International Laser Center

Bratislava, Slovakia

International Laser Center

Bratislava, Slovakia

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The classical paradigm of electrocardiographic diagnosis of left ventricular hypertrophy (LVH) is based on empirical finding of increased QRS voltage in cases of LVH and a continuous effort is devoted to finding ECG criteria that agree best with LVH classification according to an ECG-independent standard such as echocardiographic LVH (echo-LVH) based on increased left ventricular mass (LVM). Since there are more disagreements than agreements, this review is focused on discrepancies, i.e. false negative and false positive ECG findings. It summarizes the results of simulation studies on the effect of slowed conduction velocity and reduced intercellular coupling on the QRS pattern. The results from these simulation studies suggest that reduced myocardial conduction velocity which is either diffuse or regional, or reduced intracellular coupling, may account at least in part for the changes in the QRS patterns observed in patients with LVH. © 2014 Elsevier Inc.


Chorvatova A.,International Laser Center | Chorvatova A.,University of Montréal | Mateasik A.,International Laser Center | Chorvat Jr. D.,International Laser Center
Laser Physics Letters | Year: 2013

We report a novel analytical approach to identify individual components of a cell's endogenous fluorescence, recorded by spectrally-resolved time-correlated single photon counting (TCSPC). Time-resolved area-normalized emission spectroscopy (TRANES) and principal component analysis (PCA) were applied to estimate the number of spectral components after metabolic modulation of cardiac cells following excitation with a 375 nm picosecond laser. Linear unmixing of TCSPC data spectrally decomposed individual components in living cells, while using characteristics of endogenously fluorescing molecules in solvents as a reference spectral database. Our data demonstrate the presence of three individual components, corresponding to the nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) in organic and inorganic solvents and to the residual flavoprotein fluorescence. The presented analytical approach offers a new alternative for the spectral separation of multi-wavelength fluorescence lifetime spectroscopy data to the conventional analysis, and opens a new possibility for the use of pattern recognition for fast resolution of components in 2D fluorescence lifetime microscopy images.© 2013 Astro Ltd.


Cunderlikova B.,International Laser Center
Critical Reviews in Oncology/Hematology | Year: 2013

Various cancer treatment approaches have shown promising results when tested preclinically. The results of clinical trials, however, are often disappointing. While searching for the reasons responsible for their failures, the relevance of experimental and preclinical models has to be taken into account. Possible factors that should be considered, including cell modifications during in vitro cultivation, lack of both the relevant interactions and the structural context in vitro have been summarized in the present review. © 2012 Elsevier Ireland Ltd.


Bacharova L.,International Laser Center | Bacharova L.,Comenius University | Ugander M.,Karolinska University Hospital
Annals of Noninvasive Electrocardiology | Year: 2014

Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2∗ mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. © 2014 Wiley Periodicals, Inc.


Bacharova L.,International Laser Center | Szathmary V.,Slovak Academy of Sciences | Mateasik A.,International Laser Center
Journal of Electrocardiology | Year: 2011

By definition, the electrocardiographic (ECG) patterns of left bundle-branch block (LBBB) represent distinctive changes in duration and shape of the QRS complex caused by intraventricular conduction delay in the left ventricle (LV) due to structural abnormalities in the His-Purkinje conduction system and/or ventricular myocardium. However, impaired conduction in the working myocardium is not taken into consideration in the practical ECG diagnosis. Because the degree of LV myocardium impairment could be of importance for clinical evaluation of patients, we studied the effects of blocked and of delayed onsets of activation in the LV to simulate complete and incomplete LBBBs and slowed conduction in the LV myocardium by applying an analytical computer model. We demonstrated that typical LBBB patterns were caused both by block or delay in the onset of the LV activation, as well as by impaired conduction in the myocardium itself while maintaining the location and onset of the LV activation. The most important difference was the absence of initial anteriorly oriented electrical forces in cases of the simulated complete LBBB and of incomplete LBBB if the onset of LV activation was delayed (≥6 milliseconds). Under the conditions defined in this model that did not consider myocardial infarction, the presence of initial anteriorly oriented electrical forces was indicative of preserved conduction in the left bundle and of impaired conduction in LV working myocardium. Conclusion: The elucidation of the participation of working myocardium impairment in the intraventricular conduction delay in the LV could be of vital significance for the clinical management of patients with LBBB patterns, for example, indicated for resynchronization therapy. Copyright © 2011 Published by Elsevier Inc. All rights reserved.


Rodriguez-Padial L.,Complejo Hospitalario Of Toledo | Bacharova L.,International Laser Center
Journal of Electrocardiology | Year: 2012

Although electrocardiography has been used to estimate left ventricular hypertrophy and to obtain useful prognostic information in different clinical settings, its correlation with left ventricular mass is poor and, therefore, its sensitivity and specificity for the diagnosis of left ventricylar hypertrophy are low. Experimental work has demonstrated that the increase in voltage and duration of the QRS complex of the electrocardiogram are not only related to left ventricular mass but also to changes in the electrophysiological properties of the myocardium. Therefore, a new strategy is needed to use electrocardiography not to estimate left ventricular mass but aimed to add useful prognostic information. © 2012 Elsevier Inc. All rights reserved.


