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  • Author: J. Šutovský x
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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

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.