Вульвовагинальные инфекции (ВВИ) остаются одной из самых актуальных проблем современной гинекологии. Высокая распространенность инфекционных поражений влагалища, частые рецидивы, влияние ВВИ на функции репродуктивной системы, повышение риска гинекологических заболеваний и акушерских осложнений – все это побуждает к поиску эффективных методов коррекции и профилактики нарушений шеечно-влагалищной микроэкосистемы. Самыми частыми причинами патологических выделений из половых путей в мире считаются бактериальный вагиноз, вульвовагинальный кандидоз и трихомониаз. В обзоре рассматриваются вопросы диагностики и лечения частых ВВИ.
Vulvovaginal infections (VVI) remain one of the most urgent problems of modern gynecology. The high prevalence of infectious lesions of the vagina, frequent relapses, the impact of the VVI on the function of the reproductive system, increasing the risk of gynecological disease and obstetric complications – all of this encourages the search for effective methods of correction and prevention of violations of cervicovaginal microecosystem. The most common causes of abnormal discharge from the genital tract in the world are considered to be bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis. The review deals with the diagnosis and treatment of common VVI.
Key words: bacterial vaginosis, candidiasis, trichomoniasis, the treatment of vulvovaginal infections.
1. Ley RE, Lozupone C, Hamady M et al. Worlds within worlds: evolution of the vertebrate gut microbiota. Nature Rev Microbiol 2008; 6: 776–88.
2. Lamont R, Sobel J, Akins R, Hassan S et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011; 118 (5): 533–49.
3. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM et al. The human microbiome project. Nature 2007; 449 (7164): 804–10.
4. Ravel J, Gajer P, Abdo Z et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 2011; 108 (Suppl. 1): 4680–7.
5. Shi Y, Chen L, Tong J, Xu C. Preliminary characterization of vaginal microbiota in healthy Chinese women using cultivation-independent methods. J Obstet Gynaecol Res 2009; 35: 525–32.
6. Yamamoto T, Zhou X, Williams CJ et al. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol 2009; 22: 11–8.
7. Chaban B, Links MG, Jayaprakash TP et al. Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome 2014; 4 (2): 23.
8. Azad MB, Konya T, Maughan H et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 2013; 185: 385–94.
9. Ronnqvist PD, Forsgren-Brusk UB, Grahn-Hakansson EE. Lactobacilli in the female genital tract in relation to other genital microbes and vaginal pH. Acta Obstet Gynecol Scand 2006; 85: 726–35.
10. Zakaria Gomaa E. Antimicrobial and anti-adhesive properties of biosurfactant produced by lactobacilli isolates, biofilm formation and aggregation ability. J Gen Appl Microbiol 2013; 59: 425–36.
11. Yamamoto T, Zhou X, Williams CJ et al. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol 2009; 22: 11–8.
12. Castro J, Henriques A, Machado A et al. Reciprocal interference between Lactobacillus spp. and Gardnerella vaginalis on initial adherence to epithelial cells. Int J Med Sci 2013; 10 (9): 1193–8.
13. Macklaim JM, Gloor GB, Anucam KC et al. Microbes and Health Sackler Colloquium: at the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci USA 2011; 108 (1): 4688–95.
14. Zozaya-Hinchliffe V, Lillis R, Martin DH, Ferris MJ. Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J Clin Microbiol 2010; 48: 1812–9.
15. Lamont R, Sobel J, Akins R, Hassan S et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011; 118 (5): 533–49.
16. Fredricks DN. Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. Anaerobe 2011; 17 (4): 191–5.
17. Анкирская А.Е. Бактериальный вагиноз. Акушерство и гинекология. 2005; 6: 13–6. / Ankirskaia A.E. Bakterial'nyi vaginoz. Akusherstvo i ginekologiia. 2005; 6: 13–6. [in Russian]
18. Gelber SE, Aquilar JL, Lewis KLT, Ratner AJ. Functional and phylogenetic characterization of vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J Bacteriol 2008; 190: 3896–903.
