Эпителий-протективная терапия при коморбидных заболеваниях. Практические рекомендации для врачей

Симаненков В.И., Маев И.В., Ткачева О.Н., Алексеенко С.А., Андреев Д.Н., Бакулина Н.В., Бакулин И.Г., Бордин Д.С., Власов Т.Д., Воробьева Н.М., Гриневич В.Б., Губонина И.В., Дробижев М.Ю., Ефремов Н.С., Каратеев А.Е., Котовская Ю.В., Кравчук Ю.А., Кривобородов Г.Г., Кульчавеня Е.В., Лила А.М., Маевская М.В., Некрасова А.С., Полуэктова Е.А., Попкова Т.В., Саблин О.А., Соловьева О.И., Суворов А.Н., Тарасова Г.Н., Трухан Д.И., Федотова А.В. Эпителий-протективная терапия при коморбидных заболеваниях. Практические рекомендации для врачей. Терапевтический архив. 2022;94(8):6–22.
DOI: 10.26442/00403660.2022.08.201523

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Simanenkov VI, Maev IV, Tkacheva ON, Alekseenko SA, Andreev DN, Bakulina NV, Bakulin IG, Bordin DS, Vlasov TD, Vorobyeva NM, Grinevich VB, Gubonina IV, Drobizhev MYu, Efremov NS, Karateev AE, Kotovskaya YuV, Kravchuk IA, Krivoborodov GG, Kulchavenya EV, Lila AM, Maevskaya MV, Nekrasova AS, Poluektova EA, Popkova TV, Sablin OA, Solovyeva OI, Suvorov AN, Tarasova GN, Trukhan DI, Fedotova AV. Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(8):6–22.
DOI: 10.26442/00403660.2022.08.201523

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Аннотация

Документ создан при поддержке Национальной медицинской Ассоциации по изучению Сочетанных Заболеваний (НАСЗ).
В 2021 г. опубликован первый национальный междисциплинарный консенсус, посвященный патофизиологическим и клиническим аспектам синдрома повышенной эпителиальной проницаемости. Предлагаемые рекомендации разработаны на базе этого консенсуса, тем же коллективом экспертов. Двадцать восемь положений практических рекомендаций для врачей приняты экспертным советом «дельфийским» методом. В рекомендациях с позиций медицины, основанной на доказательствах, рассмотрены такие основные группы эпителий-протективных лекарственных средств, как ингибиторы протонной помпы, препараты висмута, пробиотики. Детально представлены клинико-фармакологические характеристики такого универсального эпителиопротектора, как ребамипид, действующего на преэпителиальном, эпителиальном и субэпителиальном уровнях на всем протяжении желудочно-кишечного тракта.

Ключевые слова: коморбидные заболевания пищеварительной системы, синдром повышенной эпителиальной проницаемости, эпителий-протективная терапия, ребамипид

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This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС).
In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Keywords: comorbid diseases of the digestive system, increased epithelial permeability syndrome, epithelial protective therapy, rebamipide

