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Физиологическая и патогенетическая роль кожной микробиоты. Алгоритмы лечения дерматозов, осложненных вторичным инфицированием
Физиологическая и патогенетическая роль кожной микробиоты. Алгоритмы лечения дерматозов, осложненных вторичным инфицированием
Хлебникова А.Н., Петрунин Д.Д. Физиологическая и патогенетическая роль кожной микробиоты. Алгоритмы лечения дерматозов, осложненных вторичным инфицированием. Consilium Medicum. Дерматология (Прил.). 2016; 4: 18–25.
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Аннотация
Благодаря внедрению новых научных методов (амплификация ДНК, методы секвенирования и т.д.) за последнее десятилетие получены ценнейшие сведения о микробиоценозе человеческой кожи. Активно изучается роль микроорганизмов, колонизирующих покровные ткани человека, в различных физиологических и патологических процессах. Проблема колонизации и вторичного инфицирования патогенными микроорганизмами особенно значима для воспалительных дерматозов, требующих терапии препаратами с иммуносупрессивным эффектом. Многокомпонентные препараты для наружного применения, имеющие в составе дополнительные компоненты (антибиотики, антимикотики, кератолитики и т.д.) и глюкокортикостероид, в течение нескольких десятков лет остаются востребованным классом лекарственных средств в клинической дерматологии. Они позволяют успешно лечить инфекционные осложнения воспалительных дерматозов, а широта антимикробного спектра во многих случаях дает возможность их применять для эмпирической терапии при точно не установленной этиологии заболевания. Однако по сей день существуют некоторые «белые пятна», касающиеся как фундаментальных, так и практических аспектов применения подобных препаратов. В рамках этого обзора литературы систематизированы накопленные данные о роли микробиома кожи человека в патогенезе различных кожных болезней и их инфекционных осложнениях, обобщены знания и опыт применения наружных комбинированных глюкокортикостероидных препаратов, а также сформулированы рекомендации по их выбору и оптимизации терапевтической тактики.
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Полный текст
Список литературы
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2. Lubbe J. Secondary infections in patients with atopic dermatitis. Am J Clin Dermatol 2003; 4 (9): 641–54.
3. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol 2011; 9 (4): 244–53.
4. Fyhrquist N, Salava A, Auvinen P, Lauerma A. Skin Biomes. Curr Allergy Asthma Rep 2016; 16 (5): 40.
5. Chen YE, Tsao H. The skin microbiome: current perspectives and future challenges. J Am Acad Dermatol 2013; 69 (1): 143–55.
6. Nakamizo S, Egawa G, Honda T et al. Commensal bacteria and cutaneous immunity. Semin Immunopathol 2015; 37 (1): 73–80.
7. Grice EA. The skin microbiome: potential for novel diagnostic and therapeutic approaches to cutaneous disease. Semin Cutan Med Surg 2014; 33: 98–103.
8. Grice EA, Kong HH, Renaud G et al. A diversity profile of the human skin microbiota. Genome Res 2008; 18: 1043–50.
9. Staley JT, Konopka A. Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 1985; 39: 321–46.
10. Handelsman J. Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Biol Rev 2004; 68: 669–85.
11. Fierer N, Hamady M, Lauber CL, Knight R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc Natl Acad Sci USA 2008; 105: 17994–9.
12. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30 (1): 16–34.
13. Ermertcan AT, Öztürk F, Gündüz K. Toll-like receptors and skin. J Eur Acad Dermatol Venereol 2011; 25 (9): 997–1006.
14. Di Meglio P, Perera GK, Nestle FO. The multitasking organ: recent insights into skin immune function. Immunity 2011; 35 (6): 857–69.
15. Strober, W. Epithelial cells pay a Toll for protection. Nature Med 2004; 10: 898–900.
16. Miller LS. Toll-like receptors in skin. Adv Dermatol 2008; 24: 71–87.
17. Nagy I, Pivarcsi A, Kis K et al. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect 2006; 8: 2195–205.
18. Webster GF. Skin Microecology. The Old and the New. Arch Dermatol 2007; 143: 105–6.
19. Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol 2008; 158 (3): 442–55.
20. Cogen AL, Yamasaki K, Sanchez KM et al. Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin. J Invest Dermatol 2010; 130: 192–200.
21. Cogen AL, Yamasaki K, Muto J et al. Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A streptococcus. PLoS One 2010; 5: e8557.
