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Pulmonary vascular endothelium dysfunction is one of the main pathogenic factors responsible for many clinical manifestations of the severe course of COVID-19. Circulating endothelial progenitor cells (EPCs) are the endogenous regenerative reserve that maintains the integrity of the vascular endothelium and its restoration in case of damage by pathogenic factors. A decrease in the circulating EPCs is regarded as a predictor of morbidity and mortality in conditions associated with development of endothelial dysfunction, including COVID-19. The exact phenotype of progenitor cells capable of differentiating into endothelial cells has not been determined. In most laboratories antigens CD133+, CD34+, VEGFR-2+ (CD 309) or combination of these are used to identify EPCs. The process of EPCs mobilization and migration is controlled by molecular signals from immune cells located in the damage area. Stromal cell factor 1 (SDF-1), produced by the bone marrow and many other tissues, is an important chemoattractant for EPCs which express its receptors. The results of studies carried out in 2020 indicate that SARS-Cov-2 infects both hematopoietic stem cells, transforming into EPCs, and directly circulating EPCs, causing inflammatory and procoagulant reactions that complicate the COVID-19 course. There is no consensus on the mechanism of EPCs infection with coronavirus – directly through the expression of angiotensin-converting enzyme (ACE2) receptor or through an ACE2-independent mechanism. Today there is no effective therapy for COVID-19. The use of the EPCs regenerative potential, and the search for ways to enhance the EPCs mobilization from the depot, and increase their functional activity may become a promising approach to the prevention of severe complications and mortality from COVID-19. © 2021, Remedium Group Ltd. All rights reserved.

The purpose of the study was to evaluate the protective effect of the inhaled glucocorticosteroids of beclomethasone dipropionate (BDP) using the experimental model of chronic obstructive pulmonary disease (COPD). Materials and Methods . The COPD model was reproduced in rats ( n = 30) during a discrete 60-day exposure to nitrogen dioxide, 9 individuals formed an intact group. Inhalation of BDP (50 micrograms per day) and control ( n = 15) placebo inhalation were performed for 60 days in the rats in the experimental group ( n = 15). The cell composition and cytokine enzymatic profile of bronchoalveolar lavage fluid (BALF), its content of secretory immunoglobulin A (sIgA) and surfactant protein D (SP-D) were determined by ELISA. Histological and morphometric lungs examination was performed. Results . Typical for COPD pathomorphological changes in the lungs were determined in the placebo group, the content of inflammatory cells and pro-inflammatory mediators in BALF increased, the functional activity of bronchoalveolar epithelium (SP-D, sIgA) deteriorated. There was a clear trend in the activity of neutrophilic-lymphocytic inflammation decrease with normalization of the profile of pro-inflammatory cytokines and enzymes in BALF In the group of animals receiving BDP; there was also a restoration of the morphological structure of the bronchoalveolar epithelium and improvement of its functional activity. Conclusion . The using of BDP in rats with the experimental COPD model had an expressed anti-inflammatory effect associated with the activation of physiological repair processes in the lungs, manifested by the restoration of structural, immune barrier integrity and functional activity of the bronchoalveolar epithelium.

OBJECTIVES: To assess the state of pulmonary vascular mediator systems during the stepwise formation of the chronic obstructive pulmonary disease (COPD) model. MATERIALS AND METHODS: The COPD model was induced in rats by nitrogen dioxide (NO(2)) inhalation for 60 days. At different stages of COPD (15, 30, and 60 days), the effect of reagents-vasodilators (β-adrenoceptor agonist isoproterenol, nitric oxide donor nitrosorbide, acetylcholine, activator of C-fibers capsaicin, corticosteroid beclometasone) on the isolated pulmonary arteries (diameter

In the experimental studies it was found that open run-off settling in comparison with the close settling systems improves the effect of PP disposal by 1.3 times, hexane fraction of PP – nearby 2 times, separate alkanes C22–C27 – by 2–3 times. Duration of open settling of run-off, formed in the territory of suburban parking areas, shall be 3–10 days. The effect of run-off purification from PP under sedimentation is mainly conditioned by disposing of fraction of nominally complex PP.

Improving safety of the soft targets includes protection of the objects that surround them. Compulsory element of immediate surrounding of the soft targets in urban environment is utility systems of city essential services. The sewage networks are open into ground space by means of mines and wells, located in the immediate vicinity of the soft targets as well. One of the potential preventive measures for protection of the soft targets, that are found side by side to sewage mines is engineering solutions that minimize the secondary effects, formed in these facilities: fire hazard/explosion hazard and high concentration of toxic gaseous compounds (hydrogen sulphide, alkyl sulphydrate, carbonic oxide and others). Concentration of methane in gas air environment of the sewage pipelines presents special hazard, which concentration in some areas of the sewage network exceeds the lower explosive limit. The technical solution is experimentally deduced, that allows efficiently and cost-effectively to minimize concentration of gaseous compounds in the sewage networks. The lasting monitoring of gas air environment compound in the urban sewage pipelines has been executed, as well in the mines (17.7% of total amount), located in the immediate vicinity from the various soft targets. It is found that methane concentration in gas air environment of the urban sewage mines has significantly decreased over the last 20 years. And at present the mines with explosive methane content and hazard content of toxic compounds in the neighborhood of the soft targets are not detected.

