;95: 349-53.• Steno J, Bizik I, Krajina A, Matejcik V, Surkala J, Profant M, Krist J. Meningioma of the clivus. Bratisl Lek Listy 2000; 101: 200-

5.• Šteňo A, Matejčík V, Šteňo J. Letter to the Editor: Identification of residual glioma using ultrasound miniprobes. Neurosurg

Focus 2016; 41: E15.• Šteňo A, Giussani C, Riva M. Multimodal imaging in glioma surgery. In: Prada F, Solbiati L, Martegani A, DiMeco F (eds):

Intra-operative ultrasound in neurosurgery: from standard B-mode to elastosonography. Vienna: Springer 2016; 81-97.• Šteňo A, Matejčík V, Šteňo J. Intraoperative ultrasound in low-grade glioma surgery. Clin Neurol Neurosurg 2015;135:96-9.• Šteňo J. Skull base involvement in pituitary adenomas. Surgery of the sellar region and paranasal sinuses. In: Samii M (ed.).

Berlin: Springer-Verlag 1991; 302-8.

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• Šteňo A, Karlík M, Mendel P, Čík M, Šteňo J. Navigated three-dimensional intraoperative ultrasound-guided awake resection of low-grade glioma partially infiltrating optic radiation. Acta Neurochir (Wien) 2012; 154: 1255-62.

• Šteňo A, Šteňová V, Belan V, Hollý V, Šurkala J, Šteňo J.Awake resection of adult supratentorial low-grade gliomas located within or adjacent to eloquent areas. Cesk Neurol Neurochir 2011; 74: 539-49.

• Šteňo A, Jezberová M, Hollý V, Timárová G, Šteňo J. Visualization of lenticulostriate arteries during insular low-grade glioma surgeries by navigated 3D ultrasound power Doppler: technical note. J Neurosurgery 2016, 125: 1016-23.

• Šteňo A, Matejčík V, Šteňo J. Letter to the Editor: Identification of residual glioma using ultrasound miniprobes. Neurosurg Focus 2016, 41: E15.

• Maruščáková L, Filová B, Rýchly B, Gomolčák P, Kozák J, Poljak Z, Kopani M, Matejčík V, Šteňo J, Bucová M. Immunological aspects of glioma tumorigenesis. J Neurology Neurophysiology 2016, 7: 39.

• Kubišová K, Martanovič P, Sisovský V, Tomleinova Z, Šteňo A, Janega P, Rýchly B, Babal P. Clinical Study. Dominant neurologic symptomatology in intravascular large B-cell lymphoma. Bratisl Med J 2016, 117: 308-11.

• Šteňo A, Giussani C, Riva M: Multimodal imaging in glioma surgery. In Prada F, Solbiati L, Martegani A, DiMeco F (Eds): Intra-operative ultrasound in neurosurgery: from standard B-mode to elastosonography. Vienna, Springer, 2016, pp 81-97.

• Matejčík V, Haviarová Z, Šteňo A, Kuruc J, Šteňo J. Intraspina, extradural variations of nerve roots. Annals Anat 2017, 211: 114-9.

• Šteňo A, Hollý V, Mendel P, Šteňová V, Petričková Ľ, Timárová G. Jezberová M, Belan V, Rychlý B, Šurkala J, Šteňo J. Navigated 3D- ultrasound versus conventional neuronavigation during awake resection of eloquent low-grade gliomas: a comparative study at a single institution. Acta Neurochir 2017.

• Matejčík V, Haviarová Z, Šteňo A, Kuruc R, Šteňo J. Intraspinal intradural variations of nerve roots. Surg Radiol Anat 2017, 12: 1385-95.

• Haviarová Z, Matejčík V, Kuruc R, Liška J, Šteňo J. Microscopic characteristics of extradural nerve roots anomalies Morphology 2018, 153: 51-2.

• Haviarová Z, Matejčík V, Kuruc R, Šteňo J. Extradural Characteristics of the Origins of Lumbosacral Nerve Roots. J Neurol Surg A Cent Eur Neurosurg 2018.

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B. Neuroanatomy, deep brain stimulation, brain mapping, neuromonitoring

InvestigatorsProf. Juraj Šteňo, MD, DSc ([email protected])Assoc. Prof. Gabriela Timárová, MD, PhDAssoc. Prof. Andrej Šteňo, MD, PhDVladimír Hollý, MDProf. Viktor Matejčík, MD, PhDVíťazoslav Belan, MD, PhDĽubica Pružincová, MDMartin Fabian, MDAnna Peržeľová, MDIvana Siváková, RNDr, PhDIvan Bízik, MDMichal Kľoc, MD, PhDProf. Peter Valkovič, MD, PhDZuzana Košutzká, MD, PhDPeter Matejička, MDAlice Kušnírová, MD

Plans for future research• Verification of reliability of per-operative identification of small arterioles reaching deep brain structures by MRI

and 3D-navigated sonography• Improvement of patient selection for deep brain stimulation• Improvement of electrode targeting and setting of stimulation parameters from long-term perspective

Devices and methods• Device for pre- and peri-operative stimulation of brain structures and for neuroimaging• 3D navigated sonograph• fMRI, DTI (MR) tractography (imaging of nervous pathways)• Surgical microscopes (module for 5ALA, module for ICG angiography)• Endoscope

Grants and Funding (in the last 10 years)• VEGA 1/0959/16: Correlation of imaging preciosity of lenticulostriatal arteries in patients with infiltrative

glioma of insula by intraoperative 3D-sonography with imaging by pre-operative 3-Tesla MRI (2016-2018)

Selected publications• Steno J. Microsurgical topography of craniopharyngiomas. Acta Neurochir Suppl (Wien) 1985; 35: 94-100.• Steno A, Popp AJ, Wolfsberger S, Belan V, Steno J. Persisting embryonal infundibular recess. J Neurosurg 2009; 110: 359-62.• Steňo J, Bízik I, Steňová J, Timárová G. Subtemporal transtentorial resection of cavernous malformations involving the

pyramidal tract in the upper pons and mesencephalon. Acta Neurochir (Wien) 2011; 153: 1955-62.• Siváková I, Peržeľová A, Mráz P, Bízik I, Šteňo J. GFAP-positive astrocytes are rare or absent in primary adult human brain

tissue cultures. Biologia 2009; 64: 833-9.• Steňo A, Hollý V, Fabian M, Kuniak M, Timárová G, Steňo J. Direct electrical stimulation of the optic radiation in patients with

covered eyes. Neurosurg Rev 2014; 37: 527-33.

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• Šteňo A, Jezberová M, Hollý V, Timárová G, Šteňo J. Visualization of lenticulostriate arteries during insular low-grade glioma surgeries by navigated 3D ultrasound power Doppler: technical note. J Neurosurg 2016; 125: 1016-23.

• Steno J. Compression of structures in the visual pathway by arteries of the circle of Willis in suprasellar tumors. Cesk Neurol Neurochir 1989; 52: 143-7.

• Kľoc M, Košutzká Z, Šteňo J, Valkovič P. Prevalent placement error of deep brain stimulation electrode in movement disorders (technical considerations). Bratisl Lek Listy 2017; 118: 647-53.

• Hečková E, Považan M, Strasser B, Krumpolec P, Hnilicová P, Hangel GJ, Moser PA, Andronesi OC, van der Kouwe AJ, Valkovič P, Ukropcova B, Trattnig S, Bogner W. Real-time Correction of Motion and Imager Instability Artifacts during 3D γ-Aminobutyric Acid-edited MR Spectroscopic Imaging. Radiology 2018; 286: 666-75.

• Moro E, Schüpbach M, Wächter T, Allert N, Eleopra R, Honey CR, Rueda M, Schiess MC, Shimo Y, Valkovič P, Whone A, Stoevelaar H. Referring Parkinson’s disease patients for deep brain stimulation: a RAND/UCLA appropriateness study. J Neurol 2016; 263: 112-9.

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C1. Neurodegenerative diseases - dementias

InvestigatorsProf. Peter Turčáni, MD, PhD ([email protected])Prof. Branislav Kollár, MD, PhDPavel Šiarnik, MD, PhDKatarína Klobučníková, MD, PhDAssoc. Prof. Jaroslav Pancák, MD, PhDAssoc. Prof. Stanislav Šutovský, MD, PhDMarián Kondáš, MD, PhDMária Králová, MD, PhDAssoc. Prof. Ján Chandoga, MD, PhDRobert Petrovič, RNDr, PhDMonika Siváková, MDJozef Szabo, MDAssoc. Prof. Mária Bucová, MD, PhDProf. Milan Buc, MD, DScAssoc. Prof. Ivana Shawkatova, RNDr, PhDJuraj Javor, MD, PhD

Plans for future research• Algorithms for early detection of MCI and Alzheimer’s disease• Monitoring of changes in volume of brain structure• Cerebral energetic metabolism in neurodegenerative diseases• Define effects of aerobe-powerful training and/or carnosine at the level of body and muscle-specific metabolism

(in vivo 31P-MRS), physical fitness as well as regulation of GABA/glutamatergic system in the brain (in vivo 1H-MRS) in relationship with intervention in patients with subjective or mild cognitive deficit and in early stages of Alzheimer’s or Parkinson’s disease

• Analysis of miRNA expression in serum, skeletal muscle, and cerebrospinal fluid in relationship with circulating levels of neurotrophins (BDNF), advanced product of glycation (AGEs) as well as with cognitive, motor, and metabolic functions in patients with neurodegenerative diseases

• Differential diagnosis of different types of dementias

Devices and methods• Computer-assisted evaluation of cognitive functions• MR spectroscopy• MR volumetry• In vivo imaging of amyloid and tau protein• Expression of miRNA in serum, muscle, and liquor• Determination of levels of neurotrophins and advanced product of glycation in serum and liquorGrants and Funding (in the last 10 years)• MZ-SR 2005/8-UK-011: Epidemiological and genetic aspects of Alzheimer‘s disease in Slovakia (2006-2008)• APVV- 0048-11: Cognitive-communication alterations in patients with moderate cognitive impairment and

dementia (2012-2015)• APPV-15-0253: Molecular mediators of effects of physical activity and carnosine in patients with preclinical and

early stages of neurodegenerative diseases (2016-2020)• VEGA 1/0240/16: Immunogenetic markers in Slovak patients with Alzheimer‘s disease (2016-2018)

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Selected publications• Ďurmanová V, Shawkatová I, Javor J, Párnická Z, Čopíková-Cundráková D, Turčáni P, Lisá I, Gajdošechová B, Buc M, Bucová

M. VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks. Folia Biol (Praha) 2015; 61: 8-13.• Keményová P, Siarnik P, Sutovský S, Blaho A, Turcáni P, Kollár B. Impairment of endothelial function in patients with multiple

sclerosis. Neuro Endocrinol Lett 2015; 36: 67-71.• Kemenyova P, Turcani P, Sutovsky S, Waczulikova I. Optical coherence tomography and its use in optical neuritis and multiple

sclerosis. Bratisl Lek Listy 2014; 115: 723-9.• Kuračka L, Kalnovičová T, Kucharská J, Turčáni P. Multiple sclerosis: evaluation of purine nucleotide metabolism in central

nervous system in association with serum levels of selected fat-soluble antioxidants. Mult Scler Int 2014; 2014:759808.• Krizova L, Kollar B, Jezova D, Turcani P. Genetic aspects of vitamin D receptor and metabolism in relation to the risk of

multiple sclerosis. Gen Physiol Biophys 2013; 32: 459-66.• Fazekas F, Bajenaru O, Berger T, Fabjan TH, Ledinek AH, Jakab G, Komoly S, Kobys T, Kraus J, Kurča E, Kyriakides T, Lisý

L, Milanov I, Nehrych T, Moskovko S, Panayiotou P, Jazbec SŠ, Sokolova L, Taláb R, Traykov L, Turčáni P, Vass K, Vella N, Voloshyná N, Havrdová E. How does fingolimod (gilenya(®)) fit in the treatment algorithm for highly active relapsing-remitting multiple sclerosis? Front Neurol 2013; 4:10.

• Preiningerova JL, Baumhackl U, Csepany T, Czaplinski A, Deisenhammer F, Derfuss T, Fabjan TH, Fazekas F, Fuchs S, Havrdova E, Ledinek AH, Illes Z, Jazbec SS, Klimova E, Komoly S, Kurca E, Linnebank M, Lisy L, Mares J, Prochazkova L, Csilla R, Szilasiova J, Stourac P, Talab R, Turcani P, Vachova M, Vecsei L, Vodusek D, Zapletalova O, Berger T. Recommendations for the use of prolonged-release fampridine in patients with multiple sclerosis (MS). CNS Neurosci Ther 2013; 19: 302-6.

• Čarnická Z, Kollár B, Šiarnik P, Krížová L, Klobučníková K, Turčáni P. Sleep disorders in patients with multiple sclerosis. J Clin Sleep Med 2015; 11: 553-7.

• Marková J, Horváthová Ľ, Králová M, Cséfalvay Z. Sentence comprehension in Slovak-speaking patients with Alzheimer‘s disease. Int J Lang Commun Disord 2016.

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C2. Neurodegenerative diseases - Parkinson’s disease

InvestigatorsProf. Peter Valkovič, MD, PhD ([email protected])Assoc. Prof. Michal Minár, MD, PhDKarin Gmitterová, MD, PhDZuzana Košutzká, MD, PhDJana Martinková, MD, PhDPetra Brandoburová, PhDMarianna Pápayová, PhDrIgor Straka, MDAlice Kušnírová, MDJana Švantnerová, MDProf. Zsolt Cséfalvay, PhDr, PhDProf. Boris Mravec, MD, PhDProf. Ivan Varga, RNDr, PhDAndrea Gažová, PharmDr, PhDProf. Ján Kyselovič, PharmDr, PhD.Assoc. Prof. Barbara Ukropcová, PhD.Martin Schön, MD

Plans for future research• Detection of new clinical and tissue biomarkers (pre-clinical diagnosis, differential diagnosis, and therapeutical

responses)• Improvement of genetic diagnostic• Research of balance, communication deficits, quality of life, improvement of pharmacotherapy and surgical

treatment (DBS)

Devices and methods• Complex diagnosis of balance with emphasis on 3D motion capture system coupled with virtual reality• Complex psychometric• Imaging methods including 7T and 3T MRI• Complex CSF diagnostic• Histological and immunohistochemical diagnosis

Grants and Funding (in the last 10 years)• MZSR 2007/67/FNsPBA-05: Effect of cognitive dysfunction on postural instability (2008-2010)• VEGA 1/0070/11: Perforation tests of posture in functional diagnostic of sportsmen and individuals with altered

motor functions (2011-2013)• VEGA 2/0138/13: Kinematic analysis of posture and walk in healthy individuals and patients with alteration of

balance (2013-2015)• Novartis Slovakia: Adherence to pharmacotherapy in Parkinson‘s disease (2014-2015)• VEGA 1/0373/14: Functional tests in diagnosis of postural instability and strength of thoracic muscles (2014-

2016)• VEGA 1/0490/16: Effect of catechol-O-methyltransferase inhibitor tolcapone on levodopa induced

hyperhomocysteinaemia among patients with Parkinson’s disease treated with levodopa/carbidopa intestinal gel (2016-2018)

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• APVV 15-0155: Impaired communication ability in Parkinson´s disease (2016-2019)• VEGA 2/0107/18: Synergic effects of exercise and carnosine supplementation on motor state, metabolism and

characteristics of the sceletal muscle in patients with early-stage Parkinson´s disease (2018-2021)• VEGA 1/0704/17: Study of biomarker spectrum in early Parkinson´s disease (2017-2019)• MZSR 2018/32/LFUK/6: Kinematic analysis in virtual reality environment for differential diagnosis of gait

disorders and fall prevention in elderly people (2018-2020)

Selected publications• Valkovič P, Brožová H, Bötzel K, Růžička E, Benetin J. Push and Release Test predicts better Parkinson fallers and nonfallers

than the Pull Test: comparison in OFF and ON medication states. Mov Disord 2008; 23: 1453-57.• Levin J, Krafczyk S, Valkovič P, Eggert T, Claassen J, Bötzel K. Objective measurement of muscle rigidity in parkinsonian

patients treated with subthalamic stimulation. Mov Disord 2009; 24: 57-63.• Gmitterová K, Heinemann U, Gawinecka J, Varges D, Ciesielczyk B, Valkovič P, Benetin J, Zerr I. 8-OHdG in Cerebrospinal

Fluid as a Marker of Oxidative Stress in Various Neurodegenerative Diseases. Neurodegenerative Dis 2009; 6: 263-9.• Martinková J, Trejbalová L, Sásiková M, Benetin J, Valkovič P. Impulse control disorders associated with dopaminergic

medication in patients with pituitary adenomas. Clin Neuropharmacol 2011; 34: 179-81.• Brecl Jakob G, Pelykh O, Košutzká Z, Pirtošek Z, Trošt M, Ilmberger J, Valkovic P, Mehrkens JH, Bötzel K. Postural stability

under globus pallidus internus stimulation for dystonia. Clin Neurophysiol 2015; 126: 2299-305.• Brecl Jakob G, Pelykh O, Plate A, Košutzká Z, Pirtošek Z, Trošt M, Ilmberger J, Valkovic P, Mehrkens JH, Bötzel K. Hypometric

anticipatory postural adjustments in dystonia are not affected by deep brain stimulation of globus pallidus internus. Neurosci Lett 2017; 636: 151-157.

• Škorvánek M, Rosenberger J, Minár M, Grofik M, Haň V, Groothoff JW, Valkovič P, Gdovinová Z, van Dijk JP. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson‘s disease. J Neurol Sci 2015; 353: 87-91.

• Škorvánek M, Minár M, Grofik M, Kračunová K, Haň V, Cibulčík F, Necpál J, Gurčík L, Valkovič P. Validation of the official Slovak version of the Unified Dyskinesia Rating Scale (UDysRS). Parkinsons Dis 2015; 2015: 674796.

• Valkovic P, Minar M, Singliarova H, Harsany J, Hanakova M, Martinkova J, Benetin J. Pain in Parkinson´s disease: A cross-sectional study of its prevalence, types, and relationship to depression and quality of life. PLoS One 2015; 10: e0136541.

• Gracies JM, Brashear A, Jech R, McAllister P, Banach M, Valkovic P, Walker H, Marciniak C, Deltombe T, Skoromets A, Khatkova S, Edgley S, Gul F, Catus F, De Fer BB, Vilain C, Picaut P; International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial. Lancet Neurol 2015; 14(10): 992-1001.

• Moro E, Schüpbach M, Wächter T, Allert N, Eleopra R, Honey C, Rueda M, Schiess M, Shimo Y, Valkovic P, Whone A, Stoevelaar H. Referring Parkinson’s disease patients for deep brain stimulation: results a RAND/UCLA appropriateness study. J Neurol 2016; 263: 112-9.

• Gmitterová K, Minár M, Smutný M, Valkovič P. Continuous intrajejunal levodopa-carbidopa intestinal gel in the treatment of patients with advanced Parkinson’s disease – effects on motor symptoms. Act Nerv Super Rediviva 2015; 57: 57–62.

• Mravec B, Lejavova K, Vargovic P, Ondicova K, Horvathova L, Novak P, Manz G, Filipcik P, Novak M, Kvetnansky R. Tauopathy in transgenic (SHR72) rats impairs function of central noradrenergic system and promotes neuroinflammation. J Neuroinflammation 2016; 13: 15.

• Mravec B, Lejavova K, Cubinkova V. Locus (coeruleus) minoris resistentiae in pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 2014; 11: 992-1001.

• Gmitterová K, Gawinecka J, Llorens F, Varges D, Valkovič P, Zerr I. Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia. Eur Arch Psychiatry Clin Neurosci 2018.

• Straka I, Minár M, Gažová A, Valkovič P, Kyselovič J. Clinical aspects of adherence to pharmacotherapy in Parkinson disease: A PRISMA-compliant systematic review. Medicine (Baltimore) 2018; 97(23):e10962.

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• Krumpolec P, Vallova S, Slobodova L, Tirpakova V, Vajda M, Schon M, Klepochova R, Janakova Z, Straka I, Sutovsky S, Turcani P, Cvecka J, Valkovic L, Tsai CL, Krssak M, Valkovic P, Sedliak M, Ukropcova B, Ukropec J. Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson’s Disease Patients. Front Neurol 2017; 8: 698.

• Rektor I, Bohnen NI, Korczyn AD, Gryb V, Kumar H, Kramberger MG, de Leeuw FE, Pirtošek Z, Rektorová I, Schlesinger I, Slawek J, Valkovič P, Veselý B. An updated diagnostic approach to subtype definition of vascular parkinsonism - Recommendations from an expert working group. Parkinsonism Relat Disord 2018; 49: 9-16.

• Gmitterová K, Gawinecka J, Heinemann U, Valkovič P, Zerr I. DNA versus RNA oxidation in Parkinson’s disease: Which is more important? Neurosci Lett 2018; 662: 22-28.

• Heckova E, Považan M, Strasser B, Krumpolec P, Hnilicová P, Hangel GJ, Moser PA, Andronesi OC, van der Kouwe AJ, Valkovic P, Ukropcova B, Trattnig S, Bogner W. Real-time Correction of Motion and Imager Instability Artifacts during 3D γ-Aminobutyric Acid-edited MR Spectroscopic Imaging. Radiology 2018; 286(2): 666-75.

• Schmitz M, Villar-Piqué A, Llorens F, Gmitterová K, Hermann P, Varges D, Zafar S, Lingor P, Vanderstichele H, Demeyer L, Stoops E, Trojanowski JQ, Lee VM, Zerr I. Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy. Mol Neurobiol 2018.

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D1. Multiple sclerosis

InvestigatorsProf. Peter Turčáni, MD, PhD ([email protected])Prof. Branislav Kollár, MD, PhDMonika Siváková, MDPavel Šiarnik, MD, PhDKatarína Klobučníková, MD, PhDAssoc. Prof. Mária Bucová, MD, PhDProf. Milan Buc, MD, DScAssoc. Prof. Vladimíra Ďurmanová, RNDr, PhDJuraj Javor, MD, PhD

Plans for future research• Determination of the role of mitochomdrial dysfunction on development of neurodegeneration• Determination of presence of specific miRNA in liquor and plasma in multiple sclerosis• Monitoring of changes of brain structures volume• Genetic determination of sclerosis multiplex, the role of cytokines, chemokines, new inflammatory markers

HMGB1 and TREM, miRNA and vitamin D in disease severity monitoring

Devices and methods• Completely equipped laboratory for processing of biological material (serum, liquor, saliva)• EndoPAT 2000 (Itamar-Medical), device for determination of endothelial function• Finometer (Finapres Medical Systems), device for determination of baroreflex sensitivity• PCR -SSP, PCR-RFLP, sequencing - methods for immunogenetic determination• ELISA - method for estimation of the level of cytokines and chemokines

Grants and Funding (in the last 10 years)• VEGA 1/0810/12: Immunogenetic determination of response to biological therapy in patients with multiple

sclerosis (2013-2016)• APVV-0028-10: Interaction of psychological, cardiovascular, neuroendocrine, and metabolic factors: from new

animal models to clinical applications (2011-2014)

Selected publications• Ďurmanová V, Shawkatová I, Javor J, Párnická Z, Čopíková-Cundráková D, Turčáni P, Lisá I, Gajdošechová B, Buc M, Bucová

M. VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks. Folia Biol (Praha) 2015; 61: 8-13.• Keményová P, Siarnik P, Sutovský S, Blaho A, Turcáni P, Kollár B. Impairment of endothelial function in patients with multiple

sclerosis. Neuro Endocrinol Lett 2015; 36: 67-71.• Kemenyova P, Turcani P, Sutovsky S, Waczulikova I. Optical coherence tomography and its use in optical neuritis and multiple

sclerosis. Bratisl Lek Listy 2014; 115: 723-9.• Kuračka L, Kalnovičová T, Kucharská J, Turčáni P. Multiple sclerosis: evaluation of purine nucleotide metabolism in central

nervous system in association with serum levels of selected fat-soluble antioxidants. Mult Scler Int 2014; 2014:759808.• Krizova L, Kollar B, Jezova D, Turcani P. Genetic aspects of vitamin D receptor and metabolism in relation to the risk of

multiple sclerosis. Gen Physiol Biophys 2013; 32: 459-66.

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• Fazekas F, Bajenaru O, Berger T, Fabjan TH, Ledinek AH, Jakab G, Komoly S, Kobys T, Kraus J, Kurča E, Kyriakides T, Lisý L, Milanov I, Nehrych T, Moskovko S, Panayiotou P, Jazbec SŠ, Sokolova L, Taláb R, Traykov L, Turčáni P, Vass K, Vella N, Voloshyná N, Havrdová E. How does fingolimod (gilenya(®)) fit in the treatment algorithm for highly active relapsing-remitting multiple sclerosis? Front Neurol 2013; 4:10.

• Preiningerova JL, Baumhackl U, Csepany T, Czaplinski A, Deisenhammer F, Derfuss T, Fabjan TH, Fazekas F, Fuchs S, Havrdova E, Ledinek AH, Illes Z, Jazbec SS, Klimova E, Komoly S, Kurca E, Linnebank M, Lisy L, Mares J, Prochazkova L, Csilla R, Szilasiova J, Stourac P, Talab R, Turcani P, Vachova M, Vecsei L, Vodusek D, Zapletalova O, Berger T. Recommendations for the use of prolonged-release fampridine in patients with multiple sclerosis (MS). CNS Neurosci Ther 2013; 19: 302-6.

• Čarnická Z, Kollár B, Šiarnik P, Krížová L, Klobučníková K, Turčáni P. Sleep disorders in patients with multiple sclerosis. J Clin Sleep Med 2015; 11: 553-7.

• Shawkatová I, Javor J, Párnická Z, Bucová M, Čopíková-Cudráková D, Michalík J, Gmitterová K, Čierny D, Buc M, Ďurmanová V. Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients. Folia Microbiol (Praha) 2017.

• Čierny D, Michalik J, Škereňová M, Kantorová E, Sivák Š, Javor J, Kurča E, Dobrota D, Lehotský J. ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks. Neurol Res 2016; 38: 678-84.

• Javor J, Párnická Z, Michalik J, Čopíková-Cudráková D, Shawkatová I, Ďurmanová V, Gmitterová K, Klímová E, Bucová M, Buc M. The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals. J Neurol Sci 2015; 349: 138-42.

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InvestigatorsAssoc. Prof. Michal Minár, MD, PhD ([email protected])Prof. Peter Valkovič, MD, PhDDarina Slezáková (Petrleničová), MD, PhDZuzana Košutzká, MD, PhDJana Martinková, MD, PhDIgor Straka, MDMartin Chrastina, MD, PhD

Plans for future research• Epidemiology in general population• Secundarities (pregnancy, multiple sclerosis, neurodegenerative disorders)• Predictors of therapeutic response• Quality of life

Devices and methods• Complex psychodiagnostics• Complex analysis of CSF• Neurophysiological diagnosis• Complex neuroimaging• Continual EEG monitoring

Selected publications• Minár M, Valková P, Valkovič P. Prevalence and impact of restless legs syndrome in university students. Mov Disord 2013; 28:

1157-8.• Minár M, Habánová H, Rusňák I, Planck K, Valkovič P. Prevalence and impact of restless legs syndrome in pregnancy.

Neuroendocrinol Lett 2013; 34: 366–71.• Minár M, Košutzká Z, Habánová H, Rusňák I, Planck K, Valkovič P. Restless legs syndrome in pregnancy is connected with

iron metabolism disturbances. Sleep Med 2015; 16: 589–92.• Chrastina M, Martinková J, Minár M, Žilinská Z, Valkovič P, Breza J. Impact of kidney transplantation on restless legs

syndrome. Bratisl Lek List 2015; 116: 404-7.• Minár M, Petrleničová D, Valkovič P. Restless legs syndrome in multiple sclerosis decreases health-related quality of life. Act

Nerv Super Rediviva 2016; 58: 19–21.• Minár M, Petrleničová D, Valkovič P. Higher prevalence of restless legs syndrome/Willis-Ekbom disease in multiple sclerosis

patients is related to spinal cord lesions. Mult Scler Relat Disord 2017; 12: 54-58

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InvestigatorsAssoc. Prof. Mária Bucová, MD, PhD ([email protected])Juraj Javor, MD, PhDAssoc. Prof. Vladimíra Ďurmanová, RNDr, PhDAssoc. Prof. Ivana Shawkatová, MSc, PhDZuzana Párnická, MD, PhDMagda Suchánková, MD, PhDProf. Milan Buc, MD, DSc

Plans for future research• Immunogenetic determination of inflammation in multiple sclerosis• Polymorphism of cytokines, chemokines, adhesive molecules, vitamin D, transcription factors, receptors• New inflammatory markers, cytokines, hormones, miRNA, vitamin D, soluble HLA-G, oxidative status• Association with clinical stage of patients, EDSS, results of MRI, biologic therapy• Currently, 600 samples are stored, biobanking samples and clinical data

Devices and methods• PCR cyclers, centrifuges• DNA/RNA spectrophotometer, transilluminator• ELFO, photo-recording system• ELISA, flow cytometer

Grants and Funding (in the last 10 years)• VEGA 1/0810/12: Immunogenetic determination of response to biological therapy of patients suffering from

Multiple sclerosis (2012-2014)

Selected publications• Buc M. Role of regulatory T cells in pathogenesis and biological therapy of multiple sclerosis. Mediators Inflamm 2013; 2013:

963748.• Javor J, Párnická Z, Michalik J, Čopíková-Cudráková D, Shawkatová I, Ďurmanová V, Gmitterová K, Klímová E, Bucová M, Buc

M. The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals. J Neurol Sci 2015; 349: 138-42.

• Ďurmanová V, Shawkatová I, Javor J, Párnická Z, Čopíková-Cundráková D, Turčáni P, Lisá I, Gajdošechová B, Buc M, Bucová M. VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks. Folia Biol (Praha) 2015; 61: 8-13.

• Shawkatová I, Javor J, Párnická Z, Bucová M, Čopíková-Cudráková D, Michalík J, Gmitterová K, Čierny D, Buc M, Ďurmanová V. Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients. Folia Microbiol (Praha) 2017.

• Čierny D, Michalik J, Škereňová M, Kantorová E, Sivák Š, Javor J, Kurča E, Dobrota D, Lehotský J. ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks. Neurol Res 2016; 38: 678-84.


• Gajdošechová B, Javor J, Cierny D. (...), Peterajová L, Bucová M. Association of FOXP3 polymorphisms rs3761547 and rs3761548 with multiple sclerosis in the Slovak population. Activitas Nervosa Superior Rediviva 2017; 59: 9-15.

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• Buc M. New biological agents in the treatment of multiple sclerosis. Bratisl Lek Listy 2018; 119: 191-7.• Javor J, Shawkatová I, Ďurmanová V, Párnická Z, Čierny D, Michalik J, Čopíková-Cudráková D, Smahová B, Gmitterová K,

Peterajová Ľ, Bucová M. TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population. Int J Immunogenet 2018.

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E. Cerebrovascular diseases

InvestigatorsProf. Peter Turčáni, MD, PhD ([email protected])Prof. Branislav Kollár, MD, PhDPavel Šiarnik, MD, PhDAssoc. Prof. Marek Sýkora, MD, PhDKatarína Klobučníková, MD, PhDAssoc. Prof. Jaroslav Pancák, MD, PhDAssoc. Prof. Stanislav Šutovský, MD, PhDJozef Szabo, MDZoltán Goldenberg, MD, PhDVladimír Javorka, MD, PhDMagdaléna Mižičková, MDAssoc. Prof. Ingrid Žitňanová, MEng, PhDProf. Stanislav Oravec, MD, PhDProf. Igor Farkaš, MEng, PhDBarbora Cimrová, RNDr, PhD

Plans for future research• Complex investigation of stroke etiopathogenesis• New view on the spectrum of risk factors• Evaluation of drugs effect on brain perfusion• Establishment of new therapeutic approaches in Slovakia• Experimental research of mechanisms participating on stroke development and stroke-induced changes in

organism

Devices and methods• Standard equipment of centre focused on stroke therapy• Complexly equipped laboratory for processing of biological materials (serum, liquor, saliva)• Device for USG determination of brain circulation with possibility to detect embolus• Angiograph• EndoPAT 2000 (Itamar-Medical), device for determination of endothelial functions• Finometer (Finapres Medical Systems), device for determination of baroreflex sensitivity• Polysomnograph Alice 5 and Alice 6 (Philips-Respironics)• C-Flow (Ornim), determination of non-invasive determination of cerebral blood flow• Agregometer and viscosimeter (Chronolog, A. Paar)

Grants and Funding (in the last 10 years)• European Regional Development Fund Research and Development Grant (ITMS 26240120015): Establishment

of centre of excellence for stroke at Faculty of Medicine in Bratislava (2009-2011)• European Regional Development Fund Research and Development Grant (ITMS:26240120023): Completion of

centre of excellence for stroke at Faculty of Medicine in Bratislava (2012-2014)• MZ-SR 2012/10-UKBA-10: Oxidative stress and its role in pathogenesis of stroke (2012-2016)• VEGA 1/3423/064: Pathophysiological mechanisms of cardiovaskular alterations in stroke (2006-2008)• APVV-0668-12: Interface brain-computer with adaptive robotic arm for rehabilitation (2012-2016)

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• MZ-SR 2012/56-SAV-6: Changes of sleep architecture in patients with focal brain ischemia and its influence on cognitive functions (2012-2016)

• APVV-0028-10: Interaction between psychiatric, cardiovascular, neuroendocrin, and metabolic factors: from new animal models to clinical applications (2011-2014)

Selected publications• Szárazová AS, Bartels E, Bartels S, Turčáni P. Possible morphological pathomechanisms of ischemic stroke in the posterior

circulation of patients with vertebral artery hypoplasia. J Neuroimaging 2015; 25: 408-14.• Lenti L, Brainin M, Titianova E, Morovic S, Demarin V, Kalvach P, Skoloudik D, Kobayashi A, Czlonkowska A, Muresanu

DF, Shekhovtsova K, Skvortsova VI, Sternic N, Beslac Bumbasirevic L, Svigelj V, Turcani P, Bereczki D, Csiba L. Stroke carein Central Eastern Europe: current problems and call for action. Int J Stroke 2013; 8: 365-71.

• Sykora M, Steiner T, Rocco A, Turcani P, Hacke W, Diedler J. Baroreflex sensitivity to predict malignant middle cerebral artery infarction. Stroke 2012; 43: 714-9.

• Sykora M, Steiner T, Poli S, Rocco A, Turcani P, Diedler J. Autonomic effectsof intraventricular extension in intracerebral hemorrhage. Neurocrit Care 2012; 16: 102-8.

• Sykora M, Diedler J, Poli S, Rizos T, Kellert L, Turcani P, Steiner T. Association of non-diabetic hyperglycemia with autonomic shift in acute ischaemic stroke. Eur J Neurol 2012; 19: 84-90.

• Sykora M, Diedler J, Poli S, Rizos T, Turcani P, Veltkamp R, Steiner T. Autonomic shift and increased susceptibility to infections after acute intracerebral hemorrhage. Stroke 2011; 42: 1218-23.

• Sykora M, Diedler J, Poli S, Rupp A, Turcani P, Steiner T. Blood pressure course in acute stroke relates to baroreflex dysfunction. Cerebrovasc Dis 2010; 30: 172-9.

• Martiniskova Z, Kucera P, Sykora M, Kollar B, Goldenberg Z, Turcani P. Baroreflex sensitivity in patients with type I diabetes mellitus. Neuro Endocrinol Lett 2009; 30: 491-5.

• Sykora M, Diedler J, Turcani P, Hacke W, Steiner T. Baroreflex: a new therapeutic target in human stroke? Stroke 2009; 40: e678-82.

• Sykora M, Diedler J, Turcani P, Rupp A, Steiner T. Subacute perihematomal edema in intracerebral hemorrhage is associated with impaired blood pressure regulation. J Neurol Sci 2009; 284: 108-12.

• Sykora M, Diedler J, Rupp A, Turcani P, Steiner T. Impaired baroreceptor reflex sensitivity in acute stroke is associated with insular involvement, but not with carotid atherosclerosis. Stroke 2009; 40: 737-42.

• Sykora M, Diedler J, Rupp A, Turcani P, Rocco A, Steiner T. Impaired baroreflex sensitivity predicts outcome of acute intracerebral hemorrhage. Crit Care Med 2008; 36: 3074-9.

• Šiarnik P, Kollár B, Čarnická Z, Šurda P, Klobučníková K, Sýkora M, Turčáni P. Association of sleep disordered breathing with wake-up acute ischemic stroke: a full polysomnographic study. J Clin Sleep Med 2016; 12: 549-54.

• Klobučníková K, Šiarnik P, Čarnická Z, Kollár B, Turčáni P. Causes of excessive daytime sleepiness in patients with acute stroke-A polysomnographic study. J Stroke Cerebrovasc Dis 2016; 25: 83-6.

• Šiarnik P, Kollár B, Čarnická Z, Šutovský S, Klobučníková K, Turčáni P. Characteristics of sleep-disordered breathing in etiologic subtypes of minor-to-moderate acute ischemic stroke. J Stroke Cerebrovasc Dis 2015, 24: 1087-93.

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F. Sensory diseases

InvestigatorsProf. Milan Profant, MD, PhD ([email protected])Assoc. Prof. Zuzana Kabátová, MD, PhDLukáš Varga, MD, MSc, PhDBranislava Bercíkova, MDLucia Demešová, MDZuzana Slobodova, MSc

Plans for future research• Experimental audiology and functional outcomes in different hearing devices• Molecular markers in ear diseases

Devices and methods• Audiology outpatient department• Vestibular section of the Department• Center for cochlear implantation and other implantable hearing devices

Grants and Funding (in the last 10 years)• APVV-15-0067: Identification of new gene variants of hereditary hearing disorders on the base of national

screening (2016-2020)• VEGA 1/0214/16: Wide-exome sequencing in multiplex families with hereditary hearing disorders in Slovakia

(2016-2019)• VEGA 2/0180/15: The study of molecular mechanisms exercise- and cold-induced metabolic activation of

brown/pink fat in humans in relationship with obesity and diabetes type 2 (2015-2017)• APVV-0148-10: Screening of hereditary hearing disorders in Slovakia by methods of DNA analysis (2011-2014)• ASFEU- structural founds of EU (ITMS: 26240220051): TRANSENDOGEN (Transfer of genetic knowledge of

endocrine research into clinical praxis (2010-2014)• VEGA 1/0465/11: Incidence, DNA analysis, and phenotype spectrum of most frequent hereditary hearing

disorders in Slovakia (2011-2013)

Selected publications• Jovankovičová A, Staník R, Kunzo S, Majáková L, Profant M. Surgery or implantable hearing devices in children with

congenital aural atresia: 25 years of our experience. Int J Pediatr Otorhinolaryngol 2015; 79: 975-9.• Mašindová I, Šoltýsová A, Varga L, Mátyás P, Ficek A, Hučková M, Sůrová M, Šafka-Brožková D, Anwar S, Bene J, Straka

S, Janicsek I, Ahmed ZM, Seeman P, Melegh B, Profant M, Klimeš I, Riazuddin S, Kádasi Ľ, Gašperíková D. MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin. PLoS One 2015; 10: e0124232.

• Nayak G, Varga L, Trincot C, Shahzad M, Friedman PL, Klimes I, Greinwald JH Jr, Riazuddin SA, Masindova I, Profant M, Khan SN, Friedman TB, Ahmed ZM, Gasperikova D, Riazuddin S, Riazuddin S. Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss. Hum Genet 2015; 134: 423-37.

• Suchankova M, Paulovicova E, Paulovicova L, Majer I, Tedlova E, Novosadova H, Tibenska E, Tedla M, Bucova M. Increased Antifungal Antibodies in Bronchoalveolar Lavage Fluid and Serum in Pulmonary Sarcoidosis. Scand J Immunol 2015; 81: 259-64.

mailto:profant%40fnorl.sk?subject=

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• Beltrame AM, Todt I, Sprinzl G, Profant M, Schwab B. Consensus statement on round window vibroplasty. Ann Otol Rhinol Laryngol 2014; 123: 734-40.

• Varga L, Kabátová Z, Mašindová I, Nechojdomová D, Gašperíková D, Klimeš I,Profant M. Is deafness etiology important for prediction of functional outcomes in pediatric cochlear implantation? Acta Otolaryngol 2014; 134: 571-8.

• McKinnon BJ, Dumon T, Hagen R, Lesinskas E, Mlynski R, Profant M, Spindel J, Van Beek-King J, Zernotti M. Vibrant soundbridge in aural atresia: does severity matter? Eur Arch Otorhinolaryngol 2014; 271: 1917-21.

• Varga L, Mašindová I, Hučková M, Kabátová Z, Gašperíková D, Klimeš I, Profant M. Prevalence of DFNB1 mutations among cochlear implant users in Slovakia and its clinical implications. Eur Arch Otorhinolaryngol 2014; 271: 1401-7.

• Masindova I, Varga L, Stanik J, Valentinova L, Profant M, Klimes I, Gasperikova D. Molecular and hereditary mechanisms of sensorineural hearing loss with focus on selected endocrinopathies. Endocr Regul 2012; 46: 167-86.

• Profant M, Sláviková K, Kabátová Z, Slezák P, Waczulíková I. Predictive validity of MRI in detecting and following cholesteatoma. Eur Arch Otorhinolaryngol 2012; 269: 757-65.

• Mohammed el R, Profant M. Spontaneous otogenic pneumocephalus. Acta Otolaryngol 2011; 131: 670-4.• Kabátová Z, Profant M et al. Audiology. Grada: Praha 2012; 360 pp.• Profant M Kabátová Z, Varga L. Otosclerosis and Cochlear Implantation. In: Sziklai I. (Ed.): Surgery of Stapes Fixation,

Springer, Cham, Heidelberg, New York, Dordrecht, London 2016; 105-12.• Cremers CW, O‘Connor AF, Helms J, Roberson J, Clarós P, Frenzel H, Profant M, Schmerber S, Streitberger C, Baumgartner

WD, Orfila D, Pringle M, Cenjor C, Giarbini N, Jiang D, Snik AF. International consensus on Vibrant Soundbridge® implantation in children and adolescents. Int J Pediatr Otorhinolaryngol 2010; 74: 1267-9.

• Kabatova Z, Profant M, Simkova L, Groma M, Nechojdomova D. Cochlear implantation in malformed inner ear. Bratisl Lek Listy 2009; 110: 609-13.

• Jakubíková J, Kabátová Z, Pavlovcinová G, Profant M. Newborn hearing screening and strategy for early detection of hearing loss in infants. Int J Pediatr Otorhinolaryngol 2009; 73: 607-12.

• Coninx F, Weichbold V, Tsiakpini L, Autrique E, Bescond G, Tamas L, Compernol A, Georgescu M, Koroleva I, Le Maner-Idrissi G, Liang W, Madell J, Mikić B, Obrycka A, Pankowska A, Pascu A, Popescu R, Radulescu L, Rauhamäki T, Rouev P, Kabatova Z, Spitzer J, Thodi Ch, Varzic F, Vischer M, Wang L, Zavala JS, Brachmaier J. Validation of the LittlEARS((R)) Auditory Questionnaire in children with normal hearing. Int J Pediatr Otorhinolaryngol 2009; 73: 1761-8.

• Profant M, Kabátová Z, Simková L. From hearing screening to cochlear implantation: cochlear implants in children under 3 years of age. Acta Otolaryngol 2008; 128: 369-72.

• Jakubíková J, Kabátová Z, Závodná M. Identification of hearing loss in newborns by transient otoacoustic emissions. Int J Pediatr Otorhinolaryngol 2003; 67: 15-8.

• Profant M, Steno J. Petrous apex cholesteatoma. Acta Otolaryngol 2000; 120: 164-7.

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G1. Sleep disorders

InvestigatorsProf. Peter Turčáni, MD, PhD ([email protected])Prof. Branislav Kollár, MD, PhDPavel Šiarnik, MD, PhDKatarína Klobučníková, MD, PhDAlžbeta Cvičelová, RNDr, PhDMonika Siváková, MDProf. Igor Farkaš, MEng, PhDBarbora Cimrová, RNDr, PhD

Plans for future research• Sleep disturbances in patients with extrapyramidal diseases• Effect of sleep disturbances on cognitive functions• Sleep disturbances in patients with intracerebral hemorrhage• Sleep disturbances in professional sportsmen

Devices and methods• Polysomnograph Alice 5 and Alice 6 (Philips-Respironics)• Auto-BiPAP (Philips-Respironics), device for titration of over-pressure ventilation• EndoPAT 2000 (Itamar-Medical), device for determination of endothelial functions• Finometer (Finapres Medical Systems), device for determination of baroreflex sensitivity

Grants and Funding (in the last 10 years)• MZ-SR 2012/56-SAV-6: Changes of sleep architecture in patients with focal brain ischemia and its influence on

cognitive functions (2012-2016)• European Regional Development Fund Research and Development Grant (ITMS:26240120023): Completion of

centre of excellence for stroke at Faculty of Medicine in Bratislava (2012-2014)

Selected publications• Šiarnik P, Kollár B, Čarnická Z, Šurda P, Klobučníková K, Sýkora M, Turčáni P. Association of Sleep Disordered Breathing with

Wake-Up Acute Ischemic Stroke: A Full Polysomnographic Study. J Clin Sleep Med 2016; 12: 549-54.• Klobučníková K, Šiarnik P, Čarnická Z, Kollár B, Turčáni P. Causes of Excessive Daytime Sleepiness in Patients with Acute

Stroke-A Polysomnographic Study. J Stroke Cerebrovasc Dis 2016; 25: 83-6.• Šiarnik P, Kollár B, Čarnická Z, Šutovský S, Klobučníková K, Turčáni P. Characteristics of Sleep-Disordered Breathing in

Etiologic Subtypes of Minor-to-Moderate Acute Ischemic Stroke. J Stroke Cerebrovasc Dis 2015; 24: 1087-93.• Čarnická Z, Kollár B, Šiarnik P, Krížová L, Klobučníková K, Turčáni P. Sleep disorders in patients with multiple sclerosis. J Clin

Sleep Med 2015; 11: 553-7.• Siarnik P, Carnicka Z, Krizova L, Wagnerova H, Sutovsky S, Klobucnikova K, Kollar B, Turcani P, Sykora M. Predictors of

impaired endothelial function in obstructive sleep apnea syndrome. Neuro Endocrinol Lett 2014; 35: 142-8.• Klobucníková K, Carnická Z, Wagnerová H, Siarnik P. Is nocturnal epilepsy cause of disturbed quality of sleep and elevated

daytime sleepiness? Neuro Endocrinol Lett 2014; 35: 405-10.• Klobucníková K, Kollár B, Martinisková Z. Daytime sleepiness and changes of sleep architecture in patients with epilepsy.

Neuro Endocrinol Lett 2009; 30: 599-603.

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G2. Sleep disorders

InvestigatorsProf. Peter Valkovič, MD, PhD ([email protected])Michal Minár, MD, PhDJana Martinková, MDDarina Petrleničová, MD, PhDIgor Straka, MDZuzana Košutzká, MD

Plans for future research• Epidemiology in general population• Secundarities• Predictors of therapeutic response• Quality of life

Devices and methods• Complex psychodiagnostics• Complex analysis of liquor• Neurophysiological diagnosis• Complex neuroimaging• Continual EEG monitoring

Grants and Funding (in the last 10 years)• Grant of Boehringer Ingelheim: Eporis epidemiology of RLS in Slovakia (2011-2013)

Selected publications• Minár M, Valková P, Valkovič P. Prevalence and impact of restless legs syndrome in university students. Mov Disord 2013; 28:

1157-8.• Minár M, Habánová H, Rusňák I, Planck K, Valkovič P. Prevalence and impact of restless legs syndrome in pregnancy.

Neuroendocrinol Lett 2013; 34: 366–71.• Minár M, Košutzká Z, Habánová H, Rusňák I, Planck K, Valkovič P. Restless legs syndrome in pregnancy is connected with

iron metabolism disturbances. Sleep Med 2015; 16: 589–92.• Chrastina M, Martinková J, Minár M, Žilinská Z, Valkovič P, Breza J. Impact of kidney transplantation on restless legs

syndrome. Bratisl Lek List 2015; 116: 404-7.• Minár M, Petrleničová D, Valkovič P. Restless legs syndrome in multiple sclerosis decreases health-related quality of life. Act

Nerv Super Rediviva 2016; 58: 19–21.

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H1. Depression in adults

InvestigatorsProf. JánPečeňák, MD, PhD ([email protected])Ľubomíra Izáková, MD, PhDKatarína Ondičová, MVD, PhDProf. Boris Mravec, MD, PhD

Grants and Funding (in the last 10 years)• VEGA1/0300/15: Identification of modulatory acitivity of nervus vagus in periferal and central anti-

inflammatory activity of antidepressants and antipsychotics (2015-2017)• VEGA 2/0057/15: The clinical significance of the relationship between aldosterone and depression and the

regulatory mechanisms involved (2015-2017)• VEGA 1/0258/10: The study of mechanisms of peripheral anti-inflammatory effects of antidepressants (2010-

2012)

Selected publications• Segeda V, Izakova L, Hlavacova N, Bednarova A, Jezova D. Aldosterone concentrations in saliva reflect the duration and

severity of depressive episode in a sex dependent manner. J Psychiatr Res 2017; 91: 164-8.• Pecenak J, Novotny V. Agomelatine as monotherapy for major depression: an outpatient, open-label study. Neuropsychiatr Dis

Treat 2013; 9: 1595-604.• Motovsky B, Pecenak J. Psychopathological characteristics of bipolar and unipolar depression - potential indicators of

bipolarity. Psychiatr Danub 2013; 25: 34-9.• Mravec B, Ondicova K, Tillinger A, Pecenak J. Subdiaphragmatic vagotomy enhances stress-induced epinephrine release in

rats. Auton Neurosci 2015; 190: 20-5.• Ondicova K, Pecenák J, Mravec B. The role of the vagus nerve in depression. Neuro Endocrinol Lett 2010; 31: 602-8.

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H2. Depression in children

InvestigatorsAssoc. Prof. Jana Trebatická, MD, PhD ([email protected])Prof. Zdeňka Ďuračková, MEng, PhDProf. Stanislav Oravec, MD, PhDZuzana Matzová, MD, PhDZuzana Hradečná, PhDrAssoc. Prof. Jana Muchová, RNDr, PhDZuzana Padúchová, RNDr, PhDLucia Laubertová, MEng, PhDMartina Horvíthová, MSc, PhDZuzana Deáková, MSc, PhDZuzana Szentéšiová, MScAnna Surovcová, MDBarbora Katrenčíková, MEng

TopicOur research is focused on determination of molecular bases of child psychiatric disorders (depressive disorder, anxiety disorder, ADHD), involvement of inflammation, oxidative stress, corticosteroids in stress response, metabolism of neurotransmitters. We are interested also in the effects of natural compounds as an adjuvant therapy (polyphenols, omega-3 fatty acids).

Plans for future research• Determination of metabolites of neurotransmitters in the blood (HPLC)• Determination of fatty acids composition in erythrocyte membranes (GC)• Determination of korticoids in saliva (Elisa)• Determination of membrane fluidity (fluorospectrometric method)• Determination of telomere length (molecular biology)• Determination of oxidative damage to DNA by Comet assay and kinetic of DNA reparation (Comet assay)

Devices and methods• Determination of oxidative damage to DNA by Comet assay and kinetic of DNA reparation – Comet assay• Spectrophotometric, fluorospectrometric methods, Elisa methods, HPLC and GC methods• Acrylamid electrophoresis of LDL/HDL lipoprotein subfractions (Lipoprint)

Grants and Funding (in the last 10 years)• VEGA 1/0703/13: Molecular bases of childhood psychiatric disorders (depression, anxiety states), involvement of

oxidative stress and the use of omega-3 fatty acids in therapy (2013-2015)• APVV-15-0063: Molecular bases of depressive disorders in children and adolescents, effect of omega-3 fatty acids

and oxidative stress (2016-2020)

Selected publications• Trebatická J, Ďuračková Z. Psychiatric disorders and polyphenols: Can they be helpful in therapy? Oxid Med Cell Longev 2015;

2015: 248529.

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• Vaváková M, Ďuračková Z, Trebatická J. Markers of oxidative stress and neuroprogression in depression Disorder. Oxid Med Cell Longev 2015; 2015: 898393.

• Trebatická J, Dukát A, Ďuračková Z, Muchová J. Cardiovascular diseases, depression disorders and potential effects of omega-3 fatty acids. Physiol Res 2017.

• Trebatická J, Hradečná Z, Böhmer F, Vaváková M, Waczulíková I, Garaiova I, Luha J, Škodáček I, Šuba J, Ďuračková Z. Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents – a pilot study. Child and adolescent psychiatry and mental health 2017.

• Viktorínová A, Ursínyová M, Trebatická J, Uhnáková I, Ďuračková Z, Masanová V. Were plasma trace element levels changed in the children with ADHD? Biol Trace Elem Res 2015; 168: 518-9.

• Viktorínová A, Ursínyová M, Trebatická J, Uhnáková I, Ďuračková Z, Masanová V. Changed plasma levels of zinc and copper to zinc ratio and their possible associations with parent- and teacher-rated symptoms in children with attention-deficit hyperactivity disorder. Biol Trace Elem Res 2016; 169: 1-7.

• Ďuračková Z, Trebatický B, Trebatická J, Muchová J. Targeting mitochondria with natural antioxidants, In: Gvozdjaková A., Cornélissen G a Singh RB (Eds): Recent advances in mitochondrial medicine and CoQ. Nova Biomedica Science Publish 2018; 293-323.

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I. Schizophrenia

InvestigatorsProf. Ján Pečeňák, MD, PhD ([email protected])Michal Hajdúk PhDr, PhD

Grants and Funding (in the last 10 years)• APVV-15-0037: Investigation of anatomical-functional differences between the effects of aripiprazole

and quetiapine, atypical antipsychotics with similar therapeutic indications, but different impact on brain dopaminergic receptors, in experimental animals (2016-2018)

• Slovak Psychiatric Association Grant 2016: Perception and identification of face expression and their relationship to the functioning of patients with schizophrenia (2016)

Selected publications• Pecenák J, Kopeliovic B, Turcek M. Preference for normal, reversed or chimeric self-faces with neutral emotional expression in

patients with schizophrenia and control subjects. Neuro Endocrinol Lett 2014; 35: 497-502.• Mohr P, Rodriguez M, Bravermanová A, Melicher T, Čeplová Z, Čermák J, Pečeňák J. Social and functional capacity of

schizophrenia patients: A cross-sectional study. Int J Soc Psychiatry 2014; 60: 352-8.• Peuskens J, Porsdal V, Pecenak J, Handest P, D‘yachkova Y, Brousil R, Deberdt W. Schizophrenia symptoms and functioning in

patients receiving long-term treatment with olanzapine long-acting injection formulation: a pooled analysis. BMC Psychiatry 2012; 12: 130.

• Majercikova Z, Horvathova L, Osacka J, Pecenak J, Kiss A. Impact of repeated asenapine treatment on FosB/ΔFosB expression in the forebrain structures under normal conditions and mild stress preconditioning in the rat. Brain Res Bull 2016; 127: 29-37.

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J. Autism

InvestigatorsProf. Daniela Ostatníková, MD, PhD ([email protected])Assoc. Prof. Katarína Babinská, MD, PhDSilvia Hnilicová, MD, PhDAleksandra Tomova, MD, PhDAneta Kubranská, MD, PhDMária Vidošovičová, MDJán Bakoš, RNDr, PhDJaroslava Babková, RNDr, PhDGabriela Repiská, MSc, PhDDiana Filčíková, MSc, PhDPetra Keményová, MD, PhDKatarína Janšáková, MSc, PhDKlaudia Kyselicová MSc, PhDAssoc. Prof. Peter Celec, MD, Dipl Eng, Dr Rer Nat, DSc, MPHEmese Renczés Domonkos, MSc, PhDVeronika Borbélyová, MSc, PhDAssoc. Prof. Mária Bucová, MD, PhD

TopicThe autism research project is focused on autism etiopathogenesis. The aims are defined in three lines– human studies, animal modeling and experiments on cell cultures. The general goal is the identification of possible markers (behavioral, endocrine, inflammatory or other) in homogenous subcategories of autistic population. In the Academic Centre for Autism Research being a part of this institution, the standardized diagnosis of autism spectrum disorders (ASD) is performed for indicating well-defined homogenous categories of individuals that are studied in association with possible biomarkers. The dominant approach is related to association of steroid metabolome, proteome and genome to behavioral characteristics. In human line the project also focuses on inflammatory markers and gut microbiota in ASD patients and their possible relations to specific behavioral characteristics and gastrointestinal problems. Sleep disturbances and deviations in melatonin production together with mitochondrial dysfunction is also in scope of the research. In parallel with the human research, animal studies are performed on knockout mice revealing the symptoms linked with knockout gene. The third line of research is focused on cell lines. Morphological changes of knockout mice cell cytoskeleton and synaptogenesis are studied in parallel with the effect of oxytocin on dendritic and axonal growth.

Plans for future research• Investigation of autism etiology• Interventional studies• Investigation of autism epidemiology• Investigation of the role of sex hormones, inflammation, new inflammatory molecules, cytokines and vitamin D

in disease pathology• Investigation of the dietary factors, intestinal microbiota and microbial overgrowth in autism• Investigation of sleep disorders in autism• Investigation of proteomic and metabolomic profiles in autism

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Devices and methods• Standardized international scales for Autism spectrum disorders screening and diagnosis• Sysmex – blood cell analyzer• Centrifuges, PCR cyclers, spectrophotometer, ELISA reader• Actigraph – assessment of sleep disorders by actigraphy• Multiplex cytokine assay• Mass spectrometry - proteomic and metabolomic profiling• Illumina MiSeq sequencer – microbial genome analysis• In vitro neuronal cell culturing• Gene and protein analysis• Light and fluorescent microscopy• Behavioral tests – assessment of autistic-like phenotype of mice• Tests assessing sensory-motor function during early neurodevelopment• EthoVision video-tracking software• Mouse models of autism• Colonoscopy in rodents

Grants and Funding (in the last 10 years)• APVV 15-0045: Autism spectrum disorders from genotype-phenotype perspectives (2016-2019)• APVV 15-0085: Autism in the light of emotional, cognitive and biological contexts (2016-2019)• APVV-15-0205: Alterations in neuritogenesis related to neurodevelopmental disorders (2016-2019)• APVV 0254-11: Social, emotional, and cognitive picture of autism in interdisciplinary reflections (2012-2014)• APVV-0253-10: Developmental effects of neuropetides (2011-2014)• VEGA1/0141/17: Immunogenetic factors and chronic low grade inflammation in pathomechanisms of autism

and their associations with gastrointestinal dysfunction, behavioual and biological markers (2017-2019)• VEGA1/0086/14: Molecular biological analysis of fecal microflora and its impact on inflammation and

gastrointestinal symptoms in autistic children (2014-2016)• VEGA1/0066/12: Genetic factors as modulators of hormonal influences on cognitive functions (2013-2015)• VEGA 1/0955/17: Multimodality of emotion regulation development in adolescents with the typical and atypical

development. Perspective of complex dynamic interplay of structural and functional biological, psychological and social environmental system changes (2017-2020)

• VEGA 1/0286/18: Gut microbiota in children with autism in Slovakia and its correlation with neurological markers and specific behavioral manifestations (2018-2020)

Selected publications• Kelemenova S, Schmidtova E, Ficek A, Celec P, Kubranska A, Ostatnikova D. Polymorphisms of candidate genes in Slovak

autistic patients. Psychiatr Genet 2010, 20: 137-9.• Durdiakova J, Ostatnikova D, Celec P. Testosterone and its metabolites-modulators of brain functions. Acta Neurobiol Exp

2011; 71: 434-54.• Celec P, Tretinarova D, Minarik G, Ficek A, Szemes T, Lakatosova S, Schmidtova E, Turna J, Kadasi L, Ostatnikova D. Genetic

polymorphisms related to testosterone metabolism in intellectually gifted boys. PLoS One 2013; 8: e54751.• Durdiakova J, Lakatosova S, Kubranska A, Laznibatova J, Ficek A, Ostatnikova D, Celec P. Mental rotation in intellectually

gifted boys is affected by androgen receptor CAG repeat polymorphism. Neuropsychol 2013; 51: 1693-8.• Kubranská A, Lakatošová S, Schmidtová E, Durdiaková J, Celec P, Ostatníková D. Spatial abilities are not related to testosterone

levels and variation in the androgen receptor in healthy young men. Gen Physiol Biophys 2014; 33: 311-9.

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• Babinská K, Bucová M, Ďurmanová V, Lakatošová S, Jánošíková D, Bakoš J, Hlavatá A, Ostatníková D. Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiol Res 2014; 63: S613-8.

• Pivovarciova A, Durdiakova J, Hnilicova S, Filcikova D, Ostatnikova D. Testosterone in relation to behavioral problems in pre-pubertal boys with autism spectrum disorders. Physiol Res 2015; 64: S595-601.

• Bakos J, Bacova Z, Grant SG, Castejon AM, Ostatnikova D. Are molecules involved in neuritogenesis and axon guidance related to autism pathogenesis? Neuromolecular Med 2015; 17: 297-304.

• Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, Ostatnikova D. Gastrointestinal microbiota in children with autism in Slovakia. Physiol Behav 2015; 138: 179-87.

• Husarova VM, Lakatosova S, Pivovarciova A, Babinska K, Bakos J, Durdiakova J, Kubranska A, Ondrejka I, Ostatnikova D. Plasma Oxytocin in Children with Autism and Its Correlations with Behavioral Parameters in Children and Parents. Psychiatry Investig 2016 13: 174-83.

• Pivovarciova A, Durdiakova J, Babinska K, Kubranska A, Vokalova L, Minarik G, Celec P, Murin M, Ostatnikova D. Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders. PLoS One 2016; 24: e0149657.

• Bakos J, Zatkova M, Bacova Z, Ostatnikova D. The role of hypothalamic neuropeptides in neurogenesis and neuritogenesis. Neural Plast 2016; 2016: 3276383.

• Borbélyová V, Domonkos E, Bábíčková J, Tóthová Ľ, Bosý M, Hodosy J, Celec P. No effect of testosterone on behavior in aged Wistar rats. Aging (Albany NY) 2016; 8: 2848-61.

• Babinská K, Tomova A, Celušáková H, Babková J, Repiská G, Kubranská A, Filčíková D, Siklenková L, Ostatníková D. Fecal calprotectin levels correlate with main domains of the autism diagnostic interview-revised (ADI-R) in a sample of individuals with autism spectrum disorders from Slovakia. Physiol Res 2017; 66: S517-22

• Borbélyová V, Domonkos E, Csongová M, Kačmárová M, Ostatníková D, Celec P, Hodosy J. Sex-dependent effects of letrozole on anxiety in middle-aged rats. Clin Exp Pharmacol Physiol 2017; 44 Suppl 1: 93-8.

• Domonkos E, Borbélyová V, Csongová M, Bosý M, Kačmárová M, Ostatníková D, Hodosy J, Celec P. Sex differences and sex hormones in anxiety-like behavior of aging rats. Horm Behav 2017; 93: 159-65.

• Borbélyová V, Domonkos E, Bábíčková J, Tóthová Ľ, Kačmárová M, Uličná O, Ostatníková D, Hodosy J, Celec P. Does long-term androgen deficiency lead to metabolic syndrome in middle-aged rats? Exp Gerontol 2017; 98: 38-46.

• Zatkova M, Reichova A, Bacova Z, Strbak V, Kiss A, Bakos J. Neurite Outgrowth Stimulated by Oxytocin Is Modulated by Inhibition of the Calcium Voltage-Gated Channels. Cell Mol Neurobiol 2018; 38: 371-8.

• Domonkos E, Hodosy J, Ostatníková D, Celec P. On the Role of Testosterone in Anxiety-Like Behavior Across Life in Experimental Rodents. Front Endocrinol (Lausanne) 2018; 9: 441.

• Zatkova M, Bacova Z, Puerta F, Lestanova Z, Alanazi M, Kiss A, Reichova A, Castejon AM, Ostatnikova D, Bakos J. Projection length stimulated by oxytocin is modulated by the inhibition of calcium signaling in U-87MG cells. J Neural Transm (Vienna) 2018; 25: 1847-56.

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K. Neurobiology of cancer

InvestigatorsProf. Boris Mravec, MD, PhD ([email protected])Assoc. Prof. Zdenko Pirník, PharmDr, PhDMiroslav Tibenský, MDAlena Černáčková, MScIvana Siváková, RNDr, PhD

TopicOur research is focused on elucidation of pathways and mechanisms participating on bi-directional interactions between the nervous system and cancer tissue in animal tumor models. We have found that elimination of sympathetic nerves significantly reduces growth of solid tumors in rats. In in vitro experiments, we confirmed that administration of norepinephrine potentates tumor cells proliferation. We also found that tumor growth affects activity of several brain structures in rats and that these changes are related to dynamics of cancer growth.

Plans for future research• Determination of phenotypes of nerves innervating selected human cancers• Investigation of effect of reduced nerves-tumor signaling on tumor growth• Investigation of the role of hypothalamic inflammation in mechanisms of cancer cachexia

Devices and methods• Digital stereotaxic apparatus for small laboratory animals• Surgical microscope• Devices and tools for microdissection of brain structures

Grants and Funding (in the last 10 years)• APVV-17-0090: Neurobiological research of cancer: Investigation of bi-directional interactions between the

nervous system and the tumor (2018-2022); principal investigator: Prof. Boris Mravec, MD, PhD• APVV-0007-10: Neurobiology of cancer: the study of nervous system role in cancer growth and development of

metastases (2011-2014)• APVV-0045-06: The role of nervous system in monitoring and modulation of tumorigenesis. New approach in

the study of cancer etiopathogenesis (2007-2009)

Selected publications• Mravec B, Gidron Y, Hulin I. Neurobiology of cancer: interactions between nervous, endocrine and immune systems as a base

for monitoring and modulating the tumorigenesis by the brain. Semin Cancer Biol 2008; 18: 150-63.• Ondicova K, Mravec B. Role of nervous system in cancer aetiopathogenesis. Lancet Oncol 2010; 11: 596–601.• Mravec B. The brain as a target for development of new class of drugs for the treatment of somatic diseases. Exp Opion Ther Targ

2012; 16: 433-7.• Lackovicova L, Gaykema RP, Banovska L, Kiss A, Goehler LE, Mravec B. The time-course of hindbrain neuronal activity varies

according to location during either intraperitoneal or subcutaneous tumor growth in rats: single Fos and dual Fos/dopamine β-hydroxylase immunohistochemistry. J Neuroimmunol 2013; 260: 37-46.

• Horvathova L, Tillinger A, Sivakova I, Mikova L, Mravec B, Bucova M. Chemical sympathectomy increases neutrophil-to-lymphocyte ratio in tumor-bearing rats but does not influence cancer progression. J Neuroimmunol 2015; 278:255-61.

NEUROSCIENCE | 33

• Horvathova L, Padova A, Tillinger A, Osacka J, Bizik J, Mravec B. Sympathectomy reduces tumor weight and affects expression of tumor-related genes in melanoma tissue in the mouse. Stress 2016; 19: 528-34.

• Horvathova L, Tillinger A, Padova A, Mravec B. Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas. Endocr Regul 2016; 50: 207-14.

• Horvathova L, Mravec B. Effect of the autonomic nervous system on cancer progression depends on the type of tumor: solid tumors are more affected then ascitic tumors. Endocr Regul 2016; 50: 215-24.

• Mravec B, Horvathova L, Cernackova A. Hypothalamic inflammation at a crossroad of somatic diseases. Cell Mol Neurobiol 2019; in press.

CARDIOVASCULAR DISEASES 34 |

CARDIOVASCULAR DISEASES | 35

CARDIOVASCULAR DISEASES

Cardiovascular Diseases



Cardiovascular diseases

Heart diseases

Hypertension New pharmacological approaches for protection of hypertension-induced heart damage

Heart failure Early changes in cardiovascular system in arterial hypertension

Remodeling in cardiovascular system

RAAS and remodeling

Cardiotoxicity/oncocardiology

Detection of cardiotoxicity of anti-cancer drugs

Hereditary defects Genetic polymorphisms and the risk of hereditary heart defects

Vascular diseasesVaricosity Investigation of structures of wall of primary varicose

veins

Endothelium Drug effects on endothelial dysfunction

Treatment

Pharmacoepidemiology of cardiovascular diseases

Adherence of patients to drugs used for secondary prevention of cardiovascular diseases in elderly

Drugs for the therapy of hypertension

Role of L-NAME


In the field of cardiovascular disease, research at Faculty of Medicine in Bratislava is focused mainly on investigation of etiopathogenesis of hypertension, heart failure and vessels diseases. Original data were obtained from experiments investigating mechanisms of heart failure and remodeling in cardiovascular system.