22. Gallo RL, Nakatsuji T. Microbial symbiosis with the innate immune defense system of the skin. J Invest Dermatol 2011; 131: 1974–80.
23. Kong HH, Oh J, Deming C et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 2012; 22 (5): 850–9.
24. Iwase T, Uehara Y, Shinji H et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010; 465 (7296): 346–9.
25. Lin YT, Wang CT, Chiang BL. Role of bacterial pathogens in atopic dermatitis. Clin Rev Allergy Immunol 2007; 33 (3): 167–77.
26. Iarilin A.A. Immunologiia. Uchebnik. M.: GEOTAR-Media, 2010. [in Russian]
27. Spaulding AR, Salgado-Pabón W, Kohler PL. Staphylococcal and streptococcal superantigen exotoxins. Clin Microbiol Rev 2013; 26 (3): 422–47.
28. Cardona ID, Cho SH, Leung DY. Role of bacterial superantigens in atopic dermatitis: implications for future therapeutic strategies. Am J Clin Dermatol 2006; 7 (5): 273–9.
29. Faergemann J. Atopic dermatitis and fungi. Clin Microbiol Rev 2002; 15 (4): 545–63.
30. Glatz M, Bosshard PP, Hoetzenecker W, Schmid-Grendelmeier P. The Role of Malassezia spp. in Atopic Dermatitis. J Clin Med 2015; 4 (6): 1217–28.
31. Atopicheskii dermatit. Rukovodstvo dlia vrachei. Pod red. Iu.V.Sergeeva. M: Meditsina dlia vsekh, 2002. [in Russian]
32. Macharadze D.Sh. Lechenie infektsii kozhi pri atopicheskom dermatite u detei. Lechashchii vrach. 2006; 9: 30–4. [in Russian]
33. Petry V, Bessa GR, Poziomczyck CS. Bacterial skin colonization and infections in patients with atopic dermatitis. An Bras Dermatol 2012; 87 (5): 729–34.
34. Katayama Y, Ito T, Hiramatsu K. A new class of genetic element, Staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother 2000; 44: 1549–55.
35. Chambers H., Deleo F. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 2009; 7 (9): 629–41.
36. Romanov A.V, Chernov E.A, Eidel'shtein M.V. Molekuliarnaia epidemiologiia vnutribol'nichnykh zolotistykh stafilokokkov v statsionarakh razlichnykh regionov Rossii. Molekuliarnaia meditsina. 2013; 4: 55–64. [in Russian]
37. Murashkin N.N., Gluzmin M.I, Skoblikov N.E. Rol' metitsillinrezistentnykh shtammov zolotistogo stafilokokka v patogeneze tiazhelykh form atopicheskogo dermatita v detskom vozraste. Puti dostizheniia remissii. Vestn. dermatologii i venerologii. 2012; 1: 66–74. [in Russian]
38. Lewis-Tuffin LJ, Cidlowski JA. The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann N Y Acad Sci 2006; 1069: 1–9.
39. Glatz M, Bosshard PP, Hoetzenecker W, Schmid-Grendelmeier P. The Role of Malassezia spp. in Atopic Dermatitis. J Clin Med 2015; 4 (6): 1217–28.
40. Khlebnikova A.N., Marycheva N.V. Osobennosti naruzhnoi terapii patologii kozhi u bol'nykh sakharnym diabetom. Klinicheskaia dermatologiia i venerologiia. 2011; 6: 52–8. [in Russian]
41. Mavlianova Sh.Z. Kliniko-immunologicheskaia kharakteristika kandidoznoi sensibilizatsii u bol'nykh khronicheskimi dermatozami. Vestnik dermatologii i venerologii. 2001; 5: 44–6. [in Russian]
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43. Bath-Hextall FJ, Birnie AJ, Ravenscroft JC, Williams HC. Interventions to reduce Staphylococcus aureus in the management of atopic eczema: an updated Cochrane review. Br J Dermatol 2010; 163 (1): 12–26.
44. Boguniewicz M, Sampson H, Leung SB. Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis. J Allergy Clin Immunol 2001; 108: 651–2.
45. Stalder JF, Fleury M, Sourisse M. Local steroid therapy and bacterial skin flora in atopic dermatitis. Br J Dermatol 1994; 131 (4): 536–40.