19. Van Immerseel F, Ducatelle R, De Vos M et al. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J Med Microbiol 2010; 59 (2): 141–3.
20. Mirmonsef P, Gilbert D, Zariffard MR et al. The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol 2011; 65: 190–5.
21. Rampersaud R, Planet PJ, Randis TM et al. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J Bacteriol 2010; 193: 1034–41.
22. Усова М.А. Клинико-диагностические аспекты дисбиоза влагалища и терапия бактериального вагиноза у женщин в ранние сроки беременности. Автореф. дис. … канд. мед. наук. Самара, 2010. / Usova M.A. Kliniko-diagnosticheskie aspekty disbioza vlagalishcha i terapiia bakterial'nogo vaginoza u zhenshchin v rannie sroki beremennosti. Avtoref. dis. … kand. med. nauk. Samara, 2010. [in Russian]
23. Hay P. Reccurent bacterial vaginosis. Curr Opin Infect Dis 2009; 22 (2): 120.
24. Ya W, Reifer C, Miller LE. Efficacy of probiotic capsules for reccurent bacterial vaginosis: a double-blind, randomized, placebo-controlled study. Am J Obstet Gynecol 2010; 203 (2): 120.
25. Devillard E, Burton JP, Reid G. Complexity of vaginal microflora as analyzed by PCR denaturing gradient gel electrophoresis in a patient with recurrent bacterial vaginosis. Infect Dis Obstet Gynecol 2005; 13: 25–31.
26. Marrazzo JM, Thomas KK, Fiedler TL et al. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med 2008; 149: 20–8.
27. 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: 97–106.
28. Donders G, van Calsteren K, Bellen G et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 2009; 116 (10): 1315–24.
29. Bilardi JE, Walker S, Temple-Smith M et al. The burden of bacterial vaginosis: women’s experience of the physical, emotional, sexual and social impact of living with recurrent bacterial vaginosis. PLoS ONE 2013; 8 (9): e74378.
30. Schaller M, Weindl G. Models of oral and vaginal candidiasis based on in vitro reconstituted human epithelia for the study of host- pathogen interactions. Methods Mol Biol 2009; 470: 327–45.
31. Schaller M, Zakikhany K, Naglik JR et al. Models of oral and vaginal candidiasis based on in vitro reconstituted human epithelia. Nat Protoc 2006; 1: 2767–73.
32. Richter SS, Galask RP, Messer SA et al. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol 2005; 43: 2155–62.
33. Srikantha T, Daniels KJ, Wu W et al. Dark brown is the more virulent of the switch phenotypes of Candida glabrata. Microbiology 2008; 154: 3309–18.
34. Sobel JD. Vulvovaginal candidosis. Lancet 2007; 369: 1961–71.
35. Schaller M, Borelli C, Korting HC, Hube B. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 2005; 48: 365–77.
36. Schaller M, Korting HC, Borelli C et al. Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Infect Immun 2005; 73: 2758–65.
37. Richardson M, Rautemaa R. How the host fights against Candida infections. Front Biosci 2009; 14: 4363–75.
38. Soong D, Einarson A. Vaginal yeast infections during pregnancy. Can Fam Physician 2009; 55 (3): 255–6.
39. Oddsson K, Leifels-Fischer B, De Melo NR et al. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception 2005; 71 (3): 176–82.
40. Sivasubramanian G, Sobel JD. Refractory urinary tract and vulvovaginal infection caused by Candida krusei. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20: 1379–81.
41. Esim Buyukbayrak E, Kars B, Karsidag AY et al. Diagnosis of vulvovaginitis: comparison of clinical and microbiological diagnosis. Arch Gynecol Obstet2010; 282 (5): 515–9.
