Lung epithelium damage in COPD – An unstoppable pathological event?
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01.04.2020 |
Hadzic S.
Wu C.
Avdeev S.
Weissmann N.
Schermuly R.
Kosanovic D.
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Cellular Signalling |
10.1016/j.cellsig.2020.109540 |
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Ссылка
© 2020 Elsevier Inc. Chronic obstructive pulmonary disease (COPD) is a common term for alveolar septal wall destruction resulting in emphysema, and chronic bronchitis accompanied by conductive airway remodelling. In general, this disease is characterized by a disbalance of proteolytic/anti-proteolytic activity, augmented inflammatory response, increased oxidative/nitrosative stress, rise in number of apoptotic cells and decreased proliferation. As the first responder to the various environmental stimuli, epithelium occupies an important position in different lung pathologies, including COPD. Epithelium sequentially transitions from the upper airways in the direction of the gas exchange surface in the alveoli, and every cell type possesses a distinct role in the maintenance of the homeostasis. Basically, a thick ciliated structure of the airway epithelium has a major function in mucus secretion, whereas, alveolar epithelium which forms a thin barrier covered by surfactant has a function in gas exchange. Following this line, we will try to reveal whether or not the chronic bronchitis and emphysema, being two pathological phenotypes in COPD, could originate in two different types of epithelium. In addition, this review focuses on the role of lung epithelium in COPD pathology, and summarises underlying mechanisms and potential therapeutics.
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Antibacterial inhalation therapy with thiamphenicol glycinate acetylcysteinate in pulmonology
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01.01.2018 |
Kapustina V.
Ovcharenko S.
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Pulmonologiya |
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© 2018 National Research University Higher School of Economics. All rights reserved. Thiamphenicol glycinate acetylcysteinate (TGA) is a combination of thiamphenicol, a broad-spectrum antibiotic, and mucolytic drug N-acetylcysteine. This article is a review of pharmacological, microbiological, and clinical effects of this combined drug. Inhaled TGA could be considered as a worthy alternative for oral mucolytics and oral antibiotics in treatment of upper and lower airway diseases, such as acute and chronic rhinosinusitis, otitis media, tonsillitis, acute bronchitis, and acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease, in children and adults.
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LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical compound
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01.01.2018 |
Mesonzhnik N.
Moskaleva N.
Shestakova K.
Kurynina K.
Baranov P.
Gretskaya N.
Serkov I.
Lyubimov I.
Bezuglov V.
Appolonova S.
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Drug Metabolism Letters |
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1 |
Ссылка
© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.
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