Martin University Hospital

Martin, Slovakia

Martin University Hospital

Martin, Slovakia

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Chatterjee U.R.,University of Burdwan | Majee S.K.,University of Burdwan | Nosal S.,Martin University Hospital | Ray B.,University of Burdwan
Evidence-based Complementary and Alternative Medicine | Year: 2013

Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a 1 → 3 -, 1 → 6 - and 1 → 3,6 -linked β-D-Galp together with 1 → 5 - and 1 → 3 -linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg-1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements. © 2013 Gabriela Nosalova et al.


Raja W.,University of Burdwan | Ghosh K.,University of Burdwan | Nosal S.,Martin University Hospital | Ray B.,University of Burdwan
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Solanum virginianum L. is used for the management of fever, bronchial asthma and cough for thousands of years. While the link to a particular indication has been established in human, the active principle of the formulation remains unknown. Herein, we have investigated a polysaccharide isolated from its leaves.Materials and Methods Utilizing traditional aqueous extraction protocol and using chemical, chromatographic, spectroscopic and biological methods we have analysed an antitussive pectic arabinogalactan isolated from its leaves.Results The water extracted polymer (WEP) is a highly branched arabinogalactan containing, inter alia, (1,3)-, (1,6)- and (1,3,6)-linked β-Galp residues, terminal-, (1,5)- and (1,3,5)-linked units of α-Araf together with (1,2)- and (1,2,4)-linked Rhap. In vivo investigation on the citric-acid induced cough efforts in guinea pigs shows that the antitussive activity of the orally administered pectic arabinogalactan is greater than codeine phosphate. Remarkably, this macromolecule neither altered specific airway smooth muscle reactivity significantly nor it induced considerable change on levels of NO in expiratory flow in guinea pigs.Conclusions Thus, traditional aqueous extraction method provides a molecular entity, which induces antitussive activity without addiction: this could represent an attractive approach in phytotherapeutic management. © 2014 Elsevier Ireland Ltd.


PubMed | Comenius University, St Elizabeth Cancer Institute Hospital and Martin University Hospital
Type: | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Breast cancer is a heterogeneous disease with very different responses to therapy and different length of survival. In many cases, however, the determination of the stage and histopathological characteristics of breast cancer is insufficient to predict prognosis and response to treatment for the vast heterogeneity of the disease. To understand the molecular signature of subtypes of breast cancer, we attempted to identify the methylation status of key tumour suppressor gene Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A) and a member of the paired-like homeodomain transcription factor family which functions in left-right asymmetry development (PITX2) and to correlate results with known clinicopathological features of breast cancer. Formalin-fixed, paraffin-embedded (FFPE) tissues of breast carcinomas (n=149) were used for DNA extraction. DNA was modified by bisulphite conversion. Detection of the methylation level of the genes mentioned above was performed by methylation-sensitive high-resolution melting assay (MS-HRM). Based on MS-HRM results for RASSF1A and PITX2, we subdivided the samples into four groups according to methylation level (50% methylated, >50% methylated, 100% methylated and completely unmethylated alleles). All degrees of methylation status for both genes underwent analysis of dependence with known clinicopathological features, and we found significant associations. In 134 of 149 (89.9%) primary breast carcinomas, the RASSF1A promoter was methylated. Total hypermethylation of PITX2 was observed in 60 of 135 (44.4%) breast cancer cases. RASSF1A hypermethylation had significant association with increased age (p<0.05), tumour grade (p<0.0001) and stage (p<0.0001) in the 100% methylated group. There was significant association of PITX2 hypermethylation with tumour grade (p<0.0001) and stage (p<0.0001). Association between the methylation level of both investigated genes and tumour type was significant for ductal invasive carcinoma cases only (p<0.0001). This study shows different levels of heterogeneous methylation acquired by MS-HRM assay of the promoter region of RASSF1A and PITX2 and its relationship with clinicopathological features of 149 breast cancer patients. We noticed that immunohistopathological subtypes of breast cancer contain distinct promoter methylation patterns. All these data suggest that hypermethylation of the CpG island promoters of RASSF1A and PITX2 might play an essential role in the very early stages of breast cancer pathogenesis.


Letkova L.,Comenius University | Matakova T.,Comenius University | Musak L.,Martin University Hospital | Sarlinova M.,Comenius University | And 8 more authors.
Molecular Biology Reports | Year: 2013

Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01). © 2013 Springer Science+Business Media Dordrecht.


Husarova V.,Comenius University | Husarova V.,Martin University Hospital | Bittsansky M.,Comenius University | Ondrejka I.,Comenius University | Dobrota D.,Comenius University
Psychiatry Research - Neuroimaging | Year: 2014

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel 1H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system. © 2014 Elsevier Ireland Ltd.


Balentova S.,Comenius University | Hajtmanova E.,Martin University Hospital | Trylcova R.,Comenius University | Adamkov M.,Comenius University | Lehotsky J.,Comenius University
Acta Histochemica | Year: 2014

Ionizing radiation can induce significant injury to normal brain structures. To assess radiation-induced late effects, adult male Wistar rats received whole-body exposure with fractionated doses of gamma rays (a total dose of 4. Gy) and were investigated thirty, sixty and ninety days later. Immunohistochemistry and confocal microscopy were used to determine the density of neuroblasts derived from the anterior subventricular zone (SVZa) and brain resident microglia distributed along and/or adjacent to subventricular zone-olfactory bulb axis (SVZ-OB axis). Cell counting was performed in four anatomical parts along the well defined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. Strong overdistribution of neuroblasts was seen in the SVZa thirty and sixty days after irradiation replaced by a steep decline in the following parts of the RMS and the highest decrease ninety days after radiation treatment along the entire SVZ-OB axis. Radiation treatment led to a decline or loss of microglia in almost all counted parts through the entire experiment. Results showed that ultimate decline of the SVZa descendants and loss of microglia suggests a contributory role of reduced neurogenesis in the development of radiation-induced late effects. © 2013 Elsevier GmbH.