46. Remitz A, Kyllönen H, Granlund H, Reitamo S. Tacrolimus ointment reduces staphylococcal colonization of atopic dermatitis lesions. J Allergy Clin Immunol 2001; 107 (1): 196–7.
47. Leyden JJ, Kligman AM. The case for steroid-antibiotic combinations. Br J Dermatol 1977; 96: 179–87.
48. Herbert S, Barry P, Novick RP. Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus. Infect Immun 2001; 69: 2996–3003.
49. Sutton JB. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in facial impetigo. Curr Ther Res 1992; 51: 673–8.
50. Morley PAR, Munot LD. A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis. Curr Med Res Opin 1988; 11: 142–8.
51. White DG, Collins PO, Rowsell RB. Topical antibiotics in the treatment of superficial skin infections in general practice – a comparison of mupirocin with sodium fusidate. J Infect 1989; 18: 221–9.
52. Gilbert M. Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections. J Am Acad Dermatol 1989; 20: 1083–7.
53. Jasuja K, Gupta SK, Arora DR, Gupta V. Bacteriology of primary pyodermas and comparative efficacy of topical application of mupirocin and sodium fusidate ointments in their treatment. Indian J Dermatol Venereol Leprol 2001; 67: 132–4.
54. Langdon CG, Mahapatra KS. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in acute skin sepsis. Curr Ther Res 1990; 48: 174–9.
55. Oranje AP, Chosidow O, Sacchidanand S et al. TOC100224 Study Team. Topical retapamulin ointment, 1%, versus sodium fusidate ointment, 2%, for impetigo: a randomized, observer-blinded, noninferiority study. Dermatology 2007; 215: 331–40.
56. Von Daehne W, Godtfredsen WO, Rasmussen PR. Structure-activity relationships in fusidic acid-type antibiotics. Adv Appl Microbiol 1979; 25: 95–146.
57. Bel'kova Iu.A. Fuzidovaia kislota v sovremennoi klinicheskoi praktike. Klin. mikrobiologiia i antimikrobnaia khimioterapiia. 2001; 4 (3): 324–38. [in Russian]
58. Verbist L. The antimicrobial activity of fusidic acid. J Antimicrob Chemother 1990; 25 (Suppl. B): 115.
59. Stüttgen G, Bauer E. Penetration and permeation into human skin of fusidic acid in different galenical formulation. Arzneimittelforschung 1988; 38 (5): 730–5.
60. Vickers CF. Percutaneous absorption of sodium fusidate and fusidic acid. Br J Dermatol 1969; 81 (12): 902–8.
61. Morris SD, Rycroft RJ, White IR. Comparative frequency of patch test reactions to topical antibiotics. Br J Dermatol 2002; 146 (6): 1047–51.
62. Jappe U, Schnuch A, Uter W. Frequency of sensitization to antimicrobials in patients with atopic eczema compared with nonatopic individuals: analysis of multicentre surveillance data, 1995–1999. Br J Dermatol 2003; 149 (1): 87–93.
63. Schultz Larsen F, Simonsen L, Melgaard A. An efficient new formulation of fusidic acid and betamethasone 17-valerate (fucicort lipid cream) for treatment of clinically infected atopic dermatitis. Acta Derm Venereol 2007; 87: 62–8.
64. Darabi K, Hostetler SG, Bechtel MA, Zirwas M. The role of Malassezia in atopic dermatitis affecting the head and neck of adults. J Am Acad Dermatol 2009; 60 (1): 125–36.