Principal investigatorsProf. Viera Štvrtinová, MD, PhDProf. Beáta Mladosievičová, MD, PhDProf. Jozef Mašura, MD, PhD, FSCAI, FESC, FAEPCProf. Andrej Dukát, MD, PhDProf. Ľudovít Gašpar, MD, PhDProf. Ján Murín, MD, PhDĽudovít Paulis, MD, MSc, PhDProf. Fedor Šimko, MD, PhDProf. Martin Wawruch, MD, PhDAssoc. Prof. Jana Poláková-Mištinová, MD, PhD


A. Hypertension

InvestigatorsProf. Ján Murín, MD, PhD ([email protected])Prof. Martin Wawruch, MD, PhD

Grants and Funding (in the last 10 years)• VEGA 1/0939/14: Augmentation (augmentation index) of systolic blood pressure and aortal stiffness and therapy

of arterial hypertension and its complications (2014-2016)

Selected publications• Valentová M, von Haehling S, Doehner W, Murín J, Anker SD, Sandek A. Liver dysfunction and its nutritional implications in

heart failure. Nutrition 2013; 29: 370-8.• Valentova M, von Haehling S, Bauditz J, Doehner W, Ebner N, Bekfani T, Elsner S, Sliziuk V, Scherbakov N, Murín J, Anker

SD, Sandek A. Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation and cachexia in chronic heart failure. Eur Heart J 2016; 37: 1684-91.

• Bulas J, Potočárová M, Murín J, Kozlíková K, Luha J, Čaprnda M. Central Systolic Hypertension in Patients with Well-Controlled Hypertension. Biomed Res Int 2017; 2017: 8158974.

• Celec P, Hodosy J, Jáni P, Janega P, Kúdela M, Kalousová M, Holzerová J, Parrák V, Halčák L, Zima T, Braun M, Pecháň I, Murín J, Šebeková K. Advanced glycation end products in myocardial reperfusion injury. Heart Vessels 2012; 27: 208-15.

• Dobre D, Rossignol P, Murin J, Parkhomenko A, Lamiral Z, Krum H, van Veldhuisen DJ, Pitt B, Zannad F. Statin therapy and clinical outcomes in myocardial infarction patients complicated by acute heart failure: insights from the EPHESUS trial. Eur J Heart Fail 2013; 15: 221-7.

• Gamra H, Murin J, Chiang CE, Naditch-Brûlé L, Brette S, Steg PG; RealiseAF investigators. Use of antithrombotics in atrial fibrillation in Africa, Europe, Asia and SouthAmerica: Insights from the International Realise AF Survey. Arch Cardiovasc Dis 2014; 107: 77-87.

• Chiang CE, Naditch-Brûlé L, Murin J, Goethals M, Inoue H, O‘Neill J, Silva-Cardoso J, Zharinov O, Gamra H, Alam S, Ponikowski P, Lewalter T, Rosenqvist M, Steg PG. Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice. Insight from the real-life global survey evaluating patients with Atrial Fibrillation International Registry. Circ Arrhythm Electrophysiol 2012; 5: 632-9.


B. Heart failure

InvestigatorsProf. Fedor Šimko, MD, PhD ([email protected])

Grants and Funding (in the last 10 years)• VEGA 1/3429/06: Modification of heart hypertrophy and heart failure in NO (nitric oxide)-deficient

hypertension in rats by melatonin (2006-2008)• VEGA 1/0187/09: Modification of heart hypertrophy and heart failure in continuous light-induced hypertension

in rats by melatonin and captopril (2009-2011)• VEGA 1/0227/12: Novel model of experimental hypertension, remodeling of left ventricule and heart failure

induced by inhivition of transcption nuclear factor kappa B (NF-kB): protection by melatonin and captopril (2012-2014)

• VEGA 1/0071/15: Protection of hypertensive and failing heart by blocker of I(f) channel, ivabradine: comparison with ACE-inhibition and melatonin (2015-2018)

• NOREG - Centre of Excellence for Research on the regulatory role of nitric oxide in diseases of civilization (2011-2014)

• APVV -0538-07: Hypertension and diabetes as part of the metabolic syndrome: the effect of antioxidant therapy (2007-2009)

Selected publications• Simko F. Is NO the king? Pathophysiological benefit with uncertain clinical impact. Physiol Res 2007; 56: S1-6.• Paulis L, Simko F. LA419, a novel nitric oxide donor, prevents cardiac remodeling via the endothelial nitric oxide synthase

pathway: NO donors as a means of antiremodeling. Hypertension 2007, 50: 1009-11.• Simko F. Statins: a perspective for left ventricular hypertrophy treatment. Eur J Clin Invest 2007, 37: 681-91.• Simko F, Paulis L. Melatonin as a potential antihypertensive treatment. J Pineal Res 2007; 42: 319-22.• Simko F, Paulis L. Chronotherapy beyond blood pressure reduction? J Pineal Res 2008; 45: 227-28.• Simko F, Pechanova O, Pelouch V, Krajcirovicova K, Müllerova M, Repova K, Adamcova M, Paulis L. Effect of melatonin,

captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats. J Hypertens 2009; 27: S5-10.

• Pechanova O, Simko F. Chronic antioxidant therapy fails to ameliorate hypertension: potential mechanisms behind. J Hypertens 2009; 27: S32-6.

• Simko F, Pechanova O. Recent trends in hypertension treatment: perspectives from animal studies. J Hypertens 2009; 27: S1-4.• Simko F, Pechanova O. Potential roles of melatonin and chronotherapy among the new trends in hypertension treatment. J

Pineal Res 2009; 47: 127-33.• Pechanova O, Simko F. The role of nuclear factor kappa B and nitric oxide interaction in heart remodelling. J Hypertens 2010;

28: S39-44.• Simko F, Pechanova O, Pelouch V, Krajcirovicova K, Celec P, Palffy R, Repova K, Vrankova S, Adamcova M, Paulis L.

Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril. J Hypertens 2010; 28: S13-8.

• Simko F, Pechanova O. Remodelling of the heart and vessels in experimental hypertension: advances in protection. J Hypertens 2010; 28: S1-6.

• Paulis L, Pechanova O, Zicha J, Barta A, Gardlik R, Celec P, Kunes J, Simko F. Melatonin interactions with blood pressure and vascular function during L-NAME-induced hypertension. J Pineal Res 2010; 48: 102-8.

• Simko, F, Paulis L. Hypertensive heart disese: bone marrow as a significant player in pathologic remodelling? J Hypertens 2012; 30: 1702-5.

• Simko F. Chronobiology of blood pressure: emerging implications of melatonin. Europ J Clin Invest 2012; 42: 1252-4.


• Paulis L, Simko F, Laudon M. Cardiovascular effects of melatonin receptor agonists. Expert Opin Invest Drugs 2012; 21:1661-78.• Simko F, Paulis L. Antifibrotic effect of melatonin-Perspective protection in hypertensive heart disease. Int J Cardiol 2013; 168:

2876-7.• Simko F, Reiter RJ, Pechanova O, Paulis L. Experimental models of melatonin-deficient hypertension. Front Biosci (Landmark

Ed) 2013; 18: 616-25.• Simko F, Pechanova O, Repova K, Krajcirovicova K, Celec P, Kamodyova N, Zorad S, Kucharska J, Gvozdjakova A, Adamcova

M, Paulis L. Hypertension and cardiovascular remodelling in rats exposed to continuous light: protection by ACE-inhibition andmelatonin. Mediators Inflamm 2014; 2014: 3175.

• Simko F, Repova K, Krajcirovicova K, Hrenak J, Celec P, Kamodyova N, Gajdosechova L, Zorad S, Adamcova M. Melatonin reduces cardiac remodeling and improves survival in rats with isoproterenol-induced heart failure. J Pineal Res 2014, 57: 177-84.

• Simko F, Pechanova O, Krajcirovicova K, Matuskova J, Pelouch V, Adamcova M, Paulis L. Effects of captopril,spironolactone, and simvastatin on the cardiovascular system of non-diseased Wistar rats. Int J Cardiol 2015; 190: 128-30.

• Simko F, Baka T, Paulis L, Reiter R J. Elevated heart rate and nondipping heart rate as potential targets for melatonin: a review. J Pineal Res 2016; 61: 127-37.


C. Remodeling in cardiovascular system

InvestigatorsĽudovít Paulis, MD, MSc, MPH, PhD ([email protected])Simona Trubačová, MScRomana Rajkovičová, MScNina Paššákova, MDDominika Kováčová, Eng

TopicOur research is focused on the elucidation and development of novel means for the prevention/treatment of adverse cardiovascular remodeling. Previously, we have described mechanisms responsible for the persistence ofendothelial dysfunction (enhanced formation of endothelium-derived constricting factor) even after normalization of blood pressure, the desynchronized regression of fibrosis and hypertrophy of the left ventricle and the possible effects of melatonin on these outcomes. More recently, we focused the research interest on novel means of renin-angiotensin system modulation. We have described the de-stiffening properties of AT2 receptor stimulation using the investigational compound 21 in hypertension. Currently, we participate in the development of a new therapeutic approach using novel dual aminopeptidase inhibition of the renin-angiotensin-aldosterone system.For our research, we employ methods allowing bench-to-bedside translation of experimental outcomes such as animal disease models, animal echocardiography, ex vivo vessel reactivity and biochemical tests having pendants in clinical practice. Those are being supplemented by statistical analyses, meta-analysis and systematic reviews.

Plans for future research• Development of feasible peptide/non-peptide dual renin-angiotensin-aldosterone aminopeptidase inhibitor• Investigation of the effects of dual aminopeptidase inhibition on heart failure and hemodynamically overloaded

left or right ventricle

Devices and methods• Rodent models of hypertension, pulmonary hypertension and heart failure• Rodent echocardiography• Ex vivo vessel reactivity and biochemical tests having pendants in clinical practice

Grants and Funding (in the last 10 years)• VEGA 1/0127/17: Proof of concept of renin-angiotensin system (RAS) modulation by dual aminopeptidase/

angiotenangiotensin-converting enzyme (AP/ACE) inhibition and its effect on target organ damage in hemodynamic overload (2017-2020)

• VEGA 1/0380/14: The effect of pharmacological stimulation of AT2 receptors on morphology and functional characteristics of failing myocardium in rats (2014-2016)

• APVV-0205-11: The effect of long-term stimulation of AT2 receptors on cardiovascular system: the effect on remodeling and its mechanisms (2012-2015)

• VEGA 1/0831/11: Possible modulation of myocardial and vessels remodeling by pharmacological stimulation of AT2 receptors (2011-2013)

• 7. EU FP IEF 2009-237834: COmpound21 and MElatonin in CArdiovascular REmodeling (COME-in-CARE) (2009-2011)


Selected publications• Simko F, Baka T, Poglitsch M, Repova K, Aziriova S, Krajcirovicova K, Zorad S, Adamcova M, Paulis L. Effect of Ivabradine on

a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension. Int J Mol Sci 2018; 19: E3017.

• Baka T, Hodosy J, Krajcirovicova K, Repova K, Aziriova S, Domonkos E, Borbelyova V, Slavkovsky P, Zorad S, Celec P, Paulis L, Simko F. 17β-Estradiol treatment reversed left ventricular dysfunction in castrated male rats: an echocardiographic study. Can J Physiol Pharmacol 2018; 96: 850-4.

• Simko F, Baka T, Krajcirovicova K, Repova K, Aziriova S, Zorad S, Poglitsch M, Adamcova M, Reiter RJ, Paulis L. Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in l-NAME-Induced Hypertension. Molecules 2018; 23.

• Paulis L, Franke H, Simko F. Gene therapy for hypertension. Expert Opin Biol Ther 2017; 17: 1345-61.• Madaric J, Valachovicova M, Paulis L, Pribojova J, Mateova R, Sebekova K, Postulkova L, Madaricova T, Bucova M, Mistrik

M, Vulev I. Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia. Stem Cell Res Ther 2017; 8: 165.

• van Thiel BS, Góes Martini A, Te Riet L, Severs D, Uijl E, Garrelds IM, Leijten FPJ, van der Pluijm I, Essers J, Qadri F, Alenina N, Bader M, Paulis L, Rajkovicova R, Domenig O, Poglitsch M, Danser AHJ. Brain renin-angiotensin system: Does it exist? Hypertension 2017; 69: 1136-44.

• Paulis L, Foulquier S, Namsolleck P, Recarti C, Steckelings UM, Unger T. Combined angiotensin receptor modulation in the management of cardio-metabolic disorders. Drugs 2016; 76: 1-12.

• Paulis L, Rajkovicova R, Simko F. New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon? Curr Hypertens Rep 2015; 17: 557.

• Paulis L, Fauconnier J, Cazorla O, Thireau J, Soleti R, Vidal B, Ouillé A, Bartholome M, Bideaux P, Roubille F, Le Guennec JY, Andriantsitohaina R, Martínez MC, Lacampagne A. Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts cardioprotection against ischemia reperfusion injuries. Sci Rep 2015; 5: 7983.

• Simko F, Pechanova O, Repova Bednarova K, Krajcirovicova K, Celec P, Kamodyova N, Zorad S, Kucharska J, Gvozdjakova A, Adamcova M, Paulis L. Hypertension and cardiovascular remodelling in rats exposed to continuous light: protection by ACE-inhibition and melatonin. Mediators Inflamm 2014; 2014: 703175.

• Schmerler P, Jeuthe S, O h-Ici D, Wassilew K, Lauer D, Kaschina E, Kintscher U, Müller S, Muench F, Kuehne T, Berger F, Unger T, Steckelings UM, Paulis L, Messroghli D. Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats. Acta Physiol (Oxf) 2014; 210: 889-98.

• Hrenák J, Arendášová K, Rajkovičová R, Aziriová S, Repová K, Krajčírovičová K, Celec P, Kamodyová N, Bárta A, Adamcová M, Paulis L, Simko F. Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats. Physiol Res 2013; 62: S181-9.

• Simko F, Reiter RJ, Pechanova O, Paulis L. Experimental models of melatonin-deficient hypertension. Front Biosci (Landmark Ed) 2013; 18: 616-25.

• Paulis L, Simko F, Laudon M. Cardiovascular effects of melatonin receptor agonists. Expert Opin Investig Drugs 2012; 21: 1661-78.

• Paulis L, Steckelings UM, Unger T. Key advances in antihypertensive treatment. Nat Rev Cardiol 2012; 9: 276-85.• Paulis L, Becker ST, Lucht K, Schwengel K, Slavic S, Kaschina E, Thöne-Reineke C, Dahlöf B, Baulmann J, Unger T, Steckelings

UM. Direct angiotensin II type 2 receptor stimulation in Nω-nitro-L-arginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling. Hypertension 2012; 59: 485-92.

• Unger T, Paulis L, Sica DA. Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches. Eur Heart J 2011; 32: 2739-47.

• Paulis L, Pechanova O, Zicha J, Liskova S, Celec P, Mullerova M, Kollar J, Behuliak M, Kunes J, Adamcova M, Simko F. Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment. J Hypertens 2010; 28: S19-24.

• Paulis L, Unger T. Novel therapeutic targets for hypertension. Nat Rev Cardiol 2010; 7: 431-41.• Paulis L, Pechanova O, Zicha J, Barta A, Gardlik R, Celec P, Kunes J, Simko F. Melatonin interactions with blood pressure and

vascular function during L-NAME-induced hypertension. J Pineal Res 2010; 48: 102-8.


• Paulis L, Pechanova O, Zicha J, Krajcirovicova K, Barta A, Pelouch V, Adamcova M, Simko F. Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats. J Hypertens Suppl 2009; 27: S11-6.

• Paulis L, Zicha J, Kunes J, Hojna S, Behuliak M, Celec P, Kojsova S, Pechanova O, Simko F. Regression of L-NAME-induced hypertension: the role of nitric oxide and endothelium-derived constricting factor. Hypertens Res 2008; 31: 793-803.

• Paulis L, Matuskova J, Adamcova M, Pelouch V, Simko J, Krajcirovicova K, Potacova A, Hulin I, Janega P, Pechanova O, Simko F. Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone. Acta Physiol (Oxf) 2008; 194: 45-55.

• Paulis L, Simko F. Blood pressure modulation and cardiovascular protection by melatonin: potential mechanisms behind. Physiol Res 2007; 56: 671-84.

• Paulis L, Simko F. LA419, a novel nitric oxide donor, prevents cardiac remodeling via the endothelial nitric oxide synthase pathway: NO donors as a means of antiremodeling. Hypertension 2007; 50: 1009-11.


D. Cardiotoxicity

InvestigatorsProf. Beata Mladosievičová, MD, PhD ([email protected])Ljuba Bacharova, MD, DSc, MBAProf. Angelika Batorova, MD, PhDMichal Chovanec, MD, PhDAssoc. Prof. Jozef Mardiak, MD, PhDProf. Michal Mego, MD, DScAssoc. Prof. Martin Mistrik, MD, PhDLucia Petrikova-Setteyova, MD

TopicMany standard chemotherapeutic agents (such as anthracyclines, cisplatin) as well as targeted therapy (such as tyrosine kinase inhibitors) changed progressive fatal malignancy with a poor prognosis to curable or chronic disease with significant better prognosis. Despite of their effectiveness, there is still a need of better understanding and prediction of cardiovascular complications of these agents. We have identified prevalence and dynamics of several types of cardiac and vascular toxicity and risk factors for development of these complications using modern imaging techniques, electrophysiological and biochemical methods.

Plans for future research• To confirm the role of selected biomarkers in early detection of cardiotoxicity in patients with hematologic

malignancies treated with small molecule tyrosine kinase inhibitors and testicular tumors patients after cisplatin therapy

• To estimate the prevalence of small dense LDL phenotype in these patients and identify associated treatment factors

• To detect specific genes involved in resistance to tyrosine kinase inhibitors

Devices and methods• ankle/brachial indices ultrasound device• electrocardiography• detection of cardiomarkers- specific biochemical and genetic tests

Grants and Funding (in the last 10 years)• MZ SR 2007/42-UK-18: Complex diagnostic and monitoring of consequences of anti-cancer therapy with focus

on genetic aspects of cytostatics toxicity - PharmakoGen (2007-2010)• VEGA 1/4307/07: Long-lasting complications in oncological patients treated in childhood and adolescent period

- new multidisciplinary problem (2007-2009)• VEGA 1/0906/14: Biomarkers and genetic predictors of anti-cancer drugs toxicity (2014-2016)• League against Cancer Slovak Republic: Modern diagnostics of lipoproteins in haematooncologic patients after

allogeneic haematopoietic stem cells transplantation (2015)• VEGA 1/0906/14: Biomarkers and genetic predictors of anti-cancer drugs toxicity (2014-2016)• VEGA 01/0610/18: Improvement of toxicity and resistance prediction in patients with for chronic myeloid

leukemia treated with tyrosine kinase inhibitors (2018-2020)• APVV-15-0086: Identification of biomarkers associated with late toxicity of chemotherapy of germinative

testicular cancer (2018-2020)


Selected publications• Urbanova D, Urban L, Simkova I, Danova K, Mikuskova E, Mladosievicova B. Long-term cardiac effects of treatment for

childhood leukemia. Neoplasma 2010; 57: 179-83.• Soltysova A, Minarik G, Dzurenkova A, Sufliarska S, Kadasi L, Turna J, Mladosievicova B.APEX microarray panel for

genotyping polymorphisms in cancer chemotherapy and estimation frequencies in a Slovak population. Pharmacogenomics 2011; 12: 577-92.

• Mladosievicova B, Urbanova D, Radvanska E, Slavkovsky P, Simkova I. Role of NT-proBNP in detection of myocardial damage in childhood leukemia survivors treated with and without anthracyclines. J Exp Clin Cancer Res 2012; 31:86.

• Roziakova L, Bojtarova E, Mistrik M, Dubrava J, Gergel J, Lenkova N, Mladosievicova B. Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation. J Exp Clin Cancer Res 2012; 31: 13.

• Roziakova L, Mistrik M, Batorova A, Kruzliak P, Bojtarova E, Dubrava J, Gergel J, Mladosievicova B. Can we predict clinical cardiotoxicity with cardiac biomarkers in patients after haematopoietic stem cell transplantation? Cardiovasc Toxicol 2015; 15: 210-6.

• Pitekova B, Ravi S, Shah SV, Mladosievicova B, Heitner S, Ferencik M. The role of imaging with cardiac computed tomography in cardio-oncology patients. Curr Cardiol Rep 2016; 18: 87.

• Poljak Z, Hulin I, Maruscakova L, Mladosievicova B. Are GnRH and FSH potentially damaging factors in the cardiovascular system? Pharmazie 2018; 73: 187-90.


E. Inherited heart defects

InvestigatorsProf. Jozef Mašura, MD, PhD, FSCAI, FESC, FAEPC ([email protected])

Grants and Funding (in the last 10 years)• VEGA 1/0593/11: Polymorphisms in methylentetrahydropholate reductase and risk of inherited heart defects

(2001 -2013)

Selected publications• Widimský P, Suryapranata H, Vahanian A, Mašura J. Catheterization and interventional cardiology in adult patients. 1st

edition. New York: Oxford University Press 2010; 136 pp.• Masura J, Tittel P, Gavora P, Podnar T. Long-term outcome of transcatheter patent ductus arteriosus closure using Amplatzer

duct occluders. Am Heart J 2006; 151: 755.e7-10.• Masura J, Bordacova L, Tittel P, Berden P, Podnar T. Percutaneous management of cyanosis in Fontan patients using Amplatzer

occluders. Catheter Cardiovasc Interv 2008; 71: 843-9.• Venczelova Z1, Tittel P, Masura J. The new Amplatzer duct occluder II: when is its use advantageous? Cardiol Young 2011; 21:

495-504.• Venczelova Z, Tittel P, Masura J. First experience with AndraStent XL implantation in children and adolescents with congenital

heart diseases. Catheter Cardiovasc Interv 2013; 81: 103-10.


F1. Vascular diseases

InvestigatorsProf. Viera Štvrtinová, MD, PhD ([email protected])Prof. Ľudovít Gašpar, MD, PhDAssoc. Prof. Denisa Čelovská, MD, PhDMarek Kučera, MD, PhD

TopicOur research is focused on vascular diseases (mainly, arterial and venous of lower extremities) and their most important complications like critical limb ischemia, venous insufficiency, pulmonary embolism and/or diabetic foot. We have found that prostaglandine E1 treatment of critical limb ischemia without possibility of revascularization can postpone amputation but it does not affect patient’s life expectancy. An important part of our research is arterial hypertension.

Plans for future research• Association between insulin administration by insulin pump and prognosis of patients with diabetes mellitus• Prognostic significance of diurnal pattern loss in patients with arterial hypertension• Healing of chronic venous and chronic arterial wounds during hyperbaric oxygentherapy• Holter ECG monitoring in patients with medial arterial calcinosis• Baroreflex sensitivity and prehypertension, masked hypertension, white coat hypertension, chronic heart failure

with preserved ejection fraction and prediabetes

Devices and methods• Complex non-invasive cardiovascular diagnostics (Holter ECG, ABPM, exercise load testing, echocardiography,

Laser-Doppler investigation of vessels, transcutaneous oximetry – Periflux System 5000, Perimed AB, Sweden)• Analysis of spectrum and sub-fractions of lipids by Lipoprint LDL and HDL method• Spectral analysis of heart rate variability• Diagnosis of cardiovascular autonomic neuropathy using Ewing battery of tests• Determination of ankle-brachial index and prognosis of patients with critical limb ischemia and medial artherial

calcinosis• Baroreflex sensitivity obtained by sequence and spectral method by COLIN CBM 7000 equipment

Grants and Funding (in the last 10 years)• APVV-16-0247: Changes in redox regulation and monitoring of specific biomarkers of cardiovascular diseases

(2017-2021)• VEGA 1/0807/18: Central systolic blood pressure in hypertension treatment optimalization (2018-2020)• VEGA 1/0195/16: Effect of hyperbaric oxygentherapy in treatment of patients with diabetic polyneuropathy

(2016-2017)

Selected publications• Štvrtinová V. Diseases of the vessels. 1st edition; Bratislava: SAP, 2008. 896 pp.• Krahulec B, Gašpar Ľ, Štvrtinová V. Management of patient with diabetic foot syndrome. 1st edition; Bratislava: Veda 2013; 400 pp.• Kalodiki E, Stvrtinova V, Allegra C, Andreozzi G, Antignani PL, Avram R, Brkljacic B, Cadariou F, Dzsinich C, Fareed J,

Gaspar L, Geroulakos G, Jawien A, Kozak M, Lattimer CR, Minar E, Partsch H, Passariello F, Patel M, Pécsvárady Z, Poredos P, Roztocil K, Scuderi A, Sparovec M, Szostek M, Skorski M. Superficial vein thrombosis: a consensus statement. Int Angiol 2012; 31: 203-16.


• Michiels JJ, Moosdorff W, Maasland H, Michiels JM, Lao MU, Neumann HA, Dulicek P, Stvrtinova V, Barth J, Palareti G.Duplex ultrasound, clinical score, thrombotic risk, and D-dimer testingfor evidence based diagnosis and management of deep vein thrombosis and alternative diagnoses in the primary care setting and outpatient ward. Int Angiol 2014; 33: 1-19.

• Gaspar L, Kruzliak P, Komornikova A, Celecova Z, Krahulec B, Balaz D, Sabaka P, Caprnda M, Kucera M, Rodrigo L, Uehara Y, Dukat A. Orthostatic hypotension in diabetic patients-10-year follow-up study. J Diabetes Complications 2016; 30: 67-71.

• Andreozzi GM, Kalodiki E, L Gašpar L, Martini R, Minar E, Angelides N, Nicolaides AN, Novo S, Visonà A, Prior M, Arosio E, Hussein EA, Poredos P, Antignani PL, Avram R, Roztocil K, Stvrtinova V, Kozak M, Vacula I; Central European Vascular Forum; Mediterranean League of Angiology and Vascular Surgery; North Africa and Middle East Chapter of International Union of Angiology. Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology. Int Angiol 2014; 33: 329-47.

• Gaspar L, Bendzala M, Gasparova I, Caprnda M, Kucera M, Dukat A. Dipping status and prognosis in older hypertensive patients - 5-year follow-up study. World Heart J 2016; 8: 11-21.


F2. Vascular diseases

InvestigatorsProf. Viera Kristová, MD, PhD ([email protected])Miriam Petrová, MD, PhDRobert Vojtko, MD, PhDSilvia Líšková, RNDr, PhD

TopicThe research topic of our group is divided in two main branches:• The assessment of endothelium-protective drugs in various models of endothelial dysfunction and pathological

conditions• The evaluation of regulatory mechanisms involved in the physiological adjustments of vascular tone and

in the alterations triggered during the development of pathophysiological conditions

Plans for future research• The involvement of Ca2+-dependent Cl- channels in regulation of vascular tone in different pathological models• The quantification of diverse endothelium-dependent mechanisms in contraction of isolated arteries during

ageing

Devices and methods• Isometric wire myograph• Isometric vessels measurements• Perfusion measurements of isolated arteries• Metabolic cages for small laboratory animals

Grants and Funding (in the last 10 years)• VEGA 1/0314/08: Evaluation of drug effects on endothelial dysfunction in experimental and clinical conditions

(2008-2010)• VEGA 1/ 0501/11: The role of endothelium-released factors in contraction of isolated vessels in the development

of hypertension (2011-2013)• VEGA 1/0504/19: Interaction of Ca(2+)-dependent Cl(-) channels and endothelium-derived constricting factor

(EDCF) during ageing and hypertension (2019-2021)

Selected publications• Varga Z, Nemcekova M, Carnicka S, Slezakova V, Petrova M, Majdan M, Ravingerova T, Kristova V. Naproxen and Diclofenac

Attenuate Atorvastatin-induced Preconditioning of the Myocardium. Cureus 2017; 9: e1201.• Karakitsiou M, Varga Z, Kriska M, Kristova V. Risk perception of NSAIDs in hospitalized patients in Greece. Bratisl Lek Listy

2017; 118: 427-30.• Dobias L, Petrova M, Vojtko R, Kristova V. Long-term treatment with hesperidin improves endothelium-dependent

vasodilation in femoral artery of spontaneously hypertensive rats: The involvement of NO-synthase and K(v) channels. Phytother Res 2016; 30: 1665-71.

• Vrankova S, Barta A, Klimentova J, Dovinova I, Liskova S, Dobesova Z, Pechanova O, Kunes J, Zicha J: The regulatory role of Nuclear Factor Kappa B in the heart of hereditary hypertriglyceridemic rat, Oxid Med Cell Longev 2016; 9814 038.

• Dobias L, Petrova M, Vojtko R, Ulicna O, Vancova O, Kristova V. Effect of sulodexide on vascular responses and liver mitochondrial function in diabetic rats. Physiol Res 2015; 4: 497-505.


• Liskova S, Petrova M, Karen P, Behuliak M, Zicha J. Contribution of Ca²+-dependent Cl- channels to norepinephrine-induced contraction of femoral artery is replaced by increasing EDCF contribution during ageing. Biomed Res Int 2014; 2014:289361.

• Varga Z, Kriska M, Kristova V, Petrova M. Analysis of non-steroidal anti-inflammatory drug use in hospitalized patients and perception of their risk. Interdiscip Toxicol 2013; 6: 141-4.

• Behuliak M, Pinterova M, Bencze M, Petrova M, Liskova S, Karen P, Kunes J, Vaneckova I, Zicha J. Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens 2013; 31: 2025-35.

• Petrova M, Liskova S, Vojtko R, Villaris R, Varga Z, Zicha J, Kristova V. Vascular reactivity of arteria femoralis in adult and aged spontaneously hypertensive and Wistar-Kyoto rats. Bratisl Lek Listy 2013; 114: 553-5.

• Kristova V, Kriska M, Vojtko R, Petrova M, Liskova S, Villaris R, Varga Z, Wawruch M. Trends in vascular pharmacology research in the Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava. Interdiscip Toxicol 2011; 4: 40-6.

• Liskova S, Petrova M, Karen P, Kunes J, Zicha J. Effects of aging and hypertension on the participation of endothelium-derived constricting factor (EDCF) in norepinephrine-induced contraction of rat femoral artery. Eur J Pharmacol 2011; 667: 265-70.

• Sotnikova R, Nedelcevova J, Navarova J, Nosalova V, Drabikova K, Szocs K, Krenek P, Kyselova Z, Bezek S, Knezl V, Drimal J, Broskova Z, Kristova V, Okruhlicova L, Bernatova I, Bauer V. Protection of the vascular endothelium in experimental situations. Interdiscip Toxicol 2011; 4: 20-6.

• Liskova S, Petrova M, Karen P, Kunes J, Zicha J. Influence of calcium-dependent potassium channel blockade and nitric oxide inhibition on norepinephrine-induced contractions in two forms of genetic hypertension. J Am Soc Hypertens 2010; 4: 128-34.

• Paulis L, Pechanova O, Zicha J, Liskova S, Celec P, Mullerova M, Kollar J, Behuliak M, Kunes J, Adamcova M, Simko F: Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment, J Hypertens, 2010; 28 Suppl 1: S19-24.

• Pintérová M, Lisková S, Dobesová Z, Behuliak M, Kunes J, Zicha J: Impaired control of L-type voltage-dependent calcium channels in experimental hypertension, Physiol Res, 2009; 58 Suppl 2: S43-54.

• Kristova V, Liskova S, Sotnikova R, Vojtko R, Kurtansky A. Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res 2008; 57: 491-4.

• Ulicná O, Vancová O, Waczulíková I, Bozek P, Janega P, Babál P, Liskova S, Greksák M: Does rooibos tea (Aspalathus linearis) support regeneration of rat liver after intoxication by carbon tetrachloride?, Gen Physiol Biophys, 2008; 27: 179-86.

• Durisova M, Dedik L, Kristova V, Vojtko R. Mathematical model indicates nonlinearity of noradrenaline effect on rat renal artery. Physiol Res 2008; 57: 785-8.


G. Pharmacoepidemiology of cardiovascular diseases

InvestigatorsProf. Martin Wawruch, MD, PhD ([email protected])Prof. Jan Murin, MD, PhD

TopicOur research is focused on pharmacoepidemiologic analysis of treatment in elderly patients in terms of the use of potentially inappropriate medications, drugs with anticholinergic effects, analyses of antihypertensive, antithrombotic and lipid-lowering therapy, adherence with secondary preventive medication in patients after an ischemic stroke/transient ischemic attack and peripheral artery disease of lower limbs. Using the methods of predictive statistics we identified specific groups of patients at increased risk for inappropriate medication use, suboptimal use of beneficial medications and non-adherence with preventive therapy. Identification of such risky groups of patients makes it possible to prepare educational programs for physicians and patients aimed at the improvement of physicians´ prescription and patients’ medication taking behaviour.

Plans for future research• Evaluation of risk factors for non-persistence with preventive medication in elderly patients with peripheral

artery disease• Analysis of the patterns of medication prescription using the group based trajectory modelling

Devices and methods• Statistical software IBM SPSS for Windows• Statistical software R, module Adhere R

Grants and Funding (in the last 10 years)• VEGA 1/0135/09: Specific features of pharmacotherapy in geriatrics and the possibilities of its quality assessment

(2009-2011)• VEGA 1/0886/14: Suboptimal use of drugs in secondary prevention of cardiovascular diseases in elderly patients

(2014-2016)• VEGA 1/0112/17: Adherence with pharmacotherapy – a basic precondition of successful secondary prevention

of cardiovascular diseases in elderly patients (2017-2019)

Selected publications• Wawruch M, Zikavska M, Wsolova L, Jezova D, Fialova D, Kunzo M, Kuzelova M, Lassanova M, Kruty P, Kriska M. Perception

of potentially inappropriate medication in elderly patients by Slovak physicians. Pharmacoepidemiol Drug Saf 2006; 15: 829-34.• Wawruch M, Zikavska M, Wsolova L, Kuzelova M, Tisonova J, Gajdosik J, Urbanek K, Kristova V. Polypharmacy in elderly

hospitalised patients in Slovakia. Pharm World Sci 2008; 30: 235-42.• Wawruch M, Fialova D, Zikavska M, Wsolova L, Jezova D, Kuzelova M, Liskova S, Krajcik S. Factors influencing the use of

potentially inappropriate medication in older patients in Slovakia. J Clin Pharm Ther 2008; 33: 381-92.• Wawruch M, Zikavska M, Wsolova L, Kuzelova M, Kahayova K, Strateny K, Kristova V. Adverse drug reactions related to

hospital admission in Slovak elderly patients. Arch Gerontol Geriatr 2009; 48: 186-90.• Wawruch M, Dukat A, Murin J, Wsolova L, Kuzelova M, Macugova A, Wimmer G Jr, Shah R. The effect of selected patient‘s

characteristics on the choice of antihypertensive medication in the elderly in Slovakia. Pharmacoepidemiol Drug Saf 2009; 18: 1199-205.


