Pavol Mikolka

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Verified

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• PhD
• Assistant Professor at Comenius University Bratislava

Obesity is considered an important factor contributing to the development of atherosclerosis. Inflammation plays a key role in endothelial dysfunction (ED), an initial stage of the atherosclerotic process. Several microRNAs (miRNAs) may play an important role in the inflammatory process, but there is a lack of information about their participation...

Purpose Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decr...

The inflammation present in acute respiratory distress syndrome (ARDS) and thereby associated injury to the alveolar-capillary membrane and pulmonary surfactant can potentiate respiratory failure. Even considering the high mortality rate of severe ARDS, glucocorticoids appear to be a reasonable treatment option along with an appropriate route of de...

Accumulation of reactive oxygen species during hyperoxia together with secondary bacteria-induced inflammation leads to lung damage in ventilated critically ill patients. Antioxidant N-acetylcysteine (NAC) in combination with surfactant may improve lung function. We compared the efficacy of NAC combined with surfactant in the double-hit model of lu...

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by the rapid onset of lung inflammation Therefore, monitoring the spatial distribution of the drug directly administered to heterogeneously damaged lungs is desirable. In this work, we focus on optimizing the drug N-acetylcysteine (NAC) adsorption on poly-l-lys...

Heart rate variability (HRV) as an index of cardiac autonomic control in acute lung injury (ALI) has been evaluated in anaesthetized rats intratracheally instilled with bacterial lipopolysaccharide (LPS) and ventilated with breathing frequency of 60/min, 40% oxygen, inspiratory time 40%, tidal volume of 6mL/kg. ECG was recorded before and 30, 60, 1...

Respiratory distress syndrome (RDS) in premature infants is caused by insufficient amounts of endogenous lung surfactant and is efficiently treated with replacement therapy using animal-derived surfactant preparations. On the other hand, adult/acute RDS (ARDS) occurs secondary to e.g., sepsis, aspiration of gastric contents, and multitrauma and is...

Acute respiratory distress syndrome (ARDS) is a common complication of critical illness characterized by lung inflammation, epithelial and endothelial dysfunction, alveolar-capillary leakage, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory effects of non-selective phosphodiesterase (PDE) inhibitor ami...

Inhalation of silica particles causes inflammatory changes leading to fibrotizing silicosis. Considering a lack of effective therapy, and a growing information on the wide actions of green tea polyphenols, particularly epigallocatechin-3-gallate (EGCG), the aim of this study was to evaluate the early effects of EGCG on markers of inflammation and l...

The development of acute respiratory distress syndrome (ARDS) is known to be independently attributable to aspiration-induced lung injury. Mechanical ventilation as a high pressure/volume support to maintain sufficient oxygenation of a patient could initiate ventilator-induced lung injury (VILI) and thus contribute to lung damage. Although these ph...

The development of acute respiratory distress syndrome (ARDS) is known to be independently attributable to aspiration-induced lung injury. Mechanical ventilation as a high pressure/volume support to maintain sufficient oxygenation of a patient could initiate ventilator-induced lung injury (VILI) and thus contribute to lung damage. Although these ph...

Aspirated meconium into a newborn’s airways induces the transcription of pro-oxidative mediators that cooperate in the pathogenesis of inflammatory changes and may negatively affect the commonly used exogenous surfactant therapy. However, inflammation is not treated at present, nor is the time dependence of oxidative damage known. The aim of our st...

Lung silicosis is primarily caused by inhalation of particles of silicon oxide (silica). Despite a huge progress in understanding the interactions among the pathomechanisms of lung silicosis in the last years, there is a lack of effective therapy. With respect to a wide therapeutic action of corticosteroids, the purpose of this pilot study was to e...

Acute respiratory distress syndrome (ARDS) is a common complication of critical illness characterized by lung inflammation, epithelial and endothelial dysfunction, alveolar-capillary leakage, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory effects of non-selective phosphodiesterase (PDE) inhibitor ami...

Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could be categorized according to a content entering the respiratory system into bacterial aspiration pneumonia with the gastric or oropharyngeal bacteria entering, aspiration chemical p...

Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could be categorized according to a content entering the respiratory system into bacterial aspiration pneumonia with the gastric or oropharyngeal bacteria entering, aspiration chemical p...

Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the...

Acute respiratory distress syndrome (ARDS) is a common complication of critical illness and remains a major source of morbidity and mortality in the intensive care unit (ICU). ARDS is characterised by diffuse lung inflammation, epithelial and endothelial deterioration, alveolar–capillary leak and oedema formation, and worsening respiratory failure....

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulm...

Acute respiratory distress syndrome (ARDS) is associated with diffuse inflammation, alveolar epithelial damage, and leakage of plasma proteins into the alveolar space, which together contribute to inactivation of pulmonary surfactant and respiratory failure. Exogenous surfactant delivery is therefore considered to hold potential for ARDS treatment,...

Acute damage to the lung may originate from various direct and indirect reasons. Direct lung injury may be caused by pneumonia, near-drowning, aspiration, inhalation of toxic gases etc., while indirect lung injury is secondary, following any severe extra-pulmonary disease, e.g. sepsis, acute pancreatitis, or severe trauma. Due to a complex pathophy...

The study aimed to prove the hypothesis that exogenous surfactant and an antibiotic polymyxin B (PxB) can more effectively reduce lipopolysaccharide (LPS)-induced acute lung injury (ALI) than surfactant treatment alone, and to evaluate the effect of this treatment on the gene expression of surfactant proteins (SPs). Anesthetized rats were intratrac...

This study aimed to investigate whether a selective phosphodiesterase-3 (PDE3) inhibitor olprinone can positively influence the inflammation, apoptosis, and respiratory parameters in animals with acute respiratory distress syndrome (ARDS) model induced by repetitive saline lung lavage. Adult rabbits were divided into 3 groups: ARDS without therapy...

Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of...

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia, neutrophil-mediated inflammation, and lung edema formation. Whereas lung damage might be alleviated by nitric oxide (NO), goal of this study was to evaluate if intratracheal NO donor S-nitroso-N-acetylpenicillamine (SNAP) can positively influence the lung functions in e...

Pulmonary surfactant preparations extracted from natural sources have been used to treat millions of newborn babies with respiratory distress syndrome (RDS) and can possibly also be used to treat other lung diseases. Due to costly production and limited supply of animal-derived surfactants, synthetic alternatives are attractive. The water insolubil...

Aim: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negativ...

Acute lung injury (ALI) represents a serious heterogenous pulmonary disorder with high mortality. Despite improved understanding of the pathophysiology, the efficacy of standard therapies such as lung-protective mechanical ventilation, prone positioning and administration of neuromuscular blocking agents is limited. Recent studies have shown some b...

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits we...

Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Sildenafil, phosphodiesterase 5 (PDE5) inhibitor, inhibits degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. Positive effects of sildenafil treatment resul...

Damage of alveolar-capillary barrier, inflammation, oxidative injury, and lung cell apoptosis represent the key features of acute lung injury (ALI). This study evaluated if selective phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the mentioned changes in lavage-induced model of ALI. Rabbits with ALI were divided into 2 groups: ALI witho...

Aims: Combination of exogenous surfactant with antioxidant enzyme recombinant human superoxide dismutase (rhSOD) was tested in the treatment of experimental meconium aspiration syndrome as oxidative processes play key role in its pathogenesis. Material and methods: Young New Zealand rabbits were instilled by saline (Sal group) or by meconium sus...

Aim: Meconium aspiration syndrome (MAS) is life-threatening respiratory failure of newborns which can be treated by exogenous surfactant. In response to meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil infiltration of the lungs. Local accumulation and activation of neutrophils, on-going inflammation, lung edema, an...

Introduction: Chronic obstructive diseases of airways associated with cough and/or airway smooth muscle hyperresponsiveness are usually treated with bronchodilating and anti-inflammatory drugs. Recently, selective phosphodiesterase (PDE) 4 inhibitors have been introduced into the therapy of chronic obstructive pulmonary disease. Several studies ha...

Selective phosphodiesterase (PDE) 4 inhibitors have recently been introduced into the therapy of chronic obstructive pulmonary disease. However, suppression of airway reactivity and eosinophilic inflammation by increased intracellular cAMP could be beneficial in bronchial asthma as well. PDE5 inhibitors are used for the therapy of erectile dysfunct...

Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Whereas a selective phosphodiesterase-4 (PDE4) inhibitor roflumilast has exerted potent anti-inflammatory properties, this study evaluated if its intravenous delivery can influence inflammation, edema format...

Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there...

Nitric oxide (NO) is an important endogenous mediator with significant role in the respiratory system. Many endogenous and exogenous factors influence the synthesis of NO and its level is significantly changed during the inflammation. Analysis of nasal nitric oxide (nNO) is not validated so far as the diagnostic method. There is a lack of reference...

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered...

Acute lung injury (ALI) is characterized by diffuse alveolar damage, inflammation, and transmigration and activation of inflammatory cells. This study evaluated if intravenous dexamethasone can influence lung inflammation and apoptosis in lavage-induced ALI. ALI was induced in rabbits by repetitive saline lung lavage (30 ml/kg, 9±3-times). Animals...

Severe meconium aspiration syndrome (MAS) in the neonates often requires a ventilatory support. As a method of choice, a conventional mechanical ventilation with small tidal volumes (V In the young rabbits, a model of MAS was induced by an intratracheal instillation of a suspension of neonatal meconium (4 ml/kg, 25 mg/ml). After creating the model...

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema fo...

Introduction: Phosphodiesterases (PDEs) are enzymes involved in degradation of cAMP and cGMP. The clinical effectiveness of selective PDE4 inhibitors has been confirmed previously in chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate effects of roflumilast (selective PDE4 inhibitor)...

Acute lung injury is characterized by lung edema, surfactant dysfunction, and inflammation. The main goal of our study was to evaluate effects of S-nitroso-N-acetyl-penicillamine (SNAP) on migration of cells into the lung and their activation, inducible NO synthase (iNOS) activity, and apoptosis in experimental acute lung injury (ALI) in rabbits. A...

Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5′ monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-select...

Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectivenes...

Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced co...

Systems biology provides opportunities to fully understand the genes and pathways in disease pathogenesis. We used literature knowledge and unbiased multiple data meta-analysis paradigms to analyze microarray datasets across different mouse strains and acute allergic asthma models. Our combined gene-driven and pathway-driven strategies generated a...

Patients with acute lung injury are ventilated by conventional mechanical ventilation (CMV) rather than high-frequency jet ventilation (HFJV). This study estimated the potential usefulness of HFJV in acute lung injury. The issue was addressed by comparing the effects on lung function of CMV and HFJV in two rabbit models of neonatal acute lung injur...

Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent int...

Background: Acute lung injury (ALI) is characterized by lung edema, surfactant dysfunction, and inflammation. Aims and objectives: To evaluate effects of soluble donor of nitric oxide (SNAP) on inflammation, inducible NO synthase (iNOS) and migration of cells into the lung and their activation in experimental ALI. Methods: In rabbits, ALI was induc...

Tobacco smoke, one of main cause of lung cancer, leads to chronic airway inflammation and activation of cells, which produce high levels of nitric oxide (NO) and reactive oxygen species (ROS). NO and its metabolites interact with reactive oxygen species (ROS) and produce other reactive products with potential carcinogenicity. Therefore we aimed on...

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder in early childhood characterized by impairment in communication and behavior. Recent research is focused on the immune dysregulation as a potential pathomechanism leading to ASD. Thus, we addressed the hypothesis that inflammatory activity might be enhanced in children suffering...

For treatment of severe neonatal meconium aspiration syndrome (MAS), lung-protective mechanical ventilation is essential. This study compared short-term effects of small-volume conventional mechanical ventilation and high-frequency oscillatory ventilation on lung function in experimentally-induced MAS. In conventionally-ventilated rabbits, MAS was...

Meconium aspiration syndrome (MAS) is meconium-induced respiratory failure of newborns associated with activation of inflammatory and oxidative pathways. For severe MAS, exogenous surfactant treatment is used which improves respiratory functions but does not treat the inflammation. Oxidative process can lead to later surfactant inactivation; hence,...

Diffuse alveolar damage, lung edema, and inflammation are fundamental signs of acute lung injury (ALI) of various etiology. This study evaluated possible benefits of intratracheally given corticosteroid budesonide on the lung function parameters, edema formation, number of cells in the bronchoalveolar lavage (BAL) fluid, and concentrations of proin...

