Параоксоназа: универсальный фактор антиоксидантной защиты организма человека

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.Параоксоназы – это семейство ферментов, представленное PON1, PON2 и PON3, которые обладают широкой специфичностью и каталитической универсальностью. PON1 и PON3 циркулируют в плазме в состоянии, связанном с липопротеинами высокой плотности, предотвращают окисление липропротеинов, уменьшают образование липидных пероксидов и снижают риск развития атеросклероза. PON2 является внутриклеточным ферментом и не обнаруживается в плазме.  PON2 обнаружена во многих тканях организма, включая печень, легкие, трахею, почки, сердце, поджелудочную железу, тонкий кишечник, мышцы, семенники и эндотелиальные клетки. PON2 также присутствует в дофаминергических областях головного мозга и в астроцитах. На субклеточном уровне, PON2 локализуется в митохондриях, где предотвращает накопление триглицеридов и развитие окислительного стресса. PON3 - последняя из открытых параоксоназ обладает более выраженной антиксидантной активностью. PON3 обнаружена в клетках кожи, слюнных железах, железистом эпителии желудка, кишечника, эндометрии, гепатоцитах,  клетках поджелудочной железы, сердце, жировой ткани и в легочном эпителии. PON3 недостаточно изучена, но доказано ее антиоксидантное, противовоспалительное и противомикробное действие  за счет блокирования кворум-зависимых систем бактерий. Избыточная экспрессия PON3 уменьшает образование атеросклеротических бляшек и препятствует развитию ожирения, количество PON3 увеличивается при онкологических заболеваниях, повышая сопротивление опухолевых клеток к оксидативному стрессу и апоптозу. В обзоре представлена информация о физиологической роди параоксоназ, а также их участии в развитии заболеваний, ассоциированных с окислительным стрессом (атеросклероз, эндометриоз, болезнь Паркинсона, цирроз печени, бактериальные и вирусные инфекции и опухолевые процессы)

Family planning and preconception consultation

Family planning and preconception consultation E.I. Borovkova Pirogov Russian National Research Medical University, Moscow, Russian Federation The improvement of population health and demographic indicators, in particular, active support of family, maternity, and childhood are of great importance. To achieve positive growth rate, all links of obstetrics (from out-patient consultative departments to perinatal centers) should be reorganized. In addition, women’s health should be improved. The aims of preconception consultation are to determine reproductive life plans, to avoid unplanned pregnancy, and to provide adequate prepregnancy preparation. Currently, indications for using hormonal contraceptives are very broad. Contraceptive effect of these medications is based on their central action, i.e., they suppress gonadotropin production. Therapeutic effect of combined oral contraceptives is mediated by the peripheral action of gestagenic component. Personalized approach to the prescription of combined oral contraceptives is determined by their benefits and potential adverse reactions. Adequate choice of combined contraceptives considering their potential effects minimizes the risk of adverse reactions and provides safe contraception and, if necessary, therapeutic effect. Currently, combined oral contraceptives containing levonorgestrel and ethinyl estradiol are available. Keywords: preconception consultation, prepregnancy preparation, family planning, combined oral contraceptives, levonorgestrel, ethinyl estradiol. For citation: Borovkova E.I. Family planning and preconception consultation. Russian Journal of Woman and Child Health. 2019;2(2):131–134.<br

Antenatal micronutrient support is essential for a healthy child

E.I.&nbsp;Borovkova1, A.L.&nbsp;Zaplatnikov2, E.D.&nbsp;Zhdakaeva2 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation Adequate intake of macro- and microelements during pregnancy meets the growing needs of a female organism and lays the basis for a child’s health. According to the World Health Organization, in malnutrition or chronic health conditions (i. e. gastrointestinal disorders, diabetes, hypothyroidism etc.) in a pregnant woman, additional intake of essential micronutrients is required. Cochrane Reviews demonstrate that multivitamin supplements reduce the occurrence of intrauterine growth restriction and low birthweight. Zinc is a microelement whose adequate intake is of crucial importance. Mild zinc deficiency manifests as recurrent respiratory infections, taste and smell loss, night blindness, impaired spermatogenesis, and (sometimes) mild psoriasis-like dermatitis. Severe zinc deficiency is characterized by more often respiratory infections and more severe skin conditions (e. g., acrodermatitis with erythematous, squamous, vesicular bullous, or pust ular rash in perioral and perianal areas), alopecia, persistent diarrhea, stomatitis, and glossitis, growth and developmental delay, and various psychoneurological disorders. Keywords: pregnancy, newborn, infant, vitamin mineral supplement, microelements, zinc, atopic dermatitis, deficiency. For citation: Borovkova E.I., Zaplatnikov A.L., Zhdakaeva E.D. Antenatal micronutrient support is essential for a healthy child. Russian Journal of Woman and Child Health. 2020;3(2):77–82. DOI: 10.32364/2618-8430-2020-3-2-77-82. </p

Comparative efficacy of vaginal and rectal cytokine therapy in pregnant women with cervical dysplasia