42. Морева Ж.Г., Сащенко В.П., Васильев М.М. К вопросу о значении атипичных форм трихомонад, выделенных у женщин с гинекологической патологией. Сборник тезисов Всероссийского конгресса «Амбулаторно-поликлиническая практика – новые горизонты»: 229–30. / Moreva Zh.G., Sashchenko V.P., Vasil'ev M.M. K voprosu o znachenii atipichnykh form trikhomonad, vydelennykh u zhenshchin s ginekologicheskoi patologiei. Sbornik tezisov Vserossiiskogo kongressa «Ambulatorno-poliklinicheskaia praktika – novye gorizonty»: 229–30. [in Russian]
43. Turner PJ. Extended-spectrum b-lactamases. Clin Infect Dis 2005; 41 (Suppl. 4): S273–S275.
44. Wax RG, Lewis K, Salyers AA, Taber H. Bacterial Resistance to Antimicrobials (2nd ed.). NW. Taylor & Francis Group: CRC Press, 2008.
45. Nyirjesy P, McIntosh MJ, Steinmetz JI et al. The effects of intravaginal clindamycin and metronidazole therapy on vaginal mobiluncus morphotypes in patients with bacterial vaginosis. Sex Transm Dis 2007; 34: 197–202.
46. Wertz J, Isaacs-Cosgrove N, Holzman C, Marsh TL. Temporal Shifts in Microbial Communities in Nonpregnant African-American Women with and without Bacterial Vaginosis. Interdiscip Perspect Infect Dis 2008; 2008: 181–253.
47. Spellberg BJ, Ibrahim AS, Avanesian V et al. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis 2006; 194: 256–60.
48. Spellberg BJ, Ibrahim AS, Avenissian V et al. The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect Immun. 2005; 73: 6191–3.
49. Sherrard J, Donders G, White D, Jensen JS. European IUSTI. European (IUSTI/WHO) guideline on the management of vaginal discharge 2011. Int J STD AIDS 2011; 22 (8): 421–9.
50. Workowski KA, Berman S. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59 (RR-12): 1–110.
51. Atashili J, Poole C, Ndumbe PM et al. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS 2008; 22: 1493–501.
52. Brown JM, Hess KL, Brown S et al. Intravaginal practices and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the United States. Obstet Gynecol 2013; 121 (4): 773–80.
53. Kirjavainen P, Pautler S, Baroja ML et al. Aberrant vaginal microbiota and IL-12 skewed cytokine production by antigen-presenting cells are characteristic of women prone to urinary tract infections. Clin Vaccine Immunol 2008; 16 (1): 29–36.
54. Cagayan S, Bravo SL, Fallarme A. Randomized, single-blind, one center trial comparing the efficacy, safety and acceptability of 3 day versus 7 day treatment of Gynomax in vaginitis treatment. Congress on Controversies in Obstetrics Gynecology & Infertility. Beijing, China, 2009. p. 12–5.
________________________________________________
1. Ley RE, Lozupone C, Hamady M et al. Worlds within worlds: evolution of the vertebrate gut microbiota. Nature Rev Microbiol 2008; 6: 776–88.
2. Lamont R, Sobel J, Akins R, Hassan S et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011; 118 (5): 533–49.
3. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM et al. The human microbiome project. Nature 2007; 449 (7164): 804–10.
4. Ravel J, Gajer P, Abdo Z et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 2011; 108 (Suppl. 1): 4680–7.
5. Shi Y, Chen L, Tong J, Xu C. Preliminary characterization of vaginal microbiota in healthy Chinese women using cultivation-independent methods. J Obstet Gynaecol Res 2009; 35: 525–32.
6. Yamamoto T, Zhou X, Williams CJ et al. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol 2009; 22: 11–8.
7. Chaban B, Links MG, Jayaprakash TP et al. Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome 2014; 4 (2): 23.
8. Azad MB, Konya T, Maughan H et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 2013; 185: 385–94.
9. Ronnqvist PD, Forsgren-Brusk UB, Grahn-Hakansson EE. Lactobacilli in the female genital tract in relation to other genital microbes and vaginal pH. Acta Obstet Gynecol Scand 2006; 85: 726–35.