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Список литературы

1. Симаненков В.И., Маев И.В., Ткачева О.Н., и др. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):2758 [Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):2758 (in Russian)]. DOI:10.15829/1728-8800-2021-2758
2. Robert A. Cytoprotection by prostaglandins. Gastroenterology. 1979;77(4 Pt. 1):761.
3. Андреева Н.С., Реброва О.Ю., Зорин Н.А., и др. Системы оценки достоверности научных доказательств и убедительности рекомендаций: сравнительная характеристика и перспективы унификации. Медицинские технологии. Оценка и выбор. 2012;4(10):10-24 [Andreeva N, Rebrova O, Zorin H, et al. Systems for Assessing the Reliability of Scientific Evidence and the Grades of Recommendations: Comparison and Prospects for Unification. Meditsinskie tekhnologii. Otsenka i vybor. 2012;4(10):10-24 (in Russian)].
4. Barnett K, Mercer SW, Norbury M, et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380(9836):37-43. DOI:10.1016/S0140-6736(12)60240-2
5. Лазебник Л.Б., Конев Ю.В. Исторические особенности и семантические трудности использования терминов, обозначающих множественность заболеваний у одного больного. Экспериментальная и клиническая гастроэнтерология. 2018;(6):4-9 [Lazebnik LB, Konev YuV. Historical features and semantic difficulties of using the terms denoting multiplicity of diseases in one patient. Experimental and Clinical Gastroenterology. 2018;(6):4-9 (in Russian)].
6. Оганов Р.Г., Симаненков В.И., Бакулин И.Г., и др. Коморбидная патология в клинической практике. Алгоритмы диагностики и лечения. Кардиоваскулярная терапия и профилактика. 2019;18(1):5-66 [Oganov RG, Simanenkov VI, Bakulin IG, et al. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Cardiovascular Therapy and Prevention. 2019;18(1):5-66 (in Russian)]. DOI:10.15829/1728-8800-2019-1-5-66
7. Kadambi S, Abdallah M, Loh KP. Multimorbidity, Function, and Cognition in Aging. Clin Geriatr Med. 2020;36(4):569-84. DOI:10.1016/j.cger.2020.06.002
8. Оганов Р.Г., Денисов И.Н., Симаненков В.И., и др. Коморбидная патология в клинической практике. Клинические рекомендации. Кардиоваскулярная терапия и профилактика. 2017;16(6):5-56 [Oganov RG, Denisov IN, Simanenkov VI, et al. Comorbidities in practice. Clinical guidelines. Cardiovascular Therapy and Prevention. 2017;16(6):5-56 (in Russian)]. DOI:10.15829/1728-8800-2017-6-5-56
9. Лазебник Л.Б., Голованова Е.В., Волель Б.А., и др. Функциональные заболевания органов пищеварения. Синдромы перекреста. Клинические рекомендации Российского Научного Медицинского Общества Терапевтов и Научного Общества Гастроэнтерологов России. Экспериментальная и клиническая гастроэнтерология. 2021;(8):5-117 [Lazebnik LB, Golovanova EV, Volel BA, et al. Functional gastrointestinal disorders. Overlap syndrome Clinical guidelines of the Russian Scientific Medical Society of Internal Medicine and Gastroenterological Scientific Society of Russia. Experimental and Clinical Gastroenterology. 2021;(8):5-117
(in Russian)]. DOI:10.31146/1682-8658-ecg-192-8-5-117
10. Black CH, Drossman D, Talley N, et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396(10263):1664-74.
DOI:10.1016/S0140-6736(20)32115-2
11. Richardson WS, Doster LM. Comorbidity and multimorbidity need to be placed in the context of a framework of risk, responsiveness, and vulnerability. J Clin Epidemiol. 2014;67(3):244-6. DOI:10.1016/j.jclinepi.2013.10.020
12. Talley NJ. What Causes Functional Gastrointestinal Disorders? A Proposed Disease Model. Am J Gastroenterol. 2020;115(1):41-8. DOI:10.14309/ajg.0000000000000485
13. Assimakopoulos SF, Triantos C, Maroulis I, Gogos C. The Role of the Gut Barrier Function in Health and Disease. Gastroenterology Res. 2018;11(4):261-3. DOI:10.14740/gr1053w
14. Kierszenbaum AL, Tres LL. Epithelium. Cell biology. In: Histology and Cell Biology: An Introduction to Pathology. Fifth Ed. Elsevier, 2020.
15. Ramena Y, Ramena G. Cell-Cell Junctions and Epithelial Differentiation. 2018;2:111.
16. Shashikanth N, Yeruva S, Ong MLDM, et al. Epithelial Organization: The Gut and Beyond. Compr Physiol. 2017;7(4):1497-518. DOI:10.1002/cphy.c170003
17. Dejana E, Bazzoni G, Lampugnani MG. Vascular Endothelial (VE)-Cadherin: Only an Intercellular Glue? Exp Cell Res. 1999;252(1):13-9. DOI:10.1006/excr.1999.4601
18. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869-901. DOI:10.1152/physrev.00035.2003
19. Duong CN, Vestweber D. Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin. Front Physiol. 2020;11:519. DOI:10.3389/fphys.2020.00519
20. Greene C, Hanley N, Campbell M. Claudin-5: gatekeeper of neurological function. Fluids Barriers CNS. 2019;16(1):3.
DOI:10.1186/s12987-019-0123-z
21. Komarova YA, Kruse K, Mehta D, Malik AB. Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability. Circ Res. 2017;120(1):179-206. DOI:10.1161/CIRCRESAHA.116.306534
22. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol. 2017;239:193-217. DOI:10.1007/164_2016_107
23. Al-Sadi R, Guo S, Ye D, et al. TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-kВ Pathway. Am J Pathol. 2016;186(5):1151-65. DOI:10.1016/j.ajpath.2015.12.016
24. Cunningham KE, Turner JR. Myosin light chain kinase: pulling the strings of epithelial tight junction function. Ann N Y Acad Sci. 2012;1258(1):34-42.
DOI:10.1111/j.1749-6632.2012.06526.x
25. Jacob C, Yang PC, Darmoul D, et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem. 2005;280(36):31936-48. DOI:10.1074/jbc.M506338200
26. Gangwar R, Meena AS, Shukla PK, et al. Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress. Biochem J. 2017;474(5):731-49. DOI:10.1042/BCJ20160679
27. Ohlsson L, Gustafsson A, Lavant E, et al. Leaky gut biomarkers in depression and suicidal behavior. Acta Psychiatr Scand. 2019;139(2):185-93. DOI:10.1111/acps.12978
28. Sochocka M, Donskow-Łysoniewska K, Diniz BS, et al. The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease – a Critical Review. Mol Neurobiol. 2019;56(3):1841-51. DOI:10.1007/s12035-018-1188-4
29. Schwiertz A, Spiegel J, Dillmann U, et al. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018;50:104-7. DOI:10.1016/j.parkreldis.2018.02.022
30. Nikiforova AS. Stress-induced gastrointestinal motility is responsible for epileptic susceptibility. Med Hypotheses. 2014;82(4):442-51. DOI:10.1016/j.mehy.2014.01.020
31. Crapser J, Ritzel R, Verma R, et al. Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice. Aging (Albany NY). 2016;8(5):1049-63. DOI:10.18632/aging.100952
32. Fyderek K, Strus M, Kowalska-Duplaga K, et al. Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J Gastroenterol. 2009;15(42):5287-94. DOI:10.3748/wjg.15.5287
33. Garcia-Hernandez V, Quiros M, Nusrat A. Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation. Ann N Y Acad Sci. 2017;1397(1):66-79. DOI:10.1111/nyas.13360
34. Zeissig S, Bürgel N, Günzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007;56(1):61-72. DOI:10.1136/gut.2006.094375
35. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49(6):1877-87. DOI:10.1002/hep.22848
36. Sinagra E, Pompei G, Tomasello G, et al. Inflammation in irritable bowel syndrome: Myth or new treatment target? World J Gastroenterol. 2016;22(7):2242-55. DOI:10.3748/wjg.v22.i7.224
37. Ulluwishewa D, Anderson R, McNabb W. Regulashion of tight junction permeability by intestinal bacteria and Dietary components. J Nutr. 2011;141(5):769-76. DOI:10.3945/jn.110.135657
38. Zhao Y, Chen F, Wu W, et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol. 2018;11(3):752-62. DOI:10.1038/mi.2017.118
39. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol. 2016;16(10):639-49. DOI:10.1038/nri.2016.88
40. Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients. 2020;12(4):1082. DOI:10.3390/nu12041082
41. Schoultz I, Keita ÅV. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability. Cells. 2020;9(8):1909. DOI:10.3390/cells9081909
42. De Munck TJI, Xu P, Verwijs HJA, et al. Intestinal permeability in human nonalcoholic fatty liver disease: A systematic review and meta-analysis. Liver Int. 2020;40(12):2906-16. DOI:10.1111/liv.14696