• Wawruch M, Macugova A, Kostkova L, Luha J, Dukat A, Murin J, Drobna V, Wilton L, Kuzelova M. The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients. Pharmacoepidemiol Drug Saf 2012; 21: 170-6.

• Wawruch M, Kuzelova M, Foltanova T, Ondriasova E, Luha J, Dukat A, Murin J, Shah R. Characteristics of elderly patients who consider over-the-counter medications as safe. Int J Clin Pharm 2013; 35: 121-8.

• Wawruch M, Slezakova V, Murin J, Luha J, Bozik M, Leitmann T, Kuzelova M, Shah R. Influence of hospitalisation on the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in elderly hypertensive patients. Aging Clin Exp Res 2014; 26: 307-14.

• Böhmdorfer B, Rohleder S, Wawruch M, van der Cammen TJ, Frühwald T, Jagsch C, Janowitz SM, Nagano M, Petrovic M, Sommeregger U, Iglseder B. DEL-FINE: a new tool for assessing the delirogenic properties of drugs of relevance for European pharmacotherapy. Z Gerontol Geriatr 2016; 49: 416-22.

• Wawruch M, Zatko D, Wimmer G Jr, Luha J, Kuzelova L, Kukumberg P, Murin J, Hloska A, Tesar T, Kallay Z, Shah R. Factors Influencing Non-Persistence with Antiplatelet Medications in Elderly Patients After Ischaemic Stroke. Drugs Aging 2016; 33: 365-73.

• Wawruch M, Zatko D, Wimmer G Jr, Luha J, Hricak V Jr, Murin J, Kukumberg P, Tesar T, Hloska A, Shah R. Patient-related characteristics associated with non-persistence with statin therapy in elderly patients following an ischemic stroke. Pharmacoepidemiol Drug Saf 2017; 26: 201-7.

• Wawruch M, Zatko D, Wimmer G Jr, Luha J, Wimmerova S, Kukumberg P, Murin J, Hloska A, Tesar T, Shah R. Non-persistence with antiplatelet therapy in elderly patients after a transient ischemic attack. Aging Clin Exp Res 2017; 29: 1121-7.

• Wawruch M, Zatko D, Wimmer G Jr, Luha J, Wimmerova S, Matalova P, Kukumberg P, Murin J, Tesar T, Havelkova B, Shah R. Age-related differences in non-persistence with statin treatment in patients after a transient ischaemic attack. Clin Drug Investig 2017; 37: 1047-54.


H. Drugs for hypertension therapy

InvestigatorsProf. Pavel Babál, MD, PhD ([email protected])

Grants and Funding (in the last 10 years)• VEGA 2/0021/15: New molecular mechanisms of cardiovascular system damage by ionization radiation and

possibility of its targeted pharmacological prevention (2015 -2017)• APVV-51-017905: Molecular mechanisms responsible for effect of new drugs affecting oxidative stress -

important etiopathogenetic factor of multiple diseases (2008 -2009)• VEGA 2/7064/7: Long-term administration of low dose of L-NAME: possibility for improvement of vessel wall

function in borderline hypertension (2007)• VEGA 2/4156/24: Interaction between stress and genetic factors in etiology of hypertension and behavioral

alterations: the role of nitric oxide (2004-2006)• VEGA 1/1171/04: Protective effect of polygenole compounds against endothelial damage (2004-2005)

Selected publications• Babál P, Kristová V, Cerná A, Janega P, Pechánová O, Danihel L, Andriantsitohaina R. Red wine polyphenols prevent

endothelial damage induced by CCl4 administration.Physiol Res 2006; 55: 245-51.• Bernátová I, Babál P, Grubbs RD, Morris M. Acetylcholinesterase inhibition affects cardiovascular structure in mice. Physiol

Res 2006;55: S89-97.• Bernátová I, Kopincová J, Púzserová A, Janega P, Babál P. Chronic low-dose L-NAME treatment increases nitric oxide

production and vasorelaxation in normotensive rats. Physiol Res 2007; 56: S17-24.• Hlavackova L, Janega P, Cerna A, Pechanova O, Andriantsitohaina R, Babal P. Red wine polyphenols affect the collagen

composition in the aorta after oxidative damage induced by chronic administration of CCl(4). Physiol Res 2009; 58: 337-44.• Hlavačková L, Vranková S, Janega P, Pecháňová O, Babál P. The effect of indapamide on development of myocardial

hypertrophy and fibrosis in L-NAME-induced hypertension in rat. Physiol Res 2011; 60: 845-52.• Hlavačková L, Janegová A, Uličná O, Janega P, Cerná A, Babál P. Spice up the hypertension diet - curcumin and piperine

prevent remodeling of aorta in experimental L-NAME induced hypertension. Nutr Metab (Lond) 2011; 8: 72.• Janega P, Kojsová S, Jendeková L, Babál P, Pechánová O. Indapamide-induced prevention of myocardial fibrosis in spontaneous

hypertension rats is not nitric oxide-related. Physiol Res 2007; 56: 825-8.• Mézešová L, Vlkovičová J, Kaločayová B, Jendruchová V, Barančík M, Fülöp M, Slezák J, Babál P, Janega P, Vrbjar N. Effects of

γ-irradiation on Na,K-ATPase in cardiac sarcolemma. Mol Cell Biochem 2014; 388: 241-7.• Paulis L, Vazan R, Simko F, Pechánová O, Styk J, Babál P, Janega P. Morphological alterations and NO-synthase expression in

the heart after continuous light exposure of rats. Physiol Res 2007; 56: S71-6.• Pechánová O, Rezzani R, Babál P, Bernátová I, Andriantsitohaina R. Beneficial effects of Provinols: cardiovascular system and

kidney. Physiol Res 2006; 55: S17-30.• Remková A, Halcín A, Stenová E, Babál P, Kasperová V, Vranovský A. Acute vasculitis as a first manifestation of hairy cell

leukemia. Eur J Intern Med 2007; 18: 238-40.• Strilić B, Eglinger J, Krieg M, Zeeb M, Axnick J, Babál P, Müller DJ, Lammert E. Electrostatic cell-surface repulsion initiates

lumen formation in developing blood vessels. Curr Biol 2010; 20: 2003-9.• Cačányiová S, Pecháňová O, Babál P, Cerná A, Janega P, Andriantsitohaina R. Red wine polyphenols correct vascular function

injured by chronic carbon tetrachloride intoxication. Gen Physiol Biophys 2011; 30: 207-13.

ONCOLOGICAL DISEASES 54 |

ONCOLOGICAL DISEASES | 55

ONCOLOGICAL DISEASES

Oncological Diseases



Experimental and human tumors

Mammary carcinoma

Circulating tumor cells (CTC)

Prognostic and predictive significance CTC

Tumor microenvironment and CTC

CTC and coagulation, CTC and immune system

Functional breast MRI Role of biomarkers in prediction of neoadjuvant chemotherapy response

Urologic malignity Testicular cancer

Treatment of advanced stages, relapses, and refractory diseases

Identification of biomarkers associated with resistance and late toxicity

Late toxicity in the treatment of TGCTs, quality of life

Development of experimental animal model of TGCTs

Cultivation and characterization of TGCT from cell lines

Optimization of therapy and follow-up patients with TGCT in I. clinical stage

Hormonal substitution therapy by testosterone and defects of bone density in patients with TGCT

Secondary malignity after therapy of testicular tumors

Other tumors Tumors of head and neck

Functional consequences of therapy of head and neck tumorsImmunological and immunogenetic aspects of tumors and other lesion of head and neck.The role of HMGB1, TREM-1, and TREM-2 molecules and cytokines.Salivary and other molecular markers of head and neck tumors

Diagnostic and therapy

Nuclear medicine PET/CT Innovative clinical applications of diagnostic radiopharmaceuticals

Late adverse effects Late toxicity of anti-cancer therapy

Monitoring of late toxicity in pediatric and TGCTs patients

Probiotics Probiotics as adjuvant to anti-cancer therapy

Safety of probiotics in oncological patients

Prevention of irinotekan-induced diarrhea

Prevention of chemotherapy toxicity and potentiation of its efficiency


Oncological research if currently focused on investigation of etiopathogenesis of mammary, urological, and other malignancies. Outstanding findings were obtained in the research focused on the role of circulation tumor cells.

Principal investigatorsAssoc. Prof. Jozef Mardiak, MD, PhDProf. Pavel Babál, MD, PhDDr. h. c. Prof. Ján Breza, MD, DScAssoc. Prof. Soňa Balogová, MD, PhDProf. Ľudovít Danihel, MD, PhDProf. Štefan Durdík, MD, PhDProf. Michal Mego, MD, DScProf. Beáta Mladosievičová, MD, PhDProf. Dalibor Ondruš, MD, DScProf. Vanda Repiská, RNDr, PhDProf. Juraj Šteňo, MD, DSc


A1. Mammary carcinoma

InvestigatorsProf. Michal Mego, MD, DSc ([email protected])Assoc. Prof. Jozef Mardiak, MD, PhDProf. Pavel Babál, MD, PhDAssoc. Prof. Soňa Balogová, MD, PhDProf. Ľudovít Danihel, MD, PhDProf. Štefan Durdík, MD, PhDZuzana Čierna, MD, PhD

TopicCirculating tumor cells (CTC) are independent prognostic factor in primary as well as in metastatic breast cancer. CTC are heterogenous population of tumor cells and play crucial role in metastatic cascade and tumor progression in process termed self-seeding. Presence of CTC in peripheral blood is a surrogate marker of tumor metastatic ability. We identified new subpopulation of CTCs with epithelial to mesenchymal transition phenotype, and we found prognostic value of this CTCs subpopulation. We also found association between CTCs and risk of venous thromboembolism, as well as with several clinicopathological characteristics. We identified association between CTC and immune system, coagulation factors and matrix-metalloproteinases.

Plans for future research• Genotyping of tumors in relationship with circulating tumor cells• Evaluation of predictive and prognostic value new subpopulation of circulating tumor cells with epithelial-

mesenchymal transition

Devices and methods• Standard equipment of laboratory• Laminar box

Grants and Funding (in the last 10 years)• APVV-16-0010: Identification and validation of signaling pathways associated with circulating tumor cells in

breast carcinoma (2017-2020)• VEGA 1/0044/15: Identification of factors participating on release and migration of circulating tumor cells in

mammary carcinoma (2016-2018)• VEGA 1/0724/11: Circulating tumor cells and epithelial-mesenchymal transition (2012-2014)• APVV-14-0327: Identification of new biomarkers and alternative approaches for analysis of tumor DNA

utilizable in diagnostics and prognostics of mammary carcinoma (2015-2018)

Selected publications• Kalinkova L, Zmetakova I, Smolkova B, Minarik G, Sedlackova T, Horvathova Kajabova V, Cierna Z, Mego M, Fridrichova I.

Decreased methylation in the SNAI2 and ADAM23 genes associated with de-differentiation and haematogenous dissemination in breast cancers. BMC Cancer 2018; 18: 875.

• Jurkovicova D, Smolkova B, Magyerkova M, Sestakova Z, Kajabova VH, Kulcsar L, Zmetakova I, Kalinkova L, Krivulcik T, Karaba M, Benca J, Sedlackova T, Minarik G, Cierna Z, Danihel L, Mego M, Chovanec M, Fridrichova I. Down-regulation of traditional oncomiRs in plasma of breast cancer patients. Oncotarget 2017; 8: 77369-84.

• Bystricky B, Reuben JM, Mego M. Circulating tumor cells and coagulation-Minireview. Crit Rev Oncol Hematol 2017; 114:33-42.


• Bystricky B, Cierna Z, Sieberova G, Janega P, Karaba M, Minarik G, Benca J, Sedlackova T, Jurisova S, Gronesova P, Pindak D, Macuch J, Mardiak J, Mego M. Relationship Between Circulating Tumor Cells and Annexin A2 in Early Breast Cancer Patients. Anticancer Res 2017; 37: 2727-34.

• Bystricky B, Jurisova S, Karaba M, Minarik G, Benca J, Sedlácková T, Tothova L, Vlkova B, Cierna Z, Janega P, Manasova D, Gronesova P, Pindak D, Mardiak J, Celec P, Mego M. Relationship Between Circulating Tumor Cells and Tissue Plasminogen Activator in Patients with Early Breast Cancer. Anticancer Res 2017; 37: 1787-91.

• Mego M, Gao H, Cohen EN, Anfossi S, Giordano A, Tin S, Fouad TM, De Giorgi U, Giuliano M, Woodward WA, Alvarez RH, Valero V, Ueno NT, Hortobagyi GN, Cristofanilli M, Reuben JM. Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer. Oncotarget 2016.

• Mego M, Gao H, Cohen EN, Anfossi S, Giordano A, Sanda T, Fouad TM, De Giorgi U, Giuliano M, Woodward WA, Alvarez RH, Valero V, Ueno NT, Hortobagyi GN, Cristofanilli M, Reuben JM. Circulating tumor cells (CTC) are associated with defects in adaptive immunity in patients with inflammatory breast cancer. J Cancer 2016; 7: 1095-104.

• Smolkova B, Mego M, Horvathova Kajabova V, Cierna Z, Danihel L, Sedlackova T, Minarik G, Zmetakova I, Krivulcik T, Gronesova P, Karaba M, Benca J, Pindak D, Mardiak J, Reuben JM, Fridrichova I. Expression of SOCS1 and CXCL12 proteins in primary breast cancer are associated with presence of circulating tumor cells in peripheral blood. Transl Oncol 2016; 9: 184-90.

• Mego M, Cholujova D, Minarik G, Sedlackova T, Gronesova P, Karaba M, Benca J, Cingelova S, Cierna Z, Manasova D, Pindak D, Sufliarsky J, Cristofanilli M, Reuben JM, Mardiak J. CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer. BMC Cancer 2016; 16: 127.

• Mego M, Cierna Z, Janega P, Karaba M, Minarik G, Benca J, Sedlácková T, Sieberova G, Gronesova P, Manasova D, Pindak D, Sufliarsky J, Danihel L, Reuben JM, Mardiak J. Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer. BMC Cancer 2015; 15: 533.

• Mego M, Karaba M, Minarik G, Benca J, Sedlácková T, Tothova L, Vlkova B, Cierna Z, Janega P, Luha J, Gronesova P, Pindak D, Fridrichova I, Celec P, Reuben JM, Cristofanilli M, Mardiak J. Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients. Breast J 2015; 21: 155-60.

• Mego M, Giordano A, De Giorgi U, Masuda H, Hsu L, Giuliano M, Fouad TM, Dawood S, Ueno NT, Valero V, Andreopoulou E, Alvarez RH, Woodward WA, Hortobagyi GN, Cristofanilli M, Reuben JM. Circulating tumor cells in newly diagnosed inflammatory breast cancer. Breast Cancer Res 2015; 17: 2.

• Fridrichova I, Smolkova B, Kajabova V, Zmetakova I, Krivulcik T, Mego M, Cierna Z, Karaba M, Benca J, Pindak D, Bohac M, Repiska V, Danihel L. CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers. Transl Res 2015; 165: 717-30.

• Mego M, Zuo Z, Gao H, Cohen EN, Giordano A, Tin S, Anfossi S, Jackson S, Woodward W, Ueno NT, Valero V, Alvarez RH, Hortobagyi GN, Khoury JD, Cristofanilli M, Reuben JM. Circulating tumour cells are linked to plasma D-dimer levels in patients with metastatic breast cancer. Thromb Haemost 2015; 113: 593-8.

• Giuliano M, Giordano A, Jackson S, De Giorgi U, Mego M, Cohen EN, Gao H, Anfossi S, Handy BC, Ueno NT, Alvarez RH, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Res 2014; 16: 440.

• Cierna Z, Mego M, Janega P, Karaba M, Minarik G, Benca J, Sedlácková T, Cingelova S, Gronesova P, Manasova D, Pindak D, Sufliarsky J, Danihel L, Reuben JM, Mardiak J. Matrix metalloproteinase 1 and circulating tumor cells in early breast cancer. BMC Cancer 2014; 14: 472.

• Mego M, Gao H, Lee BN, Cohen EN, Tin S, Giordano A, Wu Q, Liu P, Nieto Y, Champlin RE, Hortobagyi GN, Cristofanilli M, Ueno NT, Reuben JM. Prognostic Value of EMT-Circulating Tumor Cells in Metastatic Breast Cancer Patients Undergoing High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation. J Cancer 2012; 3: 369-80.

• Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, Gao H, Jackson SA, Giordano A, Hortobagyi GN, Cristofanilli M, Lucci A, Reuben JM. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. Int J Cancer 2012; 30: 808-16.

• Mego M, Mani SA, Cristofanilli M. Molecular mechanisms of metastasis in breast cancer--clinical applications. Nat Rev Clin Oncol 2010; 7: 693-701.


• Mego M, De Giorgi U, Dawood S, Wang X, Valero V, Andreopoulou E, Handy B, Ueno NT, Reuben JM, Cristofanilli M. Characterization of metastatic breast cancer patients with nondetectable circulating tumor cells. Int J Cancer 2011; 129: 417-23.

• Mego M, De Giorgi U, Broglio K, Dawood S, Valero V, Andreopoulou E, Handy B, Reuben JM, Cristofanilli M. Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients. Br J Cancer 2009; 101: 1813-6.


A2. Mammary carcinoma

InvestigatorsAssoc. Prof. Viera Lehotska, MD, PhD ([email protected])Lucia Vanovcanova, MD, PhDProf. Stanislav Spanik, MD, PhDProf. Stefan Durdik, MD, PhD, MHA

TopicOur research is focused on high risk women, especially on breast cancer detection rate in gene mutation carriers according their hormonal status and on elucidation, if menopausal status of gene mutation carriers at the time of breast carcinoma diagnosis influences the disease free survival. We also focuse on identification of early predictive biomarkers in monitoring of anticancer threatment response.

Plans for future research• MR-mammography in breast cancer detection rate in gene mutation carriers according to their age, type

of mutation, breast density and hormonal status• Identification of early predictive biomarkers in monitoring of response to neoadjuvant chemotherapy• Identification of risk patient population non-responding to first-line chemotherapy in breast cancer treatment

Devices and methods• 3T MR device• Stereotactic and MR navigated vacuum-assisted biopsy (VAB)• Stereotactic and US navigated breast lesion excison system (BLES)• Tumor marking set

Grants and Funding (in the last 10 years)• APVV 0297/10: Early detection of prostate cancer with 3T MRI (2010-2013)

Selected publications• Lehotska V, Rauova K, Vanovcanova L. MR-mammography - impact on disease extent determination and surgical treatment of

invasive ductal and lobular breast cancers. Neoplasma 2015; 62: 269-77.• Lehotska V, Rauova K, Vanovcanova L. Multiparametric MRI analysis of morphologico functional features of DCIS -

correlation with the grade of nuclear atypia. Neoplasma 2018; 65: 389-97.• Lehotska V, Rauova K, Vanovcanova L. Pitfalls of Contrast Enhanced Ultrasound (CEUS) in determination of breast tumor

biological dignity. Neoplasma 2018; 65: 124-31.• Lehotska V, Tothova L, Valkovic L. The role of dynamic contrast-enhanced MRI in differentiation of local recurrence and

residual soft-tissue tumor versus post-treatment changes. Bratisl Lek Listy 2013; 114: 88-92.• Tothova L, Rauova K, Valkovic L, Vanovcanova L, Lehotska V. Stereotactic vacuum-assisted breast biopsy: our experience and

comparison with stereotactic automated needle biopsy. Bratisl Lek Listy 2013; 114: 71-7.• Sevcikova K, Vertakova-Krakovska B, Spanik S. Neoadjuvant treatment in patients with HER2-positive breast cancer. ISRN

Oncol 2013; 2013: 362467.• Ondrusova D, Muzik J, Durdik S, Ondrus D. Long-term trends in the development of the epidemiology of breast cancer in the

Slovak and Czech Republic with reference to applied screening and international comparisons. Neoplasma 2012; 59: 70-8.

mailto:viera.lehotska%40ousa.sk?subject=


B. Testicular cancer

InvestigatorsAssoc. Prof. Jozef Mardiak, MD, PhD ([email protected])Prof. Michal Mego, MD, DScProf. Pavel Babál, MD, PhDDr. h. c. prof. Ján Breza, MD, DScProf. Beáta Mladosievičová, MD, PhDProf. Dalibor Ondruš, MD, DScMichal Chovanec, MD, PhDViera Miskovska, MD, PhDZuzana Cierna, MD, PhDIng. Katarina Kalavska, PhDKatarina Rejlekova, MD, PhD

TopicTesticular germ cell tumors (GCTs) are rare and unique malignancies, however, a long-term cure of >95% in all GCT patients was achieved with combination of chemotherapy, radiotherapy and surgery. Nevertheless, a proportion of patients with metastatic disease meet with dismal prognosis and these young men are dying in the prime of their lives. Experimental approaches to overcome the poor outcome in this group are scarce and lack significant efficacy since the introduction of salvage chemotherapy regimens over 20 years ago. The exciting era of novel targeting agents and immunotherapy with incredible success in other solid tumors seems to neglect GCTs and chemotherapy refractory patients remain without novel treatment options. This research initiative is aimed to explore the biology of GCTs, to overcome the resistance to conventional treatments.

Plans for future research• Treatment of advanced stages• Treatment of relapses and refractory diseases• Identification of biomarkers associated with resistance• Identification of biomarkers associated with late toxicity• Late toxicity in the treatment of TGCTs, quality of life• Development of experimental animal model of TGCTs• Cultivation and characterization of TGCT from cell lines

Devices and methods• Equipment in Department of clinical studies• Equipment of Unit of translational research at Faculty of Medicine in Bratislava and National Institute of Cancer

Grants and Funding (in the last 10 years)• Grant VEGA 1/0043/18: Using model systems to study resistance mechanisms associated with failure of

chemotherapy treatment in patients with testicular germ cell tumors (2019-2021)• Grant VEGA 1/0174/19: Use of experimental models for the study of choriocarcinoma syndrome in high-risk

patients with germ cell tumors (2019-2021)• 2018/23- SAV-1: Early diagnosis of colorectal carcinoma and canker cancer by glycoprophylation (2018-2020)• 2018/39- LFUK-13: Overcoming resistance to cisplatin in refractory testicular tumors from germ cells via

therapy directed against tumor stem cell markers (2018-2020)

mailto:jozef.mardiak%40nou.sk?subject=


• APVV-0016-11: Identification of biomarkers associated with resistance on chemotherapy in testicular tumors from germinative cells (TGCTs) (2012-2015)

• MZ-2007/30-NOU-01: Complex program of the care for patients with germinative tumors (2008-2010)

Selected publications• Chovanec M, Albany C, Mego M, Montironi R, Cimadamore A, Cheng L. Emerging prognostic biomarkers in testicular germ

cell tumors: Looking beyond established practice. Front Oncol 2018;8: 571.• Kalavska K, Kucerova L, Schmidtova S, Toro L, Kozovska Z, Plank L, Chovanec M, Palacka P, Pindak D, Macak D, Mardiak

J, Mego M. Lymphoma transformation of tumor infiltrating lymphocytes observed in testicular patient-derived xenograft models. Oncol Rep 2018.

• Mego M, van Agthoven T, Gronesova P, Chovanec M, Miskovska V, Mardiak J, Looijenga LHJ. Clinical utility of plasma miR-371a-3p in germ cell tumors. J Cell Mol Med 2018.

• Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, Svetlovska D, Macak D, Spanik S, Kajo K, Babal P, Mego M, Mardiak J. βcatenin is a marker of poor clinical characteristics and suppressed immune infiltration in testicular germ cell tumors. BMC Cancer 2018; 18: 1062.

• Chovanec M, De Giorgi U, Mego M. Immune-Related Concepts in Biology and Treatment of Germ-Cell Tumors. Adv Urol 2018; 2018: 3718165.

• Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, Svetlovska D, Macak D, Spanik S, Kajo K, Babal P, De Giorgi U, Mego M, Mardiak J. Systemic immune-inflammation index in germ-cell tumours. Br J Cancer 2018; 118: 831-8.

• Kalavska K, Conteduca V, De Giorgi U, Mego M. Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications. Curr Cancer Drug Targets 2018; 18: 967-78.

• Kalavska K, Cierna Z, Chovanec M, Takacova M, Svetlovska D, Miskovska V, Obertova J, Palacka P, Rajec J, Sycova-Mila Z, Machalekova K, Kajo K, Spanik S, Mardiak J, Babal P, Pastorekova S, Mego M. Prognostic value of intratumoral carbonic anhydrase IX expression in testicular germ cell tumors. Oncol Lett 2017; 13: 2177-85.

• Chovanec M, Cierna Z, Miskovska V, Machalekova K, Svetlovska D, Kalavska K, Rejlekova K, Spanik S, Kajo K, Babal P, Mardiak J, Mego M. Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors. Oncotarget 2017; 8: 21794-805.

• Svetlovska D, Miskovska V, Cholujova D, Gronesova P, Cingelova S, Chovanec M, Sycova-Mila Z, Obertova J, Palacka P, Rajec J, Kalavska K, Usakova V, Luha J, Ondrus D, Spanik S, Mardiak J, Mego M. Plasma cytokines correlated with disease characteristics, progression-free survival, and overall survival in testicular germ-cell tumor patients. Clin Genitourin Cancer 2017; 15: 411-6.

• Sestakova Z, Kalavska K, Hurbanova L, Jurkovicova D, Gursky J, Chovanec M, Svetlovska D, Miskovska V, Obertova J, Palacka P, Rejlekova K, Sycova-Mila Z, Cingelova S, Spanik S, Mardiak J, Chovanec M, Mego M. The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer. Oncotarget 2016; 7: 75996-6005.

• Kalavska K, Chovanec M, Zatovicova M, Takacova M, Gronesova P, Svetlovska D, Baratova M, Miskovska V, Obertova J, Palacka P, Rajec J, Sycova-Mila Z, Cierna Z, Kajo K, Spanik S, Babal P, Mardiak J, Pastorekova S, Mego M. Prognostic value of serum carbonic anhydrase IX in testicular germ cell tumor patients. Oncol Lett 2016; 12: 2590-8.

• Cierna Z, Mego M, Jurisica I, Machalekova K, Chovanec M, Miskovska V, Svetlovska D, Kalavska K, Rejlekova K, Kajo K, Mardiak J, Babal P. Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ. BMC Cancer 2016; 16: 597.

• Mego M, Svetlovska D, Miskovska V, Obertova J, Palacka P, Rajec J, Sycova-Mila Z, Chovanec M, Rejlekova K, Zuzák P, Ondrus D, Spanik S, Reckova M, Mardiak J. Phase II study of everolimus in refractory testicular germ cell tumors. Urol Oncol 2016; 34: 122.e17-22.

• Cierna Z, Mego M, Miskovska V, Machalekova K, Chovanec M, Svetlovska D, Hainova K, Rejlekova K, Macak D, Spanik S, Ondrus D, Kajo K, Mardiak J, Babal P. Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann Oncol 2016; 27: 300-5.

• Chovanec M, Oravcova I, Demitrovicova L, Mego M, Mardiak J. Malignant transformation of teratoma to adenocarcinoma with complete remission with all-trans retinoic acid-based treatment and surgery. Clin Genitourin Cancer 2016; 14: e131-3.


• Mego M, Cierna Z, Svetlovska D, Macak D, Machalekova K, Miskovska V, Chovanec M, Usakova V, Obertova J, Babal P, Mardiak J. PARP expression in germ cell tumours. J Clin Pathol 2013; 66: 607-12.

• Reckova M, Mego M, Sycova-Mila Z, Obertova J, Svetlovska D, Mardiak J. Sunitinib in patients with cisplatin-refractory germ cell tumors. Onkologie 2012; 35: 455-6.

• Mego M, Rejlekova K, Reckova M, Sycova-Mila Z, Obertova J, Rajec J, Mardiak J. Kinetics of tumor marker decline as an independent prognostic factor in patients with relapsed metastatic germ-cell tumors. Neoplasma 2009; 56: 398-403.

• Mego M, Recková M, Sycova-Mila Z, Obertova J, Brozmanova K, Salek T, Mardiak J. Bevacizumab in a growing teratoma syndrome. Case report. Ann Oncol 2007; 18: 962-3.

• Mego M. Cancer stem cell in relapsed testicular germ cell cancer: embryonic or somatic? Int J Androl 2006; 29: 627.• Maťoška J, Ondruš D, Horňák M. Metastatic spermatocytic seminoma : A case report with light microscopic, ultrastructural

and immunohistochemical findings Cancer 1988; 62: 1197-201.• Ondrus D, Hornak M, Vrabec J. Low sperm counts as a prognostic factor of progression in stage I non-seminomatous germ cell

testicular tumours. Br J Urol 1988; 62: 82-4.• Ondrus D, Hornak M. Orchiectomy alone for clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT): a

minimum follow-up period of 5 years. Tumori 1994; 80: 362-4.• Ondrus D, Ondrusova M, Dusek L. Recent patterns in testicular cancer incidence, mortality and survival in the Slovak

Republic with reference to international comparisons. Cancer Invest 2012; 30: 545-51.• Ondrus D, Ondrusova M, Friedova L. Second malignancies in long-term testicular cancer survivors. Int Urol Nephrol 2014; 46:

749-56.• Oldenburg J, Aparicio J, Beyer J, Cohn-Cedermark G, Cullen M, Gilligan T, De Giorgi U, De Santis M, de Wit R, Fosså SD,

Germà-Lluch JR, Gillessen S, Haugnes HS, Honecker F, Horwich A, Lorch A, Ondruš D, Rosti G, Stephenson AJ, Tandstad T; On behalf of: SWENOTECA (Swedish Norwegian Testicular Cancer group), the Italian Germ Cell Cancer Group (IGG), Spanish Germ Cell Cancer Group (SGCCG). Personalizing, not patronizing: the case for patient autonomy by unbiased presentation of management options in stage I testicular cancer. Ann Oncol 2015; 26: 833-8.

• Ondrusova M, Ondrus D, Miskovska V, Kajo K, Szoldova K, Usakova V, Stastna V. Management of clinical stage I testicular seminoma: active surveillance versus adjuvant chemotherapy. Int Urol Nephrol 2015; 47: 1143-7.

• Ondrus D, Hornák M, Breza J, Mat’oska J, Schnorrer M, Belan V, Kausitz J. Delayed orchiectomy after chemotherapy in patients with advanced testicular cancer. Int Urol Nephrol 2001; 32: 665-7.

• Ondrus D, Hornák M, Mat’oska J. Bilateral testicular germ-cell tumors--a single centre long-term experience. Int Urol Nephrol 2001; 33: 521-4.


C. Tumors of head and neck

InvestigatorsPatrik Štefanička, MD, PhD ([email protected])Miroslav Tedla, MD, PhDProf. Milan Profant, MD, PhDLukáš Varga, MD, RNDr, PhDJozef Ukropec, MSc, DScAssoc. Prof. Barbara Ukropcova, MD, PhD

TopicIn cooperation with Institute of Experimental Endocrinology we focused on human brown fat thermogenesis. Presence and distribution of brown fat in adult humans was discovered with the positron emission tomography with 18F-deoxyglucose. During the Head and Neck and Thyroid surgeries we meticulously identified and took brown adipose tissue samples, specifically from peritracheal area. This material was subsequently thoroughly analyzed in Biomedical Research Center. In comparative proteotype analysis we revealed significant quantitative differences in protein abundances in human brown adipose tissue versus adjacent white adipose tissue and in turn differential functional capabilities. We found that Bmp4 promotes the differentiation of brown pre-adipocytes into white-like adipocytes, Bmp4 blunts the activity of mature brown adipocytes and obese type 2 diabetic subjects have higher levels of circulating Bmp4. We also found that peroxisome proliferator-activated receptors α and β/δ are dispensable for maintaining brown adipocyte function in vivo. By combining mouse and human transcriptome data, we identified a gene signature that can classify brown and white adipocytes.

Devices and methods• Molecular and genetic analysis at Institute of Experimental Endocrinology, Biomedical Research Center, SAS• Operating theatres at the Dept&rtment of Otorhinolaryngology- Head and Neck Surgery

Grants and Funding (in the last 10 years)• VEGA 2/0096/17: Molecular mechanisms of human brown fat thermogenesis and its relations to obesity, physical

activity and ice water swimming (2017-2019)

Selected publications• Perdikari A, Leparc GG, Balaz M, Pires ND, Lidell ME, Sun W, Fernandez-Albert F, Müller S, Akchiche N, Dong H, Balazova

L, Opitz L, Röder E, Klein H, Stefanicka P, Varga L, Nuutila P, Virtanen KA, Niemi T, Taittonen M, Rudofsky G, Ukropec J, Enerbäck S, Stupka E, Neubauer H, Wolfrum C. BATLAS: Deconvoluting Brown Adipose Tissue. Cell Rep 2018; 25: 784-97.

• Lasar D, Rosenwald M, Kiehlmann E, Balaz M, Tall B, Opitz L, Lidell ME, Zamboni N, Krznar P, Sun W, Varga L, Stefanicka P, Ukropec J, Nuutila P, Virtanen K, Amri EZ, Enerbäck S, Wahli W, Wolfrum C. Peroxisome proliferator activated receptor gamma controls mature brown adipocyte inducibility through glycerol kinase. Cell Rep 2018; 22: 760-73.

• Modica S, Straub LG, Balaz M, Sun W, Varga L, Stefanicka P, Profant M, Simon E, Neubauer H, Ukropcova B, Ukropec J, Wolfrum C. Bmp4 promotes a brown to white-like adipocyte shift. Cell Rep 2016; 16: 2243-58.

• Müller S, Balaz M, Stefanicka P, Varga L, Amri EZ, Ukropec J, Wollscheid B, Wolfrum C. Proteomic analysis of human brown adipose tissue reveals utilization of coupled and uncoupled energy expenditure pathways. Sci Rep 2016; 6:30030.

• Ferris RL, Stefanicka P, Xi L, Gooding W, Seethala RR, Godfrey TE: Rapid molecular detection of metastatic head and neck squamous cell carcinoma as an intraoperative adjunct to sentinel lymph node biopsy. Laryngoscope 2012; 122: 1020-30.


D. Innovative clinical applications of diagnostic radiopharmaceuticals

InvestigatorsAssoc. Prof. Soňa Balogová, MD, PhD ([email protected])

Plans for future research• Evaluation of innovative clinical applications of diagnostic radiopharmaceuticals for PET in oncology

Grants and Funding (in the last 10 years)• VEGA 1/0196/16: Non-invasive in-vivo prediction of therapeutic response to inhibitors of angiogenesis using

68Ga-RGD PET/CT (2016-2018)

Selected publications• Cassou-Mounat T, Balogova S, Nataf V, Calzada M, Huchet V, Kerrou K, Devaux JY, Mohty M, Talbot JN, Garderet L.

