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Issue. Articles

4(63) // 2016



1. Scientific researches


Value of immunohistochemical expression of Toll-like receptors and microbe components in skin for pathogenesis of psoriasis

R.L. Stepanenko, S.G. Svirid

O.O. Bogomolets National Medical University, Kyiv

Objective — to investigate the mechanisms of local immune inflammation with consideration of changes in immu­nohistochemical expression of Toll-like receptors in case of presence of microbe components in the skin of patients with psoriasis.
Materials and methods. An immunohistochemical study was conducted of biopsies taken from areas of skin psoriasis rash and intact skin of 74 patients with psoriasis. To determine the nature and extent of local cellular immune and inflammatory responses in these areas we used immunohistochemical techniques for detecting the expression of TLR2, TLR4 markers as well as the presence and species composition of microbial colonies. To compare the results of immunohistochemical study we investigated the biopsy material of anterior abdominal wall skin in healthy age-matched individuals (5 patients) who underwent hernia repair surgery.
Results and discussion. A close contact was revealed of TLR2-positive macrophages in subepithelial areas with positively stained dendritic cells of the epidermis. In these areas, the marker expression was observed in the epithelial cells on the entire thickness of the layer down to the keratic layer. These structural features are indicative of macrophage activation by dendritic cells of the epidermis which bind and concentrate the appropriate ligands. Similar changes are determined in TLR4 expression. Even after treatment we determined a significant number of TLR4-positive dendritic cells of significantly larger size which were distributed in the epidermis down to the keratic layer. Moreover we observed an intense background cytoplasmic staining of these cells. There were colonies of microorganisms in the keratic scales. The scales of the keratic layer of patients with psoriasis have a loose structure, which creates conditions for their colonization by a significant number of microorganisms whose waste products can act as ligands to activation of Toll-like receptors. The results of immunohistochemical studies of biopsy material taken from the area of skin damaged by psoriasis, and the area of intact skin before and after a course of systemic immunosuppressive therapy, suggest a significant role of Toll-like receptors (TLR2, TLR4) expression and presence of microbial components in the development of immune inflammation.
Conclusions. Patients with psoriasis showed overproduction and hypersecretion of epithelial cells of proinflammatory biomarkers, particularly, TLR2- and TLR4-positive cells. The corresponding TLR-positive cells were found both in pso­riatic and intact skin. TLR2- and TLR4-positive macrophages after their activation in the dermal papilla migrate to the base of the papillae, where they penetrate into the inflammatory infiltrates located around blood vessels. After systemic immunosuppressive therapy we observed a reduction of number of cells (both dendritic and macrophages) marked with TLR2 and TLR4 expression. The continued presence of the bacterial component in the area of skin affected with psoriatic rash may be one of the pathogenetic factors stimulating the production of proinflammatory cytokines, which contributes to the inflammatory psoriatic process. The expression of TLR-positive cells in the epidermis and dermis of psoriasis patients indicates that an important link in the pathogenesis of this dermatosis is the antigenic stimulation of immunocompetent cells which leads to the development of inflammation in the superficial layers of the skin. Further in-depth research into the relationship of persistent skin staphylococci with factors of innate immunity, particularly, Toll-like receptors, is promising for obtaining new data on the pathogenesis of psoriasis and detailed information about violations of innate immunity and proliferative activity of keratinocytes in psoriatic plaques.

Keywords: psoriasis, Toll-like receptors, microflora of skin, systemic immunosuppressive therapy.

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Original language: Ukrainian

2. Scientific researches


Association of rubidium toxic effects on formation of atopic dermatitis in children

Ya. O. Zaychenko

Danylo Halytskiy Lviv National Medical University

Objective — to study the humoral immune response in children with manifestations of AD and comparative analysis of concentrations in the hair iron, copper, manganese, chromium, rubidium, nickel and lead.
Materials and methods. The quantitative composition of microelements in the body was determined by X-­ray fluorescence method («Elva-X med» analyzer), and serum IgE — by Roche Diagnostics test system (Switzerland).
Results and discussion. Atopic dermatitis (children form in the acute stage) was diagnosed in all children. We fixed reduced levels of essential microelements such as iodine, iron, copper, manganese, chromium and increased level of conventionally existing element rubidium. Increased IgE level in children of the study group was registered.
Conclusions. Excess of conventionally existing microelement rubidium is of toxic nature, which generates persistent manifestations of atopic dermatitis in children. The risk increases by 81 % and is associated with elevated IgE levels.

