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Молекулярные механизмы разрушения бактериальных пленок при топическом применении аскорбиновой кислоты
Молекулярные механизмы разрушения бактериальных пленок при топическом применении аскорбиновой кислоты
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Аннотация
При терапии бактериальных вагинозов антибиотиками часто забывают об одной существенной особенности бактерий – образовании так называемых бактериальных пленок, т.е. колоний бактерий с усиленной выживаемостью и резистентностью к антибиотикам. Этот фактор следует обязательно учитывать при терапии вагинозов, так как, например, наличие бактериальных пленок G. vaginalis – характерная особенность практически любого бактериального вагиноза. В то же время патогенные бактериальные пленки, характеризующиеся высокой резистентностью к антибиотикам, весьма чувствительны к изменению рН среды. В настоящей работе представлены результаты биоинформационного анализа молекулярных механизмов разрушения бактериальных пленок патогенной флоры при изменении рН. Топическое применение витамина С понижает рН, тем самым разрушая процессы кооперации бактерий в составе бактериальных пленок и снижая резистентность патогенной флоры. Снижение рН до физиологических уровней также создает оптимальные условия для выживания пленок позитивной лактобактериальной флоры.
Ключевые слова: бактериальные пленки, вагиноз, рН, аскорбиновая кислота, Вагинорм-С.
Key words: bacterial films, vaginosis, pH, ascorbic acid, Vaginorm-C.
Ключевые слова: бактериальные пленки, вагиноз, рН, аскорбиновая кислота, Вагинорм-С.
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Key words: bacterial films, vaginosis, pH, ascorbic acid, Vaginorm-C.
Полный текст
Список литературы
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28. Gopishetty B, Zhu J, Rajan R et al. Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues. J Am Chem Soc 2009; 131 (3): 1243–50.
29. Lam MH, Birch DF. Survival of Gardnerella vaginalis in human urine. Am J Clin Pathol 1991; 95 (2): 234–9.
30. Stamey TA, Mihara G. Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. J Urol 1976; 115 (4): 416–7.
31. Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis 1991; 164 (1): 94–100.
32. Catalanotti P, Rossano F, de Paolis P et al. Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells. Sex Transm Dis 1994; 21 (6): 338–44.
33. Loh JT, Gupta SS, Friedman DB et al. Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system. J Bacteriol 2010; 192 (8): 2034–43.
34. Goodwin AC, Weinberger DM, Ford CB et al. Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology 2008; 154 (8): 2231–40.
35. Forsum U, Holst E, Larsson PG et al. Bacterial vaginosis – a microbiological and immunological enigma. APMIS 2005; 113 (2): 81–90.
36. Tanaka Y, Naganawa M, Sakai M, Saito S. Fundamental study of a newly developed medium on detection of Lactobacillus. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2006; 17 (1): 23–32.
37. Saunders S, Bocking A, Challis J, Reid G. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces 2007; 55 (2): 138–42.
38. Moslehi-Jenabian S, Gori K, Jespersen L. AI-2 signalling is induced by acidic shock in probiotic strains of Lactobacillus spp. Int J Food Microbiol 2009; 135 (3): 295–302.
39. Qin X, Bachman B, Battles P, Bell A, Bess C, Bickham C, Chaboub L, Chen D, Coyle M, Deiros DR, Dinh H, Forbes L, Fowler G, Francisco L, Fu Q, Gubbala S, Hale W, Han Y expand/collapse author list, Hemphill L, Highlander SK, Hirani K, Hogues M, Jackson L, Jakkamsetti A, Javaid M, Jiang H, Korchina V, Kovar C, Lara F, Lee S, Mata R, Mathew T, Moen C, Morales K, Munidasa M, Nazareth L, Ngo R, Nguyen L, Okwuonu G, Ongeri F, Patil S, Petrosino J, Pham C, Pham P, Pu L-L, Puazo M, Raj R, Reid J, Rouhana J, Saada N, Shang Y, Simmons D, Thornton R, Warren J, Weissenberger G, Zhang J, Zhang L, Zhou C, Zhu D, Muzny D, Worley K, Gibbs R. Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases. Strain: ATCC 49540 EMBL EEJ40426.1, www.embl.org.
40. Azcarate-Peril MA, Tallon R, Klaenhammer TR. Temporal gene expression and probiotic attributes of Lactobacillus acidophilus during growth in milk. J Dairy Sci 2009; 92 (3): 870–86.
41. Кери Ф., Сандберг Р. Углубленный курс органической химии. В 2 т. М.: Химия, 1981.
42. Petersen EE. Prophylaxe durch intravaginale applikation von L-Askorbinsäure. Gyne 1999; 20.
2. Polatti F, Rampino M, Magnani P, Mascarucci P. Vaginal pH lowering effect of a vaginal tablet, containing 250 mg of Vitamin C, in subjects with high vaginal pH.
3. Уварова Е.В., Султанова Ф.Ш. Влагалище как микроэкосистема в норме и при воспалительных процессах гениталий различной этиологии. Гинекология. 2002; 4 (4).
4. Громова О.А., Торшин И.Ю., Гарасько Е.А. Молекулярные механизмы топического назначения витамина С в лечении бактериального вагиноза. Акушерство и гинекология. 2010; 11: 37–42.
5. Verstraelen H. Cutting edge: the vaginal microflora and bacterial vaginosis. Verh K Acad Geneeskd Belg 2008; 70 (3): 147–74.
6. Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology 2010; 156 (Pt 2): 392–9.
7. Swidsinski A, Mendling W, Loening-Baucke V et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005; 106 (5): 1013–23.
8. Patterson JL, Girerd PH, Karjane NW, Jefferson KK. Effect of biofilm phenotype on resistance of Gardnerella vaginalis to hydrogen peroxide and lactic acid. Am J Obstet Gynecol 2007; 197 (2): 170e1–170e7.
9. Swidsinski A, Mendling W, Loening-Baucke V et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 2008; 198 (1): 97e1–6.
10. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004; 2 (2): 95–108.
11. Rogers AH. Molecular Oral Microbiology. Caister Academic Press. 2008 ISBN 978-1-904455-24-0.
12. Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol 2003; 57: 677–701.
13. Imamura Y, Chandra J, Mukherjee PK et al. Fusarium and Candida albicans biofilms on soft contact lenses: model development, influence of lens type, and susceptibility to lens care solutions. Antimicrob Agents Chemother 2008; 52 (1): 171–82.
14. Lewis K. Riddle of biofilm resistance. Antimicrob Agents Chemother 2001; 45 (4): 999–1007.
15. Davis SC, Ricotti C, Cazzaniga A et al. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair and Regeneration 2008; 16 (1): 23–9.
16. An D, Parsek MR. The promise and peril of transcriptional profiling in biofilm communities. Curr Opin Microbiol 2007; 10 (3): 292–6.
17. Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol 2001; 55: 165–99.
18. Decho AW, Visscher PT, Ferry J et al. Autoinducers extracted from microbial mats reveal a surprising diversity of N-acylhomoserine lactones (AHLs) and abundance changes that may relate to diel pH. Environ Microbiol 2009; 11 (2): 409–20.
19. Kim K, Kim YU, Koh BH et al. HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-kappaB pathway. Immunology 2010; 129 (4): 578–88.
20. Kumari A, Pasini P, Deo SK et al. Biosensing systems for the detection of bacterial quorum signaling molecules. Anal Chem 2006; 78 (22): 7603–9.
21. Yates EA, Philipp B, Buckley C et al. N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Infect Immun 2002; 70 (10): 5635–46.
22. Cao JG, Meighen EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. J Biol Chem 1989; 264 (36): 21670–6.
23. Miller ST, Xavier KB, Campagna SR et al. Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2. Mol Cell 2004; 15 (5): 677–87.
24. Diggle SP, Gardner A, West SA, Griffin AS. Evolutionary theory of bacterial quorum sensing: when is a signal not a signal? Philos Trans R Soc Lond B Biol Sci 2007; 362 (1483): 1241–9.
25. Sun J, Daniel R, Wagner-Dobler I, Zeng AP. Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways. BMC Evol Biol 2004; 4: 36.
26. Durkin AS, Madupu R, Torralba M et al. Genome sequence of Gardnerella vaginalis 409-05. Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases, www.embl.org.
27. Wnuk SF, Robert J, Sobczak AJ et al. Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position. Bioorg Med Chem 2009; 17 (18): 6699–706.
28. Gopishetty B, Zhu J, Rajan R et al. Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues. J Am Chem Soc 2009; 131 (3): 1243–50.
29. Lam MH, Birch DF. Survival of Gardnerella vaginalis in human urine. Am J Clin Pathol 1991; 95 (2): 234–9.
30. Stamey TA, Mihara G. Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. J Urol 1976; 115 (4): 416–7.
31. Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis 1991; 164 (1): 94–100.
32. Catalanotti P, Rossano F, de Paolis P et al. Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells. Sex Transm Dis 1994; 21 (6): 338–44.
33. Loh JT, Gupta SS, Friedman DB et al. Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system. J Bacteriol 2010; 192 (8): 2034–43.
34. Goodwin AC, Weinberger DM, Ford CB et al. Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology 2008; 154 (8): 2231–40.
35. Forsum U, Holst E, Larsson PG et al. Bacterial vaginosis – a microbiological and immunological enigma. APMIS 2005; 113 (2): 81–90.