18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study. Eur J Nucl Med Mol Imaging 2016; 43: 1995-2004.

• Jorgov L, Montravers F, Balogova S, Ragu C, Pacquement H, Leblanc T, Abbou S, Ducou-Lepointe H, Landman-Parker J, Talbot JN. Paediatric and adolescent Hodgkin lymphoma: information derived from diffuse organ uptake of 18 F-fluorodeoxyglucose on pre-treatment and on interim PET/CT. Eur J Nucl Med Mol Imaging 2016; 43: 1220-30.

• Talbot JN, Gligorov J, Nataf V, Montravers F, Huchet V, Michaud L, Ohnona J, Balogova S, Cussenot O, Daraï E, Lotz JP, Kerrou K. Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone. Q J Nucl Med Mol Imaging 2015; 59: 4-17.

• Balogova S, Zakoun JB, Michaud L, Khalil A, Tassart M, Esteso A, Kerrou K, Huchet V, Carette MF, Lotz JP, Talbot JN. Whole-body 18F-fluorocholine (FCH) PET/CT and MRI of the spine for monitoring patients with castration-resistant prostate cancer metastatic to bone: a pilot study. Clin Nucl Med 2014; 39: 951-9.

• Balogova S, Talbot JN, Nataf V, Michaud L, Huchet V, Kerrou K, Montravers F. 18F-fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type. Eur J Nucl Med Mol Imaging 2013; 40: 943-66.


E. Late toxicity

InvestigatorsAssoc. Prof. Jozef Mardiak, MD, PhD ([email protected])Prof. Michal Mego, MD, DScProf. Beáta Mladosievičová, MD, PhDProf. Dalibor Ondruš, MD, DScMichal Chovanec, MD, PhDViera Miskovska, MD, PhDKatarina Kalavska, Eng, PhDKatarina Rejlekova, MD, PhD

TopicThis research is aimed to address the long-term health issues associated with anticancer treatment, focusing mainly on long term toxicity of testicular germ cell tumors (TGCTs) survivors. Several clinical and biochemical markers associated with late toxicity of TGCTs survivors were identified.

Plans for future research• Monitoring of late toxicity in patients with testicular cancer from germinative cells

Grants and Funding (in the last 10 years)• VEGA 1/0327/19. Identification of the role of microbioma and immune molecular mechanisms of cognitive

dysfunctions due to the late toxicity of treatment in germ cell testis (2019-2021)• APVV-15-0086: Identification of biomarkers associated with late toxicity of chemotherapy in germinative tumors

of testis (2016-2018)• VEGA 1/0906/14: Biomarkers and genetic predictors of toxicity of anti-cancer therapy (2014-2016)• MZ SR 2007/42-UK-18: Complex diagnostic and monitoring of consequences of anti-cancer therapy with focus

on genetic aspects of cytostatics toxicity - PharmakoGen (2007-2010)

Selected publications• Chovanec M, Vasilkova L, Setteyova L, Obertova J, Palacka P, Rejlekova K, Sycova-Mila Z, Kalavska K, Svetlovska D, Cingelova

S, Mladosievicova B, Mardiak J, Mego M. Long-Term Cognitive Functioning in Testicular Germ-Cell Tumor Survivors. Oncologist 2018; 23: 617-23.

• Urbanová D, Urban L, Carter A, Maasova D, Mladosievicova B. Cardiac troponins-biochemical markers of cardiac toxicity after cytostatic therapy. Neoplasma 2006; 53: 183-90.

• Roziakova L, Mladosievicova B. Endocrine late effects after hematopoietic stem cell transplantation. Oncol Res 2010; 18: 607-15.• Mladosievicova B, Urbanova D, Radvanska E, Slavkovsky P, Simkova I. Role of NTproBNP in detection of myocardial damage

in childhood leukemia survivors treated with and without anthracyclines. J Exp Clin Cancer Res 2012; 31:86.• Roziakova L, Mistrik M, Batorova A, Kruzliak P, Bojtarova E, Dubrava J, Gergel J, Mladosievicova B. Can we predict clinical

cardiotoxicity with cardiac biomarkers in patients after haematopoietic stem cell transplantation? Cardiovasc Toxicol 2015; 15: 210-6.


F. Probiotics

InvestigatorsProf. Michal Mego, MD, DSc ([email protected])Assoc. Prof. Jozef Mardiak, MD, PhDAssoc. Prof. Luboš Drgoňa, MD, PhD

TopicProbiotics are live microorganisms, which as drugs or food supplements help to maintain health

beneficial microbial balance in the digestive tract of a human or other host. Probiotics by their properties may help strengthen homeostasis and thus reduce side effects associated with cancer treatment. Experimental evidence suggests that probiotics might have beneficial effect on the toxicity of anticancer therapy. We found, that administration of probiotics in patients with col-orectal cancer treated with irinotecan-based chemotherapy is safe and could lead to a reduction in the incidence and severity of gastrointestinal toxicity. We identified the prevalence, side-effect experience, and aspects that most likely influence probiotic use in cancer patients.

Plans for future research• Prevention of irinotekan-induced diarrhea by probiotics. Clinical study phase III

Devices and methods• Equipment of Unit of translational research at Faculty of Medicine in Bratislava and National Institute of Cancer

Grants and Funding (in the last 10 years)• VEGA 1/0722/11: Prevention of irinotekan-induced diarrhea by probiotics (2011-2013)• APVV-0646-11: The role of bacteria in process of carcinogenesis and syndrome of acquired immunodeficiency

(2011-2013)

Selected publications• Ciernikova S, Mego M, Semanova M, Wachsmannova L, Adamcikova Z, Stevurkova V, Drgona L, Zajac V. Probiotic survey in

cancer patients treated in the outpatientdepartment in a comprehensive cancer center. Integr Cancer Ther 2017; 16: 188-95.• Mego M, Chovanec J, Vochyanova-Andrezalova I, Konkolovsky P, Mikulova M, Reckova M, Miskovska V, Bystricky B, Beniak

J, Medvecova L, Lagin A, Svetlovska D, Spanik S, Zajac V, Mardiak J, Drgona L. Prevention of irinotecan induced diarrhea by probiotics: A randomized double blind, placebo controlled pilot study. Complement Ther Med 2015; 23: 356-62.

• Ciernikova S, Mego M, Hainova K, Adamcikova Z, Stevurkova V, Zajac V. Modification of microflora imbalance: future directions for prevention and treatment of colorectal cancer? Neoplasma 2015; 62: 345-52.

• Mego M, Holec V, Drgona L, Hainova K, Ciernikova S, Zajac V. Probiotic bacteria in cancer patients undergoing chemotherapy and radiation therapy. Complement Ther Med 2013; 21: 712-23.

• Mego M, Májek J, Konceková R, Ebringer L, Cierniková S, Raovác M, Trupl J, Slezák P, Zajac V. Intramucosal bacteria in colon cancer and their elimination by probiotic strain Enterococcus faecium M-74 with organic selenium. Folia Microbiol (Praha) 2005; 50: 443-7.

• Mego M, Koncekova R, Mikuskova E, Drgona L, Ebringer L, Demitrovicova L, Nemova I, Trupl J, Mardiak J, Koza I, Zajac V. Prevention of febrile neutropeniain cancer patients by probiotic strain Enterococcus faecium M-74. Phase II study. Support Care Cancer 2006; 14: 285-90.

• Mego M, Ebringer L, Drgona L, Mardiak J, Trupl J, Greksak R, Nemova I, Oravcova E, Zajac V, Koza I. Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Pilot study phase I. Neoplasma 2005; 52: 159-64.

METABOLIC, ENDOCRINE, AND INFLAMMATORY DISEASES 70 |

METABOLIC, ENDOCRINE, AND INFLAMMATORY DISEASES | 71

METABOLIC, ENDOCRINE, AND INFLAMMATORY DISEASES

Metabolic, Endocrine, and Inflammatory Diseases



Metabolic and endocrine diseases

Endocrinology

Diabetes mellitusDiabetes mellitus and diabetic foot syndrome

Monogenic disorders of insulin secretion and action

OsteoporosisMetabolism - osteologyInvestigation of pathophysiology, diagnostic and therapy of osteoporosis

Growth and Development

Short stature in children

Disorders of sexual development

General metabolism

Endocrine glands and endocrinopathies with symptoms in ORL area

Thyroidectomy and quality of lifePhysiology and molecular-genetic characteristics of brown fat tissue in manDNA diagnostics of rare diseases and syndromes associated with ORL diseases (alteration of hearing, malformation in ORL areas associated with endocinopathies and metabolic disturbances)

Metabolic syndrome Metabolic syndrome in children

Inborn errors of metabolism

Selective screening

Environmental factors Nutrition

Nutrition and nutritional status in populationEffect of selected environmental and psychosocial factors on health and development of children and adolescents

Immunology

Alterations of immunity and autoimmune disorders

Alterations of immunity

Autoimmunity: Rheumatoid arthritis, Sjögren‘s syndrome, systemic sclerosis, diabetes mellitus, Crohn disease

Inflammation in cardiovascular diseases

Inherited alterations of immunity, bronchial asthma

Rheumatoid arthritisStudy of combination of immunosuppressive therapy and modulation of redox balance of organism in animal models of rheumatoid arthritis

Inflammatory bowel diseases (IBD)

New therapeutic options in IBDMonitoring disease activity in IBDThe role of vitamin D in IBD

InfectionInfectious diseases Legionnaires´disease, Leptospirosis, Tularemia,

nosocomial infections

Sepsis Biomarkers of sepsis and SIRS

Morphology Histology of immune system

Development and evolution of lymphatic organs, focused on thymus

Microscopic structure and blood microcirculation of spleen

Other Varia

Orphan diseases Hereditary ciliopathies, RASopathies and tubulopathies

Extracellular DNA Role of extracellular DNA in physiological and pathological conditions

Kidney diseasesNovel biomarkers in chronic kidney disease: from kidney function to kidney damage & from animal model to human kidney

Bioenergetics Investigation of bioenergetic and anti-oxidative systems of organism in selected diseases


Traditionally, research at Faculty of Medicine in Bratislava is focused on investigation of etiopathogeneis of diabetes mellitus, osteoporosis, thyroid diseases, rheumatoid arthritis, sepsis, and other immune diseases.

Principal investigatorsProf. Juraj Payer, MD, PhD, MPH, FRCPProf. Ľudmila Podracká, MD, PhDProf. Tibor Hlavatý, MD, PhDAssoc. Prof. Mária Bucová, MD, PhDAssoc. Prof. Peter Celec, MD, Dipl Eng, Dr Rer Nat, DSc, MPHAssoc. Prof. Katarína Šebeková, MD, DScProf. Mária Šimaljaková, MD, PhDProf. Ladislav Turecký, MD, PhD


A1. Diabetes mellitus - diabetic foot

InvestigatorsProf. Ľudovít Gašpar, MD, PhD ([email protected])Prof. Viera Štvrtinová, MD, PhDProf. Stanislav Oravec, MD, PhDAssoc. Prof. Jozed Bulas, MD, PhDMartin Čaprnda, MD, PhDMarek Kučera, MD, PhDDenisa Čelovská, MD, PhDAndrea Komorníková, MD

TopicOur research is focused on chronic complications of diabetes mellitus, specifically on diabetic foot and cardiovascular autonomic neuropathy. We monitor the effect of hyperbaric oxygen on changes in vasomotion and healing process of diabetic wounds. Orthostatic hypotension as the most severe grade of cardiovascular autonomic neuropathy has also a great prognostic importance, and therefore we have dedicated our immense attention to this topic.

Plans for future research• Optimization of diagnosis and therapy of patients with diabetic foot syndrome• Association between insulin administration by insulin pump and prognosis of patients with diabetes mellitus• Resistant hypertension in patients with diabetes mellitus• Diabetes mellitus, dipping status and prognosis of patients• Incidence of mediocalcinosis in patients with diabetes mellitus a their prognosis

Devices and methods• Complex non-invasive cardiovascular diagnostics (Holter ECG, ABPM, exercise load testing, echocardiography,

Laser-Doppler investigation of vessels, transcutaneous oximetry – Periflux System 5000, Perimed AB, Sweden)• Analysis of spectrum and sub-fractions of lipids by method Lipoprint LDL and HDL• Spectral analysis of heart rate variability• Diagnosis of cardiovascular autonomic neuropathy• Determination of ankle-brachial index and prognosis of patients with critical limb ischemia and medial arterial

calcinosis

Grants and Funding (in the last 10 years)• APVV-16-0247: Changes in redox regulation and monitoring of specific biomarkers of cardiovascular diseases

(2017-2021)• VEGA 1/0807/18: Central systolic blood pressure in hypertension treatment optimalization (2018-2020)• VEGA 1/0195/16: Effect of hyperbaric oxygentherapy in treatment of patients with diabetic polyneuropathy

(2016-2017)• 2012/5-UKBA-5: DNA analysis and identification of risk factors of renal disease progression in pacients with

polycystic kidney disease (2013-2015)• 14 13 02 000 96, INTERREG IIIA AT-SR: Testing of vascular endothelium integrity (2007-2008)• AV 4/0101/ 06: Evaluation of vascular endothelium integrity in population with ischemic heart disease,

peripheral artherial obliterative disease, hyperlipoproteinemias and essential hypertension (2006-2008)


Selected publications• Balaz D, Komornikova A, Sabaka P, Bendzala M, Leichenbergova E, Leichenbergova K, Novy M, Gaspar L, Dukat A. Effect of

hyperbaric oxygen on lipoprotein subfractions in diabetic patients. Undersea Hyperb Med 2015; 42: 399-407.• Gaspar L, Kruzliak P, Komornikova A, Celecova Z, Krahulec B, Balaz D, Sabaka P, Caprnda M, Kucera M, Rodrigo L, Uehara Y,

Dukat A. Orthostatic hypotension in diabetic patients-10-year follow-up study. J Diabetes Complications 2016; 30: 67-71.• Balaz D, Komornikova A, Sabaka P, Leichenbergova E, Leichenbergova K, Novy M, Kralikova D, Gaspar L, Dukat A. Changes

in vasomotion--effect of hyperbaric oxygen in patients with diabetes Type 2. Undersea Hyperb Med 2016; 43: 123-34.• Pleskovič A, Letonja MŠ, Vujkovac AC, Nikolajević Starčević J, Gazdikova K, Caprnda M, Gaspar L, Kruzliak P, Petrovič D.

C-reactive protein as a marker of progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus. Vasa 2017; 46: 187-92.

• Kasko M, Gaspar L, Dukát A, Gavorník P, Oravec S. High-density lipoprotein profile in newly-diagnosed lower extremity artery disease in Slovak population without diabetes mellitus. Neuro Endocrinol Lett 2014; 35: 531-5.

• Strbova L, Krahulec B, Waczulikova I, Gaspar L, Ambrozy E, Bendzala M, Dukat A. Influence of infection on clinical picture of diabetic foot syndrome. Bratisl Lek Listy. 2011;112: 177-82.

• Andreozzi GM, Kalodiki E, Gaspar L, Martini R, Minar E, Angelides N, Nicolaides A, Novo S, Visona A, Prior M, Arosio E, Husein E, Poredos P, Antignani P, Avram R, Roztočil K, Stvrtinova V, Kozák M, Vacula I. Consensus Document on Intermittent Claudication from the Central European Vascular Forum(CEVF)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology. Int Angiol 2014, 329-47.

• Kalodiki E1, Stvrtinova V, Allegra C, Andreozzi G, Antignani PL, Avram R, Brkljacic B, Cadariou F, Dzsinich C, Fareed J, Gaspar L, Geroulakos G, Jawien A, Kozak M, Lattimer CR, Minar E, Partsch H, Passariello F, Patel M, Pécsvárady Z, Poredos P, Roztocil K, Scuderi A, Sparovec M, Szostek M, Skorski M. Superficial vein thrombosis: a consensus statement. Int Angiol 2012; 31: 203-16.

• Gaspar L, Makovnik M, Bendzala M, Hlinstakova S, Gavornik P, Dukat A, Stvrtinova V, Stvrtina S, Danihel L, Babal P. Medial calcinosis. A marker of increased cardiovascular risk. Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2013; 172: 247-52.

• Gaspar L, Komorníková A, Kruzliak P, Rodrigo L, Gabbasov Z, Staffa R, Berezin A, Gavornik P, Dukat A, Ambrozy E, Bendzala M, Sabaka P. Contribution of prostaglandin E1 treatment in patients with critical limb ischemia. Int J Clin Exp Med 2016; 9: 3227-31.

• Gaspar L, Bendzala M, Gasparova I, Caprnda M, Kucera M, Dukat A. Dipping status and prognosis in older hypertensive patients - 5-year follow-up study. World Heart J 2016; 8: 11-21.


A2. Diabetes mellitus - monogenic disorders of insulin secretion and action

InvestigatorsAssoc. Prof. Juraj Staník, MD, PhD ([email protected])Ľubomír Barák, MD, PhDDaniela Staníková, MD, PhDDenisa Lobotková, MD, PhDLukáš Varga, MD, PhDKristína Podoláková, MD

TopicOur research is focused on clinical and genetic aspects of monogenic forms of diabetes mellitus and hypoglycemia. We have identified a genetic cause of the MEHMO syndrome, and also a first mutation in the promotor of the GCK gene causing GCK-MODY. We have also participated in several international studies focused on the pharmacogenetics in neonatal diabetes, and studies on biomarkers for various forms of Maturity Onset Diabetes of the Young (MODY).

Plans for future research• Adjusting clinical diagnostic criteria for MODY• Searching for a causal mutation in syndromic forms of diabetes using next-generation sequencing techniques• Pharmacogenetics of monogenic diabetes and congenital hyperinsulinism• Optimization of diagnosis and therapy of patients with mitochondrial diabetes

Devices and methods• Molecular-genetic analysis at Biomedical Research Center, Slovak Academy of Sciences• Clinical diagnostics and management in Children Diabetes Center at the Pediatric Department of Faculty of

Medicine in Bratislava

Projects realized in the last 10 years• APVV-17-0296: Genetic causes of rare diseases with emphasis on metabolic disorders associated with

hypoglycemia and mitochondriopathies (2018-2022)• VEGA 1/0211/18: Diagnostic and pharmacogenetic aspects of monogenic diabetes type MODY (2018-2021)• VEGA 2/0083/17: Whole-exome sequencing in patients with a suspicion on primary mitochondriopathies (2017-

2020)• APVV 0107-12: Molecular-genetic research with pharmacogenetic consequences in children with

hyperinsulinemic hypoglycemia (2013-2017); principal investigator: Assoc. Prof. Juraj Staník, MD, PhD• APVV 0187-12: Identification of new genetic aspects of monogenic endocrinophaties by next generation

sequencing (2013-2017)• VEGA 2/0166/14: Prevalence and mutation spectrum of the most common forms of monogenic obesity (2013-

2016)• VEGA 2/0151/11: Prevalence of various types of diabetes type MODY in Slovakia (2010-2014)• ASFEU- structural founds of EU (ITMS: 26240220051): TRANSENDOGEN (Transfer of genetic knowledge of

endocrine research into clinical praxis (2010-2014)• APVV: 51-0142-05: DNA analysis of monogenic forms of diabetes mellitus in Slovakia (2006-2009)


Selected publications• Stanik J, Dankovcikova A, Barak L, Skopkova M, Palko M, Divinec J, Klimes I, Gasperikova D. Sulfonylurea vs insulin therapy

in individuals with sulfonylurea-sensitive permanent neonatal diabetes mellitus, attributable to a KCNJ11 mutation, and poor glycaemic control. Diabet Med. 2018 Mar;35(3):386-391.

• Stanik J, Skopkova M, Stanikova D, Brennerova K, Barak L, Ticha L, Hornova J, Klimes I, Gasperikova D.: Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome. Physiol Res. 2018 May 4;67(2):331-337.

• Stanikova D, Buzga M, Krumpolec P, Skopkova M, Surova M, Ukropcova B, Ticha L, Petrasova M, Gabcova D, Huckova M, Piskorova L, Bozensky J, Mokan M, Ukropec J, Zavacka I, Klimes I, Stanik J, Gasperikova D. Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents. PLoS One. 2017; 12: e0177222.

• Löffler D, Behrendt S, Creemers JW, Klammt J, Aust G, Stanik J, Kiess W, Kovacs P, Körner A. Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism. Mol Metab 2016; 6: 295-305.

• Stanik J, Skopkova M, Brennerova K, Danis D, Rosolankova M, Salingova A, Bzduch V, Klimes I, Gasperikova D. Congenital hyperinsulinism and glycogenosis-like phenotype due to a novel HNF4A mutation. Diabetes Res Clin Pract 2017; 126: 144-150.

• Skopkova M, Hennig F, Shin BS, Turner CE, Stanikova D, Brennerova K, Stanik J, Fischer U, Henden L, Müller U, Steinberger D, Leshinsky-Silver E, Bottani A, Kurdiova T, Ukropec J, Nyitrayova O, Kolnikova M, Klimes I, Borck G, Bahlo M, Haas SA, Kim JR, Lotspeich-Cole LE, Gasperikova D, Dever TE, Kalscheuer VM. EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO. Hum Mutat 2017; 38: 409-25.

• Skopkova M, Ciljakova M, Havlicekova Z, Vojtkova J, Valentinova L, Danis D, Murgas D, Szepeova R, Stanik J, Banovcin P, Klimes I, Gasperikova D. Two novel RFX6 variants in siblings with Mitchell-Riley syndrome with later diabetes onset and heterotopic gastric mucosa. Eur J Med Genet 2016; 59: 429-35.

• Stanikova D, Surova M, Buzga M, Skopkova M, Ticha L, Petrasova M, Huckova M, Gabcova-Balaziova D, Valentova L, Mokan M, Zavacka I, Stanik J, Klimes I, Gasperikova D. Age of obesity onset in MC4R mutation carriers. Endocr Regul 2015; 49: 137-40.

• Stanikova D, Surova M, Ticha L, Petrasova M, Virgova D, Huckova M, Skopkova M, Lobotkova D, Valentinova L, Mokan M, Stanik J, Klimes I, Gasperikova D. Melanocortin-4 receptor gene mutations in obese Slovak children. Physiol Res 2015; 64: 883-90.

• Stanik J, Dusatkova P, Cinek O, Valentinova L, Huckova M, Skopkova M, Dusatkova L, Stanikova D, Pura M, Klimes I, Lebl J, Gasperikova D, Pruhova S. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014; 57: 480-4.

• Thanabalasingham G, Huffman JE, Kattla JJ, Novokmet M, Rudan I, Gloyn AL, Hayward C, Adamczyk B, Reynolds RM, Muzinic A, Hassanali N, Pucic M, Bennett AJ, Essafi A, Polasek O, Mughal SA, Redzic I, Primorac D, Zgaga L, Kolcic I, Hansen T, Gasperikova D, Tjora E, Strachan MW, Nielsen T, Stanik J, Klimes I, Pedersen OB, Njølstad PR, Wild SH, Gyllensten U, Gornik O, Wilson JF, Hastie ND, Campbell H, McCarthy MI, Rudd PM, Owen KR, Lauc G, Wright AF. Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes 2013; 62: 1329-37.


• Stanik J, Kusekova M, Huckova M, Valentinova L, Masindova I, Stanikova D, Ferenczova J, Gasperikova D, Klimes I. Impact of Type 2 diabetes on Glucokinase diabetes (GCK-MODY) phenotype in a Roma (Gypsy) family - case report. Endocr Regul 2012; 46: 99-105.

• Valentínová L, Beer NL, Staník J, Tribble ND, van de Bunt M, Hučková M, Barrett A, Klimeš I, Gašperíková D, Gloyn AL. Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia. PLoS One 2012; 7: e34541.

• Thanabalasingham G, Shah N, Vaxillaire M, Hansen T, Tuomi T, Gašperíková D, Szopa M, Tjora E, James TJ, Kokko P, Loiseleur F, Andersson E, Gaget S, Isomaa B, Nowak N, Raeder H, Stanik J, Njolstad PR, Malecki MT, Klimes I, Groop L, Pedersen O, Froguel P, McCarthy MI, Gloyn AL, Owen KR. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes. Diabetologia 2011; 54: 2801-10.


• Wirsing A, Johnstone KA, Harries LW, Ellard S, Ryffel GU, Stanik J, Gasperikova D, Klimes I, Murphy R. Novel monogenic diabetes mutations in the P2 promoter of the HNF4A gene are associated with impaired function in vitro. Diabet Med 2010; 27: 631-5.

• Suliman SG, Stanik J, McCulloch LJ, Wilson N, Edghill EL, Misovicova N, Gasperikova D, Sandrikova V, Elliott KS, Barak L, Ellard S, Volpi EV, Klimes I, Gloyn AL. Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism. Diabetes 2009; 58: 2954-61.

• Gasperíková D, Tribble ND, Staník J, Hucková M, Misovicová N, van de Bunt M, Valentínová L, Barrow BA, Barák L, Dobránsky R, Bereczková E, Michálek J, Wicks K, Colclough K, Knight JC, Ellard S, Klimes I, Gloyn AL. Identification of a novel beta-cell glucokinase (GCK) promoter mutation (-71G>C) that modulates GCK gene expression through loss of allele-specific Sp1 binding causing mild fasting hyperglycemia in humans. Diabetes 2009; 58: 1929-35.

• Staník J, Lethby M, Flanagan SE, Gasperíková D, Milosovicová B, Lever M, Bullman H, Zubcevic L, Hattersley AT, Ellard S, Ashcroft FM, Klimes I. Coincidence of a novel KCNJ11 missense variant R365H with a paternally inherited 6q24 duplication in a patient with transient neonatal diabetes. Diabetes Care 2008; 31: 1736-7.


B. Osteoporosis

InvestigatorsProf. Juraj Payer, MD, PhD, MPH, FRCP ([email protected])Assoc. Prof. Zdenko Killinger, MD, PhDAssoc. Prof. Peter Jackuliak, MD, PhDAssoc. Prof. Martin Kužma, MD, PhDProf. Tibor Hlavatý, MD, PhDAssoc. Prof. Tomáš Koller, MD, PhDProf. Ľudmila Podracká, MD, PhDĽubica Tichá, MD, PhD

Topic• Effect of selected therapeutic approaches on bone parameters with regards to bone structure assessment• Secondary osteoporosis in rheumatoid arthritis – bone quality and the effect of biological treatment on bone• Impact of adult growth hormone deficiency and on bone mineral density, trabecular bone score, and effect

of vitamin D as cofactor in the treatment of growth hormone deficiency• Prediction models of clinical fractures in patients with postmenopausal osteopenia• The effect of glycemic compensation on bone - bone quality in diabetic patients• Prevalence of osteoporosis in patients with inflammatory bowel diseases and the effect of treatment on bone

parameters

Plans for future research• Effect of acromegaly on bone parameters and incidence of clinical and morphometric vertebral fractures• Chronic heart failure and incidence of clinical and morphometric vertebral fractures• Effect of hydrocortisone treatment on bone in patients with Addison disease• Association between hyperthyroidism, bone quality and novel bone turnover markers• Assessment of bone quality in adults with hypophosphatasia• Prevalence of fractures in patients with rheumatoid arthritis treated with biological therapy.• Extend existing epidemiological data of osteoporotic fractures in diabetic patients• Mutual influence of other factors of secondary osteoporosis on incidence of osteoporosis in diabetic patients• Non-invasive measurement of advanced glycation end-products (AGEs)• Metabolic consequences of bone disease in children• New potential biomarkers of bone metabolism• Aassessment of sarcopenia in selected groups with secondary osteoporosis

Devices and methods• Determination of biochemical markers of bone metabolism• Determination of vitamin D• Investigation of calcium-related and calcium non-related effects of vitamin D• Dual energy X-ray absorptiometry• Trabecular bone score, hip structure analysis, 3D-DXA• AGE reader for skin autofluorescence• Serum CX3CL1/Fractalkine, IL-1Ra, IL-8


Projects realized in the last 10 years• VEGA 2/0029/16: Redox regulation of professional phagocytes in the blood and central nervous system:

Molecular mechanisms and functional significance (2016-2018)• VEGA 2/0010/13: Pharmacological regulation of phagocyte activity and apoptosis: study at cellular and

molecular level (2013 – 2015)• Center for Research on Serious Diseases and their Complications. Supported by the Operational Program

Research and Development co-funded by the European Union from the European Regional Development Fund, ITMS Code 26240120038 (2013-2015)

• LipidomicNet – 7th Framework Program, European Commission, Brussels, Belgium – Lipid droplets as dynamic organelles of fat deposition and release: translational research towards human disease

• Ministry of health scientific grant n.2005/1-DFNKE-01: Molecular aspects of teratogenic, metabolic and atherogenic effects of hyperhomocysteinemia on the fetus and child (2006-2008)

• VEGA 1/0613/17: Early diagnosis of osteoporosis in children and adolescents with mental anorexia (2017-2019)• Norwegian found SJK0017-GOL-00143-H-V2(1):The research of glucocorticoid influence on pediatric diseases –

children´s health improvement (2007-2010)

Selected publications• Kužma M, Vaňuga P, Binkley N, Ságová I, Pávai D, Blažíček P, Kužmová Z, Jackuliak P, Vaňuga A, Killinger Z, Payer J. High

Serum Fractalkine is Associated with Lower Trabecular Bone Score in Premenopausal Women with Graves’ Disease. Horm Metab Res 2018; 50: 609-14.

• Krajčovičová A, Kužma M, Hlavatý T, Hans D, Koller T, Jackuliak P, Lešková Z, Šturdík I, Killinger Z, Payer J. Decrease of trabecular bone score reflects severity of Crohn’s disease: results of a case-control study. Eur J Gastroenterol Hepatol 2018; 30: 101-6.

• Kužma M, Hans D, Koller T, Némethová E, Jackuliak P, Killinger Z, Resch H, Payer J. Less strict intervention thresholds for the FRAX and TBS-adjusted FRAX predict clinical fractures in osteopenic postmenopausal women with no prior fractures. J Bone Miner Metab 2018; 36: 580-8.

• Kužma M, Binkley N, Bednárová A, Killinger Z, Vaňuga P, Payer J. Trabecular bone score change differs with regard to 25(OH)D levels in patients treated for adult-onset growth hormone deficiency. Endocr Pract 2016; 22: 951-8.

• Kužma M, Kužmová Z, Zelinková Z, Killinger Z, Vaňuga P, Lazurová I, Tomková S, Payer J. Impact of the growth hormone replacement on bone status in growth hormone deficient adults. Growth Horm IGF Res 2014; 24: 22-8.

• Killinger Z, Kužma M, Sterančáková L, Payer J. Osteoarticular changes in acromegaly. Int J Endocrinol 2012; 2012: 839282.• Jackuliak P, Payer J. Osteoporosis, fractures, and diabetes. Int J Endocrinol 2014; 2014: 820615.• Payer J, Brázdilová K, Jackuliak P. Management of glucocorticoid-induced osteoporosis: prevalence, and emerging treatment

options. Drug Healthc Patient Saf 2010; 2: 49-59.• Baqi L, Payer J, Killinger Z, Sušienková K, Jackuliak P,Čierny D, Langer P. The level of TSH appeared favourable in maintaining

bone mineral density in postmenopausal women. Endocr Regul 2010; 44: 9-15.• Hlavaty T, Krajcovicova A, Payer J. Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much?

J Crohns Colitis 2015; 9: 198-209.• Miznerova E, Hlavaty T, Koller T, Toth J, Holociova K, Huorka M, Killinger Z, Payer J. The prevalence and risk factors for

osteoporosis in patients with inflammatory bowel disease. Bratisl Lek Listy 2013; 114: 439-45.• Krajcovicova A, Hlavaty T, Killinger Z, Miznerova E, Toth J, Letkovsky J,Nevidanska M, Cierny D, Koller T, Zelinkova Z,

Huorka M, Payer J. Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients. J Crohns Colitis 2014; 8: 1693-701.

• Šebeková K, Somoza V, Jarčušková M, Heidland A, Podracká Ľ. Plasma advanced glycation end products are decreased obese children compared with lean controls. Int J Pediatr Obes 2009, 4:112-8.


C. Short stature in children

InvestigatorsAssoc. Prof. Ľudmila Košťálová, MD, PhD ([email protected])Zuzana Pribilincová, MD, PhDEva Vitáriušová, MD PhDĽubica Tichá, MD, PhDKatarína Prochotská, MD, PhDZuzana Blusková, MD, PhD

Plans for future research• Growth hormone treatment in children with deficit of growth hormone - effect and complications• Growth hormone treatment in SGA born children - effect and complications• Growth hormone treatment in Turner syndrome and rasopathies - effect and complications• Growth hormone treatment children with disorder of sexual differentiation in mosaicism in karyotype - effect

and complications• Genetic causes of short stature (Geleophysic nanism, 3-M syndrome, Silver-Russell syndrome, Deficiency of

SHOX gene)• Onset of puberty in SGA born children

Devices and methods• Hormonal and metabolic profile• Body composition• Genetic assay• Evaluation of puberty• Evaluation of bone age

Projects realized in the last 10 years• ECOS - Easypod Connect observational Study (2012-2016)• GeNeSIS - The genetic and endocrinology of Short Stature International Study (2006-2016)• KIGS - Kabi international growth hormone study (1992-2015)

Selected publications• Cizmarova M, Kostalova L, Pribilincova Z, Lasabova Z, Hlavata A, Kovacs L, Ilencikova D. Rasopathies - dysmorphic

syndromes with short stature and risk of malignancy. Endocr Regul 2013; 47: 217-22.• Čizmárová M, Hlinková K, Bertok S, Kotnik P, Duba HC, Bertalan R, Poločková K, Košťálová Ľ, Pribilincová Z, Hlavatá

A, Kovács L, Ilenčíková D. New mutations associated with Rasopathies in a Central European population and genotype-phenotype correlations. Ann Hum Genet 2016; 80: 50-62.

• Dusatkova P, Pfäffle R, Brown MR, Akulevich N, Arnhold IJ, Kalina MA, Kot K, Krzisnik C, Lemos MC, Malikova J, Navardauskaite R, Obermannova B, Pribilincova Z, Sallai A, Stipancic G, Verkauskiene R, Cinek O, Blum WF, Parks JS, Austerlitz F, Lebl J. Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations. Eur J Hum Genet 2016; 24: 415-20.