10. Zakaria Gomaa E. Antimicrobial and anti-adhesive properties of biosurfactant produced by lactobacilli isolates, biofilm formation and aggregation ability. J Gen Appl Microbiol 2013; 59: 425–36.
11. Yamamoto T, Zhou X, Williams CJ et al. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol 2009; 22: 11–8.
12. Castro J, Henriques A, Machado A et al. Reciprocal interference between Lactobacillus spp. and Gardnerella vaginalis on initial adherence to epithelial cells. Int J Med Sci 2013; 10 (9): 1193–8.
13. Macklaim JM, Gloor GB, Anucam KC et al. Microbes and Health Sackler Colloquium: at the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci USA 2011; 108 (1): 4688–95.
14. Zozaya-Hinchliffe V, Lillis R, Martin DH, Ferris MJ. Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J Clin Microbiol 2010; 48: 1812–9.
15. Lamont R, Sobel J, Akins R, Hassan S et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011; 118 (5): 533–49.
16. Fredricks DN. Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. Anaerobe 2011; 17 (4): 191–5.
17. Ankirskaia A.E. Bakterial'nyi vaginoz. Akusherstvo i ginekologiia. 2005; 6: 13–6. [in Russian]
18. Gelber SE, Aquilar JL, Lewis KLT, Ratner AJ. Functional and phylogenetic characterization of vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J Bacteriol 2008; 190: 3896–903.
19. Van Immerseel F, Ducatelle R, De Vos M et al. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J Med Microbiol 2010; 59 (2): 141–3.
20. Mirmonsef P, Gilbert D, Zariffard MR et al. The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol 2011; 65: 190–5.
21. Rampersaud R, Planet PJ, Randis TM et al. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J Bacteriol 2010; 193: 1034–41.
22. Usova M.A. Kliniko-diagnosticheskie aspekty disbioza vlagalishcha i terapiia bakterial'nogo vaginoza u zhenshchin v rannie sroki beremennosti. Avtoref. dis. … kand. med. nauk. Samara, 2010. [in Russian]
23. Hay P. Reccurent bacterial vaginosis. Curr Opin Infect Dis 2009; 22 (2): 120.
24. Ya W, Reifer C, Miller LE. Efficacy of probiotic capsules for reccurent bacterial vaginosis: a double-blind, randomized, placebo-controlled study. Am J Obstet Gynecol 2010; 203 (2): 120.
25. Devillard E, Burton JP, Reid G. Complexity of vaginal microflora as analyzed by PCR denaturing gradient gel electrophoresis in a patient with recurrent bacterial vaginosis. Infect Dis Obstet Gynecol 2005; 13: 25–31.
26. Marrazzo JM, Thomas KK, Fiedler TL et al. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med 2008; 149: 20–8.
27. 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: 97–106.
28. Donders G, van Calsteren K, Bellen G et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 2009; 116 (10): 1315–24.
29. Bilardi JE, Walker S, Temple-Smith M et al. The burden of bacterial vaginosis: women’s experience of the physical, emotional, sexual and social impact of living with recurrent bacterial vaginosis. PLoS ONE 2013; 8 (9): e74378.
30. Schaller M, Weindl G. Models of oral and vaginal candidiasis based on in vitro reconstituted human epithelia for the study of host- pathogen interactions. Methods Mol Biol 2009; 470: 327–45.
31. Schaller M, Zakikhany K, Naglik JR et al. Models of oral and vaginal candidiasis based on in vitro reconstituted human epithelia. Nat Protoc 2006; 1: 2767–73.
32. Richter SS, Galask RP, Messer SA et al. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol 2005; 43: 2155–62.
33. Srikantha T, Daniels KJ, Wu W et al. Dark brown is the more virulent of the switch phenotypes of Candida glabrata. Microbiology 2008; 154: 3309–18.
