Целью исследования являлось изучение кинетики накопления 5-аминолевулиновой кислоты (5-АЛК) – индуцированного протопорфирина IX в слизистой кожи, влагалища и вульвы у женщин с хроническим вульвовагинальным кандидозом после применения препарата 5-АЛК и выбор оптимальных временных режимов проведения флюоресцентной диагностики и фотодинамической терапии (ФДТ) при хроническом вульвовагинальном кандидозе. В исследовании приняли участие 60 пациенток: 20 с вульвовагинальным кандидозом, 25 – с бактериальным вагинозом и 15 – с неспецифическим вагинитом, которым проводилось по 4 сеанса ФДТ. Перед каждым сеансом ФДТ и после были сняты спектры флюоресценции фотосенсибилизатора, который накапливался во влагалище и вульве у пациенток при аппликативном применении геля 5-АЛК, индуцирующего селективное накопление протопорфирина IX. С помощью метода локальной флюоресцентной спектроскопии показано, что различие между накоплением фотосенсибилизатора до сеанса в разных тканях и между 1, 2, 3 и 4-м сеансами статистически значимо (p<0,01). Отмечается, что после 4-го сеанса не было отличий накопления фотосенсибилизатора в слизистой влагалища больных хроническим вульвовагинальным кандидозом и здоровой ткани, таким образом, возможно сделать вывод о высокой эффективности проведенной терапии.
The aim of the presented research was investigation of induced by 5-ALA PPIX accumulation kinetics in mucosa, vagina and vulva chronic in women with vulvovaginal candidiasis after treatment of 5-ALA and the choice of optimal time mode of fluorescence diagnosis and photodynamic therapy (PDT) in chronic vulvovaginal candidiasis. The investigation was held in group of 60 women: 20 with vulvovaginal candidiasis, 25 – bacterial vaginosis, 15 – nonspecific vaginitis. Each woman had 4 sessions of PDT. Before and after each of the sessions fluorescence diagnosis (FD) of photosensitizer accumulated in mucosa, vagina and vulva was performed. By means of local fluorescent spectroscopy difference of accumulated PPIX was estimated with statistical methods. It was obtained, that difference between accumulation of PPIX after 1, 2, 3 and 4th session is statistically significant. After the 4th session it was estimated that there is no significant statistical difference between PPIX accumulated in healthy tissue and mucosa of vagina. According to this we concluded, that PDT in this case showed high efficiency.
1. Прилепская В.Н. Заболевания шейки матки, влагалища и вульвы. М., 2000.
2. Abdel-Hady E, Hirsch P, Keen M et al. Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res 2001; 61: 192–6.
3. Batlle AM. Porphyrins, porphyrias, cancer and photodynamic therapy – a model for carcinogenesis. J Photochem Photobiol 2005; 20: 5–22.
4. Bernard H, Chan S, Manos M. Identification and assessment of known and novel human papillomavirus by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence and phylogenetic algorithms. J Infect Dis 1998; 170: 1077–85.
5. Boegheim JPJ, Lagerberg JWM, Dubbelman TMAR et al. Photodynamic effects of hematoporphyrin derivative on the uptake of rhodamine 123 by mitochondria of intact murine L929 fibroblasls and Chinese hamster ovary Kl cells. Photochem Photobiol 1988; 48: 613–20.
6. Bonnet R, Berenbaum ML. Porphyrins as photosensitizers. In: Photosensitizing compounds: their chemistry, biology and clinical use (Eds.: Bock G, Harnett S.), John Wiley & Sons, Chichester, 1989; 40–9.
7. Bottiroli G, Croce АС, Ramponi R, Vaghi P. Distribution of di-sulfonated aluminium phthalocyanine and photofrin II in living cells: a comparative fluorometric study. Photochem Photobiol 1992; 55: 575–85.
8. Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncology 2004; 497–508.
9. Coppleson M. The origin and nature of premalignant lesions of the cervix uteri. Intl J Gynecol Obstet 1970; 8: 539.
10. Dougherty TJ. Yearly Review: Photosensitizers: Therapy and detection of malignant tumors. Photochem Photobiol 1987; 45; 879–89.