65. Instruktsiia po meditsinskomu primeneniiu preparata Pimafukort (krem i maz' dlia naruzhnogo primeneniia) P № 012689/01 i P № 012689/01 ot 01.07.2009. [in Russian]
66. Korotkii N.G., Kulikova O.D., Petrunin D.D. Differentsirovannyi podkhod k naznacheniiu kombinirovannykh topicheskikh steroidov – minimizatsiia riska nezhelatel'nykh lekarstvennykh reaktsii. Consilium Medicum. Dermatology (Suppl.). 2009; 3: 3–6. [in Russian]
67. Matushevskaia E.V., Svirshevskaia E.V. Effektivnost' i bezopasnost' mikronizirovannykh lekarstvennykh preparatov i ikh primenenie v dermatologicheskoi praktike. Klin. dermatologiia i venerologiia. 2015; 14 (5): 4–10. [in Russian]
68. Kravchenia S.S., Igonina I.A., Bakulev A.L. Kombinirovannaia naruzhnaia terapiia atopicheskogo dermatita. Klin. dermatologiia i venerologiia. 2011; 1: 41–4. [in Russian]
69. Sokolova T.E., Maliarchuk A.P. Klinicheskoe myshlenie – osnova vybora ratsional'noi taktiki vedeniia bol'nykh mikrobnoi ekzemoi. Consilium Medicum. Dermatology (Suppl.). 2011; 2: 6–13. [in Russian]
70. Malova I.O., Petrunin D.D. Natamitsin – protivogribkovoe sredstvo klassa polienovykh makrolidov s neobychnymi svoistvami. Vestn. dermatologii i venerologii. 2015; 3: 161–84. [in Russian]
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45. Stalder JF, Fleury M, Sourisse M. Local steroid therapy and bacterial skin flora in atopic dermatitis. Br J Dermatol 1994; 131 (4): 536–40.
46. Remitz A, Kyllönen H, Granlund H, Reitamo S. Tacrolimus ointment reduces staphylococcal colonization of atopic dermatitis lesions. J Allergy Clin Immunol 2001; 107 (1): 196–7.
47. Leyden JJ, Kligman AM. The case for steroid-antibiotic combinations. Br J Dermatol 1977; 96: 179–87.
48. Herbert S, Barry P, Novick RP. Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus. Infect Immun 2001; 69: 2996–3003.
49. Sutton JB. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in facial impetigo. Curr Ther Res 1992; 51: 673–8.
50. Morley PAR, Munot LD. A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis. Curr Med Res Opin 1988; 11: 142–8.
51. White DG, Collins PO, Rowsell RB. Topical antibiotics in the treatment of superficial skin infections in general practice – a comparison of mupirocin with sodium fusidate. J Infect 1989; 18: 221–9.
52. Gilbert M. Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections. J Am Acad Dermatol 1989; 20: 1083–7.
53. Jasuja K, Gupta SK, Arora DR, Gupta V. Bacteriology of primary pyodermas and comparative efficacy of topical application of mupirocin and sodium fusidate ointments in their treatment. Indian J Dermatol Venereol Leprol 2001; 67: 132–4.
54. Langdon CG, Mahapatra KS. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in acute skin sepsis. Curr Ther Res 1990; 48: 174–9.
55. Oranje AP, Chosidow O, Sacchidanand S et al. TOC100224 Study Team. Topical retapamulin ointment, 1%, versus sodium fusidate ointment, 2%, for impetigo: a randomized, observer-blinded, noninferiority study. Dermatology 2007; 215: 331–40.
56. Von Daehne W, Godtfredsen WO, Rasmussen PR. Structure-activity relationships in fusidic acid-type antibiotics. Adv Appl Microbiol 1979; 25: 95–146.
57. Белькова Ю.А. Фузидовая кислота в современной клинической практике. Клин. микробиология и антимикробная химиотерапия. 2001; 4 (3): 324–38. / Bel'kova Iu.A. Fuzidovaia kislota v sovremennoi klinicheskoi praktike. Klin. mikrobiologiia i antimikrobnaia khimioterapiia. 2001; 4 (3): 324–38. [in Russian]
58. Verbist L. The antimicrobial activity of fusidic acid. J Antimicrob Chemother 1990; 25 (Suppl. B): 115.
59. Stüttgen G, Bauer E. Penetration and permeation into human skin of fusidic acid in different galenical formulation. Arzneimittelforschung 1988; 38 (5): 730–5.
60. Vickers CF. Percutaneous absorption of sodium fusidate and fusidic acid. Br J Dermatol 1969; 81 (12): 902–8.
61. Morris SD, Rycroft RJ, White IR. Comparative frequency of patch test reactions to topical antibiotics. Br J Dermatol 2002; 146 (6): 1047–51.
62. Jappe U, Schnuch A, Uter W. Frequency of sensitization to antimicrobials in patients with atopic eczema compared with nonatopic individuals: analysis of multicentre surveillance data, 1995–1999. Br J Dermatol 2003; 149 (1): 87–93.
63. Schultz Larsen F, Simonsen L, Melgaard A. An efficient new formulation of fusidic acid and betamethasone 17-valerate (fucicort lipid cream) for treatment of clinically infected atopic dermatitis. Acta Derm Venereol 2007; 87: 62–8.
64. Darabi K, Hostetler SG, Bechtel MA, Zirwas M. The role of Malassezia in atopic dermatitis affecting the head and neck of adults. J Am Acad Dermatol 2009; 60 (1): 125–36.
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68. Кравченя С.С., Игонина И.А., Бакулев А.Л. Комбинированная наружная терапия атопического дерматита. Клин. дерматология и венерология. 2011; 1: 41–4. / Kravchenia S.S., Igonina I.A., Bakulev A.L. Kombinirovannaia naruzhnaia terapiia atopicheskogo dermatita. Klin. dermatologiia i venerologiia. 2011; 1: 41–4. [in Russian]
69. Соколова Т.Э., Малярчук А.П. Клиническое мышление – основа выбора рациональной тактики ведения больных микробной экземой. Consilium Medicum. Дерматология (Прил.). 2011; 2: 6–13. / Sokolova T.E., Maliarchuk A.P. Klinicheskoe myshlenie – osnova vybora ratsional'noi taktiki vedeniia bol'nykh mikrobnoi ekzemoi. Consilium Medicum. Dermatology (Suppl.). 2011; 2: 6–13. [in Russian]
70. Малова И.О., Петрунин Д.Д. Натамицин – противогрибковое средство класса полиеновых макролидов с необычными свойствами. Вестн. дерматологии и венерологии. 2015; 3: 161–84. / Malova I.O., Petrunin D.D. Natamitsin – protivogribkovoe sredstvo klassa polienovykh makrolidov s neobychnymi svoistvami. Vestn. dermatologii i venerologii. 2015; 3: 161–84. [in Russian]
71. Vakulenko SB, Mobashery S. Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 2003; 16 (3): 430–50.
72. Aminoglycoside antibiotics: from chemical biology to drug discovery. Arya DP (ed.). Hoboken, John Wiley & Sons, Inc 2007.
73. Сидоренко С.В. Резистентность микроорганизмов и антибактериальная терапия. Рус. мед. журн. 1998; 11: 5. / Sidorenko S.V. Rezistentnost' mikroorganizmov i antibakterial'naia terapiia. Rus. med. zhurn. 1998; 11: 5. [in Russian]
________________________________________________
2. Lubbe J. Secondary infections in patients with atopic dermatitis. Am J Clin Dermatol 2003; 4 (9): 641–54.
3. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol 2011; 9 (4): 244–53.
4. Fyhrquist N, Salava A, Auvinen P, Lauerma A. Skin Biomes. Curr Allergy Asthma Rep 2016; 16 (5): 40.
5. Chen YE, Tsao H. The skin microbiome: current perspectives and future challenges. J Am Acad Dermatol 2013; 69 (1): 143–55.
6. Nakamizo S, Egawa G, Honda T et al. Commensal bacteria and cutaneous immunity. Semin Immunopathol 2015; 37 (1): 73–80.
7. Grice EA. The skin microbiome: potential for novel diagnostic and therapeutic approaches to cutaneous disease. Semin Cutan Med Surg 2014; 33: 98–103.
8. Grice EA, Kong HH, Renaud G et al. A diversity profile of the human skin microbiota. Genome Res 2008; 18: 1043–50.
9. Staley JT, Konopka A. Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 1985; 39: 321–46.
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Авторы
А.Н.Хлебникова*1, Д.Д.Петрунин2
1. ФГБОУ ВО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2;
2. ООО «ЛЕО Фармасьютикал Продактс». 125315, Россия, Москва, Ленинградский пр-т, д. 72, корп. 2
*prof.preobrazhenskii@gmail.com
1. I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2;
2. LEO Pharmaceutical Products LLC. 125315, Russian Federation, Moscow, Leningradskii pr-t, d. 72, korp. 2
*prof.preobrazhenskii@gmail.com
1. ФГБОУ ВО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2;
2. ООО «ЛЕО Фармасьютикал Продактс». 125315, Россия, Москва, Ленинградский пр-т, д. 72, корп. 2
*prof.preobrazhenskii@gmail.com
________________________________________________
1. I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2;
2. LEO Pharmaceutical Products LLC. 125315, Russian Federation, Moscow, Leningradskii pr-t, d. 72, korp. 2
*prof.preobrazhenskii@gmail.com
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