43. Якупова А.А., Абдулхаков С.Р., Залялов Р.К., и др. Методы оценки кишечной проницаемости: обзор литературы. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2021;31(1):20-30 [Iakupova AA, Abdulkhakov SR, Zalyalov RK, et al. Intestinal Permeability Assays: a Review. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(1):20-30 (in Russian)]. DOI:10.22416/1382-4376-2021-31-1-20-30
44. Xu S, Ilyas I, Little PJ, et al. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev. 2021;73(3):924-67. DOI:10.1124/pharmrev.120.000096
45. Ивашкин В.Т., Маев И.В., Лапина Т.Л., и др. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению инфекции Helicobacter pylori у взрослых. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2018;28(1):55-70 [Ivashkin VT, Mayev IV, Lapina TL, et al. Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(1):55-70 (in Russian)]. DOI:10.22416/1382-4376-2018-28-1-55-70
46. Prados-Torres A, Cura-González ID, Prados-Torres JD, et al. MULTIPAP Study: Improving healthcare for patients with multimorbidity. Br J Gen Pract. 2020;70(Suppl. 1):bjgp20X711257. DOI:10.3399/bjgp20X711257
47. Ивашкин В.Т., Маев И.В., Трухманов А.С., и др. Депрескрайбинг ингибиторов протонной помпы и выбор оптимального препарата данной группы (по результатам научного форума, состоявшегося в рамках XXVI Объединенной Российской гастроэнтерологической недели). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(6):7-18 [Ivashkin VT, Maev IV, Trukhmanov AS, et al. Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th
United Russian Gastroenterology Week). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(6):7-18 (in Russian)].
DOI:10.22416/1382-4376-2020-30-6-7-18
48. Симаненков В.И., Сундукова З.Р., Соловьева О.И. Возможности мультитаргетной терапии больных с синдромом раздраженного кишечника. Consilium Medicum. 2017;19(8-2):37-44 [Simanenkov VI, Sundukova ZR, Solovyeva OI. Complex therapy of irritable bowel syndrome. Consilium Medicum. 2017;19(8-2):37-44 (in Russian)]. DOI:10.26442/2075-1753_19.8.2.37-44
49. Yoshimura K, Delbarre SG, Kraus E, Boland CR. The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach. Aliment Pharmacol Ther. 1996;10(1):111-7. DOI:10.1111/j.1365-2036.1996.tb00184.x
50. Skoczylas T, Sarosiek I, Sostarich S, et al. Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders. Dig Dis Sci. 2003;48(2):322-8. DOI:10.1023/a:1021983611768
51. Jaworski T, Sarosiek I, Sostarich S, et al. Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance. Dig Dis Sci. 2005;50(2):357-65. DOI:10.1007/s10620-005-1611-3
52. Wauters L, Ceulemans M, Frings D, et al. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia. Gastroenterology. 2021;160(5):1521-31.e9. DOI:10.1053/j.gastro.2020.12.016
53. Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018;3(4):231-41. DOI:10.1016/S2468-1253(18)30037-2
54. Kim JH, Park SH, Cho CS, et al. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity. Gut Liver. 2014;8(4):371-9. DOI:10.5009/gnl.2014.8.4.371
55. Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991-2000. DOI:10.1007/s10620-013-2606-0
56. Pittayanon R, Piyachaturawat P, Rerknimitr R, et al. Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial. J Gastroenterol Hepatol. 2019;34(9):1517-22. DOI:10.1111/jgh.14671
57. Zhang WT, Wang MR, Hua GD, et al. Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis. Front Pharmacol. 2021;12:730681. DOI:10.3389/fphar.2021.730681
58. Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther. 2020;51(5):505-26. DOI:10.1111/apt.15604
59. Washio E, Esaki M, Maehata Y, et al. Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury: A Randomized, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2016;14(6):809-15.e1. DOI:10.1016/j.cgh.2015.10.022
60. Kurokawa S, Katsuki S, Fujita T, et al. A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol. 2014;49(2):239-44. DOI:10.1007/s00535-013-0805-261
61. Kim TJ, Kim ER, Hong SN, et al. Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users. Sci Rep. 2019;9(1):11696. DOI:10.1038/s41598-019-48173-6
62. Xu N, Zhang C, Jing L, et al. Protective effect and mechanism of rebamipide on NSAIDs associated small bowel injury. Int Immunopharmacol. 2021;90:107136. DOI:10.1016/j.intimp.2020.107136
63. Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota. PLoS One. 2021;16(1):e0245995. DOI:10.1371/journal.pone.0245995
64. Tsang CN, Ho KS, Sun H, Chan WT. Tracking Bismuth anti-ulcer drug uptake in single Helicobacter pylori cells. J Am Chem Soc. 2011;133(19):7355-7. DOI:10.1021/ja2013278
65. Konturek SJ, Radecki T, Piastucki I, et al. Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins. Gut. 1987;28(2):201-5. DOI:10.1136/gut.28.2.201
66. Пахомова И.Г. Новые возможности в минимизации риска НПВП-индуцированных гастропатий. РМЖ. 2014;10:772 [Pahomova IG. Novye vozmozhnosti v minimizatsii riska NPVP-indutsirovannykh gastropatii. RMZh. 2014;10:772 (in Russian)].
67. Ford AC, Malfertheiner P, Giguere M, et al. Adverse events with bismuth salts for Helicobacter pylori eradication: systematic review and meta-analysis. World J Gastroenterol. 2008;14(48):7361-70. DOI:10.3748/wjg.14.7361
68. Bismuth Salts for Gastrointestinal Issues: A Review of the Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2015.
69. Yan F, Polk DB. Probiotics and Probiotic-Derived Functional Factors – Mechanistic Insights Into Applications for Intestinal Homeostasis. Front Immunol. 2020;11:1428. DOI:10.3389/fimmu.2020.01428
70. Ramezani Ahmadi A, Sadeghian M, Alipour M, et al. The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis. Iran J Public Health. 2020;49(7):1222-31. DOI:10.18502/ijph.v49i7.3575
71. La Fata G, Weber P, Mohajeri MH. Probiotics and the Gut Immune System: Indirect Regulation. Probiotics Antimicrob Proteins. 2018;10(1):11-21. DOI:10.1007/s12602-017-9322-6
72. Shimura M, Mizuma M, Nakagawa K, et al. Probiotic-related bacteremia after major hepatectomy for biliary cancer: a report of two cases. Surg Case Rep. 2021;7(1):133.
DOI:10.1186/s40792-021-01216-5.75
73. Zhu L, Han J, Li L, et al. Claudin Family Participates in the Pathogenesis of Inflammatory Bowel Diseases and Colitis-Associated Colorectal Cancer. Front Immunol. 2019;10:1441.
DOI:10.3389/fimmu.2019.01441
74. Lin S, Shen Y. The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: a systematic review and meta-analysis based on 23 randomized studies. Int J Surg. 2020;84:69-77. DOI:10.1016/j.ijsu.2020.10.012
75. Liao W, Chen C, Wen T, Zhao Q. Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Gastroenterol. 2021;55(6):469-80. DOI:10.1097/MCG.0000000000001464
76. Wang S, Xu M, Wang W, et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016;11(8):e0161174. DOI:10.1371/journal.pone.0161174
77. Fecal Microbiota for Transplantation: Safety Alert – Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms, Posted 03.12.2020. Available at: https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission. Accessed: 08.03.2022.
78. Blesl A, Stadlbauer V. The Gut-Liver Axis in Cholestatic Liver Diseases. Nutrients. 2021;13(3):1018. DOI:10.3390/nu13031018
79. Lajczak-McGinley NK, Porru E, Fallon CM, et al. The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis. Physiol Rep. 2020;8(12):e14456. DOI:10.14814/phy2.14456
80. Wang Z, Chen J, Chen Z, et al. Clinical effects of ursodeoxycholic acid on patients with ulcerative colitis may improve via the regulation of IL-23-IL-17 axis and the changes of the proportion of intestinal microflora. Saudi J Gastroenterol. 2021;27(3):149-57. DOI:10.4103/sjg.SJG_462_20
81. Лищук Н.Б., Симаненков В.И., Тихонов С.В. Дифференцированная терапия «некислых» форм гастроэзофагеальной рефлюксной болезни. Терапевтический архив. 2017;89(4):57-63 [Lishchuk NB, Simanenkov VI, Tikhonov SV. Differentiation therapy for non-acidic gastroesophageal reflux disease. Terapevticheskii arkhiv (Ter. Arkh.). 2017;89(4):57-63 (in Russian)]. DOI:10.17116/terarkh201789457-63
82. Peng S, Huo X, Rezaei D, et al. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids. Am J Physiol Gastrointest Liver Physiol. 2014;307(2):G129-39. DOI:10.1152/ajpgi.00085.2014
