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Red wine polyphenolic compounds inhibit tracheal smooth muscle contraction during allergen‐induced hyperreactivity of the airways

The aims of the study were to investigate the short and long‐term effects of Provinol (red wine polyphenolic compounds) on tracheal smooth muscle reactivity using an in‐vitro model of ovalbumin‐induced airway inflammation in guinea‐pig trachea, and to evaluate the role of nitric oxide (NO) in the bronchodilatory effect of Provinol.

Experimental Model of Allergic Asthma

The aim of the study was to prepare and evaluate the experimental model of allergic asthma. Changes in chough reflex, bronchoconstriction and the degree of inflammation were studied in ovalbumin (OVA) sensitized guinea pigs after 0, 7, 14, 21 days of exposure. The cough reflex was induced by citric acid inhalation in conscious animals in a double chamber body plethysmograph. Tracheal smooth muscle reactivity was assessed by examining the in vitro response to histamine (H) (10(-8)-10(-3) mol/l) and in vivo to H nebulization (10(-6) mol/l). BALF levels of IL-4, IL-5 and the eosinophil count were used as parameters of airway inflammation. After 7 days of OVA sensitization, there was an increase in tracheal smooth muscle contractility in vitro to cumulative concentration of H and an increase in cough parameters. After 14 days of OVA sensitization, there was a further increase in tracheal smooth muscle contractility to H, an increase in airway resistance, and a small increase in cough parameters. After 21 day of OVA sensitization, cough parameters were significantly reduced, airway resistance after H inhalation was increased, and there were significant increases in IL-4, IL-5, and eosinophils in BALF. In conclusion, progress in asthmatic inflammation during 21-day OVA sensitization caused a gradual increase in inflammatory mediators, a decline in cough reflex, and enhanced bronchoconstriction. This experimental model of allergic asthma can be used for pharmacological modulations of defense reflexes and inflammation.

CRAC Ion Channels and Airway Defense Reflexes in Experimental Allergic Inflammation

Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy.

Phytotherapy of cough

Abstract The problems emerging from the treatment of cough during many types of respiratory diseases by conventional opioid antitussive agents, such as codeine and codeine-like compounds, are well known. In recent years, much effort has been made to create drugs that exhibit minimum side effect on the organism. One of them is the medicinal plants, which are potential source of substances with high-antitussive efficiency with minimal unwanted effects. Recent trends of modern phytotherapy include specification of active substances responsible for therapeutic effect as well as their quantification in the healing drugs, which enables the treatment rationalization, especially the dosing and pursuing of adverse effects. The purpose of this chapter is to give the overview of some medicinal plants and their active compounds with cough-suppressing activity. The common information about antitussive efficiency of selected herbal products are replenished with results of our ongoing research program related to search for potentially antitussive active herbal polysaccharides.

Polyphenols and Their Components in Experimental Allergic Asthma

The aim of the study was to investigate the potential anti-inflammatory effects in -experimental allergic asthma of natural polyphenolic compounds or their single major components. The experiment was performed after 21-days sensitization of guinea pigs with ovalbumin suspension. Changes in airway reactivity after the long-term treatment with the polyphenolic compounds Provinol and Flavin-7 and their single major components quercetin and resveratrol during were assessed using a whole body plethysmography. Reactivity of tracheal smooth muscle was studied in vitro in response to cumulative doses of the bronchoconstrictive mediators histamine and acetylcholine. Furthermore, concentrations of the inflammatory cytokines IL-4 and IL-5 were measured in bronchoalveolar lavage fluid. The results demonstrate significant anti-inflammatory effects of Provinol and Flavin-7 exerted in the airways. In contrast, chronic treatment with quercetin and resveratrol, single components of the two polyphenols, did not show such activity. We conclude that polyphenolic compounds are more effective in the anti-inflammatory effects in the airways than their separate components.

Participation of BKCa2+ and KATP potassium ion channels in the contractility of human term pregnant myometrium in in vitro conditions

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.

Utero‐relaxant effect of PDE4‐selective inhibitor alone and in simultaneous administration with β2‐mimetic on oxytocin‐induced contractions in pregnant myometrium

Background:  The objective of the study was to observe the effect of rolipram, the prototype phosphodiesterase 4 selective inhibitor, on oxytocin‐induced contractions of human term myometrial strips, and compare the effect with salbutamol, β2‐adrenergic agonist, in single and the simultaneous application.

Effects of Flavin7 on allergen induced hyperreactivity of airways

Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5) in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

Bronchodilatory, antitussive and anti-inflammatory effect of morin in the setting of experimentally induced allergic asthma.

Using an experimental model of allergic asthma, we evaluated the anti‐asthmatic potential of polyphenol flavonol derivate morin after either acute or long‐term treatment of male OVA‐sensitised guinea pigs.

Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction.