Рассеянный склероз (РС) – это аутоиммунное заболевание, поражающее центральную нервную систему и являющееся основной причиной инвалидизации трудоспособных молодых людей. В последнее время широко обсуждаются вопросы влияния витамина D на риск возникновения и клиническое течение РС. В обзоре рассмотрены патогенез этого заболевания и предположительные механизмы влияния на него холекальциферола, представлены современные данные о влиянии уровня витамина D на риск развития РС, течение и исход этого заболевания.
Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system and is a major cause of disability in able-bodied young people. Recently, the question of the effect of vitamin D on the risk of occurrence and clinical course of MS has been widely discussed. The review presents pathogenesis of this disease and estimated mechanisms of the effect of cholecalciferol on it, current data on the effect of vitamin D levels on the risk of MS, the course and outcome of this disease.
1. Boyko A, Smirnova N, Petrov S, Gusev E. Epidemiology of MS in Russia, a historical review. Mult Scler Demyelinating Disord. 2016; 1: 1–6. DOI: 10.1186/s40893-016-0016-9
2. Попова Е., Бойко А., Барабанова М. Первично-прогрессирующий рассеянный склероз: современное состояние проблемы своевременной постановки диагноза. Журнал неврологии и психиатрии им. С.С. Корсакова. 2017; 117: 35–40 [Popova E, Boyko A, Barabanova M. Primary progressive multiple sclerosis: Current issues of timely diagnosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2017; 117: 35–40 (in Russian)]. DOI: 10.17116/jnevro201711710235-40
3. Feige J, Moser T, Bieler L, et al. Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020; 12 (3): 783. DOI: 10.3390/nu12030783
4. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15: 545–58. DOI: 10.1038/nri3871
5. Beckmann Y, Türe S, Duman SU. Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients. EPMA Journal. 2020;11: 65–72. DOI: 10.1007/s13167-019-00191-0
6. Tarlinton RE, Khaibullin T, Granatov E, et al. The interaction between viral and environmental risk factors in the pathogenesis of multiple sclerosis. Int J Mol Sci. 2019; 20 (2): 303. DOI: 10.3390/ijms20020303
7. Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019; 26 (1): 27–40. DOI: 10.1111/ene.13819
8. Thompson AJ, Baranzini SE, Geurts J, Hemmer B. Multiple sclerosis. Lancet. 2018; 391 (10130): 1622–36. DOI: 10.1016/S0140-6736(18)30481-1
9. Sospedra M, Martin R. Immunology of Multiple Sclerosis. Semin Neurol. 2016; 36 (02): 115–27. DOI: 10.1055/s-0036-1579739
10. Miclea A, Bagnoud M, Chan A, Hoepner R. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol. 2020: 781. DOI: 10.3389/fimmu.2020.00781
11. Витебская А.В., Тихая М.И. Дефицит витамина D и аутоиммунные заболевания. Доктор.ру. 2017; 4 (133): 45–8 [Vitebskaya AV, Tikhaya MI. Vitamin D Deficiency and Autoimmune Diseases. Doctor.ru. 2017; 4 (133): 45–8 (in Russian)].
12. Парахонский А.П. Иммуномодулирующие эффекты витамина D. Заметки ученого. 2015: 180–7 [Parakhonsky AP. The immunomodulating effects of vitamin D. Zametki uchenogo. 2015: 180–7 (in Russian)].
13. Smolders J, Torkildsen, Camu W. An Update on Vitamin D and Disease Activity in Multiple Sclerosis. CNS Drugs. 2019; 33: 1187–99. DOI: 10.1007/s40263-019-00674-8
14. Каронова Т.Л., Шмонина И.А., Тотолян Н.А. Рассеянный склероз и уровень обеспеченности витамином D. Артериальная гипертензия. 2015; 21 (2): 121–9 [Karonova TL, Shmonina IA, Totolyan NA. Multiple sclerosis and vitamin D status. Arterial’naya gipertenziya. 2015; 21 (2): 121–9 (in Russian)]. DOI: 10.18705/1607-419X-2015-21-2-121-129
15. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurology. 2015; 28 (3): 206–19. DOI: 10.1097/WCO.0000000000000205
16. Пигарова Е.А., Плещева А.В. Влияние витамина D на иммунную систему. Иммунология. 2015; 1: 62–6 [Pigarova EA, Pleshcheva AV. Influence of vitamin D on the immune system. Immunologya. 2015; 1: 62–6 (in Russian)].
17. Пигарова Е.А., Петрушкина А.А. Неклассические эффекты витамина D. Остеопороз и остеопатии. 2017; 20 (3): 90–101 [Pigarova EA, Petrushkina AA. Non-classical effects of vitamin D. Osteoporosis and Bone Desiases. 2017; 20 (3): 90–101 (in Russian)].
18. Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: An update. Mult Scler Relat Disord. 2017; 14: 35–45. DOI: 10.1016/j.msard.2017.03.014
19. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010; 9 (7): 727–39. DOI: 10.1016/S1474-4422(10)70094-6
20. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004; 62 (1): 60–5. DOI: 10.1212/01.WNL.0000101723.79681.38
21. Munger KL, Levin LI, Hollis BW, et al. A Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296 (23): 2832–8. DOI: 10.1001/jama.296.23.2832
22. Клинические рекомендации. Дефицит витамина D у взрослых: диагностика, лечение и профилактика. 2015 [Clinical guidelines. Vitamin D deficiency in adults: diagnosis, treatment and prevention. 2015 (in Russian)].
23. Salzer J, Hallmans G, Nyström M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012; 79: 2140–5. DOI: 10.1212/WNL.0b013e3182752ea8
24. Décard BF, Von Ahsen N, Grunwald T, et al. Low vitamin D and elevated immunoreactivity against Epstein–Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatr. 2012; 83: 1170–3. DOI: 10.1136/jnnp-2012-303068
25. Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to Vitamin D supplementation compared to healthy controls. Mult Scler J. 2016; 22: 753–60. DOI: 10.1177/1352458515600248
26. Mirzaei F, Michels KB, Munger K, et al. Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol. 2011; 70: 30–40. DOI: 10.1002/ana.22456
27. Munger KL, Åivo J, Hongell K, et al. Vitamin D status during pregnancy and risk of multiple sclerosis in offspring of women in the Finnish Maternity Cohort. JAMA. 2016; 73: 515–9. DOI: 10.1001/jamaneurol.2015.4800
28. Cortese M, Riise T, Bjørnevik K, et al. Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study. Mult Scler J. 2015; 21: 1856–64. DOI: 10.1177/1352458515578770
29. Bäärnhielm M, Olsson T, Alfredsson L. Fatty fish intake is associated with decreased occurrence of multiple sclerosis. Mult Scler J. 2014; 20: 726–32. DOI: 10.1177/1352458513509508
30. Simpson S, Blizzard L, Otahal P, et al. Latitude is significantly associated with the prevalence of multiple sclerosis: A meta-analysis. J Neurol Neurosurg Psychiatr. 2011; 82: 1132–41. DOI: 10.1136/jnnp.2011.240432
31. Martínez-Lapiscina EH, Mahatanan R, Lee CH, et al. Associations of serum 25(OH) vitamin D levels with clinical and radiological outcomes in multiple sclerosis, a systematic review and meta-analysis. J Neurol Sci. 2020; 411: 116668. DOI: 10.1016/j.jns.2020.116668
32. Cortese M, Munger KL, Martínez-Lapiscina EH, et al. Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT. Neurology. 2020; 94 (18): e1950–60.DOI: 10.1212/WNL.0000000000009371
33. Yochum A, Movva K. Does vitamin D supplementation in patients with relapsing-remitting multiple sclerosis decrease the number of relapses? Evidence-Based Pract Ovid Technologies. 2020; 23 (5): 34–5. DOI: 10.1097/EBP.0000000000000279
34. Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: Exploratory outcomes from a double-blind randomised controlled trial. Mult Scler J. 2012; 18: 1144–51. DOI: 10.1177/1352458511434607
35. Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011; 77: 1611–8. DOI: 10.1212/WNL.0b013e3182343274
36. Dörr J, Bäcker-Koduah P, Wernecke K-D, et al. High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial. Mult Scler J – Exp Transl Clin. 2020; 6 (1). DOI: 10.1177/2055217320903474
37. Ashtari F, Toghianifar N, Zarkesh-Esfahani SH, Mansourian M. High dose Vitamin D intake and quality of life in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Neurol Res. 2016; 38 (10): 888–92. DOI: 10.1080/01616412.2016.1227913
38. Does evidence support Vitamin D treatment for multiple sclerosis? DTB. 2019; 57: 163. DOI: 10.1136/dtb.2019.000070
39. Mclaughlin L, Clarke L, Khalilidehkordi E, et al. Vitamin D in the treatment of multiple sclerosis: A meta-analysis. J Neurol Neurosurg Psychiatr. 2017; 88(5): e1.95–e1. DOI: 10.1136/jnnp-2017-316074.92
40. Hupperts R, Smolders J, Vieth R, et al. Randomized trial of daily high-dose Vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a. Neurology. 2019; 93 (20): E1906–16. DOI: 10.1212/WNL.0000000000008445
41. Camu W, Lehert P, Pierrot-Deseilligny C, et al. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE). Neurol Neuroimmunol Neuroinflamm. 2019; 6 (5): e597. DOI: 10.1212/NXI.0000000000000597
42. Muris AH, Smolders J, Rolf L, et al. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study. J Neuroimmunol. 2016; 300: 47–56. DOI: 10.1016/j.jneuroim.2016.09.018
43. Feige J, Salmhofer H, Hecker C, et al. Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: A note of caution. Mult Scler J. 2019; 25: 1326–8. DOI: 10.1177/1352458518807059
44. Fragoso YD, Adoni T, Damasceno A, et al. Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D. J Neurolog Sci. 2014; 346 (1–2): 341–2.
DOI: 10.1016/j.jns.2014.08.019
45. Bittker SS. Elevated levels of 1,25-dihydroxyvitamin D in plasma as a missing risk factor for celiac disease. Clin Exp Gastroenterol. 2020; 13: 1–15. DOI: 10.2147/CEG.S222353
46. Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press, 2011. DOI: 10.17226/13050
47. Atkinson SA, Fleet JC. Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis. J Steroid Biochem Mol Biol. 2020; 199: 105606. DOI: 10.1016/j.jsbmb.2020.105606
________________________________________________
1. Boyko A, Smirnova N, Petrov S, Gusev E. Epidemiology of MS in Russia, a historical review. Mult Scler Demyelinating Disord. 2016; 1: 1–6. DOI: 10.1186/s40893-016-0016-9
2. Popova E, Boyko A, Barabanova M. Primary progressive multiple sclerosis: Current issues of timely diagnosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2017; 117: 35–40 (in Russian) DOI: 10.17116/jnevro201711710235-40
3. Feige J, Moser T, Bieler L, et al. Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020; 12 (3): 783. DOI: 10.3390/nu12030783
4. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15: 545–58. DOI: 10.1038/nri3871
5. Beckmann Y, Türe S, Duman SU. Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients. EPMA Journal. 2020;11: 65–72. DOI: 10.1007/s13167-019-00191-0
6. Tarlinton RE, Khaibullin T, Granatov E, et al. The interaction between viral and environmental risk factors in the pathogenesis of multiple sclerosis. Int J Mol Sci. 2019; 20 (2): 303. DOI: 10.3390/ijms20020303
7. Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019; 26 (1): 27–40. DOI: 10.1111/ene.13819
8. Thompson AJ, Baranzini SE, Geurts J, Hemmer B. Multiple sclerosis. Lancet. 2018; 391 (10130): 1622–36. DOI: 10.1016/S0140-6736(18)30481-1
9. Sospedra M, Martin R. Immunology of Multiple Sclerosis. Semin Neurol. 2016; 36 (02): 115–27. DOI: 10.1055/s-0036-1579739
10. Miclea A, Bagnoud M, Chan A, Hoepner R. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol. 2020: 781. DOI: 10.3389/fimmu.2020.00781
11. Vitebskaya AV, Tikhaya MI. Vitamin D Deficiency and Autoimmune Diseases. Doctor.ru. 2017; 4 (133): 45–8 (in Russian)
12. Parakhonsky AP. The immunomodulating effects of vitamin D. Zametki uchenogo. 2015: 180–7 (in Russian)
13. Smolders J, Torkildsen, Camu W. An Update on Vitamin D and Disease Activity in Multiple Sclerosis. CNS Drugs. 2019; 33: 1187–99. DOI: 10.1007/s40263-019-00674-8
14. Karonova TL, Shmonina IA, Totolyan NA. Multiple sclerosis and vitamin D status. Arterial’naya gipertenziya. 2015; 21 (2): 121–9 (in Russian) DOI: 10.18705/1607-419X-2015-21-2-121-129
15. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of multiple sclerosis. Curr Opin Neurology. 2015; 28 (3): 206–19. DOI: 10.1097/WCO.0000000000000205
16. Pigarova EA, Pleshcheva AV. Influence of vitamin D on the immune system. Immunologya. 2015; 1: 62–6 (in Russian)
17. Pigarova EA, Petrushkina AA. Non-classical effects of vitamin D. Osteoporosis and Bone Desiases. 2017; 20 (3): 90–101 (in Russian)
18. Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: An update. Mult Scler Relat Disord. 2017; 14: 35–45. DOI: 10.1016/j.msard.2017.03.014
19. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010; 9 (7): 727–39. DOI: 10.1016/S1474-4422(10)70094-6
20. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004; 62 (1): 60–5. DOI: 10.1212/01.WNL.0000101723.79681.38
21. Munger KL, Levin LI, Hollis BW, et al. A Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296 (23): 2832–8. DOI: 10.1001/jama.296.23.2832
22. Clinical guidelines. Vitamin D deficiency in adults: diagnosis, treatment and prevention. 2015 (in Russian)
23. Salzer J, Hallmans G, Nyström M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012; 79: 2140–5. DOI: 10.1212/WNL.0b013e3182752ea8
24. Décard BF, Von Ahsen N, Grunwald T, et al. Low vitamin D and elevated immunoreactivity against Epstein–Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatr. 2012; 83: 1170–3. DOI: 10.1136/jnnp-2012-303068
25. Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to Vitamin D supplementation compared to healthy controls. Mult Scler J. 2016; 22: 753–60. DOI: 10.1177/1352458515600248
26. Mirzaei F, Michels KB, Munger K, et al. Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol. 2011; 70: 30–40. DOI: 10.1002/ana.22456
27. Munger KL, Åivo J, Hongell K, et al. Vitamin D status during pregnancy and risk of multiple sclerosis in offspring of women in the Finnish Maternity Cohort. JAMA. 2016; 73: 515–9. DOI: 10.1001/jamaneurol.2015.4800
28. Cortese M, Riise T, Bjørnevik K, et al. Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study. Mult Scler J. 2015; 21: 1856–64. DOI: 10.1177/1352458515578770
29. Bäärnhielm M, Olsson T, Alfredsson L. Fatty fish intake is associated with decreased occurrence of multiple sclerosis. Mult Scler J. 2014; 20: 726–32. DOI: 10.1177/1352458513509508
30. Simpson S, Blizzard L, Otahal P, et al. Latitude is significantly associated with the prevalence of multiple sclerosis: A meta-analysis. J Neurol Neurosurg Psychiatr. 2011; 82: 1132–41. DOI: 10.1136/jnnp.2011.240432
31. Martínez-Lapiscina EH, Mahatanan R, Lee CH, et al. Associations of serum 25(OH) vitamin D levels with clinical and radiological outcomes in multiple sclerosis, a systematic review and meta-analysis. J Neurol Sci. 2020; 411: 116668. DOI: 10.1016/j.jns.2020.116668
32. Cortese M, Munger KL, Martínez-Lapiscina EH, et al. Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT. Neurology. 2020; 94 (18): e1950–60.DOI: 10.1212/WNL.0000000000009371
33. Yochum A, Movva K. Does vitamin D supplementation in patients with relapsing-remitting multiple sclerosis decrease the number of relapses? Evidence-Based Pract Ovid Technologies. 2020; 23 (5): 34–5. DOI: 10.1097/EBP.0000000000000279
34. Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: Exploratory outcomes from a double-blind randomised controlled trial. Mult Scler J. 2012; 18: 1144–51. DOI: 10.1177/1352458511434607
35. Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011; 77: 1611–8. DOI: 10.1212/WNL.0b013e3182343274
36. Dörr J, Bäcker-Koduah P, Wernecke K-D, et al. High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial. Mult Scler J – Exp Transl Clin. 2020; 6 (1). DOI: 10.1177/2055217320903474
37. Ashtari F, Toghianifar N, Zarkesh-Esfahani SH, Mansourian M. High dose Vitamin D intake and quality of life in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Neurol Res. 2016; 38 (10): 888–92. DOI: 10.1080/01616412.2016.1227913
38. Does evidence support Vitamin D treatment for multiple sclerosis? DTB. 2019; 57: 163. DOI: 10.1136/dtb.2019.000070
39. Mclaughlin L, Clarke L, Khalilidehkordi E, et al. Vitamin D in the treatment of multiple sclerosis: A meta-analysis. J Neurol Neurosurg Psychiatr. 2017; 88(5): e1.95–e1. DOI: 10.1136/jnnp-2017-316074.92
40. Hupperts R, Smolders J, Vieth R, et al. Randomized trial of daily high-dose Vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a. Neurology. 2019; 93 (20): E1906–16. DOI: 10.1212/WNL.0000000000008445
41. Camu W, Lehert P, Pierrot-Deseilligny C, et al. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE). Neurol Neuroimmunol Neuroinflamm. 2019; 6 (5): e597. DOI: 10.1212/NXI.0000000000000597
42. Muris AH, Smolders J, Rolf L, et al. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study. J Neuroimmunol. 2016; 300: 47–56. DOI: 10.1016/j.jneuroim.2016.09.018
43. Feige J, Salmhofer H, Hecker C, et al. Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: A note of caution. Mult Scler J. 2019; 25: 1326–8. DOI: 10.1177/1352458518807059
44. Fragoso YD, Adoni T, Damasceno A, et al. Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D. J Neurolog Sci. 2014; 346 (1–2): 341–2.
DOI: 10.1016/j.jns.2014.08.019
45. Bittker SS. Elevated levels of 1,25-dihydroxyvitamin D in plasma as a missing risk factor for celiac disease. Clin Exp Gastroenterol. 2020; 13: 1–15. DOI: 10.2147/CEG.S222353
46. Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press, 2011. DOI: 10.17226/13050
47. Atkinson SA, Fleet JC. Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis. J Steroid Biochem Mol Biol. 2020; 199: 105606. DOI: 10.1016/j.jsbmb.2020.105606
Авторы
В.Р. Череданова*1, И.А.Чабин1, Р.Ц. Бембеева2
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*vcheredanova@yandex.ru
________________________________________________
Viktoriia R. Cheredanova*1, Ivan A. Chabin1, Raisa Ts. Bembeeva2
1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia
*vcheredanova@yandex.ru