83. Kim BT, Kim KM, Kim KN. The Effect of Ursodeoxycholic Acid on Small Intestinal Bacterial Overgrowth in Patients with Functional Dyspepsia: A Pilot Randomized Controlled Trial. Nutrients. 2020;12(5):1410. DOI:10.3390/nu12051410
84. Keely SJ, Steer CJ, Lajczak-McGinley NK. Ursodeoxycholic acid: a promising therapeutic target for inflammatory bowel diseases? Am J Physiol Gastrointest Liver Physiol. 2019;317(6):G872-81. DOI:10.1152/ajpgi.00163.2019
85. Golden JM, Escobar OH, Nguyen MVL, et al. Ursodeoxycholic acid protects against intestinal barrier breakdown by promoting enterocyte migration via EGFR- and COX-2-dependent mechanisms. Am J Physiol Gastrointest Liver Physiol. 2018;315(2):G259-71. DOI:10.1152/ajpgi.00354.2017
86. Звяглова М.Ю., Князев О.В., Парфенов А.И. Фармакологический и клинический профиль ребамипида: новые терапевтические мишени. Терапевтический архив. 2020;92(2):104-11 [Zvyaglova MYu, Knyazev OV, Parfenov AI. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Therapeutic Archive (Ter. Arkh.). 2020;92(2):104-11 (in Russian)]. DOI:10.26442/00403660.2020.02.000569
87. Markovic M, Zur M, Dahan A, Cvijić S. Biopharmaceutical characterization of rebamipide: The role of mucus binding in regional-dependent intestinal permeability. Eur J Pharm Sci. 2020;152:105440. DOI:10.1016/j.ejps.2020.105440
88. Kim CE, Kim YJ, Hwang MW, et al. Cevimeline-induced anti-inflammatory effect through upregulations of mucins in the ocular surface of a dry eye mouse model. Biomed Pharmacother. 2021;139:111571. DOI:10.1016/j.biopha.2021.111571
89. Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota. PLoS One. 2021;16(1):e0245995. DOI:10.1371/journal.pone.0245995
90. Lee JS, Jeon SW, Lee HS, et al. Rebamipide for the improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study. Dig Dis Sci. 2021. DOI:10.1007/s10620-021-07038-7
91. Cryer B. Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. Gastroenterol Clin North Am. 2001;30(4):877-vi.
DOI:10.1016/s0889-8553(05)70218-1
92. Suetsugu H, Ishihara S, Moriyama N, et al. Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med. 2000;136(1):50-7. DOI:10.1067/mlc.2000.107303
93. Tanigawa T, Watanabe T, Ohkawa F, et al. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr. 2011;48(2):149-53. DOI:10.3164/jcbn.10-75
94. Gweon TG, Park JH, Kim BW, et al. Incheon and Western Kyonggi Gastrointestinal Study. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut Liver. 2018;12(1):46-50. DOI:10.5009/gnl17078
95. Jaafar MH, Safi SZ, Tan MP, et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2018;63(5):1250-60. DOI:10.1007/s10620-017-4871-9
96. Del Valle-Pinero AY, Van Deventer HE, Fourie NH, et al. Gastrointestinal permeability in patients with irritable bowel syndrome assessed using a four probe permeability solution. Clin Chim Acta. 2013;418:97-101. DOI:10.1016/j.cca.2012.12.032
97. Симаненков В.И., Бакулина Н.В., Некрасова А.С., и др. Динамика клинических проявлений синдрома раздраженного кишечника на фоне применения цитопротектора ребамипида. Промежуточные результаты программы СОКРАТ. Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. 2021;13(3):75-82 [Simanenkov VI, Bakulina NV, Nekrasova AS, et al. Dynamics of clinical manifestations of irritable bowel syndrome against the back-ground of cytoprotector rebamipide intake: intermediate results of the SOKRAT program. Herald of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):75-82 (in Russian)]. DOI:10.17816/mechnikov88094
98. Ивашкин В.Т., Трухманов А.С., Гоник М.И. Применение ребамипида в лечении гастроэзофагеальной рефлюксной болезни. Терапевтический архив. 2020;92(4):98-104 [Ivashkin VT, Trukhmanov AS, Gonik MI. Rebamipide using in gastroesophageal reflux disease treatment. Terapevticheskii arkhiv (Ter. Arkh.). 2020;92(4):98-104
(in Russian)]. DOI:10.26442/00403660.2020.04.000568
99. Kim GH, Lee HL, Joo MK, et al. Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double-Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study. Gut Liver. 2021;15(6):841-50. DOI:10.5009/gnl20338
100. Liu J, Xiong Z, Geng X, Cui M. Rebamipide with Proton Pump Inhibitors (PPIs) versus PPIs Alone for the Treatment of Endoscopic Submucosal Dissection-Induced Ulcers: A Meta-analysis. Biomed Res Int. 2020;2020:7196782. DOI:10.1155/2020/7196782
101. Ивашкин В.Т., Маев И.В., Царьков П.В., и др. Диагностика и лечение язвенной болезни у взрослых (Клинические рекомендации Российской гастроэнтерологической ассоциации, Российского общества колоректальных хирургов и Российского эндоскопического общества). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(1):49-70 [Ivashkin VT, Maev IV, Tsarkov P, et al. Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):49-70 (in Russian)]. DOI:10.22416/1382-4376-2020-30-1-49-70
102. Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991-2000. DOI:10.1007/s10620-013-2606-0
103. Makiyama K, Takeshima F, Hamamoto T. Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report. Dig Dis Sci. 2005;50(12):2323-9. DOI:10.1007/s10620-005-3055-1
104. Honcharuk LM, Fediv OI, Hresko SO, et al. Analysis of long-term results of pathogenetic treatment of Helicobacter pylori-associated gastroduodenopathies induced by nonsteroidal anti-inflammatory drugs in patients with osteoarthritis. J Med Life. 2021;14(2):176-80. DOI:10.25122/jml-2020-0176
105. Andreev DN, Maev IV, Dicheva DT. Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies. J Clin Med. 2019;8(9):1498. DOI:10.3390/jcm8091498
106. Kamada T, Sato M, Tokutomi T, et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int. 2015;2015:865146. DOI:10.1155/2015/865146
107. Lawrance IC. Novel topical therapies for distal colitis. World J Gastrointest Pharmacol Ther. 2010;1(5):87-93. DOI:10.4292/wjgpt.v1.i5.87
108. Min DS. A Potential Efficacy of Rebamipide as Anti-gastric Cancer Drug. J Life Sci. 2016;26(10):1214-7. DOI:10.5352/JLS.2016.26.10.1214
109. Tanigawa T, Pai R, Arakawa T, Tarnawski A.S. Rebamipide Inhibits Gastric Cancer Cell Growth. Dig Dis Sci. 2007;52(1):240-7. DOI:10.1007/s10620-006-9226-x
110. Seo GH, Lee H. Chemopreventive Effect of Rebamipide against Gastric Cancer in Patients who undergo Endoscopic Resection for Early Gastric Neoplasms: A Nationwide Claims Study. Digestion. 2019;100(4):221-8. DOI:10.1159/000495288
111. Pimentel-Nunes P, Libânio D, Marcos-Pinto R, et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51(04):365-88. DOI:10.1055/a-0859-1883
112. Гриневич В.Б., Губонина И.В., Дощицин В.Л., и др. Особенности ведения коморбидных пациентов в период пандемии новой коронавирусной инфекции (COVID-19). Национальный Консенсус 2020. Кардиоваскулярная терапия и профилактика. 2020;19(4):2630 [Grinevich VB, Gubonina IV, Doshchitsin VL, et al. Management of patients with comorbidity during novel coronavirus (COVID-19) pandemic. National Consensus Statement 2020. Cardiovascular Therapy and Prevention. 2020;19(4):2630 (in Russian)].
DOI:10.15829/1728-8800-2020-2630
113. Ткачева О.Н., Котовская Ю.В., Алексанян Л.А., и др. Новая коронавирусная инфекция SARS-CoV-2 у пациентов пожилого и старческого возраста: особенности профилактики, диагностики и лечения. Согласованная позиция экспертов Российской ассоциации геронтологов и гериатров. Кардиоваскулярная терапия и профилактика. 2020;19(3):2601 [Tkacheva ON, Kotovskaya YuV, Aleksanyan LA, et al. Novel coronavirus infection SARS-CoV-2 in elderly and senile patients: prevention, diagnosis and treatment. Expert Position Paper of the Russian Association of Gerontology and Geriatrics. Cardiovascular Therapy and Prevention. 2020;19(3):2601 (in Russian)]. DOI:10.15829/1728-8800-2020-2601
114. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010;4(3):261-70. DOI:10.1586/egh.10.25
115. Toshikazu Y. Rebamipide: a gastrointestinal protective drug with pleiotropic activities Expert Rev. Gastroenterol Hepatol. 2010;4(3):261-70. DOI:10.1586 / egh.10.25
116. Seo GH, Lee H. Chemopreventive Effect of Rebamipide against Gastric Cancer in Patients who undergo Endoscopic Resection for Early Gastric Neoplasms: A Nationwide Claims Study. Digestion. 2019;100(4):221-8. DOI:10.1159/000495288