36. Tanaka Y, Naganawa M, Sakai M, Saito S. Fundamental study of a newly developed medium on detection of Lactobacillus. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2006; 17 (1): 23–32.
37. Saunders S, Bocking A, Challis J, Reid G. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces 2007; 55 (2): 138–42.
38. Moslehi-Jenabian S, Gori K, Jespersen L. AI-2 signalling is induced by acidic shock in probiotic strains of Lactobacillus spp. Int J Food Microbiol 2009; 135 (3): 295–302.
39. Qin X, Bachman B, Battles P, Bell A, Bess C, Bickham C, Chaboub L, Chen D, Coyle M, Deiros DR, Dinh H, Forbes L, Fowler G, Francisco L, Fu Q, Gubbala S, Hale W, Han Y expand/collapse author list, Hemphill L, Highlander SK, Hirani K, Hogues M, Jackson L, Jakkamsetti A, Javaid M, Jiang H, Korchina V, Kovar C, Lara F, Lee S, Mata R, Mathew T, Moen C, Morales K, Munidasa M, Nazareth L, Ngo R, Nguyen L, Okwuonu G, Ongeri F, Patil S, Petrosino J, Pham C, Pham P, Pu L-L, Puazo M, Raj R, Reid J, Rouhana J, Saada N, Shang Y, Simmons D, Thornton R, Warren J, Weissenberger G, Zhang J, Zhang L, Zhou C, Zhu D, Muzny D, Worley K, Gibbs R. Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases. Strain: ATCC 49540 EMBL EEJ40426.1, www.embl.org.
40. Azcarate-Peril MA, Tallon R, Klaenhammer TR. Temporal gene expression and probiotic attributes of Lactobacillus acidophilus during growth in milk. J Dairy Sci 2009; 92 (3): 870–86.
41. Кери Ф., Сандберг Р. Углубленный курс органической химии. В 2 т. М.: Химия, 1981.
42. Petersen EE. Prophylaxe durch intravaginale applikation von L-Askorbinsäure. Gyne 1999; 20.
2. Polatti F, Rampino M, Magnani P, Mascarucci P. Vaginal pH lowering effect of a vaginal tablet, containing 250 mg of Vitamin C, in subjects with high vaginal pH.
3. Уварова Е.В., Султанова Ф.Ш. Влагалище как микроэкосистема в норме и при воспалительных процессах гениталий различной этиологии. Гинекология. 2002; 4 (4).
4. Громова О.А., Торшин И.Ю., Гарасько Е.А. Молекулярные механизмы топического назначения витамина С в лечении бактериального вагиноза. Акушерство и гинекология. 2010; 11: 37–42.
5. Verstraelen H. Cutting edge: the vaginal microflora and bacterial vaginosis. Verh K Acad Geneeskd Belg 2008; 70 (3): 147–74.
6. Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology 2010; 156 (Pt 2): 392–9.
7. Swidsinski A, Mendling W, Loening-Baucke V et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005; 106 (5): 1013–23.
8. Patterson JL, Girerd PH, Karjane NW, Jefferson KK. Effect of biofilm phenotype on resistance of Gardnerella vaginalis to hydrogen peroxide and lactic acid. Am J Obstet Gynecol 2007; 197 (2): 170e1–170e7.
9. Swidsinski A, Mendling W, Loening-Baucke V et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 2008; 198 (1): 97e1–6.
10. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004; 2 (2): 95–108.
11. Rogers AH. Molecular Oral Microbiology. Caister Academic Press. 2008 ISBN 978-1-904455-24-0.
12. Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol 2003; 57: 677–701.
13. Imamura Y, Chandra J, Mukherjee PK et al. Fusarium and Candida albicans biofilms on soft contact lenses: model development, influence of lens type, and susceptibility to lens care solutions. Antimicrob Agents Chemother 2008; 52 (1): 171–82.
14. Lewis K. Riddle of biofilm resistance. Antimicrob Agents Chemother 2001; 45 (4): 999–1007.
15. Davis SC, Ricotti C, Cazzaniga A et al. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair and Regeneration 2008; 16 (1): 23–9.
16. An D, Parsek MR. The promise and peril of transcriptional profiling in biofilm communities. Curr Opin Microbiol 2007; 10 (3): 292–6.
17. Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol 2001; 55: 165–99.
18. Decho AW, Visscher PT, Ferry J et al. Autoinducers extracted from microbial mats reveal a surprising diversity of N-acylhomoserine lactones (AHLs) and abundance changes that may relate to diel pH. Environ Microbiol 2009; 11 (2): 409–20.
19. Kim K, Kim YU, Koh BH et al. HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-kappaB pathway. Immunology 2010; 129 (4): 578–88.
20. Kumari A, Pasini P, Deo SK et al. Biosensing systems for the detection of bacterial quorum signaling molecules. Anal Chem 2006; 78 (22): 7603–9.
21. Yates EA, Philipp B, Buckley C et al. N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Infect Immun 2002; 70 (10): 5635–46.
22. Cao JG, Meighen EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. J Biol Chem 1989; 264 (36): 21670–6.
23. Miller ST, Xavier KB, Campagna SR et al. Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2. Mol Cell 2004; 15 (5): 677–87.
24. Diggle SP, Gardner A, West SA, Griffin AS. Evolutionary theory of bacterial quorum sensing: when is a signal not a signal? Philos Trans R Soc Lond B Biol Sci 2007; 362 (1483): 1241–9.
25. Sun J, Daniel R, Wagner-Dobler I, Zeng AP. Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways. BMC Evol Biol 2004; 4: 36.
26. Durkin AS, Madupu R, Torralba M et al. Genome sequence of Gardnerella vaginalis 409-05. Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases, www.embl.org.
27. Wnuk SF, Robert J, Sobczak AJ et al. Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position. Bioorg Med Chem 2009; 17 (18): 6699–706.
28. Gopishetty B, Zhu J, Rajan R et al. Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues. J Am Chem Soc 2009; 131 (3): 1243–50.
29. Lam MH, Birch DF. Survival of Gardnerella vaginalis in human urine. Am J Clin Pathol 1991; 95 (2): 234–9.
30. Stamey TA, Mihara G. Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. J Urol 1976; 115 (4): 416–7.
31. Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis 1991; 164 (1): 94–100.
32. Catalanotti P, Rossano F, de Paolis P et al. Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells. Sex Transm Dis 1994; 21 (6): 338–44.
33. Loh JT, Gupta SS, Friedman DB et al. Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system. J Bacteriol 2010; 192 (8): 2034–43.
34. Goodwin AC, Weinberger DM, Ford CB et al. Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology 2008; 154 (8): 2231–40.
35. Forsum U, Holst E, Larsson PG et al. Bacterial vaginosis – a microbiological and immunological enigma. APMIS 2005; 113 (2): 81–90.
36. Tanaka Y, Naganawa M, Sakai M, Saito S. Fundamental study of a newly developed medium on detection of Lactobacillus. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi 2006; 17 (1): 23–32.
37. Saunders S, Bocking A, Challis J, Reid G. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces 2007; 55 (2): 138–42.
38. Moslehi-Jenabian S, Gori K, Jespersen L. AI-2 signalling is induced by acidic shock in probiotic strains of Lactobacillus spp. Int J Food Microbiol 2009; 135 (3): 295–302.
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39. Qin X, Bachman B, Battles P, Bell A, Bess C, Bickham C, Chaboub L, Chen D, Coyle M, Deiros DR, Dinh H, Forbes L, Fowler G, Francisco L, Fu Q, Gubbala S, Hale W, Han Y expand/collapse author list, Hemphill L, Highlander SK, Hirani K, Hogues M, Jackson L, Jakkamsetti A, Javaid M, Jiang H, Korchina V, Kovar C, Lara F, Lee S, Mata R, Mathew T, Moen C, Morales K, Munidasa M, Nazareth L, Ngo R, Nguyen L, Okwuonu G, Ongeri F, Patil S, Petrosino J, Pham C, Pham P, Pu L-L, Puazo M, Raj R, Reid J, Rouhana J, Saada N, Shang Y, Simmons D, Thornton R, Warren J, Weissenberger G, Zhang J, Zhang L, Zhou C, Zhu D, Muzny D, Worley K, Gibbs R. Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases. Strain: ATCC 49540 EMBL EEJ40426.1, www.embl.org.
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41. Кери Ф., Сандберг Р. Углубленный курс органической химии. В 2 т. М.: Химия, 1981.
42. Petersen EE. Prophylaxe durch intravaginale applikation von L-Askorbinsäure. Gyne 1999; 20.
Авторы
О.А.Громова1, 2, И.Ю.Торшин2, Е.А.Гарасько2
1. Российский сателлитный центр Международного института микроэлементов ЮНЕСКО, Москва
2. ГОУ ВПО Ивановская государственная медицинская академия Минздравсоцразвития РФ
RSC UNESCO, Trace Element Institute, Moscow
GOU VPO Ivanovo State Medical Academy
1. Российский сателлитный центр Международного института микроэлементов ЮНЕСКО, Москва
2. ГОУ ВПО Ивановская государственная медицинская академия Минздравсоцразвития РФ
________________________________________________
RSC UNESCO, Trace Element Institute, Moscow
GOU VPO Ivanovo State Medical Academy
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