In experimental studies it is found that the petrol stations create the highest specific (based on 1 car traffic) emissions and contamination by petroleum products these pollutants of surrounding areas soils among the objects of the auto-road complex. Activity of soil “self-cleaning” from the petrochemicals depends on the concentration of organic carbon, which increases the activity of soil oxidoreductase enzymes carrying the oxidative degradation of hydrocarbons among the objects of the auto-road complex.

Goal: to evaluate the effect of induced immunosuppression on the nature and speed of structural-functional disturbances formation in the lungs on the COPD model. Methods: The COPD model was created in Wistar rats by exposure with nitrogen dioxide (NO2, 15-19 ppm): three 30-minute exposures per day with 30 min intervals for 60 days. To create immunosuppression, an alkylating agent cyclophosphamide was injected intraperitoneally twice, the control group got 0.9% NaCl. BAL fluid cytogram was determined. The presence of IL-8, IL-17, neutrophil elastase (NE), sIgA, SP-D in BAL fluid was measured by ELISA method. Histological preparations were stained with HE TNFα-up to 35.48±2.08 vs 25.45±1.33 pg/ml in control, p Conclusion: When aggressive pollutants damaging the respiratory epithelium are exposed, the initial immune dysfunction maycontribute to the formation of a pro-inflammatory environment and the phenotype of premature lungs aging, predisposing to the development of chronic obstructive pulmonary pathology.

The concentration of hydrogen sulfide and other gases in the sewerage pipelines of the Kharkov city was measured during the experimental studies. Based on the obtained figures the emission of hydrogen sulphide through the sewer shafts in urban environment and its dispersion in the atmosphere of specific urban areas were estimated. The interface of the page for the monitored indicators of the environmental safety and operational reliability of specific areas of the water disposal pipelines was developed. It can be used for the geographic information system of the urban sewer networks.

On the model of chronic obstructive pulmonary disease, the effect of therapy with low-molecular-weight peptides on restructuring and functional activity of bronchial epithelium for restoring the immune and barrier function of the lungs and prevention of inflammatory process progression was studied. Chronic obstructive pulmonary disease was modeled in rats by 60-day intermittent exposure to NO2. Administration of tetrapeptide Bronchogen for 1 month eliminates symptoms of remodeling of the bronchial epithelium and lung tissue typical of chronic obstructive pulmonary disease (goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, and restoration of ciliated cells). Enhanced production of secretory IgA, a local immunity marker, attested to normalization of functional activity of bronchial epithelium, while normalization of cell composition and profile of proinflammatory cytokines in the bronchoalveolar space reflected reduction of neutrophilic inflammation.

There is an opinion, that the local inhibition of hypoxia-inducible factor-1α (HIF-1α) in lung may represent a therapeutic strategy for the treatment of inflammatory pulmonary diseases. Aim: to evaluate the modifying effect of cyclooxygenase-2 (COX-2) inhibition on lung inflammation and change of HIF-1α in COPD model. Methods: Model of COPD was induced in rats by nitrogen dioxide (15-19 ppm) exposure: three 30-min exposures/day with 30-min intervals for 60 days. Celecoxib (C) was used as a COX-2 inhibitor. From 30th to 60th day rats of 1st group received C via esophageal probe, rats of 2nd group (control) received 0,9% NaCl. 3rd group was intact. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of COX-2, HIF-1α, IL-17, surfactant protein D (SP-D) were measured in BALF by ELISA. Results: Treatment with C decreased COX-2 level in BALF: 18,8±2,2 vs. 26,5±2,3 pg/ml in control group, p Conclusion: The inhibition of COX-2 had a supressive effect on lung inflammation. It can be assumed that COX-2-dependent mechanism is involved in the inhibition of HIF-1α signalling, that can contribute to restoring the structure of bronchial epithelium.

Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide. Glucocorticoids are currently the most applicable anti-inflammatory treatment for COPD. However, a subset of COPD subjects is relatively insensitive to this treatment. Fenspiride, a non-corticosteroid anti-inflammatory drug, has been described to have beneficial effects in patients with COPD, although the mechanism of its action is not well known. The effect of fenspiride on contractile activity of bronchial smooth muscle was studied in a rat model of COPD induced by long-term exposure of the animals to nitrogen dioxide (NO2). Contractile activity of bronchial smooth muscle was evaluated in vitro. Isometric contraction of bronchial preparations was measured following electrical stimulation. Fenspiride administration to rats during the acute stage of COPD (15 days of NO2 exposure) prevented the bronchial constriction induced by NO2. The bronchodilator effect of a low-dose of fenspiride (0.15 mg/kg) was mediated by interaction with the nerve endings of capsaicin-sensitive C-fibers. Interaction of fenspiride with C-fibers was shown to prevent initiation of neurogenic inflammation, as evidenced by lack of COPD-like structural changes in the lungs. The bronchodilator effect of a high-dose of fenspiride (15 mg/kg) was mediated not only by the afferent component, but also involved a direct relaxing effect on smooth muscle cells. The anti-inflammatory and bronchodilator effects of a low-dose of fenspiride may be used for prevention of COPD development in individuals from high-risk cohorts exposed to aggressive environmental factors.

The contribution of mast cells (MCs) to inflammatory response and lung remodeling in COPD is not well documented. Aim: to assess the effect of MC degranulation blockade on inflammatory response outcome and lung tissue structure in COPD model. Methods: Model of COPD was induced in rats by NO 2 (15-19 ppm) exposure: 1,5-2 h/day for 60 days. Sodium cromoglicate (SC, Aventis) was used as MC membrane stabilizer. From 30th to 60th day one group was inhaled with SC before NO 2 exposure, control group received 0.9% NaCl. Lung sections were stained with H&E and toluidine blue for MCs. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of mast cell tryptase (MCT) and chymase (MCC), TNFa, surfactant protein B (SP-B) were measured in BALF by ELISA. Results: A lot of MCs, inflammatory infiltration, foci of emphysema were revealed in control lung tissue. The BALF levels of TNFa, SP-B, MCT and MCC increased respectively 10-, 2-, 6- and 3-fold (p Conclusion: The results confirm the involvement of MCs in the development of airway inflammation. Prevention of MC degranulation reduces the activity of the airway inflammation and severity of lung tissue remodeling in rats with COPD model.

A method for experimental reproduction of stages of chronic obstructive pulmonary disease formation (from acute inflammation to bronchopulmonary tissue restructuring characteristic of this disease) is presented. Lung injury and inflammation were induced by nitrogen dioxide. Hyperplasia and hypersecretion of goblet cells, squamous cell metaplasia of the ciliary epithelium, emphysema, and focal fibrosis served as the morphological substrate for the formation of bronchial obstruction. The adequacy of the model is confirmed by signs characteristic of chronic obstructive pulmonary disease: hyperexpression of CD3 lymphocytes in the bronchial wall and parenchyma, manifold increased production of TNFα and TGFβ, high concentrations of circulating pathogenic immune complexes. Persistence of the structural and functional shifts throughout 6 months after exposure to nitrogen dioxide indicated a chronic course of the resultant pathological process.

Aim: to evaluate the effect of drugs with pleiotropic propertieson the smooth muscle activity of small pulmonary arteries (PA) and bronchi in rats with COPD model. Methods: Model of COPD was induced in rats by nitrogen dioxide exposure (15 ppm, 1,5 h/day, 60 days). From 30th to 60th day the rats were treated with sulodexide (S) or rosuvastatin (R). Control rats received 0.9% NaCl.We evaluated the contractile activity of bronchial strips caused by stimulation of the preganglionicnerve or smooth muscle, and changes in tone of isolated PA (diameter < 0.5 mm) rings at application of reagents-vasodilators (b-adrenoreceptor agonist izopreterenol, nitric oxide donor nitrosorbid, corticosteroid beclometasone).Bronchial and PA reactivity was assessed by determining isometric contraction (tension in mg) usingelectromechanical transducer. Results: Amplitude of relaxation of control rat PAs decreased by 30% (as compared to intact PAs) in response to all vasodilators. The treatment with S restored NO-dependent mechanism of vasodilatation and improved β-adrenergic regulation of the PA tone.The use of R had no effect on the dilator activity of PAs.Both S and R improved the functional status of bronchial smooth muscles and intrabronchial nervous system that was accompanied by decrease in the contractile activity of airway smooth muscle. Conclusion: The one-way relaxing effect of sulodexide on smooth muscles of pulmonary arteries and bronchi enables the recovery of coordinated regulation of the tone of these structures, which is essential for maintaining the optimal ratio of ventilation and pulmonary blood flow for efficient gas exchange.

The physiological role of I to has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current ( I to) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4‐aminopyridine (4AP) as I to blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area ( n strips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill's equation. APD20 raised by 70% and spike duration of AP increased by 15–25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP‐sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4‐AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60–70% with a control.