Keywords: atopic dermatitis, IgE, rubidium.

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Original language: Ukrainian

3. Scientific researches


Immuno-morphological features of cytotoxic cells in the lesion focus at the advanced stage of mycosis fungoides

L.M. Hamadeh

O.O. Bogomolets National Medical University, Kyiv

Objective — to study the state of the qualitative and quantitative composition of the cytotoxic cells (CD8+ T-lymphocytes, NK cells and granzyme B positive cells) of affected skin of patients with advanced form of mycosis fungoides.
Materials and methods. The material for the study of skin biopsies were taken from 5 patients with a patchy form of mycosis fungoides (MF). Full complex immunological examination was performed at the Department of Clinical Immunology and Allergology together with Medical Genetics Section of O.O. Bogomolets National Medical University. The immunohistochemical reactions were studied with the use of a standardized procedure involving serial paraffin sections of 3—5 micrometers thick, placed on the adhesive glass coated with poly L-lysine (Menzel-Glaser, Germany) and reagents of DAKO company. Immunohistochemical panel included the following antibodies: CD3, CD4, CD8 and CD56 by Dako Cytomation. For visualization we used Processor EnVision ™ FLEX+, Mouse, High pH (Link), Code K8012 on DAKO autosteiner.
Results and discussion. In the skin of patients with a patchy form of mycosis fungoides during microscopy with hematoxylin-eosin staining we observed moderate thickening of the epidermis (due to the proliferation of cells of the Malpighian layer), a slight spongiosis, acanthosis and moderate hyperkeratosis. Infiltrate cells were characterized by a moderate cell polymorphism: cell size, core density, single cells of Sezary type. There was no clearly marked presence of neutrophil and eosinophil leucocytes. In patients with progressive stage of MF, immunohistochemical reactions with CD4 and CD8 monoclonal antibodies are characterized by sharp increase in lymphocyte cell number in the dermal infiltrate with a predominance of CD8 positive cytotoxic T-lymphocytes found in the 5 fields at a magnification of 200. The presence of a sufficiently large number of cytotoxic cells at progressive stage of mycosis fungoides is probably caused by the phenotypic characteristics of the antigens of the tumor infiltrating lymphocytes. Perhaps they are cells-«witnesses» that are non-specifically involved in the formation of metastases in cutaneous T-cell lymphoma, and do not make any direct threat to the cytotoxic tumor cells. The activation of these cells can be considered as a response of the body to the proliferation of the tumor. The latter option is confirmed by other studies which analyzed the proportion of CD8+ and NK-cells in relation to the various forms of mycosis fungoides. These studies have shown that patients with progressive form of MF had an increased number of tumor infiltrating CD8+ T-lymphocytes in their skin lesions compared to patients who have a limited manifestation of the disease. At the same time, patients with a higher proportion of tumor infiltrating CD8+ T-lymphocytes showed better survival rate than those with the reduced number of CD8+-lymphocytes.
Conclusions. Patients with progressive course of mycosis fungoides are characterized by high percentages of cytotoxic cells (CD8+ T-lymphocytes, NK-cells and granzyme B positive cells) in infiltrates of the lesions, which can be used as a diagnostic criterion for the prediction and progression of the disease.

Keywords: mycosis fungoides, progressive stage, immunomorphology, CD4+/CD8+-lymphocytes ratio, NK-cells, granzyme B positive cells.