D. Disorders of sexual development

InvestigatorsZuzana Pribilincová, MD, PhD ([email protected])Assoc. Prof. Ľudmila Košťálová, MD, PhDEva Vitáriušová, MD PhDKatarína Prochotská, MD, PhDPeter Bartoň, MDJozef Babala, MD, PhDZuzana Nižňanská, MD, PhDJudita Puškáčová, MD, PhD

Plans for future research• Database of DSD in Slovakia• Genotype – phenotype correlations in DSD patients• EvaIuating risk of gonadal cancer in DSD patients• Role of Androstendione in evaluating treatment of CAH and other hyperandrogenic states• Blood pressure and insulin resistance in paediatric CAH patients• Surgical outcomes in DSD patients – novel approach

Devices and methods• Genotyping DSD populatin• Examination of metabolic status in CAH patients• Analysis of circadian rhytms of blood pressure in CAH patients• Immunohistochemistry in operated gonads in DSD patients, correlation with genotype

Projects realized in the last 10 years• MESPE CAH study group, CEEPUS grant (1999-2002)• VEGA 1/0497/08: Risk factors of metabolic syndrome in population of patients with exogenous obesity, mutation

of melanocortin receptor 4 and classic form of congenital adrenal hyperplasia with 21 hydroxylase deficiency (2008-2012)

Selected publications• Kovács J, Votava F, Heinze G, Sólyom J, Lebl J, Pribilincová Z, Frisch H, Battelino T, Waldhauser F; Middle European Workshop

on Paediatric Endocrinology-Congenital Adrenal Hyperplasia Study Group. Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle european countries. J Clin Endocrinol Metab 2001; 86: 2958-64.

• Frish H, Waldhauser F, Lebl J, Solyom J, Hargitai G, Kovacs J, Pribilincova Z. Krzisnik C, Battelino T. Congenital adrenal hyperplasia: lessons from a multinational study. Horm Res 2002: 58: 95-101.

• Votava F, Török D, Kovács J, Möslinger D, Baumgartner-Parzer S, M, Sólyom J, Pribilincová Z, Battelino T, Lebl J, Frisch H, Waldhauser F. Estimation of Fals- Negative Rate in Newborn screening for Congenital Adrenal Hyperplasia. Horm Res 2002; 58: 98-9.

• Dolzan V, Solyom J, Fekete G, Kovacs J, Rakosnikova V, Votava F, Lebl J, Pribilincova Z, Baumgartner-Parzer SM, Riedl S, Waldhauser F, Frisch H, Stopar-Obreza M, Krzisnik C, Battelino T. Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia. Eur J Endocrinol 2006; 153: 99-106.


• Vitáriušová E, Košťálová Ľ, Pribilincová Z, Hlavatá A, Kovács L. Problems of metabolic syndrome diagnostics in children. Endocr Regul 2010; 44: 115-20.

• Blusková Z, Košťálová Ľ, Celec P, Vitáriušová E, Pribilincová Z, Maršálková M, Šemberová J, Kyselová T, Hlavatá A, Kovács L. Evaluation of lipid and glucose metabolism and cortisol and thyroid hormone levels in obese appropriate for gestational age (AGA) born and non-obese small for gestational age (SGA) born prepubertal Slovak children. J Pediatr Endocrinol Metab 2014; 27: 693-9.


E. Metabolic syndrome in children

InvestigatorsAssoc. Prof. Ľudmila Košťálová, MD, PhD ([email protected])Zuzana Pribilincová, MD, PhDEva Vitáriušová, MD PhDKatarína Prochotská, MD, PhDAnna Hlavatá, MD, PhD, MPHZuzana Blusková, MD, PhDKatarína Krivošíková, MD

Plans for future research• Etiology of pediatric metabolic syndrome• Components of metabolic syndrome and hormonal disturbances in praepubertal and pubertal SGA born

children• Components of metabolic syndrome and hormonal disturbances in Roma SGA born children• Metabolic syndrome in Slovak Roma population• Etiology pediatric primary hypertension• Salt consumption and its influence on blood pressure• Mineral and electrolyte metabolism in children with metabolic syndrome• Changes in metabolic syndrome after intervention treatment

Devices and methods• 24 hour blood pressure monitoring• Adipokines• Body composition, bioimpedance• Examination of renal function and renal salt excretion• Mineral and electrolyte metabolism• Biochemical and humoral markers of metabolic syndrome• Analysis of circadian and ultradian rhythms of blood pressure

Projects realized in the last 10 years• VEGA 1/4278/07: Current state of nutrition and incidence of obesity in 6-15 years old children in selected

regions of Slovakia (2007-2011)• VEGA 1/0497/08: Risk factors of metabolic syndrome in population of patients with exogenous obesity, mutation

of melanocortin receptor 4 and classic form of congenital adrenal hyperplasia with 21 hydroxylase deficiency (2008-2012)

• VEGA 1/1267/12: Chronic microinflammation of visceral fat and its role in development of cardiovascular and bone complications in obese children and in children with chronic inflammatory bowel disease (2012-2016)

• VEGA 1/0202/17: Humoral, renal and psychological factors in pediatric obesity and hypertension (2017-2019)

Selected publications• Švec P, Vásárhelyi B, Pászthy B, Körner A, Kovács L, Tulassay T, Treszl A. Do regulatory T cells contribute to Th1 skewness in

obesity? Exp Clin Endocrinol Diabet 2007; 115: 439-43.• Kovács L, Babinska K, Ševčiková Ľ. New trends in infant and child nutrition. TRIAD s.r.o. 2008; 92 pp.• Kovács L, Babinská K et al. Obesity, nutrition and physical activity in children. LF UK 2008.


• Vitáriušová E, Košťálová Ľ, Pribilincová Z, Hlavatá A, Kovács L. Problems of metabolic syndrome diagnostics in children. Endocr Regul 2010; 44: 115-20.

• Vitáriušová E, Babinská K, Košťálová Ľ, Rosinský J, Hlavatá A, Pribilincová Z, Babinská K.jr, , Kovács L. Food intake , leisure time activities and the prevalence of obesity in school children in Slovakia, Cent Eur J Public Health 2010; 18: 192-7.

• Ondrejčáková M, Bakos J, Garafová A, Kovács L, Kvetňanský R, Ježová D. Neuroendocrine and cardiovascular parameters during simulation of stress-induced rise in circulating oxytocin in the rat. Stress 2010; 13: 315-23.

• Babinska K, Kovacs L, Janko V, Dallos T, Feber J. Association between obesity and the severity of ambulatory hypertension in children and adolescents. J Am Soc Hypertens 2012; 6: 356-63.

• Blusková Z, Košťálová Ľ, Celec P, Vitáriušová E, Pribilincová Z, Maršálková M, Šemberová J, Kyselová T, Hlavatá A, Kovács L. Evaluation of lipid and glucose metabolism and cortisol and thyroid hormone levels in obese appropriate for gestational age (AGA) born and non-obese small for gestational age (SGA) born prepubertal Slovak children. J Pediatr Endocrinol Metab 2014; 27: 693-9.

• Polák E, Vitáriušová E, Celec P, Pribilincová Z, Košťálová Ľ, Hlavatá A, Kovács L, Kádaši Ľ. The prevalence of melanocortin – 4 receptor gene mutations in Slovak obese children and adolescents. J Pediatr Endocrinol Metab 2016; 29: 55-61.

• Prochotská K, Kovacs L, Vitariušová E, Feber J. Is arterial stiffness predicted by continuous metabolic syndrome score in obese children? J Am Soc Hypertens 2016; 10: 47-54.


F. Inborn errors of metabolism

InvestigatorsAssoc. Prof. Vladimír Bzdúch, MD, PhD ([email protected])Darina Behúlova, MD, PhDKatarína Brennerová, MDAnna Hlavatá, MD, PhDKatarína Juríčková, MDMiriam Kolníková, MD, PhDFrantišek Horn, MD, PhD

TopicOur research is focused on analysis of clinical features of inborn errors of metabolism with dysmorphic features and use of new approaches to treatment. In disorder of cholesterol biosynthesis, Smith-Lemli-Opitz syndrome we discovered sacral dimple as a new skin manifestation of this syndrome. In nonketotic hyperglycinemia we used a new treatment with ketogenic diet and in lysosomal storage diseases, we used new combination of ERT a substrate inhibition therapy in Pompe disease. We used a new intrathecal baclofen therapy for improvement of quality of life in patients with mucopolysaccharidosis type II (Hunter syndrome).

Plans for future research• We will continue obtain new experience with novel therapy of inborn errors of metabolism

Devices and methods• Gas Chromatography mass spectrometry (GC/MS)• Amino Acid Analyzer• New biochemical methods for selective screening

Projects realized in the last 10 years• VEGA 2/0083/17: Whole-exome sequencing in patients with a suspicion on primary mitochondriopathies (2017-

2020)• VEGA 1/0211/18: Diagnostic and pharmacogenetic aspects of monogenic diabetes type MODY (2018-2021)• APVV-17-0296: Genetic causes of rare disease with emphasis on metabolic disorders associated with

hypoglycemia and mitochondriopatjies (2018-2022)

Selected publications• Horn F, Dúbravová D, Hornová J, Brennerová K, Bzdúch V. Intrathecal baclofen in mucopolysaccharidosis type II (Hunter

syndrome): case report. Child´s Nervous System 2018;34: 2325-2327.• Bzduch V, Tomcikova D, Gerinec A, Behulova D. Cataract and early nystagmus due to galactokinase deficiency. J Inherit Metab

Dis 2017; 40: 749-750.• Dvorakova L, Vlaskova H, Sarajlija A, Ramadza DP, Poupetova H, Hruba E, Hlavata A, Bzduch V, Peskova K, Storkanova

G, Kecman B, Djordjevic M, Baric I, Fumic K, Barisic I, Reboun M, Kulhanek J, Zeman J, Magner M. Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II.Clin Genet 2017; 91: 787-96.

• Stanik J, Skopkova M, Brennerova K, Danis D, Rosolankova M, Salingova A, Bzduch V, Klimes I, Gasperikova D. Congenital hyperinsulinism and glycogenosis-like phenotype due to a novel HNF4A mutation. Diabetes Res Clin Pract 2017; 126: 144-50.

• Straka M, Danišovič L, Bzdúch V, Polák Š, Varga I. The significance of electron microscopic examination of gingiva in cases of Hunter syndrome & hereditary gingival fibromatosis.Neuro Endocrinol Lett 2016; 37: 353-60.


• Magner M, Dvorakova V, Tesarova M, Mazurova S, Hansikova H, Zahorec M, Brennerova K, Bzduch V, Spiegel R, Horovitz Y, Mandel H, Eminoglu FT, Mayr JA, Koch J, Martinelli D, Bertini E, Konstantopoulou V, Smet J, Rahman S, Broomfield A, Stojanovic V, Dionisi-Vici D, van Coster R, Morava-Kozicz E, Sperl W, Zeman J, Honzik T. TMEM70 deficiency: long-term outcome of 48 patients. J Inherit Metab Dis 2015; 38: 417-26.

• Lobotková D, Staníková D, Staník J, Červeňová O, Bzdúch V, Tichá L. Lack of association between peripheral activity of thyroid hormones and elevated TSH levels in childhood obesity. JCRPE 2014; 6: 100-4.

• Behulova D, Sebova C, Syrova D, Ostrozlikova M, Bzduch V, Vasilenkova A. Transient hyperphosphatasemia: Revisited diagnostic criteria base on the study of 533 cases. Clin Biochem 2011; 44: 523.

• Lubanda JC, Anijalg E, Bzduch V, Thurberg BL, Benichou B, Tylki/Szymanska A. Evaluation of a low dose, after standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 2009; 11: 256-64.

• Bzduch V, Behulova D, Kozak L. Sacral dimple as a skin manifestation of the Smith-Lemli-Opitz syndrome. J Inherit Metab Dis 2007; 30: 269-70.

• Zahorakova D, Rosipal R, Hadac J, Zumrova A, Bzduch V, Misovicova N, Baxova A, Zeman J, Martasek P. Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms. J Hum Genet 2007; 52: 342-8.

• Kure S, KatoK, Dinopoulos A, Gail C, deGrauw TJ, Christodoulos J, Bzduch V, Kalmanchey R, Fekete G, Trojovsky A, Plecko B, Breningstall G, Tohyama J, Aoki Y, Matsubara Y. Comprehensive Mutation Analysis of GLDC, AMT, and GCSH in Nonketotic Hyperglycinemia. Hum Mutat 2006; 27: 343-52.


G. Thyroid gland and ORL

InvestigatorsAssoc. Prof. Miroslav Tedla, MD, MPH, PhD ([email protected])Patrik Štefanička, MD, PhDLukáš Varga, MD, PhDProf. Milan Profant, MD, PhD

TopicOne branch of our research focuses on various aspects of quality of life in relation to the thyroid gland surgery (neurophysiology complications, QoL, voice, swallowing alterations).With conjunction with BMC SAV we also plan stratification of thyroid nodules with intermediate risk of malignancy using methods of molecular – genetic analysis.

Plans for future research• Effect of thyroid gland surgery on quality of life (neurophysiology complications, QoL, voice, swallowing

alterations)• Thyroid gland and obesity

Devices and methods• Molecular-genetic analysis at BMC SAV• Surgical unit of ORL department in UNB• Voice and swallowing analysys unit

Selected publications• Kyrou I, Adesanya O, Hedley N, Wayte S, Grammatopoulos D, Thomas CL, Weedall A, Sivaraman S, Pelluri L, Barber TM,

Menon V, Randeva HS, Tedla M and Weickert MO. Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in Euthyroid Adults With Severe Obesity—a Pilot Study. Front Endocrinol 2018; 9: 488.

• Fussey JM, Crunkhorn R, Tedla M, Weickert MO, Mehanna H. External beam radiotherapy in differentiated thyroid carcinoma: A systematic review. Head Neck 2016; 38: E2297-305.

• Al Maqbali T, Tedla M, Weickert MO, Mehanna H. Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid. PLoS One 2012; 7: e49078.



H. Nutrition

InvestigatorsProf. Jana Jurkovičová, MD, PhD ([email protected])Prof. Ľudmila Ševčíková, MD, PhDAssoc. Prof. Ľubica Argalášová, MD, PhDZuzana Štefániková, MD, PhDJana Babjaková, MD, PhDKatarína Hirošová, RNDr, PhDMartin Samohýl, MEng, PhDr, PhDAlexandra Filová, MSc, PhDDiana Vondrová, RNDr, PhD

TopicResearch of the institute has been oriented towards study of interactions between environment, nutrition and population health status, health protection and promotion of children and youth, study of psychosocial, behavioral and environmental risk factors of cardiovascular diseases and effects of noise on human health.The most important results:• the original comprehensive methodology for the risk assessment of cardiovascular diseases based on the

evaluation of 32 risk factors suitable for screening was elaborated and verified in practice; valid data on the current state of nutrition and selected indicators of cardiovascular disease risk in the Slovak population were obtained;

• the impact of the risk of excessive noise pollution on the area of psychological and vegetative functions and the organ of hearing was verified - acceptance of the results of noise studies and their inclusion in the publications NASA/CR - 2001-211257, ENNAH Report 2012, WHO Environmental Noise Guidelines for European Region 2018; objectification of physiological reactions of a child’s body to noise were the basis for innovation of standards IEC 601-2-19 and IEC 601-2-20;

• the current growth and development standards of the Slovak children and adolescent population have been developed for individual assessment of the child’s development in pediatric practice; for quantification of the depot body fat for selected population groups; for group diagnostics in the field of state health surveillance and for research international comparative studies with regard to the new age categorization that has not yet been developed.

Plans for future research• Detection of selected environmental, behavioral, and psychosocial risk factors of cardiovascular diseases

prevalence in adolescents and university students• Analysis of selected cardiometabolic parameters in adolescents for cardiovascular and other chronic diseases

prevention and intervention• Monitoring of risk factors and biological markers distribution in relation to age, gender, education, residence

location• Study of behavioral and physical risk factors in adolescents and adults

Devices and methods• Reflotron – automatic device for screening of blood lipids and other biochemical parameters in capillary blood• Futrex - NIR method for determination of body fat percentage• Omron - BIA method for determination of body fat and lean body mass content

mailto:jana.jurkovicova%40fmed.uniba.sk?subject=


• Caliper method for determination of body fat percentage• InBody 720 – precision body composition analyzer• Software for nutrients intake and energy expenditure analysis and for relative cardiovascular risk calculation• Bruel & Kjaer 2250 Handheld Sound Level Analyzer with Logging Software BZ7224

Grants and Funding (in the last 10 years)• VEGA 1/3433/06: Study of somatic development in children and adolescents in relationship with selected genetic

and psychosocial factors (2006-2008)• VEGA 1/4274/07: Study of environmental, behavioral, and psychosocial risk factors in relationship to biological

markers of cardiovascular diseases (2007-2009)• ENNAH-European Network on Noise and Health – 7. Frame Program of EU No. 226442, FP7-ENV-2008-1,

Z-10-101/0001-00 (2009 – 2011)• SF EU Program Education, ITMS 26140230009: Preparation of study program Master of Public Health (2013-

2015)• VEGA 1/1045/12: Physical activity in relationship to somatic development, physical fitness, and psychical

balance (2012 – 2014)• VEGA 1/0637/13: Metabolic syndrome in adolescents (2013-2015)• VEGA 2/0084/14: Epicatechine in prevention of early development of primary hypertension: mechanisms of

action in cardiovascular and central nervous system (2014 – 2016)• Project proposal in the framework of the Memorandum of Understanding on Academic Exchanges between

School of Medicine Comenius University in Bratislava and New York University School of Medicine No. O-15-101-/0001-00: The Youth and Parents Risk Factor Behaviour Survey in Slovakia (YABS) (2015-2016)

Selected publications• Jurkovičová J. Do we know how to live healthy? The incidence of cardiovascular diseases risk factors in the Slovak population

sample and the prevention possibilities. Bratislava: Comenius University 2005; 166 pp.• Štefániková Z, Jurkovičová J, Ševčíková Ľ, Argalášová Ľ, Ághová Ľ. Did the nutrition of Slovak medical students change? A

comparison after 15 years. Cent Eur J Public Health 2001; 9: 223-7.• Štefániková Z, Ševčíková Ľ, Jurkovičová J, Argalášová Ľ, Ághová Ľ. Positive and negative trends in university students´ food

intake. Bratisl Lek Listy 2006; 107: 217-20.• Jurkovičová J, Štefániková Z, Argalášová Ľ, Ševčíková Ľ, Ághová Ľ. Psychosocial factors in relation to cardiovascular diseases

risk in Slovak population sample. Homeostasis 2006; 44: 151-4.• Jurkovičová J, Štefániková Z, Argalášová Ľ, Ševčíková Ľ, Ághová Ľ. Cardiovascular disease risk factors in a sample group of 65+

year-old people in the Slovak Republic. Cardiology 2009; 18: 47-62.• Argalášová Ľ, Jurkovičová J, Štefániková Z, Ševčíková Ľ, Ághová Ľ. Community response to environmental noise and the

impact on cardiovascular risk score. Sci Total Environ 2010; 408: 1264-70.• Argalášová Ľ, Lekaviciute J, Jeram S, Ševčíková Ľ, Jurkovičová J. Environmental noise and cardiovascular disease in adults:

Research in Central, Eastern and South-Eastern Europe and Newly Independent States. Noise Health 2013; 15: 22-31.• Siváková D, Vondrová D, Valkovič P, Cvíčelová M, Danková Z, Luptáková L. Bioelectrical Impedance Vector Analysis (BIVA)

in Slovak population: application in a clinical sample. Cent Eur J Biol 2013; 8: 1094-101.• Jusko TA, Oktapodas M, Palkovičová Murinová L, Babinská K, Babjaková J, Verner MA, DeWitt JC, Thevenet-Morrison K,

Čonka K, Drobná B, Chovancová J, Thurston SW, Lawrence BP, Dozier AM, Järvinen KM, Patayová H, Trnovec T, Legler J, Hertz-Picciotto I, Lamoree MH. Demographic, Reproductive, and Dietary Determinants of Perfluorooctane Sulfonic (PFOS) and Perfluorooctanoic Acid (PFOA) Concentrations in Human Colostrum. Environ Sci Technol 2016; 50: 7152-62.

• Hirošová K, Gerová Z, Samohýl M, Kapsdorfer D, Vondrová D, Argalášová Ľ, Ševčíková Ľ, Jurkovičová J. Prevalence of overweight and obesity in adolescents and their association with cardiometabolic risk factors and life-style. Hygiena 2016; 61: 100-7.


• Samohýl M, Rams R, Hirošová K, Vondrová D, Kapsdorfer D, Filová A, Jurkovičová J. Impact of nutrition and the mother´s lifestyle risk factors on the birth weight and birth length of newborns´. Hygiena 2016; 61: 48-55.

• Argalasova L, Filova A, Hirosova K, Vondrova D, Samohyl M, Krajcova D, Jurkovicova J, Sevcikova L. The Risks of Social Noise Exposure in the Vulnerable Population in Slovakia. Arch Acoust 2016; 41: 535-41.

• Panulinova E, Harabinová S, Argalášová L. Tram squealing noise and its impact on human health. Noise Health 2016; 18: 329-37.

• Vondrová D, Kapsdorfer D, Argalášová Ľ, Hirošová K, Samohýl M, Ševčíková Ľ. The impact of selected environmental, behavioral and psychosocial factors on schoolchildrens´ somatic and mental health. Rev Environ Health 2017; 32: 189-92.

• Argalášová Ľ, Ševčíková Ľ, Jurkovičová J, Babjaková J, Janeková E, Totka A, Šimko M, Weitzman M. Determinants of ETS exposure in a sample of Slovak pregnant women. Rev Environ Health 2017; 32: 201-5.

• Samohyl M, Nadazdyova A, Hirosova K, Vondrova D, Krajcova D, Jurkovicova J. Patients satisfaction with dental care in the Slovak Republic: A cross-sectional questionnaire study. Iran J Public Health 2017; 46: 1143-4.

• Samohyl M, Solovic I, Svecova J, Rams R, Hirosova K, Jurkovicova J. Tuberculosis as Public Health Problem in the Slovak Republic. Iran J Public Health 2017; 46: 852-3.

• Sevcikova L, Babjakova J, Jurkovicova J, Samohyl M, Stefanikova Z, Machacova E, Vondrova D, Janekova E, Hirosova K. Filova A, Weitzman M, Argalasova L. Exposure to Environmental Tobacco Smoke in Relation to Behavioral, Emotional, Social and Health Indicators of Slovak School Children. Int J Environ Res Public Health 2018; 15: 1374.

• Kapsdorfer D, Hlavacova N, Vondrova D, Argalasova L, Sevcikova L, Jezova D. Neuroendocrine response to school load in prepubertal children: focus on trait anxiety. Cell Mol Neurobiol 2018; 38: 155-62.

• Pultznerova A, Panulinova E, Kucharova D, Argalasova L. Railway Noise Annoyance on the Railway Track in Northwest Slovakia. Noise Health 2018; 20: 90-100.


I. Autoimmunity and autoinflammation

InvestigatorsProf. Milan Buc, MD, DSc ([email protected])Assoc. Prof. Mária Bucová, MD, PhDAssoc. Prof. Vladimíra Ďurmanová, RNDr, PhDMonika Homolová, MD, PhDJuraj Javor, MD, PhDZuzana Párnická, MD, PhDAssoc. Prof. Ivana Shawkatová, MSc, PhDMagda Suchánková, MD, PhDAssoc. Prof. Peter Čižnár, PhDTomáš Dallos, MD, PhD

TopicThe goal of our contemporary research activities concentrate on genetic determination of two diseases, multiple sclerosis (MS) and Alzheimer disease (AD). We have been studying associations between polymorphisms of genes coding for proinflammatory cytokines (TNF), adhesive molecules (VLA4, ICAM1) and MS, and AD respectively. In the field of paediatric rheumatology, we study a new approach to the treatment (a biological therapy) of juvenile idiopathic arthritis (JIA) in the frame of international projects. New classifications of subtypes of JIA were proposed and we try to apply it to our cohort of patients.

Plans for future research• By means of association studies, we intend to contribute to the identification of suitable immunogenetic markers

of Alzheimer´s disease within the groups of candidate genes studied• Focus on autoinflammatory diseases: prevalence of autoinflammatory diseases• Genetic aspects of primary immunodeficiencies

Devices and methods• PCR cyclers, ELISA-reader, transilluminator, spectrophotometer, photo-recording system• PCR-based methods (PCR-RFLP, PCR-SSP)• HLA typing of classical and non-classical genes• SNP typing of genes coding cytokines, cytokines receptors, adhesive molecules, membrane antigens and other

immune-related molecules• DNA sequencing• ELISA for protein detections (cytokines, acute phase proteins, pattern recognition receptors, inflammatory

markers)• Flow cytometry (cell surface markers – CDs, cytokines)• ELFO (agarose and polyacrylamide gels)

Grants and Funding (in the last 10 years)• VEGA: 1/0240/16: Immunogenetic markers in Slovak patients with Alzheimer´s disease (2016-2018)• VEGA: 1/0810/12: Imunogenetic determination of response to biological treatment of patients suffering from

multiple sclerosis (2012-2014)• VEGA: 1/0145/09: Imunogenetic determination of psoriasis vulgaris and pemphigus vulgaris (2009-2011)• KEGA 080UK-4/2013. Autoimmunity and autoimmune diseases (2013-2015)


Selected publications• Krivosikova M, Dallos T, Maslinski W, Buc M. B cell activating factor, its role in autoimmunity, and targeting in autoimmune

diseases. Bratislava Med J 2009; 110: 137-45.• Dallos T, Krivosikova M, Chorazy-Massalska M, Warnawin E, Zanova E, Rudnicka W, Maslinski W. BAFF from bone marrow-

derived mesenchymal stromal cells of rheumatoid arthritis patients improves their B-cell viability-supporting properties. Folia Biol 2009; 55: 166-76.

• Javor J, Ferencik S, Bucova M, Stuchlikova M, Martinka E, Barak L, Strbova L, Grosse-Wilde H, Buc M. Polymorphisms in the genes encoding TGF-beta1, TNF-alpha, and IL-6 show association with type 1 diabetes mellitus in the Slovak population. Arch Immunol Ther Exp (Warsz). 2010; 24: 65-8.

• Javor J, Chmurova N, Parnicka Z, Ferencik S, Grosse-Wilde H, Buc M, Svecova D. TNF-alpha and IL-10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population. J Eur Acad Dermatol Venereol 2010; 24: 65-8.

• Dallos T, Heiland GR, Strehl J, Karonitsch T, Gross W, Moosig F, Holl-Ulrich C, Distler JH, Manger B, Schett G, Zwerina J. Chemokine CCL17/TARC in Churg-Strauss syndrome. Arthritis Rheum. 2010; 62(11):3496-3503.

• Kovács L, Hlavatá A, Baldovič M, Paulovičová E, Dallos T, Fehérvízyová Z, Kadasi L. Elevated IgD levels in children with PFAPA syndrome. Neuro Endocrinol Lett 2010; 31: 743-6.

• Buc M. Basic and Clinical Immunology. Bratislava, 2nd edition. Veda 2012; 831 pp. (in Slovak)• Shawkatová I, Javor J, Párnická Z, Kozub P, Žilinková M, Frey P, Ferenčík S, Buc M. HLA-C, DRB1 and DQB1 alleles involved

in genetic predisposition to psoriasis vulgaris in the Slovak population. Folia Microbiol 2013; 58: 319-24.• Párnická Z, Švecová D, Javor J, Shawkatová I, Buc M. High susceptibility to pemphigus vulgaris due to HLA-DRB1*14:54 in the

Slovak population. Int J Immunogenet 2013; 40: 471-5.• Dallos T, Oppl B, Kovács L, Zwerina J. Pachydermodactyly: a review. Curr Rheumatol Rep 2014; 16: 442.• Švecova D, Parnická Z, Luha J, Buc M. HLA-DRB1 and DQB1 alleles are associated with disease severity in patients with

pemphigus vulgaris. Int J Dermatol 2015; 54: 168-73.• Ďurmanová V, Shawkatová I, Javor J, Párnická Z, Čopíková-Cundráková D, Turčáni P, Lisá I, Gajdošechová B, Buc M, Bucová

M. VLA4 gene polymorphism and susceptibility to multiple sclerosis in Slovaks. Folia Biol (Praha) 2015; 61: 8-13.• Michalik J, Čierny D, Kantorová E, Kantárová D, Juraj J, Párnická Z, Kurča E, Dobrota D, Lehotský J. The association of HLA-

DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population. Neurol Res 2015; 37: 1060-7.


• Conti, F., Lugo-Reyes, S.O., Blancas Galicia, L., Ciznar, P. et al. Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases (2016) J Allergy Clin Immunol, 138 (1): 241-248.

• Buc M. Autoimmunity and autoimmune diseases. Bratislava, 2nd edition. Veda 2016; 667 pp.• Shawkatová I, Javor J, Párnická Z, Bucová M, Čopíková-Cudráková D, Michalík J, Gmitterová K, Čierny D, Buc M, Ďurmanová

V. Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients. Folia Microbiol (Praha) 2017.• Shawkatova I et al. Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients. Folia Microbiol 2017; 62: 287-

93.• Buc M. New biological agents in the treatment of multiple sclerosis. Bratislava Med J 2018; 119: 191-7.• Doležalová P, Böhm M, Dallos T, Consolaro A et al. For the paediatric Rheumatology International Trials Organisation

(PRINTO). The Slovak version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Rheumatol Int 2018; 38 (Suppl 1): 5123-30.


J. Inflammation in cardiovascular diseases

InvestigatorsAssoc. Prof. Mária Bucová, MD, PhD ([email protected])Assoc. Prof. Ján Lietava, MD, PhDProf. Marian Bernadic, MD, PhDAssoc. Prof. Július Hodosy, MD, MSc, PhD, MPH

Plans for future research• Cytokine polymorphism and inflammation in cardiovascular diseases• Determination of cytokines, chemokines, and new markers of inflammation, gene expression of TREM-1 and

HMGB1, adhesive molecules• Determination of new circulating nucleic acids as a marker of inflammation and myocardial damage• Early predictors of mortality in myocardial infarction, the role of DNAse activity and extracellular DNA

Devices and methods• PCR cyclers, PCR-SSP, RFLP, Taq Man, centrifuges• DNA/RNA spectrophotometer, transilluminator• ELFO, photo-recording system• DNA/RNA isolation• DNAse activity maeasurement• ELISA

Grants and Funding (in the last 10 years)• VEGA 2/0105/15: Early molecular markers of myocardial infarction (2015-2017)

Selected publications• Bucova M, Lietava J, Penz P, Mrazek F, Petrkova J, Bernadic M, Petrek M. Association of MCP-1 -2518 A/G single nucleotide

polymorphism with the serum level of CRP in Slovak patients with ischemic heart disease, angina pectoris, and hypertension. Mediators Inflamm 2009; 2009: 390951.

• Bucova M, Lietava J, Mrazek F, Petrkova J, Bernadic M, Buckingham T, Petrek M. Association of chronic stable angina pectoris with MCP-1-2518 A/G single nucleotide polymorphism in the Slovak population. Clin Chim Acta 2008; 392: 71-2.

• Lietava J, Vohnout B, Penz P, Kuka P, Bucova M, Kosmalova V, Atalay M.Relationship of self-reported exercise tolerance with inflammatory markers in women with stable ischemic heart disease. Neuro Endocrinol Lett 2012; 33: 50-4.

• Bucova M. Inflammation and genetics of inflammation in cardiovascular diseases. (1-34). Angina pectoris. Federico Piscione, intech open acces Publisher, 2011, 184 pp.

• Bucova M, Lietava J, Mrazek F, Petrkova J, Penz P, Bernadic M, Buckingham TA, Petrek M.The MCP-1 -2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population. Bratisl Lek Listy 2009; 110: 385-9.

• Bucova M, Bernadic M, Buckingham T. C-reactive protein, cytokines and inflammation in cardiovascular diseases.Bratisl Lek Listy 2008; 109: 333-40.

• Kuka P, Bucova M, Penz P, Paulovicova E, Blazicek P, Atalay M, Lietava J. HSP60, oxidative stress parameters and cardiometabolic risk markers in hypertensive and normotensive Slovak females. Bratisl Lek Listy 2010; 111: 527-34.

• Penz P, Bucova M, Lietava J, Blazicek P, Paulovicova E, Mrazek F, Bernadic M, Buckingham TA, Petrek M. MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects. Bratisl Lek Listy 2010; 111: 420-5.


• Martakova L, Olejarova I, Danova K, Fischer V, Parrak V, Bucova M, Pechan I. Cytokine levels in patients with a very low left ventricular ejection fraction after open heart surgery. Bratisl Lek Listy 2001; 102: 548-51.

• Bucova M. Inflammation and genetics of inflammatory response in cardiovascular diseases. Kardiologia 2008; 17: 15-22.• Madaric J, Klepanec A, Valachovicova M, Mistrik M, Bucova M, Olejarova I, Necpal R, Madaricova T, Paulis L, Vulev I.

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia. Stem Cell Res Ther 2016; 7: 116.

• Madaric J, Valachovicova M, Paulis L, Pribojova J, Mateova R, Sebekova K, Postulkova L, Madaricova T, Bucova M, Mistrik M, Vulev I. Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia. Stem Cell Res Ther 2017; 8: 165.

• Lietava J, B BV, Dukat A, Fodor GJ. Homocysteine Slovakia study: study design and occurrence of hyperhomocysteinaemia and other risk factors. Bratisl Lek Listy 2012; 113: 80-6.

• Benacka O, Benacka J, Blazicek P, Belansky M, Payer J, Killinger Z, Lietava J. Speckle tracking can detect subclinical myocardial dysfunction in rheumatoid arthritis patients. Bratisl Lek Listy 2017; 118: 28-33.

• Aziriova S, Repova K, Krajcirovicova K, Baka T, Zorad S, Mojto V, Slavkovsky P, Hodosy J, Adamcova M, Paulis L, Simko F. Effect of ivabradine, captopril and melatonin on the behaviour of rats in L-nitro-arginine methyl ester-induced hypertension. J Physiol Pharmacol 2016; 67: 895-902.