Balentova S.,Comenius University | Hajtmanova E.,Martin University Hospital | Kinclova I.,Martin University Hospital | Lehotsky J.,Comenius University | And 2 more authors.
Klinicka Onkologie | Year: 2012

Backgrounds: The aim of the present study was to investigate the effect of ionizing radiation on the cell population that co-forms hippocampal formation in an adult rat brain. Materials and Methods: Adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Thirty, 60 and 90 days after irradiation the cell-specific types housed in the CA1, CA3 subregions and adjacent layers were labelled using immunohistochemistry for specific cell phenotypes; Ki-67 marker was used for proliferating cells and GFAP for detection of astrocytes. Results: During the 30th day post-exposure, a considerable increase in the numbers of Ki-67-positive cells was seen. Moreover, significant decline in the density of neurons, mostly in the CA1 subregion, was observed on the 60th day. Slight overaccumulation of Ki-67-positive cells was seen in CA1 area 90 days after radiation treatment. Temporary decrease of GFAP-positive astrocytes was seen thirty days after irradiation, followed by their subsequent increase 60 days after exposure. Secondary decrease of GFAP-positive cells in both of regions was found in the group surviving 90 days post-irradiation. Conclusion: Results showed that radiation response of neurons and astrocytes that form the adult hippocampus may play contributory role in the development of prognostically unfavourable adverse radiation-induced late effect.


Sadlonova V.,Comenius University | Franova S.,Comenius University | Dokus K.,Martin University Hospital | Janicek F.,Martin University Hospital | And 2 more authors.
Journal of Obstetrics and Gynaecology Research | Year: 2011

Aim: The aim of this study was to assess the participation of ligand-sensitive potassium large conductance calcium-activated ion channels (BKCa2+) and adenosine triphosphate (ATP)-sensitive potassium ion channels (KATP) using its openers (NS1619 and pinacidil) in the contractility of human term pregnant myometrium in in vitro conditions. Methods: Human myometrium tissue samples were collected from term pregnant laboring women who had to undergo cesarean section. The contractility of myometrium was induced by the application of oxytocin into the organ bath. Myometrial strips were incubated with the opener of BKCa2+ potassium ion channels NS1619 and its antagonist tetraethylammonium or with the opener of KATP potassium ion channels pinacidil and its antagonist glibenclamide. Results: KATP potassium ion channel's opener pinacidil significantly decreased amplitude of myometrial contractions (P < 0.05) as well as frequency of myometrial contractions (P < 0.05) provoked by oxytocin in human term pregnant myometrium in in vitro conditions. The inhibition of the human myometrial contractions of pinacidil was significantly antagonized by its specific antagonist glibenclamide (P < 0.05). BKCa2+ potassium ion channel's opener NS1619 did not significantly affect the contractile activity of human term pregnant myometrium induced by the application of oxytocin in in vitro conditions. Conclusion: In our experimental study we found that the participation of BKCa2+ and KATP potassium ion channels in the contractility of human term pregnant myometrium in labor is probably different. © 2011 Japan Society of Obstetrics and Gynecology.


Balentova S.,Comenius University | Hajtmanova E.,Martin University Hospital | Plevkova J.,Comenius University | Lehotsky J.,Comenius University | Adamkov M.,Comenius University
Acta Histochemica | Year: 2013

Ionizing radiation as one of the strongest cytogenetic factors can induce significant injury to the adult brain. In the present study, adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (a total dose of 3. Gy). Seven, 14 and 21 days after irradiation the cell types located in the neurogenic anterior subventricular zone (SVZa) were labeled using immunohistochemistry for SVZa-derived young neurons and astrocytes. Cell counting was performed in four anatomical parts along the pathway known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. A considerable increase was seen in the number of neuroblasts in the SVZa, vertical arm and elbow on day 7 after irradiation. Until days 14 and 21 there was a marked decline in the density of young neurons, mostly in the horizontal arm of the RMS. In contrast, the number of astrocytes gradually increased in the caudal parts of the RMS until day 14 after irradiation. Strong enhancement was replaced by a steep decline within the RMS up to 21 days after treatment. Our results showed that the radiation response of proliferating cells originating from the SVZa may play a contributory role in the development of more adverse late radiation-induced effects. © 2012 Elsevier GmbH.


Balentova S.,Comenius University | Hajtmanova E.,Martin University Hospital | Adamkov M.,Comenius University | Lehotsky J.,Comenius University
Neurochemical Research | Year: 2015

Ionizing radiation induces altered brain tissue homeostasis and can lead to morphological and functional deficits. In this study, adult male Wistar rats received whole-body exposure with fractionated doses of gamma rays (a total dose of 5 Gy) and were investigated 30 and 60 days later. Immunohistochemistry and confocal microscopy were used to determine proliferation rate of cells residing or derived from the forebrain anterior subventricular zone (SVZa) and microglia distributed along and/or adjacent to subventricular zone–olfactory bulb axis. Cell counting was performed in four anatomical parts along the well-defined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. Different spatiotemporal distribution pattern of cell proliferation was seen up to 60 days after irradiation through the migratory pathway. A population of neuroblasts underwent less evident changes up to 60 days after treatment. Fractionated exposure led to decline or loss of resting as well as reactive forms of microglia until 60 days after irradiation. Results showed that altered expression of the SVZa derived cells and ultimative decrease of microglia may contribute to development of radiation-induced late effects. © 2014, Springer Science+Business Media New York.

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