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Original language: Russian

4. Reviews


The dark side of visible light

C. Diehl

Universitá Degli Studi Guglielmo Marconi, Rome, Italy

Visible light features the portion of electromagnetic radiation visible to the human eye (400 to 700 nm). The visible spectrum comprises 38.9% of sunlight when it reaches the surface of the earth, but visible light also encompasses artificial light used in daily life. Due to its wavelength, visible light is able to penetrate deep in dermis and even reach the hypodermis. For this reason, it displays various physiological effects on the skin, among them inducing skin pigmentation or promoting the production of reactive oxygen species (ROS) as much as ultraviolet radiations (UVR). It is also able to increase the production of pro-inflammatory cytokines and matrix metalloproteinases (MMP) which play a major role in skin aging.
Visible light also affects DNA through the formation of oxidized DNA bases, thus promoting skin aging and carcinogenesis.
For various decades, dermatologists are promoting the use of photo protectors, which in reality only protect against ultraviolet A (UVA) and ultraviolet B (UVB) radiation. It is time to consider that visible light is a threat for the skin and that an effective photo protection should also include protection against visible light.

Keywords: Visible light, skin pigmentation, ROS, carcinogenicity, solar urticarial, chronic actinic dermatitis, polymorphous light eruption.

List of references:  
1.    Diffey B.L., Kochevar I.E. Basic principles of photobiology. In: Photodermatology (Lim H.W., Hönigsmann H., Hawk J.L., eds), New York: Informa Healthcare USA, 2007.— P. 15—27.
2.    Frederick J.E., Snell H.E., Haywood E.K. Solar ultraviolet radiation at theearth’s surface // Photochem. Photobiol.— 1989.— Vol. 50.— P. 443—450.
3.    Mahmoud B.H., Ruvolo E., Hexsel C.L. et al. Impact of long-wavelength UVA and visible light on melanocompetent skin // J. Invest. Dermatol.— 2010.— Vol. 130 (8).— P. 2092—2097.
4.    Fodor L. et al. Aesthetic Applications of Intense Pulsed Light. Chap 2: Light Tissue Interactions Springer-Verlag London Limited.— 2011.
5.    From laser safety training, http://oregonstate.edu/ehs/book/export/html/381 Last access 10 September 2016.
6.    Pathak M.A., Riley F.C., Fitzpatrick T.B. () Melanogenesis in human skin following exposure to long-wave ultraviolet and visible light // J. Invest. Dermatol.— 1962.— Vol. 39.— P. 435—443.
7.    Kollias N., Baqer A. An experimental study on the changes in pigmentation in human skin in vivo with visible and near infrared light // Photochem. Photobiol.— 1984.— Vol. 39 (5).— P. 651—659.
8.    Porges S.B., Kaidbey K.H., Grove G.L. Quantification of visible light-induced melanogenesis in human skin // Photodermatol.— 1988.— Vol. 5 (5).— P. 197—200.
9.    Duteil L., Cardot-Leccia N., Queille-Roussel C. et al. Diffe­rences in visible light-induced pigmentation according towavelengths: a clinical and histological study in comparison with UVBexposure // Pigment Cell Melanoma Res.— 2014.— Vol. 27 (5).— P. 822—826.
10.    Randhawa M., Seo I.S., Liebel F. et al. Visible light induces melanogenesis in human skin through a photoadaptive response // PLoS One.— 2015.— Vol. 10 (6).— P. e0130949.
11.    Verallo-Rowell V.M., Pua J.M., Bautista D. Visible light photopatch testing of common photocontactants in fema­lefilipino adults with and without melasma: a cross-sectional study // J. Drugs. Dermatol.— 2008.— Vol. 7 (2).— P. 149—156.