________________________________________________

1. Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):2758 (in Russian). DOI:10.15829/1728-8800-2021-2758
2. Robert A. Cytoprotection by prostaglandins. Gastroenterology. 1979;77(4 Pt. 1):761.
3. Andreeva N, Rebrova O, Zorin H, et al. Systems for Assessing the Reliability of Scientific Evidence and the Grades of Recommendations: Comparison and Prospects for Unification. Meditsinskie tekhnologii. Otsenka i vybor. 2012;4(10):10-24 (in Russian).
4. Barnett K, Mercer SW, Norbury M, et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380(9836):37-43. DOI:10.1016/S0140-6736(12)60240-2
5. Lazebnik LB, Konev YuV. Historical features and semantic difficulties of using the terms denoting multiplicity of diseases in one patient. Experimental and Clinical Gastroenterology. 2018;(6):4-9 (in Russian).
6. Oganov RG, Simanenkov VI, Bakulin IG, et al. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Cardiovascular Therapy and Prevention. 2019;18(1):5-66 (in Russian). DOI:10.15829/1728-8800-2019-1-5-66
7. Kadambi S, Abdallah M, Loh KP. Multimorbidity, Function, and Cognition in Aging. Clin Geriatr Med. 2020;36(4):569-84. DOI:10.1016/j.cger.2020.06.002
8. Oganov RG, Denisov IN, Simanenkov VI, et al. Comorbidities in practice. Clinical guidelines. Cardiovascular Therapy and Prevention. 2017;16(6):5-56 (in Russian).
DOI:10.15829/1728-8800-2017-6-5-56
9. Lazebnik LB, Golovanova EV, Volel BA, et al. Functional gastrointestinal disorders. Overlap syndrome Clinical guidelines of the Russian Scientific Medical Society of Internal Medicine and Gastroenterological Scientific Society of Russia. Experimental and Clinical Gastroenterology. 2021;(8):5-117 (in Russian). DOI:10.31146/1682-8658-ecg-192-8-5-117
10. Black CH, Drossman D, Talley N, et al. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396(10263):1664-74.
DOI:10.1016/S0140-6736(20)32115-2
11. Richardson WS, Doster LM. Comorbidity and multimorbidity need to be placed in the context of a framework of risk, responsiveness, and vulnerability. J Clin Epidemiol. 2014;67(3):244-6. DOI:10.1016/j.jclinepi.2013.10.020
12. Talley NJ. What Causes Functional Gastrointestinal Disorders? A Proposed Disease Model. Am J Gastroenterol. 2020;115(1):41-8. DOI:10.14309/ajg.0000000000000485
13. Assimakopoulos SF, Triantos C, Maroulis I, Gogos C. The Role of the Gut Barrier Function in Health and Disease. Gastroenterology Res. 2018;11(4):261-3. DOI:10.14740/gr1053w
14. Kierszenbaum AL, Tres LL. Epithelium. Cell biology. In: Histology and Cell Biology: An Introduction to Pathology. Fifth Ed. Elsevier, 2020.
15. Ramena Y, Ramena G. Cell-Cell Junctions and Epithelial Differentiation. 2018;2:111.
16. Shashikanth N, Yeruva S, Ong MLDM, et al. Epithelial Organization: The Gut and Beyond. Compr Physiol. 2017;7(4):1497-518. DOI:10.1002/cphy.c170003
17. Dejana E, Bazzoni G, Lampugnani MG. Vascular Endothelial (VE)-Cadherin: Only an Intercellular Glue? Exp Cell Res. 1999;252(1):13-9. DOI:10.1006/excr.1999.4601
18. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869-901. DOI:10.1152/physrev.00035.2003
19. Duong CN, Vestweber D. Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin. Front Physiol. 2020;11:519. DOI:10.3389/fphys.2020.00519
20. Greene C, Hanley N, Campbell M. Claudin-5: gatekeeper of neurological function. Fluids Barriers CNS. 2019;16(1):3. DOI:10.1186/s12987-019-0123-z
21. Komarova YA, Kruse K, Mehta D, Malik AB. Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability. Circ Res. 2017;120(1):179-206. DOI:10.1161/CIRCRESAHA.116.306534
22. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol. 2017;239:193-217. DOI:10.1007/164_2016_107
23. Al-Sadi R, Guo S, Ye D, et al. TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-kВ Pathway. Am J Pathol. 2016;186(5):1151-65. DOI:10.1016/j.ajpath.2015.12.016
24. Cunningham KE, Turner JR. Myosin light chain kinase: pulling the strings of epithelial tight junction function. Ann N Y Acad Sci. 2012;1258(1):34-42.
DOI:10.1111/j.1749-6632.2012.06526.x
25. Jacob C, Yang PC, Darmoul D, et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem. 2005;280(36):31936-48. DOI:10.1074/jbc.M506338200
26. Gangwar R, Meena AS, Shukla PK, et al. Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress. Biochem J. 2017;474(5):731-49. DOI:10.1042/BCJ20160679
27. Ohlsson L, Gustafsson A, Lavant E, et al. Leaky gut biomarkers in depression and suicidal behavior. Acta Psychiatr Scand. 2019;139(2):185-93. DOI:10.1111/acps.12978
28. Sochocka M, Donskow-Łysoniewska K, Diniz BS, et al. The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease – a Critical Review. Mol Neurobiol. 2019;56(3):1841-51. DOI:10.1007/s12035-018-1188-4
29. Schwiertz A, Spiegel J, Dillmann U, et al. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018;50:104-7. DOI:10.1016/j.parkreldis.2018.02.022
30. Nikiforova AS. Stress-induced gastrointestinal motility is responsible for epileptic susceptibility. Med Hypotheses. 2014;82(4):442-51. DOI:10.1016/j.mehy.2014.01.020
31. Crapser J, Ritzel R, Verma R, et al. Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice. Aging (Albany NY). 2016;8(5):1049-63. DOI:10.18632/aging.100952
32. Fyderek K, Strus M, Kowalska-Duplaga K, et al. Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J Gastroenterol. 2009;15(42):5287-94. DOI:10.3748/wjg.15.5287
33. Garcia-Hernandez V, Quiros M, Nusrat A. Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation. Ann N Y Acad Sci. 2017;1397(1):66-79. DOI:10.1111/nyas.13360
34. Zeissig S, Bürgel N, Günzel D, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007;56(1):61-72. DOI:10.1136/gut.2006.094375
35. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49(6):1877-87. DOI:10.1002/hep.22848
36. Sinagra E, Pompei G, Tomasello G, et al. Inflammation in irritable bowel syndrome: Myth or new treatment target? World J Gastroenterol. 2016;22(7):2242-55. DOI:10.3748/wjg.v22.i7.224
37. Ulluwishewa D, Anderson R, McNabb W. Regulashion of tight junction permeability by intestinal bacteria and Dietary components. J Nutr. 2011;141(5):769-76. DOI:10.3945/jn.110.135657
38. Zhao Y, Chen F, Wu W, et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol. 2018;11(3):752-62. DOI:10.1038/mi.2017.118
39. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol. 2016;16(10):639-49. DOI:10.1038/nri.2016.88
40. Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients. 2020;12(4):1082. DOI:10.3390/nu12041082
41. Schoultz I, Keita ÅV. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability. Cells. 2020;9(8):1909. DOI:10.3390/cells9081909
42. De Munck TJI, Xu P, Verwijs HJA, et al. Intestinal permeability in human nonalcoholic fatty liver disease: A systematic review and meta-analysis. Liver Int. 2020;40(12):2906-16. DOI:10.1111/liv.14696
