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  • Author: I. Kazimierová x
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Open access

I. Kazimierová, L. Pappová, M. Šútovská and S. Fraňová

Abstract

Background: Fisetin, a derivate from the flavonol group may possess a variety of pharmacological effects. The aim of the presented study was to evaluate the bronchodilatory effect of fisetin after the acute or the chronic administration to guinea pigs with allergic airway inflammation.

Methods: Experimental animals were sensitized and challenged by ovalbumin. Fisetin was administered in dose 5mg/kg/p.o., either once after the end of 21-days sensitization or daily during the 21-days sensitization. By using the whole-body plethysmograph, we monitored the specific airway resistance, a parameter of airway hyperreactivity in vivo. The changes of the specific airway resistance were evaluated after the short-term inhalation of the bronchoconstriction mediator-histamine (10−6 mol.1−1).

Results: Our results showed that the short-term as well as the long-term administration of fisetin caused decrease of the specific airway resistance values. The bronchodilatory effect of fisetin was comparable to the long-acting beta2 sympathomimetic – salmeterol after the long-term administration. The measurements of the bronchodilatory activity after single administration have revealed more prolonged effect of fisetin comparing to the short-acting beta2 sympathomimetic – salbutamol, as this remained even after the 5 hours, when salbutamol was already ineffective.

Conclusion: In conclusion, flavonol – fisetin has shown bronchodilatory potential. In the light of this fact, fisetin may represent potential substance that can be effective in both prevention as well as control of airway inflammation symptoms.

Open access

M. Kocmálová and I. Kazimierová

Abstract

The present in vitro study was focused on the differences in expression and activity of calcium release-activated calcium (CRAC) channels of human term-pregnant and non-pregnant myometrium. The expression of Orai1 protein, as a functional subunit of CRAC channel, was significantly higher than in non-pregnant myometrium. Lower Orai1 protein expression did not influence the amplitude of contractile response of term-pregnant myometrium, but higher Orai1 expression observed in non-pregnant myometrium was related to the different influence of CRAC blocker on contraction frequency.

Open access

M. Kocmálová, J. Ľupták, J. Barboríková, I. Kazimierová, M. Grendár and J. Šutovský

Abstract

Background: This study specified the role of several significant ion channels regulating the metabolism of calcium ions in contraction and relaxation of human detrusor muscle in order to identify possible target for future drugs that are capable of treating diseases resulting from impaired detrusor activity, e.g. overactive bladder. Although this disease can be successfully treated with muscarinic receptor antagonists or β3 agonist, many patients may not be suitable for chronic therapy, especially due to the relatively high side effects of the treatment.

Material and Methods: The study used the isolated detrusor tissue samples, which were obtained from the macroscopic healthy tissue of urinary bladder from 19 patients undergoing a total prostatectomy because of localized prostate cancer. Each biological sample was prepared into 8 strips. We used oxybutynin and mirabegron as control drugs and several blockers of specific subtypes calcium and potassium ion channels as tested substances. The contractility of bladder was investigated by an organ tissue bath method in vitro and contraction was induced by carbachol.

Results: The amplitude of contraction was successfully decreased by positive control drugs and, from tested agents, the comparable effect had the substance capable of influencing IP3 receptors and Orai-STIM channels and combination consisting of drugs possessing an inhibitory effect on IP3 receptors, L- and T-type voltage-gated calcium channels and Orai-STIM channels.

Conclusion: The present work represents a new finding about handling Ca2+ in urinary bladder contraction and pointed to a dominant role of IP3 receptor-mediated pathway in the regulation of Ca2+ metabolism, which may represent a future strategy in pharmacotherapy of impaired detrusor activity.

Open access

L. Pappová, I. Kazimierová and M. Kocmálová

Abstract

Aim: N-acetylcysteine is the prototype of mucolytic agents. The aim of this study was to evaluate the acute and chronic effect of inhaled and oral N-acetylcysteine on airway reactivity, cough reflex and ciliary beat frequency and parameters of mentioned defense mechanisms were assessed in physiological conditions.

Methods: An experiment was performed using healthy guinea pigs treated with inhaled (0.6 M; 5min) and oral N-acetylcysteine (20 mg/kg), administrated either acutely as a single dose or chronically during 7 days. The cough reflex and specific airway resistance were assessed by in vivo method, using a double chamber plethysmograph box. The ciliary beat frequency was evaluated in in vitro conditions on tracheal brushed samples using light microscope coupled to high speed video camera.

Results: Inhaled and oral N-acetylcysteine, either administrated as a single dose or during 7 days, have shown a tendency to decrease sensitivity of the cough reflex and increase the airway reactivity. Acute administration of inhaled and oral N-acetylcysteine had no statistically relevant effect on the ciliary beat frequency, whereas chronic administration of both inhaled and oral N-acetylcysteine led to a marked reduction in the ciliary beat frequency.

Conclusion: Chronic administration of oral and inhaled N-acetylcysteine had a negative impact on the ciliary beat frequency, which represents one of the key factors determining the rate of mucociliary clearance. Thus, administration of N-acetylcysteine is less likely to increase the expulsion of mucus by ciliary movement. In addition, the observed tendency of inhaled and oral N-acetylcysteine to increase the airway reactivity may limit its use in conditions with severe airflow obstruction.

Open access

J. Sutovsky, M. Kocmalova, M. Benco, I. Kazimierova, L. Pappova, A. Frano and M. Sutovska

Abstract

Background: Degenerative spine disorders (DSD) are the most frequent reason of morbidity in adults. Commonly DSD includes degenerative disorders of intervertebral discs (IVDs), spinal stenosis and degenerative spondylolisthesis (SL). There is increasing evidence about significant role of cytokines in DSD pathogenesis, symptomathology and progression, but their protective levels remain still unknown.

Material and Methods: The aim of presented study was to provide quantitative and qualitative analysis of cytokine, chemokine and growth factors levels in individual parts of IVDs - annulus fibrosus (AF) and nucleus pulposus (NP) - separately and in facet joints (FJ) subchondral bone of patients with DSD and in controls - healthy subjects during a multiorgan procurement procedure. Bio-Plex® assay was used to measure concentrations of 27 different cytokines in tissue of patients with DSD. Their concentrations in tissues of healthy subjects during a multiorgan procurement procedure represented protective levels.

Results: The Bio-Plex® assay revealed significant differences between the patients suffered from degenerated and herniated IVDs and from lumbar SL and controls in cytokines, chemokines and growth factor profiles suggested that pro-inflammatory changes of both NP and AF were dominated in herniated IVDs, whereas the same tissue of lumbar SL patients exhibited much more complex changes in cytokine levels suggested o only ongoing inflammation (IL-6, IL-8, MCP-1, TNF-α), abut also antiinflammatory processes (IL-ra, IL-10) or connective tissue remodeling (PDGF-bb, IL-17, VEGF). The different mediators were found elevated in lumbar SL samples of subchondral FJ bone. These also confirmed ongoing inflammation, accelerated bone resorption and formation and increased fibroblasts activity in FJ bone.

Conclusion: The study supported the significant involvement of several cytokines, chemokines and growth factors in the pathogenesis of DSD. These cytokines should represent future potential targets for new biological treatment able to slow DSD progression as well as factor determining prognosis of DSD.