Chronic inflammatory diseases, associated with airway obstruction and cough, are usually treated with bronchodilating and anti-inflammatory drugs. Inhibition of phosphodiesterases (PDE) leads to both of these effects and influences apoptosis of immune cells. In chronic obstructive pulmonary disease, roflumilast, a selective PDE4 inhibitor, has been...

We studied a potential impact of chronic psychosocial load on the allostatic biomarkers - cardiac vagal activity, inflammation, and oxidative stress in healthy undergraduate students. Continuous resting ECG signals were monitored in a group of 16 female healthy students (age: 23.2 ± 0.2 years, BMI: 20.9 ± 0.5 ;kg/m(2)) at two time periods: right af...

Nitric oxide (NO) effects in airways are influenced by the activity of NO-synthase isoforms and NO metabolism. Inducible NO-synthase (iNOS), which produces large amounts of NO, is active during the inflammatory process. NO quickly reacts, producing reactive oxygen species (ROS). In this study we attemepted to detect the expression of iNOS and marke...

Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratra...

Number: 2459 Abstract Group: 7.5. Neonatology and Paediatric Intensive Care Keyword 1: Acute respiratory failure Keyword 2: Anti-inflammatory Keyword 3: Biomarkers

The best-studied store-operated Ca2+ channels (SOCs), Ca2+ release activated Ca2+ (CRAC) channels, are activated by depleting endoplasmic reticulum Ca2+ pool and mediate Ca2+ influx vitally important for Ca2+ restoration and many cellular function. CRAC channels were identified on immune and airway smooth muscle (ASM) cells. Emerging evidence point...

strain DAL-1 is a human uncultivable pathogen causing the sexually transmitted disease syphilis. Strain DAL-1 was isolated from the amniotic fluid of a pregnant woman in the secondary stage of syphilis. Here we describe the 1,139,971 bp long genome of strain DAL-1 which was sequenced using two independent sequencing methods (454 pyrosequencing and...

Changes in Several Inflammatory and Oxidation Markers after Ovalbumin-Sensitization in a Guinea Pig Model of Allergic Asthma - A Pilot Study Ovalbumin (OVA)-sensitization is a common way to evoke changes similar to changes in allergic asthma in humans. Activated cells produce various pro-inflammatory and vasoactive substances including reactive oxy...

Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on E...

Analysis FGFR3 and LRP6 transgene expression in RCS cells. (A) Cells were transfected with high amounts of either V5-tagged LRP6 (upper panel) or FGFR3 (lower panel) vectors (6 µg of plasmid per 1×105 cells), and analyzed for the indicated molecules 48 hours later. K508M - kinase inactive FGFR3 mutant. Note the high amounts of Ser1490 phosphorylati...

Constitutively active forms of RAF, RAS and SRC signal via ERK/LRP6 pathway. (A, D) RCS cells were transfected with empty plasmid or plasmid encoding RafCAAX, RAS-V12 or SRC-Y529F, grown for 48 hours, and analyzed for indicated molecules by WB. (B, E) Cells were transfected as indicated together with Topflash firefly luciferase (F-Luc) and control...

Effect of activating FGFR3 mutants on basal levels of Topflash activity. Cells were transfected with the indicated FGFR3 vectors together with Topflash firefly luciferase (F-Luc) and control Renilla luciferase (R-Luc) vectors, and analyzed for luciferase activity 48 hours later. Data represent an average from four transfections (each measured twice...

Effect of FGF signaling on WNT/β-catenin signaling in PC12 cells. Cells were transfected with Topflash vector, the indicated FGFR3 expression plasmid, and Renilla luciferase vector at a ratio of 1∶1∶0.1. Cells were transfected with a total of 10.5 µg DNA using Lipofectamine 2000 (Invitrogen). The following day, cells were serum-starved 3 hours, tre...

FGF2 upregulates WNT/β-catenin signaling independent of the PI3K/AKT pathway. (A) RCS cells were treated with FGF2 (10 ng/ml) for the indicated times and analyzed for activatory Ser473 phosphorylation of AKT by WB. (B) AKT was immunoprecipitated from FGF2-treated cells and used in a kinase assay with recombinant GSK3 as a substrate. C1, C2 - untrea...

In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent...