Физиологические и молекулярные механизмы топического воздействия аскорбиновой кислоты на вагинальную флору

1. Уварова Е.В., Султанова Ф.Ш. Влагалище как микроэкосистема в норме и при воспалительных процессах гениталий различной этиологии. Гинекология 2002; 4 (4): 21–4.
2. Petersen EE. Prophylaxe durch intravaginale applikation von L-Askorbinsäure. Gyne 1999; 20.
3. Petersen EE. Der Einsatz von Vitamin C (Vagi-C) zur Normalisierung der Vaginalflora. Gyne 1998; 19.
4. Кери Ф., Сандберг Р. Углубленный курс органической химии. В 2-х т. М.: Химия, 1981.
5. Ребров В.Г., Громова О.А. Витамины, макро- и микроэлементы. М.: ГеотарМед, 2008.
6. Melis GB, Ibba MT, Steri B et al. Role of pH as a regulator of vaginal physiological environment Minerva. Ginecol 2000; 52 (4): 111–21.
7. Boskey ER, Cone RA, Whaley KJ, Moench TR. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod. 2001; 16 (9): 1809–13.
8. Falagas ME, Betsi GI, Athanasiou S. Probiotics for the treatment of women with bacterial vaginosis. Clin Microbiol Infect 2007; 13 (7): 657–64.
9. Liu H, Liu X, Zhang J, Chen J. Acetate accumulation and shift of bacterial community during anaerobic sewage sludge fermentation by pH adjustment. Wei Sheng Wu Xue Bao 2009; 49 (12): 1643–9.
10. 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.
11. 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.
12. Ramirez N, Abel-Santos E. Requirements for germination of Clostridium sordellii spores in vitro. J Bacteriol 2010; 192 (2): 418–25.
13. Peeters M, Piot P. Adhesion of Gardnerella vaginalis to vaginal epithelial cells: variables affecting adhesion and inhibition by metronidazole. Genitourin Med 1985; 61 (6): 391–5.
14. Stamey TA, Kaufman MF. Studies of introital colonization in women with recurrent urinary infections. II. A comparison of growth in normal vaginal fluid of common versus uncommon serogroups of Escherichia coli. J Urol 1975; 114 (2): 264–7.
15. Hanna NF, Taylor-Robinson D, Kalodiki-Karamanoli M et al. The relation between vaginal pH and the microbiological status in vaginitis. Br J Obstet Gynaecol 1985; 92 (12): 1267–71.
16. Masover GK, Sawyer JE, Hayflick L. Urea-hydrolyzing activity of a T-strain mycoplasma: Ureaplasma urealyticum. J Bacteriol 1976; 125 (2): 581–7.
17. Forsum U, Holst E, Larsson PG et al. Bacterial vaginosis – a microbiological and immunological enigma. APMIS 2005; 113 (2): 81–90.
18. 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.
19. Lam MH, Birch DF. Survival of Gardnerella vaginalis in human urine. Am J Clin Pathol 1991; 95 (2): 234–9.
20. 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.
21. Hengst P, Uhlig B, Bollmann R, Kokott T. Uses of vaginal pH measurement for prevention of premature labor. Results of a prospective study. Z Geburtshilfe Perinatol 1992; 196 (6): 238–41.
22. Jakobsson T, Forsum U. Lactobacillus iners: a marker of changes in the vaginal flora? J Clin Microbiol 2007; 45 (9): 3145.
23. Yan DH, Lu Z, Su JR. Comparison of main lactobacillus species between healthy women and women with bacterial vaginosis. Chin Med J (Engl). 2009; 122 (22): 2748–51.
24. Miller EM, Fowler JF, Kinsella TJ. Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. I. Radiosensitization of human colon cancer cells by iododeoxyuridine. Radiat Res 1992; 131 (1): 81–9.
25. 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.
26. 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.
27. Нечаева Г.И., Яковлев В.М., Громова О.А., Торшин И.Ю. и др. Дисплазии соединительной ткани у детей и подростков. Инновационные стационар-сберегающие технологии диагностики и лечения в педиатрии. М.: Союз Педиатров России, 2009.
28. Vihtamaki T, Parantainen J, Koivisto AM et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002; 42 (2): 129–35.
29. Keith MO, Pelletier O. The effects of an oral contraceptive, ascorbic acid and iron on glucose and copper metabolism in the rat. Nutr Rep Int 1976; 13 (3): 273–80.
30. Michos C, Kiortsis DN, Evangelou A, Karkabounas S. Antioxidant protection during the menstrual cycle: the effects of estradiol on ascorbic-dehydroascorbic acid plasma levels and total antioxidant plasma status in eumenorrhoic women during the menstrual cycle. Acta Obstet Gynecol Scand 2006; 85 (8): 960–5.
31. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol 2009; 113 (1–2): 17–24.
32. Torshin I.Yu. Bioinformatics in the post-genomic era: sensing the change from molecular genetics to personalized medicine. Series «Bioinformatics in the Post-Genomic Era». Nova Biomedical Books, NY, USA, 2009.
33. Li SS, Hou EW. Estrogen-induced expression of mouse lactate dehydrogenase-A gene. Cell Biol Int Rep 1989; 13 (7): 619–24.
34. Caillouette JC, Sharp CF Jr, Zimmerman GJ, Roy S. Vaginal pH as a marker for bacterial pathogens and menopausal status. Am J Obstet Gynecol 1997; 176 (6): 1270–5.
35. Parsons CL, Schmidt JD. Control of recurrent lower urinary tract infection in the postmenopausal woman. J Urol 1982; 128 (6): 1224–6.
36. Strohle A, Hahn A. Vitamin C and immune function. Med Monatsschr Pharm 2009; 32 (2): 49–54.
37. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002; 5 (2): 66–74.
38.Aleszczyk J. Connection between changing the vitamin and immune status and the character of the throat microflora in patients with chronic tonsillitis. Otolaryngol Pol 2003; 57 (2): 221–4.
39. Banic S. Immunostimulation by vitamin C. Int J Vitam Nutr Res Suppl 1982; 23: 49–52.
40.Thomas WR, Holt PG. Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol 1978; 32 (2): 370–9.
41. Leibovitz B, Siegel BV. Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res 1978; 48 (2): 159–64.
42. Moyad MA, Combs MA, Vrablic AS et al. Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Adv Ther 2008; 25 (10): 995–1009.
43. Grant MM, Mistry N, Lunec J, Griffiths HR. Dose-dependent modulation of the T cell proteome by ascorbic acid. Br J Nutr 2007; 97 (1): 19–26.
44. Campbell JD, Cole M, Bunditrutavorn B, Vella AT. Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis. Cell Immunol. 1999; 194 (1): 1–5.
45. Perez-Cruz I, Carcamo JM, Golde DW. Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells. Blood 2003; 102 (1): 336–43.
46. Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 2002; 41 (43): 12995–3002.
47. Schwager J, Schulze J. Modulation of interleukin production by ascorbic acid. Vet Immunol Immunopathol 1998; 64 (1): 45–57.
48. Polatti F, Rampino M, Magnani P, Mascarucci P. Vaginal pH-lowering effect of locally applied vitamin C in subjects with high vaginal pH. Gynecol Endocrinol 2006; 22 (4): 230–4.
49. Petersen EE, Magnani P. Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2004; 117 (1): 70–5.

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1. Уварова Е.В., Султанова Ф.Ш. Влагалище как микроэкосистема в норме и при воспалительных процессах гениталий различной этиологии. Гинекология 2002; 4 (4): 21–4.
2. Petersen EE. Prophylaxe durch intravaginale applikation von L-Askorbinsäure. Gyne 1999; 20.
3. Petersen EE. Der Einsatz von Vitamin C (Vagi-C) zur Normalisierung der Vaginalflora. Gyne 1998; 19.
4. Кери Ф., Сандберг Р. Углубленный курс органической химии. В 2-х т. М.: Химия, 1981.
5. Ребров В.Г., Громова О.А. Витамины, макро- и микроэлементы. М.: ГеотарМед, 2008.
6. Melis GB, Ibba MT, Steri B et al. Role of pH as a regulator of vaginal physiological environment Minerva. Ginecol 2000; 52 (4): 111–21.
7. Boskey ER, Cone RA, Whaley KJ, Moench TR. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod. 2001; 16 (9): 1809–13.
8. Falagas ME, Betsi GI, Athanasiou S. Probiotics for the treatment of women with bacterial vaginosis. Clin Microbiol Infect 2007; 13 (7): 657–64.
9. Liu H, Liu X, Zhang J, Chen J. Acetate accumulation and shift of bacterial community during anaerobic sewage sludge fermentation by pH adjustment. Wei Sheng Wu Xue Bao 2009; 49 (12): 1643–9.
10. 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.
11. 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.
12. Ramirez N, Abel-Santos E. Requirements for germination of Clostridium sordellii spores in vitro. J Bacteriol 2010; 192 (2): 418–25.
13. Peeters M, Piot P. Adhesion of Gardnerella vaginalis to vaginal epithelial cells: variables affecting adhesion and inhibition by metronidazole. Genitourin Med 1985; 61 (6): 391–5.
14. Stamey TA, Kaufman MF. Studies of introital colonization in women with recurrent urinary infections. II. A comparison of growth in normal vaginal fluid of common versus uncommon serogroups of Escherichia coli. J Urol 1975; 114 (2): 264–7.
15. Hanna NF, Taylor-Robinson D, Kalodiki-Karamanoli M et al. The relation between vaginal pH and the microbiological status in vaginitis. Br J Obstet Gynaecol 1985; 92 (12): 1267–71.
16. Masover GK, Sawyer JE, Hayflick L. Urea-hydrolyzing activity of a T-strain mycoplasma: Ureaplasma urealyticum. J Bacteriol 1976; 125 (2): 581–7.