34. Sobel JD. Vulvovaginal candidosis. Lancet 2007; 369: 1961–71.
35. Schaller M, Borelli C, Korting HC, Hube B. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 2005; 48: 365–77.
36. Schaller M, Korting HC, Borelli C et al. Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Infect Immun 2005; 73: 2758–65.
37. Richardson M, Rautemaa R. How the host fights against Candida infections. Front Biosci 2009; 14: 4363–75.
38. Soong D, Einarson A. Vaginal yeast infections during pregnancy. Can Fam Physician 2009; 55 (3): 255–6.
39. Oddsson K, Leifels-Fischer B, De Melo NR et al. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception 2005; 71 (3): 176–82.
40. Sivasubramanian G, Sobel JD. Refractory urinary tract and vulvovaginal infection caused by Candida krusei. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20: 1379–81.
41. Esim Buyukbayrak E, Kars B, Karsidag AY et al. Diagnosis of vulvovaginitis: comparison of clinical and microbiological diagnosis. Arch Gynecol Obstet2010; 282 (5): 515–9.
42. Moreva Zh.G., Sashchenko V.P., Vasil'ev M.M. K voprosu o znachenii atipichnykh form trikhomonad, vydelennykh u zhenshchin s ginekologicheskoi patologiei. Sbornik tezisov Vserossiiskogo kongressa «Ambulatorno-poliklinicheskaia praktika – novye gorizonty»: 229–30. [in Russian]
43. Turner PJ. Extended-spectrum b-lactamases. Clin Infect Dis 2005; 41 (Suppl. 4): S273–S275.
44. Wax RG, Lewis K, Salyers AA, Taber H. Bacterial Resistance to Antimicrobials (2nd ed.). NW. Taylor & Francis Group: CRC Press, 2008.
45. Nyirjesy P, McIntosh MJ, Steinmetz JI et al. The effects of intravaginal clindamycin and metronidazole therapy on vaginal mobiluncus morphotypes in patients with bacterial vaginosis. Sex Transm Dis 2007; 34: 197–202.
46. Wertz J, Isaacs-Cosgrove N, Holzman C, Marsh TL. Temporal Shifts in Microbial Communities in Nonpregnant African-American Women with and without Bacterial Vaginosis. Interdiscip Perspect Infect Dis 2008; 2008: 181–253.
47. Spellberg BJ, Ibrahim AS, Avanesian V et al. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis 2006; 194: 256–60.
48. Spellberg BJ, Ibrahim AS, Avenissian V et al. The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect Immun. 2005; 73: 6191–3.
49. Sherrard J, Donders G, White D, Jensen JS. European IUSTI. European (IUSTI/WHO) guideline on the management of vaginal discharge 2011. Int J STD AIDS 2011; 22 (8): 421–9.
50. Workowski KA, Berman S. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59 (RR-12): 1–110.
51. Atashili J, Poole C, Ndumbe PM et al. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS 2008; 22: 1493–501.
52. Brown JM, Hess KL, Brown S et al. Intravaginal practices and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the United States. Obstet Gynecol 2013; 121 (4): 773–80.
53. Kirjavainen P, Pautler S, Baroja ML et al. Aberrant vaginal microbiota and IL-12 skewed cytokine production by antigen-presenting cells are characteristic of women prone to urinary tract infections. Clin Vaccine Immunol 2008; 16 (1): 29–36.
54. Cagayan S, Bravo SL, Fallarme A. Randomized, single-blind, one center trial comparing the efficacy, safety and acceptability of 3 day versus 7 day treatment of Gynomax in vaginitis treatment. Congress on Controversies in Obstetrics Gynecology & Infertility. Beijing, China, 2009. p. 12–5.
Авторы
И.В.Кузнецова*, Ю.Б.Успенская, В.А.Каптильный
ГБОУ ВПО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2 *ms_smith@list.ru
________________________________________________
I.V.Kuznetsova*, Yu.B.Uspenskaya, V.A.Kaptilny
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 *ms_smith@list.ru