12.    Seo I., Baqer A., Kollias N. The effect of visible light and near-infrared radiation on constitutive pigment of patients with vitiligo // Br. J. Dermatol.— 2010.— Vol. 163 (1).— P. 211—213.
13.    Boonstra H.E., van Weelden H., Toonstra J., van Vloten W.A. Polymorphous light eruption: A clinical, photobiologic, and follow-upstudy of 110 patients // J. Am. Acad. Dermatol.— 2000.— Vol. 42 (2 Pt. 1).— P. 199—207.
14.    Liebel F., Kaur S., Ruvolo E. et al. Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes // J. Invest. Dermatol.— 2012.— Vol. 132 (7).— P. 1901—1907.
15.    Jost M., Kari C., Rodeck U. The EGF receptor — ​an essential regulator of multiple epidermal functions // Eur. J. Dermatol.— 2000.— Vol. 10 (7).— P. 505—510.
16.    Zastrow L., Groth N., Klein F. et al. The missing link — ​light-induced (280—1,600 nm) free radical formation in human skin // Skin Pharmacol. Physiol.— 2009.— Vol. 22 (1).— P. 31—44.
17.    Chiarelli-Neto O., Ferreira A.S., Martins W.K. et al. Melanin photosensitization and the effect of visible light on epithelial cells // PLoS One.— 2014.— Vol. 9 (11).— P.  e113266.
18.    Ogilby P.R. (2010) Singlet oxygen: there is indeed something new under the sun.Chemical Society reviews 39: 3181—3209.
19.    Papp A.M., Nyilas R., Szepesi Z. et al. Visible light induces matrix metalloproteinase‑9 expression in rat eye // J. Neu­rochem.— 2007.— Vol. 103 (6).— P. 2224—2233.
20.    Cho S., Lee M.J., Kim M.S. et al. Infrared plus visible light and heat from natural sunlight participate inthe expression of MMPs and type I procollagen as well as infiltrationof inflammatory cell in human skin in vivo // J. Dermatol. Sci.— 2008.— Vol. 50 (2).— P. 123—133.
21.    Cadet J., Berger M., Douki T. et al. Effects of UV and visible radiation on DNA-final base damage // Biol. Chem.— 1997.— Vol. 378 (11).— P. 1275—1286.
22.    Kielbassa C., Roza L., Epe B. Wavelength dependence of oxidative DNA damage induced by UV and visible light //Carcinogenesis.— 1997.— Vol. 18 (4).— P. 811—816.
23.    Pflaum M., Kielbassa C., Garmyn M., Epe B. Oxidative DNA damage induced by visible light in mammalian cells: extent, inhibition by antioxidants and genotoxic effects // Mutat. Res.— 1998.— Vol. 408 (2).— P. 137—146.
24.    Hoffmann-Dörr S., Greinert R., Volkmer B., Epe B. Visible light (> 395 nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers // Mutat. Res.— 2005.— Vol. 572 (1—2).— P. 142—149.
25.    Denda M., Fuziwara S. Visible Radiation Affects Epidermal Permeability BarrierRecovery: Selective Effects of Red and Blue Light // J. Invest. Dermatol.— 2008.— Vol. 128.— P. 1335—1336.
26.    Hölzle E. Lichturtikaria. In: Hölzle E: Photodermatosenund Lichtreaktionender Haut. Wissenschaftliche Verlags­gesellschaft, Stuttgart, 2003.— P. 130—153.
27.    Botto N.C., Warshaw E.M. Solar urticaria // J. Am. Acad. Dermatol.— 2008.— Vol. 59.— P. 909—920.
28.    Paek S.Y., Lim H.W. Chronic actinic dermatitis // Dermatol. Clin.— 2014.— Vol. 32 (3).— P. 355—361.
29.    Kurumaji Y., Miyamoto C., Fukuro S. et al.Chronic actinic dermatitis: a clinical and photobiological study in 6 Japanese patients // Dermatology.— 1994.— Vol. 189 (3).— P. 241—247.
30.    Hu S.C.S., Lan C.C.E. Tungsten lamp and chronic actinic dermatitis // Australas. J. Dermatol.— 2015.— Doi: 10.1111.
31.    Gruber-Wackernagel A., Byrne S.N., Wolf P. Pathoge­nicme­chanisms of polymorphic light eruption // Front Biosci (Elite Ed).— 2009.— Vol. 1.— P. 341—354.
32.    Frain-Bell W., Dickson A., Herd J., Sturrock I. The action spectrum in polymorphic light eruption // Br. J. Dermatol.— 1973.— Vol. 89.— P. 243—249.