43. Iakupova AA, Abdulkhakov SR, Zalyalov RK, et al. Intestinal Permeability Assays: a Review. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(1):20-30 (in Russian). DOI:10.22416/1382-4376-2021-31-1-20-30
44. Xu S, Ilyas I, Little PJ, et al. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev. 2021;73(3):924-67. DOI:10.1124/pharmrev.120.000096
45. Ivashkin VT, Mayev IV, Lapina TL, et al. Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(1):55-70 (in Russian). DOI:10.22416/1382-4376-2018-28-1-55-70
46. Prados-Torres A, Cura-González ID, Prados-Torres JD, et al. MULTIPAP Study: Improving healthcare for patients with multimorbidity. Br J Gen Pract. 2020;70(Suppl. 1):bjgp20X711257. DOI:10.3399/bjgp20X711257
47. Ivashkin VT, Maev IV, Trukhmanov AS, et al. Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th United Russian Gastroenterology Week). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(6):7-18 (in Russian). DOI:10.22416/1382-4376-2020-30-6-7-18
48. Simanenkov VI, Sundukova ZR, Solovyeva OI. Complex therapy of irritable bowel syndrome. Consilium Medicum. 2017;19(8-2):37-44 (in Russian).
DOI:10.26442/2075-1753_19.8.2.37-44
49. Yoshimura K, Delbarre SG, Kraus E, Boland CR. The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach. Aliment Pharmacol Ther. 1996;10(1):111-7. DOI:10.1111/j.1365-2036.1996.tb00184.x
50. Skoczylas T, Sarosiek I, Sostarich S, et al. Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders. Dig Dis Sci. 2003;48(2):322-8. DOI:10.1023/a:1021983611768
51. Jaworski T, Sarosiek I, Sostarich S, et al. Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance. Dig Dis Sci. 2005;50(2):357-65. DOI:10.1007/s10620-005-1611-3
52. Wauters L, Ceulemans M, Frings D, et al. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia. Gastroenterology. 2021;160(5):1521-31.e9. DOI:10.1053/j.gastro.2020.12.016
53. Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018;3(4):231-41. DOI:10.1016/S2468-1253(18)30037-2
54. Kim JH, Park SH, Cho CS, et al. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity. Gut Liver. 2014;8(4):371-9. DOI:10.5009/gnl.2014.8.4.371
55. Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991-2000. DOI:10.1007/s10620-013-2606-0
56. Pittayanon R, Piyachaturawat P, Rerknimitr R, et al. Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial. J Gastroenterol Hepatol. 2019;34(9):1517-22. DOI:10.1111/jgh.14671
57. Zhang WT, Wang MR, Hua GD, et al. Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis. Front Pharmacol. 2021;12:730681. DOI:10.3389/fphar.2021.730681
58. Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther. 2020;51(5):505-26. DOI:10.1111/apt.15604
59. Washio E, Esaki M, Maehata Y, et al. Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury: A Randomized, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2016;14(6):809-15.e1. DOI:10.1016/j.cgh.2015.10.022
60. Kurokawa S, Katsuki S, Fujita T, et al. A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol. 2014;49(2):239-44. DOI:10.1007/s00535-013-0805-261
61. Kim TJ, Kim ER, Hong SN, et al. Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users. Sci Rep. 2019;9(1):11696. DOI:10.1038/s41598-019-48173-6
62. Xu N, Zhang C, Jing L, et al. Protective effect and mechanism of rebamipide on NSAIDs associated small bowel injury. Int Immunopharmacol. 2021;90:107136. DOI:10.1016/j.intimp.2020.107136
63. Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota. PLoS One. 2021;16(1):e0245995. DOI:10.1371/journal.pone.0245995
64. Tsang CN, Ho KS, Sun H, Chan WT. Tracking Bismuth anti-ulcer drug uptake in single Helicobacter pylori cells. J Am Chem Soc. 2011;133(19):7355-7. DOI:10.1021/ja2013278
65. Konturek SJ, Radecki T, Piastucki I, et al. Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins. Gut. 1987;28(2):201-5. DOI:10.1136/gut.28.2.201
66. Пахомова И.Г. Новые возможности в минимизации риска НПВП-индуцированных гастропатий. РМЖ. 2014;10:772 [Pahomova IG. Novye vozmozhnosti v minimizatsii riska NPVP-indutsirovannykh gastropatii. RMZh. 2014;10:772 (in Russian)].
67. Ford AC, Malfertheiner P, Giguere M, et al. Adverse events with bismuth salts for Helicobacter pylori eradication: systematic review and meta-analysis. World J Gastroenterol. 2008;14(48):7361-70. DOI:10.3748/wjg.14.7361
68. Bismuth Salts for Gastrointestinal Issues: A Review of the Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2015.
69. Yan F, Polk DB. Probiotics and Probiotic-Derived Functional Factors – Mechanistic Insights Into Applications for Intestinal Homeostasis. Front Immunol. 2020;11:1428. DOI:10.3389/fimmu.2020.01428
70. Ramezani Ahmadi A, Sadeghian M, Alipour M, et al. The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis. Iran J Public Health. 2020;49(7):1222-31. DOI:10.18502/ijph.v49i7.3575
71. La Fata G, Weber P, Mohajeri MH. Probiotics and the Gut Immune System: Indirect Regulation. Probiotics Antimicrob Proteins. 2018;10(1):11-21. DOI:10.1007/s12602-017-9322-6
72. Shimura M, Mizuma M, Nakagawa K, et al. Probiotic-related bacteremia after major hepatectomy for biliary cancer: a report of two cases. Surg Case Rep. 2021;7(1):133.
DOI:10.1186/s40792-021-01216-5.75
73. Zhu L, Han J, Li L, et al. Claudin Family Participates in the Pathogenesis of Inflammatory Bowel Diseases and Colitis-Associated Colorectal Cancer. Front Immunol. 2019;10:1441.
DOI:10.3389/fimmu.2019.01441
74. Lin S, Shen Y. The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: a systematic review and meta-analysis based on 23 randomized studies. Int J Surg. 2020;84:69-77. DOI:10.1016/j.ijsu.2020.10.012
75. Liao W, Chen C, Wen T, Zhao Q. Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Gastroenterol. 2021;55(6):469-80. DOI:10.1097/MCG.0000000000001464
76. Wang S, Xu M, Wang W, et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016;11(8):e0161174. DOI:10.1371/journal.pone.0161174
77. Fecal Microbiota for Transplantation: Safety Alert – Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms, Posted 03.12.2020. Available at: https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission. Accessed: 08.03.2022.
78. Blesl A, Stadlbauer V. The Gut-Liver Axis in Cholestatic Liver Diseases. Nutrients. 2021;13(3):1018. DOI:10.3390/nu13031018
79. Lajczak-McGinley NK, Porru E, Fallon CM, et al. The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis. Physiol Rep. 2020;8(12):e14456. DOI:10.14814/phy2.14456
80. Wang Z, Chen J, Chen Z, et al. Clinical effects of ursodeoxycholic acid on patients with ulcerative colitis may improve via the regulation of IL-23-IL-17 axis and the changes of the proportion of intestinal microflora. Saudi J Gastroenterol. 2021;27(3):149-57. DOI:10.4103/sjg.SJG_462_20
81. Lishchuk NB, Simanenkov VI, Tikhonov SV. Differentiation therapy for non-acidic gastroesophageal reflux disease. Terapevticheskii arkhiv (Ter. Arkh.). 2017;89(4):57-63 (in Russian). DOI:10.17116/terarkh201789457-63