K. Rheumatoid arthritis

InvestigatorsAssoc. Prof. Zdenko Killinger, MD, PhD ([email protected])Prof. Juraj Payer, MD, PhD, MPH, FRCPAssoc. Prof. Peter Jackuliak, PhDAssoc. Prof. Martin Kužma PhDKristína Brázdilová, MD, PhDDaniel Čierny, MD, PhDMonika Adamcová MD

Plans for future research• Determination of effect of inflammatory rheumatic diseases on bone metabolism, metabolic syndrome and

cardiovascular risk• Evaluation of bone quality in secondary osteoporosis with focus on inflammatory rheumatic diseases• Effect of biological therapy on bone metabolism and parameters related to bone quality• Evaluation of sarcopenia and frailty syndrome using bioimpedance spectroscopy

Devices and methods• Whole body densitometer (Discovery Wi Hologic) enabling to measure bone density, morphological scan of

spine (software IVA, Hologic), Hip structure analysis software - measurement of several indexes characterizing solidity of femoral cervix, whole body composition - ration of fat, muscle and bone

• Non-invasive evaluation of aortal calcifications by DXA method• Determination of parameters characterizing bone turnover, calcium phosphate metabolism• Assessment of bone microarchitecture with trabecular bone score • Sarcopenia assesement – bioimpedance spectroscopy, whole body densitometry, hand-grip , SARQoL

questionnaire

Projects realized in the last 10 years• Determination of cellular and molecular mechanisms responsible for pharmacological modulation of activity of

phagocytes - neutrophil granulocytes and microglia cells• Elucidation of effects of drugs affecting production of free oxygen and nitrate species• Elucidation of changes in neutrophils activity in patients with rheumatoid arthritis

Selected publications• Killinger Z, Gajdarova L, Kuzma M, Krajcovicova A, Brazdilova K, Jackuliak P, Payer J. Biologic treatment in comparison to

methotrexate has positive effect on trabecular bone score in rheumatoid arthritis patients: 1-year follow-up. ActaClin Belg 2018; 23:1-5.

• JančInová V, Nosáľ R, Payer J, Killinger Z. Increased intracellular and extracellular oxidant production in phagocytes of rheumatic patients treated with biological therapy - whole blood quantification. Interdiscip Toxicol 2017; 10: 52-5.

• Kužma M, Vanuga P, Sagova I, Pavai D, Jackuliak P, Killinger Z, Binkley N, Winzenrieth R, Genant H, Payer J. Non-invasive DXA-derived bone structure assessment of acromegaly patients: A cross-sectional study. Eur J Endocrinol 2018; pii: EJE-18-0881.R2.

• Kužma M, Vaňuga P, Binkley N, Ságová I, Pávai D, Blažíček P, Kužmová Z, Jackuliak P, Vaňuga A, Killinger Z, Payer J. High Serum Fractalkine is Associated with Lower Trabecular Bone Score in Premenopausal Women with Graves’ Disease. Horm Metab Res 2018; 50: 609-14.

mailto:killinger%40ru.unb.sk?subject=


• Krajcovicova A, Kuzma M, Hlavaty T, Hans D, Koller T, Jackuliak P, Leskova Z, Sturdik I, Killinger Z, Payer J. Decrease of trabecular bone score reflects severity of Crohn’s disease: results of a case-control study. Eur J Gastroenterol Hepatol 2018; 30: 101-6.

• Killinger Z, Kužma M, Sterančáková L, Payer J. Osteoarticular changes in acromegaly. Int J Endocrinol 2012; 2012: 839282.• Killinger Z, Cierny D, Jackuliak P, Zelinkova Z, Rovensky J, Payer J. Long-term efficacy of infliximab for treating Takayasu

arteritis. Isr Med Assoc J 2012; 14: 771-3.• Brazdilova K, Dlesk A, Koller T, Killinger Z, Payer J. Vitamin D deficiency - a possible link between osteoporosis and metabolic

syndrome. Bratisl Lek Listy 2012; 113: 412-6.• Kužma M, Binkley N, Bednárová A Killinger Z, Vaňuga P, Payer J. Trabecular bone score change differs with regard to 25(OH)

D levels in patients treated for adult-onset growth hormone deficiency. Endocr Pract 2016; 22: 951-8.


L. Inflammatory bowel diseases

InvestigatorsProf. Tibor Hlavatý, MD, PhD ([email protected])Assoc. Prof. Tomáš Koller, MD, PhDAssoc. Prof. Peter Celec, MD, Dipl Eng, Dr Rer Nat, DSc, MPHProf. Juraj Payer, MD, PhD, MPH, FRCPAnna Krajčovičová, MD, PhDIgor Šturdík, MD, PhDZuzana Lešková-Vráblicová, MDYashar Jaliali, MD

TopicOur research is focused on elucidating the ethiology and pathogenesis of inflammatory bowel diseases (IBD), improving the diagnostic possibilities and researching new therapeutic options of patients with IBD. In a cross sectional study on a large cohort of IBD patients and healthy controls we identified risk factors associated with higher risk of IBD, i.e. shorter period of breastfeeding and reduced physical activity in childhood. We also researched the role of vitamin D in IBD and found a strong correlation between vitamin D serum concentrations and disease activity, further we identified mRNA microarrays of key cytokines that are influenced by vitamin D. We have studied also the role of chromoendoscopy and confocal laser endomicroscopy in the screening of CRC in IBD. Recently we focused on research of new therapeutic options. We study the role of faecal microbiota transplantation, possibilities to de-escalate medication in patients in deep remission and the role of therapeutic drug monitoring in tailoring the therapy of IBD.

Plans for future research• Assessment of the optimal therapeutic regimen of vitamin D supplementation• Evaluation of efficacy and safety of medical treatment of IBD• Evaluation of efficacy and safety of fecal microbiota transplantation for IBD• Evaluation of the role of therapeutic drug monitoring• Systematic reviews and meta-analysis

Devices and methods• Endoscopy department including videocolonoscopy, enteroscopy, chromoendoscopy• Abdominal and small bowel ultrasound• Infusion unit at the IBD centre• Investigation of infliximab through levels and antibody formation• Investigation of calcium related and calcium not related effects of vitamin D

Projects realized in the last 10 years• Grant APVV (APVV-0672-11): The role of vitamin D in inflammatory bowel diseases (2012-2015)• Ministry of Health scientific grant (2007/19-UK-02): Extraintestinal complications of inflammatory bowel

diseases (2008-2013)• Ferring international scientific grant: Screening of colorectal dysplasia in IBD patients (2008-2011)• VEGA (VEGA 1/0007/08): Pharmacogenetics of therapy for inflammatory bowel diseases (2008-2011)

mailto:tibor.hlavaty%40gmail.com?subject=


Selected publications• Hlavaty T, Pierik M, Henckaerts L, Ferrante M, Joossens S, van Schuerbeek N, Noman M, Rutgeerts P, Vermeire S.

Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther 2005; 22: 613-26.

• Hlavaty T, Ferrante M, Henckaerts L, Pierik M, Rutgeerts P, Vermeire S. Predictive model for the outcome of infliximab therapy in Crohn’s disease based on apoptotic pharmacogenetic index and clinical predictors. Inflam Bowel Dis 2007; 13: 372-9.

• Hlavaty T, Huorka M, Koller T, Zita P, Kresanova E, Rychly B, Toth J. Colorectal cancer screening in patients with ulcerative and Crohn’s colitis with use of colonoscopy, chromoendoscopy and confocal endomicroscopy. Eur J Gastroenterol Hepat 2011; 23: 680-9.

• Hlavaty T, Batovsky M, Balakova D, Pav I, Celec P, Gregus M, Zakuciova M, Hlista M, Horakova M, Desatova B, Koller T, Toth J, Kadasi L, Huorka M; Slovak IBD study group (SK IBD). The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases. Bratisl Lek Listy 2013; 114:199-205.

• Hlavaty T, Krajcovicova A, Koller T, Toth J, Nevidanska M, Huorka M, Payer J. Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World J Gastroenterol 2014; 20: 15787-96.

• Hlavaty T, Krajcovicova A, Payer J. Vitamin D Therapy in Inflammatory Bowel Diseases: Who, in What Form, and How Much? J Crohns Colitis 2014; 9: 198-209.

• Krajcovicova A, Hlavaty T, Killinger Z, Miznerova E, Toth J, Letkovsky J, Nevidanska M, Cierny D, Koller T, Zelinkova Z, Huorka M, Payer J. Combination therapy with an immunomodulator and anti-TNFalpha agent improves bone mineral density in IBD patients. J Crohns Colitis 2014; 8: 1693-701.

• Rencz F, Péntek M, Bortlik M, Zagorowicz E, Hlavaty T, Śliwczyński A, Diculescu MM, Kupcinskas L, Gecse KB, Gulácsi L, Lakatos PL Biological therapy in inflammatory bowel diseases: Access in Central and Eastern Europe. World J Gastroenterol 2015; 21: 1728-37.

• Hlavaty T, Krajcovicova A, Letkovsky J, Sturdik I, Koller T, Toth J, Huorka M. Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy. Bratisl Lek Listy 2016; 117: 205-11.

• Hlavatý T, Krajcovicova A, Sturdik I, Letkovský J, Koller T, Tóth J, Huorka M. Biosimilar infliximab CT-P13 treatment in patients with inflammatory bowel diseases - a one year, single centre retrospective study. Gastrenterol Hepatol 2016; 70: 27-36.

• Hlavaty T, Krajcovicova A, Zakuciova M, et al. Guidelines of the IBD working group of the Slovak Gastroenterology Society on the management of ulcerative colitis. Gastroent Hepatol 2017; 71: 229-40.

• Koller T, Tóth J, Hlavatý T, et al. Guidelines of the IBD working group of the Slovak Gastroenterology Society on the management of Crohn’s disease. Gastrenterol Hepatol 2018; 72: 27-40.

• Gregus M, Hlavaty T, Krajcovicova A, et al. Guidelines of the IBD working group of the SGS on the management on the IBD – optimizing biological treatment in the IBD after loss of response. Gastrenterol Hepatol 2018; 72: 426-31.

• Vrablicova Z, Soltys K, Krajcovicova A, Sturdik I, Koller T, Huorka M, Payer J, Stuchlik S, Killinger Z, Jackuliak P, Stuchlikova M, Drahovska H, Hlavaty T. Influence of vitamin D on the expression of mRNA of cytokines in the mucosa of inflammatory bowel disease patients. Bratisl Lek Listy 2018; 119: 408-15.

• Krajcovicova A, Kuzma M, Hlavaty T, Hans D, Koller T, Jackuliak P, Leskova Z, Sturdik I, Killinger Z, Payer J. Decrease of trabecular bone score reflects severity of Crohn’s disease: results of a case-control study. Eur J Gastroenterol Hepatol 2018; 30: 101-6.


M. Legionnaires´disease, Leptospirosis, Tularemia, nosocomial infections

InvestigatorsAssoc. Prof. Margita Špaleková, MD, PhD ([email protected])Assoc. Prof. Alexandra Bražinová, MD, PhD, MPHMartina Kotrbancová, MSc, PhDMiriam Fulová MD, MScVanda Výrosteková, MD, PhDErika Macháčová, MD, PhDJana Perželová, RNDr, PhDJana Korcová, RNDr, PhDPetra Vadovičová, PhDr, MSc, PhDVeronika Sivčová, MSc

TopicSurveillance of some selected notifiable communicable diseases (legionella infections, leptospira infections, tularemia, invasive pneumoccocal infections, HPV infections, nosocomial infections).

Plans for future research• Surveillance of legionelloses in Slovakia – annually published epidemiologic patterns/characteristics of legionella

infections in Slovakia – confirmation, notification and classification of legionella cases in national EPIS (Epidemiologic Information System) of communicable system

• Diagnostics of legionelloses (cultivation, detection of legionella antigen in urine -ELISA, PCR, serological tests (immunofluorescence, agglutination), participation in international external control (ELISA, PCR)

• Epidemiological investigation and analysis of community and nosocomial legionella cases• Investigation of legionellae colonisation in water systems, risk assessment in hospitals, monitoring of legionella

in hospital´s water system and other water aerosol producing devices for treatment, wellness, etc.• Cooperation with ECDC (European Centre for Prevention and Control) - ELDSNet (annual notification of

Slovak cases in TESSY, national focal point, collaboration in investigation of TALD - (travel associated legionella cases)

• Surveillance of leptospiroses in Slovakia – annually published since 1970 with documented changing epidemiologic characteristics of leptospira infections in Slovakia last decades

• Diagnostics of leptospiroses (serological tests – agglutination -MAT, ELISA), cultivation, microscopy in dark field, detection of nucleic acid of leptospirae in PCR, participation in international external control (MAT)

• Notification of human leptospira infection to national EPIS• Investigation of leptospiral infections in foci (association with animal infections), risk assessment,• Epidemiological investigation and analysis of community leptospira cases• Surveillance of tularemia in Slovakia - annually published epidemiologic characteristics of francisellae infections• Diagnostics of human tularemia - serological tests - agglutination, cultivation, PCR, investigation of natural

focus – sampling animal sera, risk assessment, monitoring of natural focuses of infection• Epidemiological investigation and analysis of tularemia community cases and other vector-borne zoonotic

infections• Cooperation with Veterinary Authorities and Slovak Academy of Sciences• Assessment of surveillance system of notifiable communicable diseases, invasive pneumococcal infections,

influenza• Setting up surveillance system for Human Papillomavirus infection• Surveillance of nosocomial infections in Slovakia


• Surveillance of nosocomial legionella infections in Slovakia – epidemiologic characteristics and notification in national EPIS with proposed control measures

• Epidemiological analysis of nosocomial infections in paediatric wards/hospitals in Slovakia, occurrence of legionella infections in children with oncologic diseases, in ICU and other risk units in legionella colonized hospital

• Diagnostics of nosocomial legionelloses in adult patients with underlying diseases in hospitals (cultivation, detection of legionella antigen in urine - ELISA, PCR, serological tests (immunofluorescence, agglutination), cooperation with ECDC – ELDSNet (notification of nosocomial cases in TESSY, national focal point)

Devices and methods• PCR termocycler, centrifuges, spectrophotometer, transilluminator• ELFO, photo-recording system, ELISA reader, incubator

Projects realized in the last 10 years• VEGA 1/4281/07: Complex epidemiologic investigation of selected infections with natural focality in Slovakia in

genomic era (2007 – 2009)• VEGA 2/7020/7: Species competensis of vectors in circulation of tick-borne transmitted microorganisms (2007-

2009)• VEGA 2/0142/10: Importance of ectoparasitic arthropodes (mites, ticks) in circulation of intracelular

proteobacteriae (rickettsiae, anaplasmae, Francisella tularensis) in natural foci on infections (2010-2012)• VEGA 1/0426/11: Epidemiology and diagnostics of selected infectious diseases – tularemia, leptospiroses and

legioneloses by classic and molecular biological methods (2011-2014)• Project of League against cancer: Risk of legionelloses for paediatric oncologic patients (2016)

Selected publications• Spalekova M. Epidemiology of legionellosis in Europe and in the Slovak Republic. Bratisl Lek Listy 2006; 107: 221.• Gurycová D, Tináková K, Výrosteková V, Gacíková E. Occurrence of tularemia in Slovakia 1997 - 2008. Epidemiol Mikrobiol

Imunol 2010; 59: 39-44.• Resch G, Awad-Masalmeh M, Bakoss P, Jareková J. Utility of phylogenetic studies in the identification of Leptospira strains.

Epidemiol Infect 2007; 135: 1266-73.• Bakoss P, Jareková J, Labuda M. An attempt to control a natural focus of leptospirosis grippotyphosa by rodenticide - a long-

term study (1977-2004). Ann Agric Environ Med 2007; 14: 51-6.• Bakoss P, Macháčová E, Jareková J. Long-term trends in the epidemiology of human leptospirosis (Slovak Republic, 1954 -

2006). Eur J Clin Microbiol Infect Dis 2012; 31: 2167-76.• Awad-Masalmeh M, Resch G, Bakoss P, Jarekova J. DNA relatedness and serotyping of Leptospira strains. Bratisl Lek Listy

2012; 113: 70-2.• Fulová M, Špaleková M. Nosocomial infections problem in Slovakia. Lekársky obzor 2016; 65: 70-3.• Kotrbancová M, Špaleková M, Fulová M, Trnková K, Perželová J. Legionellosis and its diagnosis. Epidemiol Mikrobiol Imunol

2017; 66: 133-9.• Perželová J, Jareková J, Kotrbancová M, Špaleková M. Possibilities for laboratory diagnosis of leptospirosis. Epidemiol

Mikrobiol Imunol 2017; 66: 140-5.• Trnková K, Kotrbancová M, Špaleková M, Fulová M, Boledovičová J, Vesteg M. MALDI-TOF MS analysis as a useful tool for

an identification of Legionella pneumophila, a facultatively pathogenic bacterium interacting with free-living amoebae: A case study from water supply system of hospitals in Bratislava (Slovakia). Exp Parasitol 2018; 184: 97e102.

• Bakoss P, Awad-Masalmeh M, Resch G, Jareková J, Stanko M, Perželová J. Human Mozdok leptospirosis first diagnosed by serum agglutinin-absorption tests in the Slovak Republic. Epidemiol Mikrobiol Imunol 2018; 67: 114-20.


N. Sepsis

InvestigatorsAssoc. Prof. Mária Bucová, MD, PhD ([email protected])Michaela Olejárová, MDMagda Suchánková, MD, PhDAnna Dobišová, MD, PhDAssoc. Prof. Vladimíra Ďurmanová, RNDr, PhDAssoc. Prof. Juraj Koutun, MD, PhDAssoc. Prof. Peter Celec, MD, Ing, RNDr, MPH, DScBarbora Izrael Vlková, RNDr, PhD

Plans for future research• Determination of biomarkers of early diagnosis of sepsis, differentiation from SIRS and for monitoring and

prediction of mortality• New inflammatory markers HMGB1, TREM-1, TREM-2, sTREM-1, sTREM2, CD64, presepsin, IL-6, IL-10, IL-35,

IFN-γ, and others• Immunogenetic determination of cytokines polymorphism and polymorphism of TREM and HMGB1 molecules

and cytokines• The role of vitamin D in sepsis outcome, early and late mortality and degree of inflammation• The role of HLA-G polymorphism and level of HLA-G in sepsis outcome, early and late mortality and degree of

inflammation• The role of extracellular DNA in sepsis outcome, early and late mortality and degree of inflammation

Devices and methods• PCR cyclers, PCR-SSP, RFLP, Taq Man, centrifuges• DNA/RNA spectrophotometer, transilluminator• ELFO, photo-recording system• ELISA• Flow cytometry

Grants and Funding (in the last 10 years)• VEGA 1/0156/17: The role of NETosis in the pathogenesis of preeclampsia (2017-2019)• VEGA 1/0159/12: Fetal DNA and preeclampsia in the animal experiment (2012-2014)• APVV-0754-10: The role of circulating nucleic acids in the pathogenesis of preeclampsia (2010-2012)

Selected publications• Bucová M, Záhorec R, Buc M. Immunomodulatory effect of recombinant human procalcitonin on mitogenic activity of

lymphocytes. Centr Eur J Immunol 2006; 31: 87-93.• Naglova H, Bucova M. HMGB1 and its physiological and pathological roles. Bratisl Lek Listy 2012; 113: 163-71.• Pinčíková T, Bucová M, Slobodníková L. Influence of recombinant human procalcitonin on phagocytic and candidacidal

ability of polymorphonuclear le and on killing mechanisms of serum and blood against bacteria Staphylococcus aureus and Escherichia coli. Vnitr Lek 2005; 51: 1365-70.

• Bucová M. Inflammation and sepsis. In: Ferenčík M (ed.): Inflammation – fundamental principle of diseases origin. Balneotherma 2008; 234-45.

• Bucová, M. Role of cytokines in the development of local and systemic inflammation and septic shock. Vnitr Lek 2002; 48: 755-62.


• Bucová M. Procalcitonin - prohormon, hormokine, mediator of inflammation, diagnostic and prognostic marker of systemic inflammation. Cesk Fyziol 2005; 54: 97-108.

• Lauková L, Konečná B, Bábíčková J, Wagnerová A, Melišková V, Vlková B, Celec P. Exogenous deoxyribonuclease has a protective effect in a mouse model of sepsis. Biomed Pharmacother 2017; 93: 8-16.

• Lauková L, Bertolo EMJ, Zelinková M, Borbélyová V, Čonka J, Kovalčíková AG, Domonkos E, Vlková B, Celec P. Early dynamics of plasma DNA in a mouse model of sepsis. Shock 2018.


O1. Microscopic structure, development and evolution of thymus

InvestigatorsProf. Ivan Varga, RNDr, PhD ([email protected])Prof. Štefan Polák, MD, PhDProf. Ľudovít Danihel, MD, PhDAssoc. Prof. Jozef Záhumenský, MD, PhDMichal Miko, MD, PhDPaulína Gálfiová, MD, PhDMartin Klein, MDPetra Pšenková, MD

TopicThe last decade of research confirmed the presence of newly discovered population of cells within the interstitium of female genital organs. About the real significance of these cells – telocytes – are holding highly hypothetical conjectures. However, exist presumptions that these are the cells that functionally interconnect other cells within the microenvironment of female genital organs. That is why they appear in reflections on their possible involvement in a wide range of diseases, such as infertility, tubal pregnancy, pre-eclampsia or uterus myomatosus. Therefore, one of the topics of our research team is a detailed morphological identification and characterization of telocytes (electron microscopy, immunohistochemistry, in vitro culture) in normal and diseased tissues. However, telocytes are not the only “mysterious and neglected” structure within the histology of the female reproductive organs. Since 1904, no one paid any comprehensive attention to lymphatic drainage of the uterine tubes and uterus at the level of the lymph capillaries. Similarly, in the scientific, histological literature is ignored the issue of nomenclature of the epithelial cells of the uterine tubes, even though this tubal epithelium may be the source of high-grade ovarian carcinomas. Detailed identification of intraepithelial immunologically active cells can elucidate the questions regarding the immune suppression within the uterine tubes during sperm and/or embryo transport.

Plans for future research• Identification of the immunologically active cells within the epithelium of uterine tubes and uterus• Identification of telocytes in uterine tubes and uterus in health and disease• Description of the lymphatic drainage of the mucosa of uterine tubes with respect to the function of uterine

tubes in human reproduction

Devices and methods• Light and fluorescent microscopy, include immunohistochemistry and histochemistry• Transmission and scanning electron microscopy• EDAX analysis

Grants and Funding (in the last 10 years)• VEGA 1/0902/11: Thymus in human ontogenesis - changes in microscopic structure and ultrastructure of

thymus in children with congenital heart defects (2011-2013)• APVV-0434-12: Morphologic characterization of reparative and regenerative processes in myocardium during

chronic diseases (2013-2017)• VEGA 1/0086/17: Congenital gut motility disorders: histological and molecular biological study of aganglionar

parts of colon of pediatric patients with Hirschsprung disease (2017-2021)

mailto:ivan.varga%40fmed.uniba.sk?subject=


Selected publications• Varga I, Kachlík D, Žišková M, Miko M. Lymphatic lacunae of the mucosal folds of human uterine tubes - A rediscovery of

forgotten structures and their possible role in reproduction. Ann Anat. 2018; 219: 121-128.• Varga I, Klein M, Urban L, et al. Recently discovered interstitial cells “telocytes” as players in the pathogenesis of uterine

leiomyomas. Med Hypoth. 2018; 110: 64-67.• Klein M, Urban L, Dečkov I, …, Varga I. Distribution of telocytes in the corpus and cervix of human uterus: an

immunohistochemical study. Biologia. 2017; 72(10): 1217-1223.• Varga I, Urban L, Kajanová M, Polák Š. Functional histology and possible clinical significance of recently discovered telocytes

inside the female reproductive system. Arch Gyn Obstet. 2016; 294(2): 417-422.• Cierna Z, Varga I, Danihel L Jr, et al. Intermediate trophoblast - A distinctive, unique and often unrecognized population of

trophoblastic cells. Ann Anat. 2016; 204: 45-50.• Mikušová R, Mešťanová V, Polák Š, Varga I. What do we know about the structure of human thymic Hassall’s corpuscles? A

histochemical, immuno-histochemical,and electron microscopic study. Ann Anat 2017; 211: 140-8.• Klein M, Varga I. Microenvironment of immune cells within the visceral adipose tissue sensu lato vs. epicardial adipose tissue.

What do we know? Inflammation. 2018; 41(4): 1142-1156.• Varga I, Blankova A, Konarik M, et al. The Terminologia Histologica after 10years: Inconsistencies, mistakes, and new

proposals. Ann Anat. 2018; 219: 65-75.• Varga I, Babala J, Kachlik D. Anatomic variations of the spleen: current state of terminology, classification, and embryological

background. Surg Radiol Anat. 2018; 40(1): 21-29.• Boháč M, Danišovič Ľ, Koller J, Dragúňová J, Varga I. What happens to an acellular dermal matrix after implantation in the

human body? A histological and electron microscopic study. Eur J Histochem. 2018; 62(1): 2873.• Varga I, Bódi I, Mešťanová V, et l. Association between histological alterations in the thymus and sudden infant death

syndrome. J Foren Legal Med. 2018; 55: 8-13.• Varga I, Galfiova P, Gazova A, et al. The end-stage failing human myocardium - Where changes in ultrastructure of human

cardiac muscle cells do not appear to dictate clinical outcomes. Med Hypoth. 2018; 110: 105-109.• Bohac M, Varga I, Polak S, et al. Delayed post mastectomy breast reconstructions with allogeneic acellular dermal matrix

prepared by a new decellularization method. Cell Tissue Bank. 2018; 19(1): 61-68.• Kaldararova M, Simkova I, Varga I, et al. Double aortic arch anomalies in children: A systematic 20-year single center study.

Clin Anat. 2017; 30(7): 929-939.• Varga I, Kyselovič J, Galfiova P, Danisovic L. The non-cardiomyocyte cells of the heart. their possible roles in exercise-induced

cardiac regeneration and remodeling. Adv Exp Med Biol. 2017; 999: 117-136.• Varga I, Danisovic L, Kyselovic J, et al. The functional morphology and role of cardiac telocytes in myocardium regeneration.

Can J Physiol Pharmacol. 2016; 94(11): 1117-1121.• Juríková M, Danihel Ľ, Polák Š, Varga I. Ki67, PCNA, and MCM proteins: Markers of proliferation in the diagnosis of breast

cancer. Acta Histochem. 2016; 118(5): 544-52.• Miko M, Danišovič L, Majidi A, Varga I. Ultrastructural analysis of different human mesenchymal stem cells after in vitro

expansion: a technical review. Eur J Histochem. 2015; 59(4): 2528.• Psenkova P, Bucko M, Braticak M, Baneszova R, Zahumensky J. Impact of introducing specific measures to reduce the

frequency of cesarean delivery for non-obstetric indications. Int J Gynaecol Obstet. 2018; 142(1): 23-27.• Zahumensky J, Braticak M, Hlavek R, Bucko M. Vaginal delivery with prior cesarean delivery following appendix rupture and

diffuse purulent peritonitis in a patient with complete wound dehiscence. Int J Gynaecol Obstet. 2017; 136(3): 355-356.


O2. Microscopic structure and blood microcirculation of spleen

InvestigatorsProf. Štefan Polák, MD, PhD ([email protected])Prof. Ivan Varga, RNDr, PhDPaulína Gálfiová, MD, PhDSimona Polakovičová, MD, PhDRenáta Mikušová, MD, PhDJán Liška, MVD, PhDMichal Miko, MD, PhDMária Csöbönyeiová, RNDr, PhDMichaela Vrabcová, MSc, PhDMartin Klein, MD

TopicOur research is focused on the morphological description on human splenic blood microcirculation, and on the microscopic structure of human spleen and thymus during prenatal and postnatal period via methods of light and electron microscopy.

Plans for future research• Detailed description of the “enigmatic” blood microcirculation of human spleen• Association between microscopic changes of human thymus and congenital anomalies of heart, nutritional status

of child or sudden infant death syndromes• Evolutionary view on the immune system• The role of thymic Hassall´s bodies in the development of immunity• Clinical anatomical aspects of congenital anomalies of human lymphatic organs• Determination of the role of enteric nervous system in the development of immune system, especially in cases of

gut aganglionosis (e.g, Hirschsprung disease)

Devices and methods• Light microscopes• Fluorescent microscopes• Electron microscope - transmission and scanning with EDAX analysis

Grants and Funding (in the last 10 years)• VEGA 1/4252/07: The structure of blood microcirculation of human spleen (2007-2009)• VEGA 1/0902/11: Thymus in human ontogenesis - changes in microscopic structure and ultrastructure of

thymus in children with congenital heart defects (2011-2013)• APVV-0434-12: Morphologic characterization of reparative and regenerative processes in myocardium during

chronic diseases (2013-2017)• VEGA 1/0086/17: Congenital gut motility disorders: histological and molecular biological study of aganglionar

parts of colon of pediatric patients with Hirschsprung disease (2017-2021)

Selected publications• Polák Š, Gálfiová P, Varga I. Ultrastructure of human spleen in transmission and scanning electron microscope. Biologia 2009;

64: 402-8.


• Galfiova P, Pospisilova V, Varga I, Sikuta J, Kiss A, Majesky I, Jakubovsky J, Polak S. Endocrine organs and laser scanning confocal microscopy (LSCM) imaging: vascular bed in human spleen. Endocr Regul 2010; 44: 137-42.

• Gálfiová P, Varga I, Kopáni M, Michalka P, Michalková J, Jakubovský J, Polák Š. Some possibilities of representing microcirculation in human spleen. Biologia 2009; 64: 1242-6.

• Biro C, Busikova P, Fujerikova G, El-Hassoun O, Kopaniova A, Caplovicova M, Galfiova P, Sisovsky V, Kopani M, Jakubovsky J. Iron-rich complexes in human spleen in hereditary spherocytosis. Bratisl Lek Listy 2012; 113: 214-6.

• Biro C, Kopani M, Kopaniova A, Zitnanova I, El-Hassoun O, Minoo P, Kolenova L, Sisovsky V, Caplovicova M, Stvrtina S, Galfiova P, Guller L, Jakubovsky J. Iron accumulation in human spleen in autoimmune thrombocytopenia and hereditary spherocytosis. Bratisl Lek Listy 2012; 113: 92-4.

• Mikušová R, Mešťanová V, Polák Š, Varga I. What do we know about the structure of human thymic Hassall’s corpuscles? A histochemical, immuno-histochemical,and electron microscopic study. Ann Anat 2017; 211: 140-8.

• Varga I, Galfiova P, Adamkov M, Danisovic L, Polak S, Kubikova E, Galbavy S. Congenital anomalies of the spleen from an embryological point of view. Med Sci Monit 2009; 15: 269-76.

• Klein M, Varga I. Microenvironment of immune cells within the visceral adipose tissue sensu lato vs. epicardial adipose tissue. What do we know? Inflammation. 2018; 41(4): 1142-1156.

• Varga I, Babala J, Kachlik D. Anatomic variations of the spleen: current state of terminology, classification, and embryological background. Surg Radiol Anat. 2018; 40(1): 21-29.

• Varga I, Bódi I, Mešťanová V, Kováč M, Klein M. Association between histological alterations in the thymus and sudden infant death syndrome. J Foren Legal Med. 2018; 55: 8-13.

• Varga I. Thymus. In Tubbs RS, Shoja MM, Loukas M (Eds). Bergman´s Comprehensive Encyclopedia of Human Anatomic Variation. Hoboken: John Wiley & Sons 2016; 914-8.

• Béder I, Varga I, Béder I. Systema lymphaticum hominis. Bratislava: Herba 2015; 112 pp.• Mešťanová V, Varga I. Morphological view on the evolution of the immunity and lymphoid organs of vertebrates, focus on

thymus. Biologia 2016; 71: 1080-97.• Jablonská-Mešťanová V, Šišovský V, Danišovič Ľ, Polák Š, Varga I. The normal human newborns thymus. Bratisl Lek Listy 2013;

114: 402-8.• Varga I, Neščáková E, Tóth F, Uhrinová A, Adamkov M. Nutrition and immune system: the size of the thymus as an indicator

of the newborn´s nutrition status. Anthropol Anz 2011; 68: 265-74.• Varga I, Uhrinová A, Tóth F, Mištinová J. Assessment of the thymic morphometry using ultrasound in full-term newborns.

Surg Radiol Anat 2011; 33: 689-95.• Varga I, Pospíšilová V, Mešťanová V, Gálfiová P, Polák Š. The thymus: picture review of human thymus prenatal development.

Bratisl Lek Listy 2011; 112: 368-76.• Varga I, Jablonská-Mešťanová V, Cingel V, Kubíková E, Dorko F, Polák Š. The first histological and immunohistological

examination of thymus in a case of fetus in fetu. Ann Anat 2010; 192: 232-6.• Varga I, Mikušová R, Pospíšilová V, Gálfiová P, Adamkov M, Polák Š, Galbavý Š. Morphologic heterogeneity of human thymic

nonlymphocytic cells. Neuro Endocrinol Lett 2009; 30: 275-83.• Varga I, Pospíšilová V, Gmitterová K, Gálfiová P, Polák Š, Galbavý Š. The phylogenesis and ontogenesis of the human

pharyngeal region focused on the thymus, parathyroid, and thyroid glands. Neuro Endocrinol Lett 2008; 29: 837-45.


P. Hereditary ciliopathies, RASopathies and tubulopathies

InvestigatorsProf. Ľudovit Danihel, MD, PhDKatarína Skalická, RNDr, PhDAnna Hlavatá, MD, PhD, MPHViktor Jankó, MD, PhDGabriela Hrčková, MDPavol Janega, MD, PhDÁgnes Baranyaiová, MScAnita Vaská, MSc

Plans for future research• NGS mutational analysis of genes affecting structure and function of cilia and their relationship to human

diseases including polycystic kidney disease and primary ciliary dyskinesia. Pathogenesis of interstitial inflammation at the molecular level and identification of genetic changes along key signal pathways influencing cystic growth and progression of the disease to terminal renal failure. Building and extension of Slovak patient registries for ciliopathies.

• NGS mutational analysis of genes involved in the pathogenesis of rasopathies. Effect of genetic, genomic and immunologic alterations in children with dysregulation of the (MAPK)-RAS signal pathway and predilection to malignancies. Development and extension of registry for Slovak patients with rasopathies, including neurofibromatosis.

• Molecular analysis of causal genes responsible for various inherited forms of diabetes insipidus and renal tubular defects. Development of patient registry for renal tubulopathies.