Additional: Dr. Christian Diehl, Department of Dermatology, Universitá Degli Studi Guglielmo Marconi
Via Plinio, 44, 00193, Rome, Italy. -mail: chdiehl@hotmail.com

Original language: English

5. Reviews


Acne: current concepts f pathogenesis, treatment and identification of promising ways to increase effectiveness of therapy

A. S. Svyryd-Dzyadykevych

O.O. Bogomolets National Medical University, Kyiv

Objective — to analyze the contemporary literary publications on pathogenesis and complex treatment of acne, explore the state of metabolic processes in peripheral blood leukocytes of patients with this dermatosis and determine the prospects of improving the efficiency of treatment involving new techniques, including plasma therapy.
Materials and methods. We analysed current literary publications on the possible factors of occurrence, mechanisms of development, clinical course and proposed methods of treatment of acne. Our own studies were conducted of 26 patients with acne (15 women, 14 men) with an average severity of the clinical course of dermatosis. Age of the patients ranged from 18 to 34 years. The state of metabolism in leukocytes of peripheral blood of the patients was assessed by determining the parameters of phospholipids and glycogen content. The level of phospholipids was determined by reaction of sudanophilic color, and glycogen content — by PAS reaction. The control group consisted of 15 healthy individuals of similar age. The reaction was assessed by determining the mean cytochemical coefficient (MCC). Statistical analysis of the survey results was performed using the computer program Microsoft Excel 2000.
Results and discussion. Reliable reduction of phospholipids in cells of peripheral blood was found in the patients under surveillance. Particularly, in neutrophils MCC = 1.72 ± 0.10 (in the control group MCC = 2.34 ± 0.07, p < 0.05), and in monocytes MCC = 0.87 ± 0.08 (in  the control group MCC = 1.19 ± 0.06, p < 0.05). Levels of glycogen changed in another way. Thus, in neutrophils we recorded reliable suppression of the contents of this metabolite, MCC = 1.76 ± 0.12 (in the control group MCC = 2.31 ± 0.08, p < 0.05), while in monocytes we recorded the growth to MCC = 1.13 ± 0.05 (in the control group MCC = 0.70 ± 0.03, p <0.05). Analysis of the relationship of changes in these metabolites showed its expressiveness. In particular, for phospholipids 2 = +0.82, and for glycogen 2 = –0.61.
Conclusions. Patients with acne had a reliable decrease of phospholipids level and increase of glycogen in peripheral blood monocytes, which indicates the development of intracellular metabolic imbalance. The metabolic changes in the body of patients with acne indicate the advisability of using allopathic and antihomotoxic therapy for this dermatosis, which will enhance the effectiveness of therapy.

Keywords: acne, pathogenesis, clinical picture, metabolic imbalances in peripheral blood leukocytes, comprehensive treatment.

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Original language: Ukrainian



Probiotic-vitamin-mineral complex in treatment of microsporia

S. I. Nakonechna

Poltava Regional Clinical Dermatovenerologic Dispensary

Objective — to increase the effectiveness of treatment of children suffering from microsporia by application of probiotic-vitamin-mineral complex therapy.
Materials and methods. The study involved 55 sick children aged 4 to 15 (28 girls and 27 boys): 12 of them suffered from microsporia of the scalp, 10 patients suffered from microsporia of the scalp and smooth skin. 45 patients were recorded to suffer from cold-related diseases: respiratory infections (33 cases) and their complications (12 cases), pharyngitis (4 cases), bronchitis (5 cases) and pneumonia (3 cases). All patients with microsporia of the scalp, microsporia of the scalp and smooth skin were prescribed griseofulvin tablets at a rate of 21—22 mg per 1 kg of body weight of the patient. The daily dose was divided into three intakes. All patients suffering from microsporia of smooth skin were prescribed terbinafine depending on body weight, with a body weight less than 20 kg — 62.5 mg/day (1/4 tablet), from 20 to 40 kg — 125 mg/day (1/2 tablets), more than 40 kg — 250 mg/day (1 tablet) once a day. Treatment duration ranged from 3 to 6 weeks. Systemic therapy was combined with external treatment. All patients were prescribed probiotic-vitamin-mineral complex «Bion 3 Kid» depending on age: for children from 4 to 12 years — 1 chewing tablet a day, for children from 12 years and older — 2 chewable tablets a day for 30 days.
Results and discussion. As a result of griseofulvin and terbinafine treatment in combination with the probiotic-vitamin-mineral complex«Bion 3 Kid» we achieved clinical and etiological recovery of all 55 patients suffering from microsporia. The treatment duration ranged from 3 to 6 weeks. There was good tolerability of drugs, unchanged indicators of general and biochemical blood and urine tests after completion of therapy.
Conclusions. The original probiotic-vitamin-mineral complex «Bion 3 Kid» is effective and safe for treatment of children suffering from microsporia of scalp and smooth skin. Inclusion of «Bion 3 Kid» combined with systemic antimycotics terbinafine and griseofulvin in the complex treatment provided an opportunity to improve outcomes, accelerate clinical and mycological cure, and prevent disease recurrence. This comprehensive treatment was effective for microsporia and concomitant cold-related diseases and their complications.