82. Peng S, Huo X, Rezaei D, et al. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids. Am J Physiol Gastrointest Liver Physiol. 2014;307(2):G129-39. DOI:10.1152/ajpgi.00085.2014
83. Kim BT, Kim KM, Kim KN. The Effect of Ursodeoxycholic Acid on Small Intestinal Bacterial Overgrowth in Patients with Functional Dyspepsia: A Pilot Randomized Controlled Trial. Nutrients. 2020;12(5):1410. DOI:10.3390/nu12051410
84. Keely SJ, Steer CJ, Lajczak-McGinley NK. Ursodeoxycholic acid: a promising therapeutic target for inflammatory bowel diseases? Am J Physiol Gastrointest Liver Physiol. 2019;317(6):G872-81. DOI:10.1152/ajpgi.00163.2019
85. Golden JM, Escobar OH, Nguyen MVL, et al. Ursodeoxycholic acid protects against intestinal barrier breakdown by promoting enterocyte migration via EGFR- and COX-2-dependent mechanisms. Am J Physiol Gastrointest Liver Physiol. 2018;315(2):G259-71. DOI:10.1152/ajpgi.00354.2017
86. Zvyaglova MYu, Knyazev OV, Parfenov AI. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Therapeutic Archive (Ter. Arkh.). 2020;92(2):104-11 (in Russian). DOI:10.26442/00403660.2020.02.000569
87. Markovic M, Zur M, Dahan A, Cvijić S. Biopharmaceutical characterization of rebamipide: The role of mucus binding in regional-dependent intestinal permeability. Eur J Pharm Sci. 2020;152:105440. DOI:10.1016/j.ejps.2020.105440
88. Kim CE, Kim YJ, Hwang MW, et al. Cevimeline-induced anti-inflammatory effect through upregulations of mucins in the ocular surface of a dry eye mouse model. Biomed Pharmacother. 2021;139:111571. DOI:10.1016/j.biopha.2021.111571
89. Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota. PLoS One. 2021;16(1):e0245995. DOI:10.1371/journal.pone.0245995
90. Lee JS, Jeon SW, Lee HS, et al. Rebamipide for the improvement of Gastric Atrophy and Intestinal Metaplasia: A Prospective, Randomized, Pilot Study. Dig Dis Sci. 2021. DOI:10.1007/s10620-021-07038-7
91. Cryer B. Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. Gastroenterol Clin North Am. 2001;30(4):877-vi.
DOI:10.1016/s0889-8553(05)70218-1
92. Suetsugu H, Ishihara S, Moriyama N, et al. Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med. 2000;136(1):50-7. DOI:10.1067/mlc.2000.107303
93. Tanigawa T, Watanabe T, Ohkawa F, et al. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr. 2011;48(2):149-53. DOI:10.3164/jcbn.10-75
94. Gweon TG, Park JH, Kim BW, et al. Incheon and Western Kyonggi Gastrointestinal Study. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut Liver. 2018;12(1):46-50. DOI:10.5009/gnl17078
95. Jaafar MH, Safi SZ, Tan MP, et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2018;63(5):1250-60. DOI:10.1007/s10620-017-4871-9
96. Del Valle-Pinero AY, Van Deventer HE, Fourie NH, et al. Gastrointestinal permeability in patients with irritable bowel syndrome assessed using a four probe permeability solution. Clin Chim Acta. 2013;418:97-101. DOI:10.1016/j.cca.2012.12.032
97. Simanenkov VI, Bakulina NV, Nekrasova AS, et al. Dynamics of clinical manifestations of irritable bowel syndrome against the back-ground of cytoprotector rebamipide intake: intermediate results of the SOKRAT program. Herald of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):75-82 (in Russian). DOI:10.17816/mechnikov88094
98. Ivashkin VT, Trukhmanov AS, Gonik MI. Rebamipide using in gastroesophageal reflux disease treatment. Terapevticheskii arkhiv (Ter. Arkh.). 2020;92(4):98-104
(in Russian). DOI:10.26442/00403660.2020.04.000568
99. Kim GH, Lee HL, Joo MK, et al. Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double-Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study. Gut Liver. 2021;15(6):841-50. DOI:10.5009/gnl20338
100. Liu J, Xiong Z, Geng X, Cui M. Rebamipide with Proton Pump Inhibitors (PPIs) versus PPIs Alone for the Treatment of Endoscopic Submucosal Dissection-Induced Ulcers: A Meta-analysis. Biomed Res Int. 2020;2020:7196782. DOI:10.1155/2020/7196782
101. Ivashkin VT, Maev IV, Tsarkov P, et al. Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):49-70 (in Russian).
DOI:10.22416/1382-4376-2020-30-1-49-70
102. Zhang S, Qing Q, Bai Y, et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991-2000. DOI:10.1007/s10620-013-2606-0
103. Makiyama K, Takeshima F, Hamamoto T. Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report. Dig Dis Sci. 2005;50(12):2323-9. DOI:10.1007/s10620-005-3055-1
104. Honcharuk LM, Fediv OI, Hresko SO, et al. Analysis of long-term results of pathogenetic treatment of Helicobacter pylori-associated gastroduodenopathies induced by nonsteroidal anti-inflammatory drugs in patients with osteoarthritis. J Med Life. 2021;14(2):176-80. DOI:10.25122/jml-2020-0176
105. Andreev DN, Maev IV, Dicheva DT. Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies. J Clin Med. 2019;8(9):1498. DOI:10.3390/jcm8091498
106. Kamada T, Sato M, Tokutomi T, et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int. 2015;2015:865146. DOI:10.1155/2015/865146
107. Lawrance IC. Novel topical therapies for distal colitis. World J Gastrointest Pharmacol Ther. 2010;1(5):87-93. DOI:10.4292/wjgpt.v1.i5.87
108. Min DS. A Potential Efficacy of Rebamipide as Anti-gastric Cancer Drug. J Life Sci. 2016;26(10):1214-7. DOI:10.5352/JLS.2016.26.10.1214
109. Tanigawa T, Pai R, Arakawa T, Tarnawski A.S. Rebamipide Inhibits Gastric Cancer Cell Growth. Dig Dis Sci. 2007;52(1):240-7. DOI:10.1007/s10620-006-9226-x
110. Seo GH, Lee H. Chemopreventive Effect of Rebamipide against Gastric Cancer in Patients who undergo Endoscopic Resection for Early Gastric Neoplasms: A Nationwide Claims Study. Digestion. 2019;100(4):221-8. DOI:10.1159/000495288
111. Pimentel-Nunes P, Libânio D, Marcos-Pinto R, et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51(04):365-88. DOI:10.1055/a-0859-1883
112. Grinevich VB, Gubonina IV, Doshchitsin VL, et al. Management of patients with comorbidity during novel coronavirus (COVID-19) pandemic. National Consensus Statement 2020. Cardiovascular Therapy and Prevention. 2020;19(4):2630 (in Russian). DOI:10.15829/1728-8800-2020-2630
113. Tkacheva ON, Kotovskaya YuV, Aleksanyan LA, et al. Novel coronavirus infection SARS-CoV-2 in elderly and senile patients: prevention, diagnosis and treatment. Expert Position Paper of the Russian Association of Gerontology and Geriatrics. Cardiovascular Therapy and Prevention. 2020;19(3):2601 (in Russian). DOI:10.15829/1728-8800-2020-2601
114. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010;4(3):261-70. DOI:10.1586/egh.10.25
115. Toshikazu Y. Rebamipide: a gastrointestinal protective drug with pleiotropic activities Expert Rev. Gastroenterol Hepatol. 2010;4(3):261-70. DOI:10.1586 / egh.10.25
116. Seo GH, Lee H. Chemopreventive Effect of Rebamipide against Gastric Cancer in Patients who undergo Endoscopic Resection for Early Gastric Neoplasms: A Nationwide Claims Study. Digestion. 2019;100(4):221-8. DOI:10.1159/000495288