Cunderlikova B.,Comenius University | Cunderlikova B.,International Laser Center
Critical Reviews in Oncology/Hematology | Year: 2016

Our understanding of cancer has evolved mainly from results of studies utilizing experimental models. Simplification inherent to . in vitro cell culture models enabled potential ways of cell behaviour in response to various external stimuli to be described, but it has led also to disappointments in clinical trials, presumably due to the lack of crucial tissue components, including extracellular matrix (ECM). ECM and its role in healthy and diseased tissues are being explored extensively and significance of ECM for cell behaviour has been evidenced experimentally. Part of the information gathered in such research that is relevant for natural conditions of a human body can be identified by carefully designed analyses of human tissue samples. This review summarizes published information on clinical significance of ECM in cancer and examines whether effects of ECM on cell behaviour evidenced . in vitro, could be supported by clinically based data acquired from analysis of tissue samples. Based on current approaches of clinical immunohistochemical analyses, impact of ECM components on tumour cell behaviour is vague. Except of traditionally considered limitations, other reasons may include lack of stratification of analyzed cases based on clinicopathologic parameters, inclusion of patients treated postoperatively by different treatments or neglecting complexity of interactions among tumour constituents. Nevertheless, reliable immunohistochemical studies represent a source of crucial information for design of tumour models comprising ECM corresponding to real clinical situation. Knowledge gathered from such immunohistochemical studies combined with achievements in tissue engineering hold promise for reversal of the unfavourable trends in the current translational oncologic research. © 2016 Elsevier Ireland Ltd.


Chorvatova A.M.,International Laser Center
Springer Series in Chemical Physics | Year: 2015

Monitoring cell and tissue physiological parameters, such as metabolic state in real time and in their true environment is a continuous challenge. In the last decades, advanced photonics techniques were developed, combining fluorescence spectroscopy with time-resolved and imaging techniques, thus opening completely new opportunities for investigation of fluorescence parameters in living cells. This is particularly true in the case of evaluation of endogenous fluorescence or autofluorescence (AF) of living cells, derived from nicotinamide dinucleotide (phosphate) (NAD(P)H). We have pioneered the application of time-resolved fluorescence spectroscopy to evaluate changes in metabolic oxidative state directly in living cardiac cells by means of endogenous NAD(P)H fluorescence. NAD(P)H fingerprinting was investigated in living cardiac myocytes isolated from left ventricle (LV) of rats by spectrally-resolved lifetime detection using spectrally-resolved time-correlated single photon counting (TCSPC). Metabolic modulation was employed to evaluate individual NAD(P)H fluorescence components. Advanced data analysis leading to development of techniques and analytical approaches aimed at precise separation of individual fluorescence components from the recorded AF signals was also performed. Spectral decomposition of time-resolved NAD(P)H fluorescence signals by linear unmixing approach was successfully achieved. Gathered results demonstrate that combined approaches between time-resolved, spectroscopic and imaging systems open new possibilities for understanding the precise role of mitochondria in complex pathophysiological conditions and for finding new non-invasive clinically-relevant diagnostic applications. © Springer International Publishing Switzerland 2015.


Bacharova L.,International Laser Center | Bacharova L.,Comenius University | Szathmary V.,Slovak Academy of Sciences | Mateasik A.,International Laser Center
Journal of Electrocardiology | Year: 2013

Objective Reduction or interruption of the blood supply to myocardium due to occlusion of coronary artery and consequent ischemia leads to changes of electrogenesis: changes in morphology and duration of action potentials and slowing of conduction velocity in the affected area. In this study we simulated the effects of localized changes in depolarization sequence on the QRS and ST segment patterns, using computer modeling. Methods The model defines the geometry of cardiac ventricles analytically as parts of ellipsoids and allows changing the velocity of impulse propagation in the myocardium. An intramural electrically inactive area encircled by a transmural area with slowed impulse propagation velocity was introduced in anteroseptal and inferior locations. The effects on the QRS complex and the ST segment of the 12-lead electrocardiogram are presented. Results The intramural electrically inactive area caused QRS changes typical for corresponding locations of a myocardial infarction observed in patients, which were further considerably modified by slowed impulse propagation velocity in the surrounding area. Additionally, areas of slowed impulse propagation velocity led to ST segment deviations in the "reciprocal" leads, shifting the ST segment towards the affected areas. Conclusion Using computer modeling we showed that the localized alteration of impulse propagation not only modified the QRS complex, but produced also changes in the ST segment consistent with changes which are usually interpreted as the effect of "injury current". © 2013 Elsevier Inc.


Talafova K.,Slovak Academy of Sciences | Hrabarova E.,Slovak Academy of Sciences | Chorvat D.,International Laser Center | Nahalka J.,Slovak Academy of Sciences
Microbial Cell Factories | Year: 2013

Background: Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances.Results: In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks.Conclusions: The tailored inclusion bodies are promising " nanopills" for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release. © 2013 Talafová et al.; licensee BioMed Central Ltd.

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