Keywords: microsporia, children, cold-related diseases, complications, treatment, griseofulvin, terbinafine, probiotic-vitamin-mineral complex.

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Original language: Ukrainian



Atopic dermatitis in adults: principles of local treatment and cosmetic care

E.A. Bardova

P.L. Shupyk National Medical Academy of Postgraduate Education, Ministry of Healthcare of Ukraine, Kyiv

The aim of the work is treatment of atopic dermatitis, elimination of inflammation and negative influence of related microflora and infection of the skin, restoration of barrier function of epidermis, decrease of lesions of the skin caused by scratches and control of initiating agents.

Keywords: atopic dermatitis, topical corticosteroids, treatment, dry skin.

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Original language: Ukrainian



New opportunities of external therapy of scalp psoriasis

L.D. Kalyuzhna1, L.V. Grechanska1, N.V. Turik2, A.M. Boychuk2, A.A. Makhamova2

1 P.L. Shupyk National Medical Academy of Postgraduate Education, Ministry of Healthcare of Ukraine, Kyiv
2 Kyiv City Clinical Skin and Venereal Diseases Hospital

The article presents data of clinical observations of patients with scalp psoriasis who were treated by medication «Dermalex Scalp Psoriasis gel» as external therapy. It showed high clinical efficacy and good tolerability that allows recommending it for long­term non­hormonal treatment of scalp psoriasis.

Keywords: psoriasis, scalp, external treatment, index PSSI.

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Original language: Ukrainian



Differential diagnostic and clinical features of pyoderma gangrenosum

M. E. Zapolskiy1, M. N. Lebediuk1, N. B. Prokofyeva1, S. I. Komarov2, K.A. Borisova2, A.V. Dobrovolskaya3

1 Odessa National Medical University, Odessa, Ukraine
2 Regional Dermatovenereological dispensary, Odessa, Ukraine
3 Clinic «Medical Renaissance», Odessa, Ukraine

The article deals with the etiopathogenetical aspects of gangrenous pyoderma (GP), the main trigger factors and features of clinical forms of the disease based on the international classification of the European Association of Dermatologists (2015). The main differential diagnostic criteria of GP are discussed. The clinical observation of 18 patients with a morphologically confirmed diagnosis of GP are presented. The disease is more common in women aged 46 to 65 years. The most common manifestation of the GP was its ulcerous form with the localization in the lower legs (61.1 % of cases). Less commonly encountered were pustular, vegetans, bullous forms of the disease. Bullous forms of pyoderma gangrenosum with a tendency to dissemination were the most aggressive.

Keywords: pyoderma gangrenosum, diagnostic criteria, differential diagnosis.

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Original language: Russian



Formation of national female medical education as example of optimization of medical education

K.V. Kolyadenko

O.O. Bogomolets National Medical University, Kyiv

The development of higher female medical education had a great influence on the development of medicine as a whole. Now, when we are looking for ways to improve the national health service, we need to know and be able to compare the present with the past experience.
The famous dermatologist Professor Sergey Petrovich Tomaszewski can be seen as an example of desire to optimize higher medical education which led to the change of his attitude towards its provision for women. Many qualified doctors came to medicine as a result. Today, women have no obstacles, but the events of that time can be an example for today’s students of desire for higher education, which changed the whole system of medical education. Also the example of Nadia Payot shows how the profession of dermato-cosmetology has been evolving.
Bibliographic and archival methods as well as method of structural and logical analysis were used.

Keywords: female medical education, S. Tomashevsky, St. Vladimir University, medical science.

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Original language: Ukrainian