11. Fehr M, Hornung R, Degen A et al. Phodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulenic acid. Lasers Surg Med 2002; 20: 273–9.
12. Fukuda H, Batlle MC, Riley PA. Kinetics of porphyrin accumulation in cultured epithelial cells exposed to ALA. Int J Biochem 1993; 25: 1407–10.
13. Gissmann L, Zur Hausen H. Partial: characterisation of viral DNA from genital warts. Inst J Cancer 1980; 25; 605–9.
14. Goff BA, Bachor R, Kollias N, Hasan Т. Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. J Photochem Photobiol В 1992; 15: 239–51.
15. Gross G, Ikenberg H, Gissmann L, Hagedorn M. Papillomavirus infection of the anogenital tract: con-elation between histology, clinical picture and virus type. Proposal of new nomenclature. J Invest Dermatol 1985; 85: 147–52.
16. Gross G, Pfister H, Hagedorn M, Gissmann L. Correlation between human papillomavirus type and histology of warts. J Invest Dermatol 1982; 78; 160–4.
17. Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol 1992; 55: 145–57.
18. Henderson BW, Bellnier DA. Tissue localisation of photosensitizers and the mechanism of photodynamic tissue destruction. In: Photosensitizing compounds: their chemistry, biology and clinical use, (Eds.: Bock, G., Harnett, S.), John Wiley & Sons, Chichester, 2005; 112–30.
19. Hillemanns P, Landsmann H, Kiinmig R. Behandlung der Zervixdysplasien. Empfehlungen zur Diagnostik, Therapie und Nachsorge Zervixkarzinom, 2004; 31–40.
20. Hillemanns P, Thaler C, Kimmig R. Epidemiologie und Diagnostik der zervikalen intraepithelialen Neoplasie: 1st das derzeitige Konzept von Screening und Diagnostik noch aktuell? Gynakol Geburtshilfliche Rundsch 1997; 37: 179–90.
21. Jones H. Cone biopsy and hysterectomy in the management of cervical intraepithelial neoplasia. Clin Obstet Gyneacol 2005; 9; 221–36.
22. Lin C. Photodynamic Therapy of malignant tumours – recent developments. Cancer Cells 1991; 3: 437–44.
23. MacRobert AJ, Bown SG, Phillips D. What are the ideal photoproperties for a sensitizer? In: Photosensitizing compounds: their chemistry, biology and clinical use, (Eds.: Bock G, Harnett S), John Wiley & Sons, Chichester, 2004; 4–16.
24. Michaeli A, Feitelson J. Reactivity of singlet oxygen toward ammo acids and peptides. Photochem Photobiol 2001; 59: 284–9.
25. Moan J, Berg K. Photochemotherapy of cancer: experimental research. Photochem Photobiol 2001; 55: 931–48.
26. Modrow S, Falke D. Aufbau der Papillomviren, in Spectrum: Molekulare Virologie. Spectrum 2001; 374–90.
________________________________________________
1. Прилепская В.Н. Заболевания шейки матки, влагалища и вульвы. М., 2000.
2. Abdel-Hady E, Hirsch P, Keen M et al. Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res 2001; 61: 192–6.
3. Batlle AM. Porphyrins, porphyrias, cancer and photodynamic therapy – a model for carcinogenesis. J Photochem Photobiol 2005; 20: 5–22.
4. Bernard H, Chan S, Manos M. Identification and assessment of known and novel human papillomavirus by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence and phylogenetic algorithms. J Infect Dis 1998; 170: 1077–85.
5. Boegheim JPJ, Lagerberg JWM, Dubbelman TMAR et al. Photodynamic effects of hematoporphyrin derivative on the uptake of rhodamine 123 by mitochondria of intact murine L929 fibroblasls and Chinese hamster ovary Kl cells. Photochem Photobiol 1988; 48: 613–20.