Авторы

В.И. Симаненков*1, И.В. Маев2, О.Н. Ткачева3, С.А. Алексеенко4, Д.Н. Андреев2, Н.В. Бакулина1, И.Г. Бакулин1, Д.С. Бордин2,5,6, Т.Д. Власов7, Н.М. Воробьева3, В.Б. Гриневич8, И.В. Губонина8, М.Ю. Дробижев9, Н.С. Ефремов3,10, А.Е. Каратеев11, Ю.В. Котовская3, Ю.А. Кравчук8, Г.Г. Кривобородов3,10, Е.В. Кульчавеня12,13, А.М. Лила11,14, М.В. Маевская15, А.С. Некрасова1, Е.А. Полуэктова15, Т.В. Попкова11, О.А. Саблин16, О.И. Соловьева1, А.Н. Суворов17, Г.Н. Тарасова18, Д.И. Трухан19, А.В. Федотова10

1 ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
3 ОСП «Российский геронтологический научно-клинический центр» ФГАОУ ВО «Российский национальный исследовательский
медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
4 ФГБОУ ВО «Дальневосточный государственный медицинский университет» Минздрава России, Хабаровск, Россия;
5 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия;
6 ФГБОУ ВО «Тверской государственный медицинский университет», Тверь, Россия;
7 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Санкт-Петербург, Россия;
8 ФГБВОУ ВО «Военно-медицинская академия имени С.М. Кирова» Минобороны России, Санкт-Петербург, Россия;
9 ФГБНУ «Национальный научно-исследовательский институт общественного здоровья им. Н.А. Семашко», Москва, Россия;
10 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
11 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
12 ФГБУ «Новосибирский научно-исследовательский институт туберкулеза» Минздрава России, Новосибирск, Россия;
13 ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России, Новосибирск, Россия;
14 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
15 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
16 ФГБУ «Всероссийский центр экстренной и радиационной медицины им. А.М. Никифорова» МЧС России, Санкт-Петербург, Россия;
17 ФГБНУ «Институт экспериментальной медицины» РАН, Санкт-Петербург, Россия;
18 ФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России, Ростов-на-Дону, Россия;
19 ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия
*visimanenkov@mail.ru

________________________________________________

Vladimir I. Simanenkov*1, Igor V. Maev2, Olga N. Tkacheva3, Sergei A. Alekseenko4, Dmitry N. Andreev2, Natalia V. Bakulina1, Igor G. Bakulin1, Dmitry S. Bordin2,5,6, Timur D. Vlasov7, Natalya M. Vorobyeva3, Vladimir B. Grinevich8, Irina V. Gubonina8, Michail Yu. Drobizhev9, Nikolay S. Efremov3,10, Andrey E. Karateev11, Yulia V. Kotovskaya3, Iurii A. Kravchuk8, Grigory G. Krivoborodov3,10, Ekaterina V. Kulchavenya12,13, Aleksander M. Lila11,14, Marina V. Maevskaya15, Anna S. Nekrasova1, Elena A. Poluektova15, Tatiana V. Popkova11, Oleg A. Sablin16, Olga I. Solovyeva1, Alexander N. Suvorov17, Galina N. Tarasova18, Dmity I. Trukhan19, Anastasia V. Fedotova10

1 Mechnikov North-Western State Medical University, Saint Petersburg, Russia;
2 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
3 Russian Clinical and Research Center of Gerontology of Pirogov Russian National Research Medical University, Moscow, Russia;
4 Far-East State Medical University, Khabarovsk, Russia;
5 Loginov Moscow Clinical Scientific Center, Moscow, Russia;
6 Tver State Medical University, Tver, Russia;
7 Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia;
8 Kirov Military Medical Academy, Saint Petersburg, Russia;
9 Semashko National Research Institute of Public Health, Moscow, Russia;
10 Pirogov Russian National Research Medical University, Moscow, Russia;
11 Nasonova Research Institute of Rheumatology, Moscow, Russia;
12 Novosibirsk Research Institute of Tuberculosis, Novosibirsk, Russia;
13 Novosibirsk State Medical University, Novosibirsk, Russia;
14 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
15 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
16 Nikiforov All-Russian Center for Emergency and Radiation Medicine, Saint Petersburg, Russia;
17 Institute of Experimental Medicine, Saint Petersburg, Russia;
18 Rostov State Medical University, Rostov on Don, Russia;
19 Omsk State Medical University, Omsk, Russia
*visimanenkov@mail.ru

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