Devices and methods• ABI PRISM 3100 Avant genetic analyzer (Applied Biosystems), MiSeq (Illumina),• Bioanalyzer 2100 (Agilent technologies), AriaMX real-time PCR system (Agilent technologies)• Covaris ultrasonificator with AFA technology (Covaris), CentriVap DNAVacuum Concentrator (Labconco),

Blotting equipments

Projects realized in the last 10 years• APVV 14/0234: Mutational analysis of genes affecting structure and function of primary cilia and their

importance in polycystic kidney disease (2014-2017)• Grant Slovak Ministry of Health 2012/5-UKBA-5: DNA analysis and identification of risk factors of progression

of renal disease in patients with polycystic kidney disease (2014-2017)• Grant Slovak Ministry of Health 2012/21-UKBA-21: Evaluation of effect of genetic, genomic and immunologic

alterations in children with dysregulation of the (MAPK)-RAS signal pathway s predilection to malignities. (RASGEN) (2014-2017)

• VEGA 1/0955/11: Mutational anylysis, log-term clinical follow-up and therapeutics of autosomal dominant polycystic kidney disease in Slovak children and their family members (2011-2013)

• VEGA 1/0497/08: Obesity in children and metabolic syndrome (2009-2011)• VEGA 1/4314/07: Screening and mutational analysis of Fabri disease and hyper-IgD syndrome in Slovak

population (2007-2009)• Grant Slovak Ministry of Health 2005/4-DFNsPBA-02: Mutational analysis, early DNA diagnosis and prevention

of frequent and severe hereditary diseases of childhood (2005-2008)


Selected publications• Šufliarska S, Minárik G, Horáková J, Boďová I, Bojtárová E, Czako B, Mistrík M, Drgoňa Ľ, Demitrovičová M, Lakota J. Homolová

M, Kovács L. Establishing the method of chimerism monitoring after allogeneic stem cell transplantation using multiplex polymerase chain reaction amplification of short tandem repeat markers and Amelogenin. Neoplasma 2007; 54: 424-30.

• Kolesár P, Minárik G, Baldovič M, Ficek A, Kovács L, Kádaši Ľ. Mutation analysis of the CFTR gene in Slovak cystic fibrosis patients by DHPLC and subsequent sequencing: identification of four novel mutations. Gen Physiol Biophys 2008; 27: 299-305.

• Dallos, T, Avbelj M, Barák, Ľ, Zapletalová, J, Pribilincová, Z, Krajčírová, M, Košťálová, Ľ, Battelino, T, Kovács, L. CTLA-4 gene polymorphisms predispose to autoimmune endocrinopathies but not to celiac disease. Neuro Endocrinol Lett 2008; 29: 334-40.

• Radvanská, E, Kamperis, K, Kleif, A, Kovács, L, Rittig, S. Effect of laser acupuncture for monosymptomatic nocturnal enuresis on bladder reservoir function and nocturnal urine output. J Urol 2011; 185: 1857-61.

• Ilenčíková D, Cižmárová M, Krajčiová A, Požgayová S, Rybárová A, Kovács L. Clinical dysmorphic syndromes with tumorigenesis. Klin Onkol 2012; 25: S39-48.

• Bolčeková, A, Némethová, M, Zaťková, A, Skalická, K, Požgayová, S, Hlavatá, A, Kádaši, Ľ, Ďurovčíková, D, Gerinec, A, Husáková, K, Pavlovičová, Z, Holobradá, M, Kovács, L, Ilenčíková, D. Clustering of mutations in the 5’tertile of the NF1 gene in Slovak patients with optic pathway glioma. Neoplasma 2013; 60: 655-65.

• Čizmarova M, Kostalova L, Pribilincova Z, Lasabova Z, Hlavata A, Kovacs L, Ilencikova D. Rasopathies - dysmorphic syndromes with short stature and risk of malignancy. Endocr Regul 2013; 47: 217-22.

• Čižmárová, M, Nagyová, G, Jankó, V, Pribilincová, Z, Virgová, D, Ilenčíková, D, Kovács, L. Late onset of familial neurogenic diabetes insipidus in monozygotic twins. Endocr Regul 2013; 47: 211-16.

• Nemethova M, Bolcekova A, Ilencikova D, Durovcikova D, Hlinkova K, Hlavata A, Kovacs L, Kadasi L, Zatkova A. Thirty-nine novel neurofibromatosis 1 (NF1) gene mutations identified in Slovak patients. Ann Hum Genet 2013; 77: 364-79.

• Čizmárová M, Hlinková K, Bertok S, Kotnik P, Duba HC, Bertalan R, Poločková K, Košťálová Ľ, Pribilincová Z, Hlavatá A, Kovács L, Ilenčíková D. New Mutations Associated with Rasopathies in a Central European Population and Genotype-Phenotype Correlations. Ann Hum Genet 2016; 80: 50-62.

• Hrčková G, Jankó V, Kytnarová J, Čižmárová M, Tesařová M, Košťálová Ľ, Virgová D, Dallos T, Hána V, Lebl J, Zeman J, Kovács L. Two novel mutations in seven Czech and Slovak kindreds with familial neurohypophyseal diabetes insipidus-benefit of genetic testing. Eur J Pediatr 2016; 175: 1199-207.

• Skalická K, Kovács L. Ciliotherapy–new opportunity for targeted therapy in autosomal dominant polycystic kidney disease. J Genet Syndr Gene Ther 2016; 7: 310-5.


Q. Extracellular DNA

InvestigatorsAssoc. Prof. Peter Celec, MD, Dipl Eng, RNDr, DSc, MPH ([email protected])Assoc. Prof. Katarína Šebeková, MD, DScAssoc. Prof. Július Hodosy, MD, MSc, PhD, MPHRoman Gardlík, MD, RNDr, PhDMichal Pastorek, MSc, PhDĽubomíra Tóthová, RNDr, PhDBarbora Vlková, RNDr, PhD

TopicThe Institute of Molecular Biomedicine (IMBM) is currently focusing on extracellular DNA. DNA outside cells is used as a source of genetic information for non-invasive prenatal diagnosis and cancer screening, but it also recognized as a damage-associated molecular pattern and induces inflammation. We are analyzing this DNA in plasma, urine and saliva especially in various animal models of sepsis, colitis and urinary tract infection. In addition, researchers IMBM in collaboration with other research institutes around the globe are studying the role of deoxyribonucleases, either exogenous or endogenous, that cleave extracellular DNA in the etiopathogenesis of diseases in clinical samples and animal experiments. Besides acute and chronic inflammatory diseases, liver and kidney injury as well as trauma complications might be associated with quantitative changes of extracellular DNA. Especially mitochondrial DNA is under investigation at IMBM as a potential determinant of metabolic risk in obesity. Sex differences in deoxyribonuclease activity could cause the higher risk for autoimmune disorders in women, but also potentially the behavioral differences and risk for autism.

Plans for future research• Plasma deoxyribonuclease activity and extracellular DNA in the pathogenesis of inflammatory diseases such as

sepsis, colitis and urinary tract infection• Metabolic effects of prenatal dietary advanced glycation end products• Pathomechanisms of neurodevelopmental disorders in animal models• Molecular biomarkers for point of care testing

Devices and methods• Animal models of human diseases• Quantification and characterization of plasma DNA• Behavioral phenotyping of experimental rodents• Analysis of markers of oxidative and carbonyl stress

Grants and Funding (in the last 10 years)• APVV-16-0273: Deoxyribonuclease activity in plasma and its role in the cleavage of extracellular DNA (2017-

2020)• VEGA 1/0092/17: Extracellular DNA and its role in the pathogenesis of renal and metabolic complications of

various diseases (2017-2019)• VEGA 1/0156/17: The role of NETosis in the pathogenesis of preeclampsia (2017-2019)• VEGA 1/0234/18: Molecular mechanism of the antimicrobial effects of steroids on uropathogenic bacteria (2018-

2020)


Selected publications• Čonka J, Konečná B, Lauková L, Vlková B, Celec P. Fetal DNA does not induce preeclampsia-like symptoms when delivered in

late pregnancy in the mouse. Placenta 2017; 52: 100-5.• Vokálová L, Lauková L, Čonka J, Melišková V, Borbélyová V, Bábíčková J, Tóthová L, Hodosy J, Vlková B, Celec P.

Deoxyribonuclease partially ameliorates thioacetamide-induced hepatorenal injury. Am J Physiol Gastrointest Liver Physiol 2017; 312: G457-63.

• Bábíčková J, Borbélyová V, Tóthová L, Kubišová K, Janega P, Hodosy J, Celec P. The renal effects of prenatal testosterone in rats. J Urol 2015; 193: 1700-8.

• Celec P, Tretinárová D, Minárik G, Ficek A, Szemes T, Lakatošová S, Schmidtová E, Turňa J, Kádaši Ľ, Ostatníková D. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys. PLoS One 2013; 8: e54751.

• Šebeková K, Dušinská M, Simon Klenovics K, Kollárová R, Boor P, Kebis A, Staruchová M, Vlková B, Celec P, Hodosy J, Bačiak L, Tušková R, Beňo M, Tulinská J, Príbojová J, Bilaničová D, Pojana G, Marcomini A, Volkovová K. Comprehensive assessment of nephrotoxicity of intravenously administered sodium-oleate-coated ultra-small superparamagnetic iron oxide (USPIO) and titanium dioxide (TiO2) nanoparticles in rats. Nanotoxicology 2014; 8: 142-57.

• Hodosy J, Zelmanová D, Majzúnová M, Filová B, Malinová M, Ostatníková D, Celec P. The anxiolytic effect of testosterone in the rat is mediated via the androgen receptor. Pharmacol Biochem Behav 2012; 102: 191-5.

• Celec P, Hodosy J, Gardlík R, Behuliak M, Pálffy R, Pribula M, Jáni P, Turňa J, Šebeková K. The effects of anti-inflammatory and anti-angiogenic DNA vaccination on diabetic nephropathy in rats. Hum Gene Ther 2012; 23: 158-66.

• Boor P, Celec P, Martin IV, Villa L, Hodosy J, Klenovicsová K, Esposito C, Schäfer S, Albrecht-Küpper B, Ostendorf T, Heidland A, Šebeková K. The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats. Kidney Int 2011; 80: 1182-97.

• Celec P, Hodosy J, Jáni P, Janega P, Kúdela M, Kalousová M, Holzerová J, Parrák V, Halčák L, Zima T, Braun M, Pecháň I, Murín J, Šebeková K. Advanced glycation end products in myocardial reperfusion injury. Heart Vessels 2012; 27: 208-15.

• Tóthová L, Hodosy J, Kamodyová N, Janega P, Slobodníková L, Liptáková A, Boor P, Celec P. Bactofection with toll-like receptor 4 in a murine model of urinary tract infection. Curr Microbiol 2011; 62: 1739-42.

• Celec P, Pálffy R, Gardlík R, Behuliak M, Hodosy J, Jáni P, Božek P, Šebeková K. Renal and metabolic effects of three months of decarbonated cola beverages in rats. Exp Biol Med (Maywood) 2010; 235: 1321-7.

• Wagnerová A, Bábíčková J, Lipták R, Vlková B, Celec P, Gardlík R. Sex differences in the effect of resveratrol on DSS-induced colitis in mice. Gastroenterol Res Pract 2017; 2017: 8051870.

• Lauková L, Konečná B, Bábíčková J, Wagnerová A, Melišková V, Vlková B, Celec P. Exogenous deoxyribonuclease has a protective effect in a mouse model of sepsis. Biomed Pharmacother 2017; 93: 8-16.

• Kacerovsky M, Vlkova B, Musilova I, Andrys C, Pliskova L, Zemlickova H, Stranik J, Halada P, Jacobsson B, Celec P. Amniotic fluid cell-free DNA in preterm prelabor rupture of membranes. Prenat Diagn 2018; 38: 1086-95.

• Lauková L, Konečná B, Vlková B, Mlynáriková V, Celec P, Šteňová E. Anti-cytokine therapy and plasma DNA in patients with rheumatoid arthritis. Rheumatol Int 2018; 38: 1449-54.

• Celec P, Vlková B, Lauková L, Bábíčková J, Boor P. Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases. Expert Rev Mol Med 2018; 20:e1.


R. Novel biomarkers in chronic kidney disease

InvestigatorsAssoc. Prof. Katarína Šebeková, MD, DSc ([email protected])Prof. Ľudmila Podracká, MD, PhDAssoc. Prof. Peter Celec, MD, Dipl Eng, RNDr, DSc, MPHKristina Simon Klenovics, MD, PhDĽubomíra Tóthová, RNDr, PhDAlexandra Kovalčíková, MSc, PhD

Plans for future research• Analysis of salivary markers of renal functions• Pathogenesis of complications of renal insufficiency• Non-invasive measurement of advanced glycation end-products (AGEs)• Metabolic consequences of renal diseases• New potential biomarkers of detecting kidney damage prior to the currently used markers• Renal and metabolic consequences of changes in diet during the prenatal development

Devices and methods• Salivary diagnostics in nephrology• Non-invasive measurement of oxidative and carbonyl stress• AGE reader for skin autofluorescence• Metabolic cages for urine collection from experimental rodents• Experimental models of renal diseases

Grants and Funding (in the last 10 years)• VEGA 1/3362/06: Polymorphism of 5,10 MTHR gene and deficiency of folic acid in Slovak pediatric population

– incidence and role in multifactorial diseases (2007-2009)• Norwegian found SJK0017-GOL-00143-H-V2(1):The research of glucocorticoid influence on pediatric diseases -

children´s health improvement (2007-2010)• MZ SR 2007/65-UPJS-02: Genomic data on birth defects (2008-2010)• VEGA 1/0525/10: Defects of folate metabolism in patogenesis of multiple malformations (2010-2011)• VEGA 1/0805/08: New markers of cardiovascular risks in children and adolescents with chronic renal diseases

(2008-2011)• 7FP EC EU, Health-F5-2008-201335, NANOtest - Alternative testing strategies for the assessment of the

toxicological profile of nanoparticles used in medical diagnostics (2008-2012)• VEGA 01/0715/11: Molecular and genetic diagnosis of nephrotic syndrome in children (2012-2014)• VEGA 1/0172/14: Saliva as a potencial diagnostic fluid in monitoring of ocidative and carbonyl stress in relation

to cardiovascular risk in children with chronic nephropaties (2014-2016)• VEGA 1/0613/17: Early diagnosis of osteoporosis in children and adolescents with mental anorexia (2017-2019)• VEGA 1/0637/13: Metabolic syndrome in adolescents (2013-2015)• VEGA 1/0062/16: Influence of prenatal exposure to unhealthy diet on early neuromotor development and later

metabolic status of rat offspring (2016-2018)

Selected publications• Šebeková K, Somoza V, Jarčušková M, Heidland A, Podracká Ľ. Plasma advanced glycation end products are decreased obese

children compared with lean controls. Int J Pediatr Obes 2009; 4: 112-8.


• Behunova J, Klimcakova L, Zavadilikova E, Potocekova D, Sykora P, Podracka L. Methylenetetrahydrofolate Reductase Gene Polymorphisms and Neural Tube Defects Epidemiology in the Slovak Population. Birth Defects Res A Clin Mol Teratol 2010; 88: 695-700.

• Hedvig J., Podracka L., Potocekova D. Elevated Brain Natriuretic Peptide Is Associated with Abnormal Heart Geometry in Children with Chronic Kidney Disease. Kidney Blood Press Res 2010; 33: 87-93.

• Rusai K, Banki NF, Prokai A, Podracka L, Szebeni B, Tulassay T, Reusz GS, Sallay P, Koermendy R, Szabo AJ, Fekete A. Heat Shock Protein Polymorphism Predisposes to Urinary Tract Malformations and Renal Transplantation in Children. Transplant Proc 2010; 42: 2309-11.

• Behunova J, Klimčaková L, Podracká Ľ. Urinary ract Anomalies Associated with MTHFR Gene Polymorphism C677T in Girls. Kidney Blood Press Res 2011; 34: 465-71.

• Boor P, Celec P, Martin IV, Villa L, Hodosy J, Klenovicsova K, Esposito C, Schafer S, Albrecht-Kupper B, Ostendorf T, Heidland A, Sebekova K. The peroxisome proliferator-activated receptor-™ agonist, BAY PP1, attenuates renal fi brosis in rats. Kidney International 2011; 80: 1182-97.

• Šebeková K, Klenovicsová K, Ferenczová J, Hedvig J, Podracká L, Heidland A. Advanced oxidation protein products and advanced glycation end products in children and adolescents with chronic renal insufficiency. J Ren Nutr 2012; 22: 143-8.

• Celec P, Gardlik R, Sebekova K. The effects of antiinfl ammatory and anti-angiogenic DNA vaccination on diabetic nephropathy in rats. Hum Gene Ther 2012; 23: 158-66.

• Šebeková K, Ramuscak A, Boor P, Heidland A, Amann K. The Selective TP Receptor Antagonist, S18886 (Terutroban), Attenuates Renal Damage in the Double Transgenic Rat Model of Hypertension. Am J Nephrol 2008; 28: 47-53.

• Simon Klenovics K, Kollárová R, Hodosy J, Celec P, Sebeková K. Reference values of skin autofluorescence as an estimation of tissue accumulation of advanced glycation end products in a general Slovak population. Diabet Med 2014; 31: 581-5.

• Kolvek G, Podracka L, Rosenberger J, Stewart RE, van Dijk JP, Reijneveld SA. Solitary Functioning Kidney in Children - A Follow-Up Study. Kidney Blood Press Res 2014; 39: 272-8.

• Čižmáriková M, Podracká Ľ, Klimčáková L, Habalová V, Boor A, Mojžiš J, Mirossay L. MDR1 Polymorphisms and idiopathic Nephrotic Syndrome in Slovak Children: Preliminary Results. Med Sci Monit 2015; 21: 59-68.

• Yung Gee H, Zhang F, Ashraf S, Kohl S, Sadowski EC, Vega-Warner V, Zhou W, Lovric S, Fang H, Nettleton M, Zhu J, Hoefele J,Weber LT, Podracka L, Boor A, Fehrenbach H, Jeffrey WI, Washburn J, Levy S, Lifton R, Edgar A, Han Z, Hildebrandt F. KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. Clin Invest 2015; 125: 2375–84.

• Krischock LA, van Stralen KJ, Verrina E, Tizard EJ, Bonthuis M, Reusz G, Hussain FK, Jankauskiene A, Novljan G, Spasojević-Dimitrijeva B, Podracka L, Zaller V, Jager KJ, Schaefer F; ESPN/ERA-EDTA Registry. Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry. Pediatr Nephrol 2016; 31: 325-33.

• Bonthuis M, Busutti M, van Stralen KJ, Jager KJ, Baiko S, Bakkaloğlu S, Battelino N, Gaydarova M, Gianoglio B, Parvex P, Gomes C, Heaf JG, Podracka L, Kuzmanovska D, Molchanova MS, Pankratenko TE, Papachristou F, Reusz G, Sanahuja MJ, Shroff R, Groothoff JW, Schaefer F, Verrina E. Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study. Clin J Am Soc Nephrol 2015; 10: 767-75.

• Celec P, Tóthová Ľ, Šebeková K, Podracká Ľ, Boor P. Salivary markers of kidney function - Potentials and limitations. Clin Chim Acta 2016; 453: 28-37.

• Tothova L, Babickova J, Borbelyova V, Filova Barbora, Sebekova K, Hodosy J. Chronic renal insufficiency does not induce behavioral and cognitive alteration in rats. Physiol Behav 2015; 138: 133-40.

• Koborová I, Gurecká R, Csongová M, Šebek J, Šebeková K. Plasma markers of oxidative status were associated with increasing continuous cardiometabolic risk scores in healthy students aged 16-20 years without central obesity. Acta Paediatr 2018; 107: 2137-45.

• Csongová M, Gurecká R, Koborová I, Celec P, Domonkos E, Uličná O, Somoza V, Šebeková K. The effects of a maternal advanced glycation end product-rich diet on somatic features, reflex ontogeny and metabolic parameters of offspring mice. Food Funct 2018; 9: 3432-46.

• Kovalčíková A, Janšáková K, Gyurászová M, Podracká Ľ, Šebeková K, Celec P, Tóthová Ľ. Salivary creatinine and urea are higher in an experimental model of acute but not chronic renal disease. PLoS One 2018; 13: e0200391.


S. Bioenergetics and anti-oxidative systems

InvestigatorsProf. Anna Gvozdjáková, RNDr, DSc ([email protected])Jarmila Kucharská, PharmDr, PhDOľga Uličná, RNDr, PhDOľga Vančová, MEngZuzana Sumbalová, RNDr, PhDZuzana Rausová, MSc, PhDAssoc. Prof. Viliam Mojto, MD, PhD, MHA, MPH

TopicAt present we are devoting ourselves to the development and perspectives of Mitochondrial Medicine. An invasive approach to the determination of mitochondrial functions in human medicine - skeletal muscle biopsy is commonly used. In 2018, we introduced a new non-invasive methodology for the examination of mitochondrial bioenergetics in isolated platelets (using the High-Resolution Respiromentry, OROBOROS, Austria). The aim of these research activities is the development of Mitochondrial Medicine. The application of a new non-invasive methodology of mitochondrial bioenergetics in clinical and experimental medicine belongs to the current development direction of Mitochondrial Medicine in terms of diagnosis and targeted supportive therapy of diseases associated with dysfunction of mitochondria. We performed these investigations in healthy young people (collaboration with Slovak Academy of Sciences), in elderly people and in patients with nephropathies. Determination of coenzyme Q10 concentrations (using HPLC) in isolated platelets, whole blood, and plasma is part of the research.We have been working with the Institute of Molecular Biomedicine, Faculty of Medicine, on a study where has been monitored how Western-type diet containing large amount of advanced glycation end products (AGEs) during pregnancy can predict metabolic and behavioral disorders in the progeny in later life. The results show that if mothers receive AGE-rich diet during pregnancy, it may accelerate the aging of reflexes in progeny, predestinate male offspring to weight gain, and affect glucose homeostasis. We will continue in this research and cooperation.We also participate in ongoing grant projects mentioned above.

Plans for future research• New diagnostic methods for determination of mitochondria features in isolated thrombocytes and lymphocytes

in patients with different alteration of mitochondria• Build up unit of Mitochondrial Medicine

Devices and methods• Oxygraph-2k (Oroboros Instruments) high resolution respirometry enabling to measure parameters of

mitochondrial respiration and complexes of respiratory chain of mitochondria• Oxygraph 5/6 H Gilson enabling measurement of parameters of oxidative phosphorylation in mitochondria• High-performance liquid chromatograph with programmed UV detector• Programmed UV-VIS spectrophotometer Biochrom 4060• Cooled centrifuges

Grants and Funding (in the last 10 years)• VEGA 2/0083/09: Cerebral energy metabolism studied by magnetic resonance spectroscopy as a basis for studying

mechanisms of hypoxia-ischemic damage of the neonatal brain (2009-2011)


• VEGA 1/0328/10: Inhibitors of HMG-CoA reductase and their possible side effects: the role of mitochondria and coenzyme Q (2010-2011)

• VEGA 1/0272/10: Neurodegenerative diseases in animal models including therapeutic effect monitored by means in vivo magnetic resonance imaging and spectroscopy (metabolic profile and brain bioenergetics) (2010-2011)

• VEGA 1/1133/11: Biomodulative effects of natural substances in experimental diabetes and liver cirrhosis (2011-2013)

• VEGA 2/0045/11: Study of combination of immunosuppressive treatment and substances affecting redox balance of organism on animal models of rheumatoid arthritis (2011-2014)

• VEGA 2/0101/12: The role of mitochondria in adaptation of cardiac energetics to various pathological stimuli and noxae: ischemia, diabetes, hypertension (2012-2014)

• VEGA 1/0614/12: Role of oxidative stress and antioxidants in the pathogenesis of urothelial carcinoma (2012-2014)• VEGA 2/0133/15: Bioenergetic aspects of myocardial protection by means of remote ischemic preconditioning. The

role of cardiac mitochondria (2015-2017)• APVV-15-0308: Molecular pharmacological approaches to innovative therapy for rheumatoid arthritis evaluated

under experimental conditions in vivo and in vitro (2016-2020)• Project supported by the EU grant from the CBC programme Interreg V-A SK-AT VO14: Nutriaging: Nutrition

and healthy aging (2018-2021)

Selected publications• Gvozdjáková A. Mitochondrial Medicine: Mitochondrial metabolism, Diseases, Diagnosis and Therapy, Springer, Netherlands

2008; 409 pp.• Sumbalová Z, Kucharská J, Kristek F. Losartan improved respiratory function and coenzyme Q content in brain mitochondria

of young spontaneously hypertensive rats. Cell Mol Neurobiol 2010; 30: 751-8.• Vančová O, Bačiak L, Kašparová S, Kucharská J, Palacios H, Horecký J, Aliev G. In vivo and in vitro assessment of brain

bioenergetics in aging rats. J Cell Mol Med 2010; 14: 2667-74.• Labienec M, Ulicna O, Vancova O, Kucharska J, Gabryelak T, Watala C. Effect of poly(amido)amine (PAMAM) G4 dendrimer

on heart and liver mitochondria in an animal model of diabetes. Cell Biol Int 2010; 34: 89-97.• Kucharska J, Ulicna O, Gvozdjakova A, Vancova O, Waczulikova I, Bozek P, Bada V. Effects of atorvastatin on heart

mitochondrial function and coenzyme Q content in the experiment. Bratisl Med J 2011; 112: 603-4.• Horecký J, Gvozdjáková A, Kucharská J, Obrenovich ME, Palacios HH, Li Y, Vančová O, Aliev G. Effects of coenzyme Q and

creatine supplementation on brain energy metabolism in rats exposed to chronic cerebral hypoperfusion. Current Alzheimer Research 2011; 8: 868-75.

• Uličná O, Vančová O, Waczulíková I, Božek P, Šikurová L, Bada V, Kucharská J. Liver mitochondrial respiratory function and coenzyme Q content in rats on a hypercholesterolemic diet treated with atorvastatin. Physiol Res 2012; 61: 185-93.

• Gvozdjáková A, Mravec B, Kucharská J, Lackovičová Ľ, Ondičová K, Tkačov M, Singh RB. Increased ubiquinone concentration after intracerebrovascularly-administered ubiquinol to selected brain regions. Gen Physiol Biophys 2012; 31: 469-72.

• Ferko M, Kancirová I, Jašová M, Čárnická S, Muráriková M, Waczulíková I, Sumbalová Z, Kucharská J, Uličná O, Ravingerová T, Ziegelhoffer A. Remote ischemic preconditioning of the heart: Protective responses in functional and biophysical properties of cardiac mitochondria. Physiol Res, 2014; 63: S469-78.

• Gvozdjáková A, Mikulecký M, Crane FL, Kucharská J, Cornelissen G, Kumar A, Palacka P, Singh RB. Mitochondrial cardiomyopathy and coenzyme Q10. World Heart J 2014; 6: 29-46.

• Krumschnabel G, Fontana-Ayoub M, Sumbalova Z, Heidler J,Gauper K, Fasching M, Gnaiger E. Simultaneous high-resolution measurement of mitochondrial resiration and hydrogen peroxide production In: Mitochondrial Medicine Volume 1: Probing Mitochondrial Function. New York: Springer 2015; 245-61.

• Dobiáš L, Petrová M, Vojtko R, Uličná O, Vančová O, Kristová V. Effect of sulodexide on vascular responses and liver mitochondrial function in diabetic rats. Physiol Res 2015; 64: S497-505.


• Volkovova K, Handy RD, Staruchova M, Tulinska J, Kebis A, Pribojova J, Ulicna O, Kucharska J, Dusinska M. Health effects of selected nanoparticles in vivo: Liver function and hepatotoxicity following intravenous injection of titanium dioxide and Na-oleate-coated iron oxide nanoparticles in rodents. Nanotoxicology 2015; 9: 95-105.

• Ferko M, Kancirová I, Jašová M, Waczulíková I, Čarnická S, Kucharská J, Uličná O, Vančová O, Muráriková M, Ravingerová T, Ziegelhöffer A. Participation of heart mitochondria in myocardial protection against ischemia/reperfusion injury: benefit effects of short-term adaptation processes. Physiol Res; 64: S617-25.

• Gvozdjáková A, Kucharská J, Vančová O, Uličná O, Mojto V, Singh RB, Cornelissen G. Mitochondrial coenzyme Q and oxidative phosphorylation in brain and myocardium of control and diabetic rats. World Heart J 2015; 7: 119-29.

• Mikulecký M, Gvozdjáková A, Kucharská J, Mojto V, Mikulecký M, Singh RB, Cornelissen G. Are mitochondrial energetics in the rat under control of the solar (24 hours) and/or lunar (24.8 hours) day? World Heart J 2015; 7: 119-27.

• Kancirová I, Jašová M, Muráriková M, Sumbalová Z, Uličná O, Ravingerová T, Waczulíková I, Ziegelhöffer A, Ferko M. Cardioprotection induced by remote ischemic preconditioning preserves the mitochondrial respiratory function in acute diabetic myocardium. Physiol Res 2016; 65: S611-9.

• Gvozdjáková A, Kucharská J, Singh RB, Vančová O, Uličná O, Mojto V, Fedačko J, Pella D, Verma NS, Cornélissen G. Statin-induced mitochondrial dysfunction and targeting coenzyme Q10 therapy. World Heart J 2016; 8: 171-81.

• Gvozdjáková A. Mitochondrial Medicine and Coenzyme Q10. Herba Bratislava 2017; 228 pp.• Gvozdjáková A, Cornélissen G, Singh RB, editors. Recent advances in mitochondrial medicine and coenzyme Q10. New York:

Nova Science Publishers, Inc. 2018; 450 p.• Kucharská J, Gvozdjáková A, Kura B, Rausová Z, Slezák J. Effect of molecular hydrogen on coenzyme Q in plasma, myocardial

tissue and mitochondria of rats. J Nutr Health Food Eng 2018; 8: 362-4.• Csongová M, Gurecká R, Koborová I, Celec P, Domonkos M, Uličná O, Somoza V, Šebeková K. The effects of a maternal

advanced glycation end product-rich diet on somatic features, reflex ontogeny and metabolic parameters of offspring mice. Food Func 2018; 9: 3432-46.

• Mojto V, Singh RB, Gvozdjáková A, Pella D, Fedacko J, Pella D. Molecular hydrogen: A new approach for the management of cardiovascular diseases. World Heart J 2018; 10: 83-93.


T. Epidemiology of non-communicable diseases

InvestigatorsAssoc. Prof. Alexandra Bražinová, MD, PhD, MPH ([email protected])Assoc. Prof. Margita Špaleková, MD, PhDMartina Kotrbancová, MSc, PhDMiriam Fulová MD, MScVanda Výrosteková, MD, PhDErika Macháčová, MD, PhDJana Perželová, RNDr, PhDJana Korcová, RNDr, PhDPetra Vadovičová, PhDr, MSc, PhDVeronika Sivčová, MSc

Topic• Epidemiology of non-communicable diseases –collection and processing data of Epidemiology of Myastenia

gravis, Global Burden of Disease Study by participation in the international work group for assessment of the global premature mortality and global disability burden of diseases

• Epidemiology of traumatic brain injury, epidemiology of mental health and mental disorders• Prevalence of risk factors in cardiovascular diseases-study in healthy population

Plans for future research• Epidemiology of Myastenia gravis - Cooperation with Centre for neuromuscular diseases Neurologic Clinic of

Slovak Medical University in Bratislava• Global Burden of Disease Study - Participation in the international work group for assessment of the global

premature mortality and global disability burden of diseases• Epidemiology of traumatic brain injury - Epidemiology of traumatic brain injury in Europe: incidence, mortality,

disability, prognosis.• Mental Health and Epidemiology of Mental Disorders - Epidemiology of mental health and mental disorders:

population survey of mental disorder prevalence, use and unmet need of care, use of pharmacotherapy in psychiatry and general practice, International Study of Medical students’ attitudes towards people with mental illness

• Risk factors of cardiovascular diseases - Description and analysis of data collected in Health Counseling offices in Regional Public Health Authorities in the Slovak Republic in 1993-201

• Metabolic syndrome in clients of Health Counseling offices in Regional Public Health Authorities in the Slovak Republic in 1993-2017

• Efficiency of counseling in Health Counseling offices in Regional Public Health Authorities in the Slovak Republic in 1993-2017

Devices and methods• Data collection, description and analysis in software STATA, r project

Grants and Funding (in the last 10 years)• 7th Framework Programme of European Commission – Theme (Health. 2013.2.2.1.-1) Prospective longitudinal

data collection and comparative effectiveness research for traumatic brain injury (CENTER-TBI study) (2013-2020)

mailto:alexandra.brazinova%40fmed.uniba.sk?subject=


Selected publications• Martinka I, Fulova M., Spalekova, M., Spalek, P. Epidemiology of Myasthenia Gravis in Slovakia in the Years 1977–2015

Neuroepidemiology 2018; 50:153-9.• Martinka I, Fulová M, Schnorrer M, Cibulčík F, Špalek P. Myasthenia gravis associated with thymoma - a cohort of patients in

the Slovak Republic (1978-2015). Neurology 2017; 16: 987-1048.• James SL, Theadom A, Ellenbogen RG, Bannick MS, Montjoy-Venning W, ... Brazinova A, et al. Global, regional, and national

burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018; S1474-4422.

• Lozano R, Fullman N, Abate D, Abay SM, Abbafati C, ... Brazinova A, et al. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 2091-138.

• Murray CJL, Callender CSKH, Kulikoff XR, Srinivasan V, Abate D, Abate KH,... Brazinova A, et al. Population and fertility by age and sex for 195 countries and territories, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1995-2051.

• Stanaway JD, Afshin A, Gakidou E, Lim SS, Abate D, Abate KH, ... Brazinova A, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1923-94.

• James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, ... Brazinova A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1789-858.

• Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, ... Brazinova A, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1736-88.

• Dicker D, Nguyen G, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, ... Brazinova A, et al. Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1684-735.

• Kyu HH, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, ...Brazinova A, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1859-922.

• Naghavi M, et al. Global Mortality From Firearms, 1990-2016. Global Burden of Disease 2016 Injury Collaborators. JAMA 2018; 320: 792-814.

• Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. GBD 2016 Healthcare Access and Quality Collaborators. Lancet 2018; 391: 2236-71.

• van Veen E, van der Jagt M, Cnossen MC, Maas AIR, de Beaufort ID, Menon DK, Citerio G, Stocchetti N, Rietdijk WJR, van Dijck JTJM, Kompanje EJO, Brazinova A, et al. Brain death and postmortem organ donation: report of a questionnaire from the CENTER-TBI study. Crit Care 2018; 22: 306.

• Huijben JA, Volovici V, Cnossen MC, Haitsma IK, Stocchetti N, Maas AIR, Menon DK, Ercole A, Citerio G, Nelson D, Polinder S, Steyerberg EW, Lingsma HF, van der Jagt M, Brazinova A. Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. CENTER-TBI investigators and participants. Crit Care 2018; 22: 90.

• Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurology 2017; 16: 987-1048.

• Pathare S, Brazinova A, Levav I. Care gap: a comprehensive measure to quantify unmet needs in mental health. Epidemiol Psychiatr Sci 2018; 27: 463-7.

Faculty of MedicineComenius University in BratislavaŠpitálska 24813 72 BratislavaSlovakia

Dean’s office: +421 2 593 57 466e-mail: [email protected]://www.fmed.uniba.sk/en/

http://www.fmed.uniba.sk/en/

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