6. Bonnet R, Berenbaum ML. Porphyrins as photosensitizers. In: Photosensitizing compounds: their chemistry, biology and clinical use (Eds.: Bock G, Harnett S.), John Wiley & Sons, Chichester, 1989; 40–9.
7. Bottiroli G, Croce АС, Ramponi R, Vaghi P. Distribution of di-sulfonated aluminium phthalocyanine and photofrin II in living cells: a comparative fluorometric study. Photochem Photobiol 1992; 55: 575–85.
8. Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncology 2004; 497–508.
9. Coppleson M. The origin and nature of premalignant lesions of the cervix uteri. Intl J Gynecol Obstet 1970; 8: 539.
10. Dougherty TJ. Yearly Review: Photosensitizers: Therapy and detection of malignant tumors. Photochem Photobiol 1987; 45; 879–89.
11. Fehr M, Hornung R, Degen A et al. Phodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolevulenic acid. Lasers Surg Med 2002; 20: 273–9.
12. Fukuda H, Batlle MC, Riley PA. Kinetics of porphyrin accumulation in cultured epithelial cells exposed to ALA. Int J Biochem 1993; 25: 1407–10.
13. Gissmann L, Zur Hausen H. Partial: characterisation of viral DNA from genital warts. Inst J Cancer 1980; 25; 605–9.
14. Goff BA, Bachor R, Kollias N, Hasan Т. Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. J Photochem Photobiol В 1992; 15: 239–51.
15. Gross G, Ikenberg H, Gissmann L, Hagedorn M. Papillomavirus infection of the anogenital tract: con-elation between histology, clinical picture and virus type. Proposal of new nomenclature. J Invest Dermatol 1985; 85: 147–52.
16. Gross G, Pfister H, Hagedorn M, Gissmann L. Correlation between human papillomavirus type and histology of warts. J Invest Dermatol 1982; 78; 160–4.
17. Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol 1992; 55: 145–57.
18. Henderson BW, Bellnier DA. Tissue localisation of photosensitizers and the mechanism of photodynamic tissue destruction. In: Photosensitizing compounds: their chemistry, biology and clinical use, (Eds.: Bock, G., Harnett, S.), John Wiley & Sons, Chichester, 2005; 112–30.
19. Hillemanns P, Landsmann H, Kiinmig R. Behandlung der Zervixdysplasien. Empfehlungen zur Diagnostik, Therapie und Nachsorge Zervixkarzinom, 2004; 31–40.
20. Hillemanns P, Thaler C, Kimmig R. Epidemiologie und Diagnostik der zervikalen intraepithelialen Neoplasie: 1st das derzeitige Konzept von Screening und Diagnostik noch aktuell? Gynakol Geburtshilfliche Rundsch 1997; 37: 179–90.
21. Jones H. Cone biopsy and hysterectomy in the management of cervical intraepithelial neoplasia. Clin Obstet Gyneacol 2005; 9; 221–36.
22. Lin C. Photodynamic Therapy of malignant tumours – recent developments. Cancer Cells 1991; 3: 437–44.
23. MacRobert AJ, Bown SG, Phillips D. What are the ideal photoproperties for a sensitizer? In: Photosensitizing compounds: their chemistry, biology and clinical use, (Eds.: Bock G, Harnett S), John Wiley & Sons, Chichester, 2004; 4–16.
24. Michaeli A, Feitelson J. Reactivity of singlet oxygen toward ammo acids and peptides. Photochem Photobiol 2001; 59: 284–9.
25. Moan J, Berg K. Photochemotherapy of cancer: experimental research. Photochem Photobiol 2001; 55: 931–48.
26. Modrow S, Falke D. Aufbau der Papillomviren, in Spectrum: Molekulare Virologie. Spectrum 2001; 374–90.
1. Кафедра акушерства, гинекологии, перинатологии и репродуктологии ИПО ГБОУ ВПО Первый МГМУим. И.М.Сеченова Минздрава России;
2. ФГБУ Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова Минздрава России; 3ИОФ РАН Лаборатория лазерной биоспектроскопии Universite de Lorraiene, CRAN, ENSEM, Франция