17. Forsum U, Holst E, Larsson PG et al. Bacterial vaginosis – a microbiological and immunological enigma. APMIS 2005; 113 (2): 81–90.
18. 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.
19. Lam MH, Birch DF. Survival of Gardnerella vaginalis in human urine. Am J Clin Pathol 1991; 95 (2): 234–9.
20. 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.
21. Hengst P, Uhlig B, Bollmann R, Kokott T. Uses of vaginal pH measurement for prevention of premature labor. Results of a prospective study. Z Geburtshilfe Perinatol 1992; 196 (6): 238–41.
22. Jakobsson T, Forsum U. Lactobacillus iners: a marker of changes in the vaginal flora? J Clin Microbiol 2007; 45 (9): 3145.
23. Yan DH, Lu Z, Su JR. Comparison of main lactobacillus species between healthy women and women with bacterial vaginosis. Chin Med J (Engl). 2009; 122 (22): 2748–51.
24. Miller EM, Fowler JF, Kinsella TJ. Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. I. Radiosensitization of human colon cancer cells by iododeoxyuridine. Radiat Res 1992; 131 (1): 81–9.
25. 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.
26. 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.
27. Нечаева Г.И., Яковлев В.М., Громова О.А., Торшин И.Ю. и др. Дисплазии соединительной ткани у детей и подростков. Инновационные стационар-сберегающие технологии диагностики и лечения в педиатрии. М.: Союз Педиатров России, 2009.
28. Vihtamaki T, Parantainen J, Koivisto AM et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002; 42 (2): 129–35.
29. Keith MO, Pelletier O. The effects of an oral contraceptive, ascorbic acid and iron on glucose and copper metabolism in the rat. Nutr Rep Int 1976; 13 (3): 273–80.
30. Michos C, Kiortsis DN, Evangelou A, Karkabounas S. Antioxidant protection during the menstrual cycle: the effects of estradiol on ascorbic-dehydroascorbic acid plasma levels and total antioxidant plasma status in eumenorrhoic women during the menstrual cycle. Acta Obstet Gynecol Scand 2006; 85 (8): 960–5.
31. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol 2009; 113 (1–2): 17–24.
32. Torshin I.Yu. Bioinformatics in the post-genomic era: sensing the change from molecular genetics to personalized medicine. Series «Bioinformatics in the Post-Genomic Era». Nova Biomedical Books, NY, USA, 2009.
33. Li SS, Hou EW. Estrogen-induced expression of mouse lactate dehydrogenase-A gene. Cell Biol Int Rep 1989; 13 (7): 619–24.
34. Caillouette JC, Sharp CF Jr, Zimmerman GJ, Roy S. Vaginal pH as a marker for bacterial pathogens and menopausal status. Am J Obstet Gynecol 1997; 176 (6): 1270–5.
35. Parsons CL, Schmidt JD. Control of recurrent lower urinary tract infection in the postmenopausal woman. J Urol 1982; 128 (6): 1224–6.
36. Strohle A, Hahn A. Vitamin C and immune function. Med Monatsschr Pharm 2009; 32 (2): 49–54.
37. Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002; 5 (2): 66–74.
38.Aleszczyk J. Connection between changing the vitamin and immune status and the character of the throat microflora in patients with chronic tonsillitis. Otolaryngol Pol 2003; 57 (2): 221–4.
39. Banic S. Immunostimulation by vitamin C. Int J Vitam Nutr Res Suppl 1982; 23: 49–52.
40.Thomas WR, Holt PG. Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol 1978; 32 (2): 370–9.
41. Leibovitz B, Siegel BV. Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res 1978; 48 (2): 159–64.
42. Moyad MA, Combs MA, Vrablic AS et al. Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Adv Ther 2008; 25 (10): 995–1009.
43. Grant MM, Mistry N, Lunec J, Griffiths HR. Dose-dependent modulation of the T cell proteome by ascorbic acid. Br J Nutr 2007; 97 (1): 19–26.
44. Campbell JD, Cole M, Bunditrutavorn B, Vella AT. Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis. Cell Immunol. 1999; 194 (1): 1–5.
45. Perez-Cruz I, Carcamo JM, Golde DW. Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells. Blood 2003; 102 (1): 336–43.
46. Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 2002; 41 (43): 12995–3002.
47. Schwager J, Schulze J. Modulation of interleukin production by ascorbic acid. Vet Immunol Immunopathol 1998; 64 (1): 45–57.
48. Polatti F, Rampino M, Magnani P, Mascarucci P. Vaginal pH-lowering effect of locally applied vitamin C in subjects with high vaginal pH. Gynecol Endocrinol 2006; 22 (4): 230–4.
49. Petersen EE, Magnani P. Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2004; 117 (1): 70–5.

О.А.Громова1, 2, И.Ю.Торшин1, Е.В.Гарасько2
1. Российский сателлитный центр «Нейробиология» международного института 
микроэлементов ЮНЕСКО, Москва;