E.I.&nbsp;Borovkova1, S.A.&nbsp;Zalesskaya1, I.V.&nbsp;Stepanyants2 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2City Clinical Hospital No. 40, Moscow, Russian Federation Aim: to assess the efficacy of vaginal and rectal cytokine therapy with Superlymph in pregnant women with cervical dysplasia. Patients and Methods: 50 pregnant women with moderate cervical dysplasia were enrolled in this prospective study. 30 women received vaginal cytokine therapy and 20 women received rectal cytokine therapy. Human papillomavirus (HPV) viral load and innate immunity gene (TNF-α, TLR-9, TLR-2, HBD-1) expression levels in endocervical and vaginal epithelium were measured before and 20 days after the treatment. Results: HPV was identified in 100% of cases. HPV A9 group was identified in 83.3% in the study group and 55% in the control group. HPV-51 and HPV-56 was identified in 10% and 35%, respectively and HPV A7 group (HPV-18) in 5.6% and 10%, respectively. Vaginal cytokine therapy with Superlymph reduced HPV A9 group viral load by 1.3 times and HPV A7 group viral load by 1.8 times. No significant changes were demonstrated for HPV-51 and HPV-56. Rectal cytokine therapy reduced HPV A7 group viral load by 1.4 times. Superlymph modulated innate immunity factor expression independently of its administration route. TLR-2 and TLR-9 expression increased in vaginal epithelium while TNF-α and HBD-1 levels increased both in endocervical and vaginal epithelium. Conclusion: vaginal cytokine therapy with Superlymph provides more significant therapeutic effect manifested by elevated expression of innate immunity factors in genital tract epithelium and greater viral load reduction. Keywords: cervical dysplasia, pregnancy, human papillomavirus, innate immunity, tumor necrosis factor, TLR-9, TLR-2, HDB-1, cytokine therapy, Superlymph. For citation: Borovkova E.I., Zalesskaya S.A., Stepanyants I.V. Comparative efficacy of vaginal and rectal cytokine therapy in pregnant women with cervical dysplasia. Russian Journal of Woman and Child Health. 2019;2(3):173–176. </p

Large bowel obstruction during pregnancy: the efficacy of dietary fibers

Yu.E. Dobrokhotova, E.I.&nbsp;Borovkova, T.D.&nbsp;Simonyan, D.S.&nbsp;Selimshaeva Pirogov Russian National Research Medical University, Moscow, Russian Federation Aim: to evaluate the clinical efficacy of dietary fibers and lactulose in pregnant women with large bowel obstruction. Patients and Methods: this prospective study included 60 pregnant women (20–24 weeks of pregnancy) with large bowel obstruction occurred during pregnancy and persisted for at least 3 months. All women were randomized and divided into two groups. Group 1 received soluble fibers and group 2 received group 2 received lactulose. Clinical efficacy of treatment was evaluated using a specialized questionnaire filled at baseline, 48 h, 4 days, and 14 days after starting treatment. Results: mean age was 27.1±4.0 years in group 1 and 28.3±5.0 years in group 2. Bowel evacuation less than 3 times a week occurred in 87% and 77%, respectively, the duration of pushing occupied more than 25% of defecation in 70% and 60%, respectively, hard stool occurred in 100%, anal fissures and a feeling of incomplete evacuation were reported in 47% and 57%, respectively. Comfort bowel evacuation 48 h after starting treatment was reported in 63% of women who received dietary fibers and 47% of patients who received lactulose. Normal defecation by day 4 was observed in 80% of women in group 1 and 53% in group 2. Treatment effect was achieved by day 14 in 87% in group 1 and 70% in group 2. The most common complaint was abdominal distension that occurred 3.5 times more common after treatment with lactulose (р&lt;0.05). Conclusions: dietary fibers were more effective in terms of achieving the desired outcome and patient satisfaction. Keywords: large bowel obstruction, defecation, pregnancy, dietary fibers, OptiFibere, lactulose. For citation: Dobrokhotova Yu.E., Borovkova E.I., Simonyan T.D., Selimshaeva D.S. Large bowel obstruction during pregnancy: the efficacy of dietary fibers. Russian Journal of Woman and Child Health. 2021;4(1):36–41. DOI: 10.32364/2618-8430-2021-4-1-36-41. </p

Managing invasive cervical cancer in pregnancy

Managing invasive cervical cancer in pregnancy Yu.G.Payanidi1, E.I. Borovkova2, Yu.E. Dobrohotova2, A.M. Arutunyan2 1 Blokhin Cancer Research Center, Moscow, Russian Federation 2 Pirogov Russian National Research Medical University, Moscow, Russian Federation Cervical cancer is one of the most common cancers diagnosed during the pregnancy. Its incidence is 1.5 cases per 10 000 births. During gestation, cancer staging and treatment should meet current standards and be similar to the treatment strategy in non-pregnant women. Key treatment approaches to the invasive cervical cancer are surgery and pharmacotherapy (chemotherapy). Treatment strategy is determined by the gestational period when the condition was diagnosed, cancer stage, tumor size, and regional lymph nodes involvement. When diagnosed up to 20 weeks, treatment approach choice depends on the decision of whether to proceed a pregnancy or not. In cervix cancer stage ІА2 and stage IB1 and in tumor size less than 2 cm, conization and lymph node dissection are recommended. In case of lymph node involvement in a women who is pregnant less than 22 weeks, abortion is recommended. If a woman decides to proceed her pregnancy, neoadjuvant chemotherapy is recommended. At 22 weeks pregnancy, lymphadenectomy is challenging; cancer staging is performed by histological examination. Standard chemotherapeutic strategy involves cisplatin monotherapy or cisplatin plus paclitaxel. Keywords: pregnancy, cervical cancer, clinical guidelines, conization, neoadjuvant chemotherapy. For citation: Payanidi Yu.G., Borovkova E.I., Dobrohotova Yu.E., Arutunyan A.M. Managing invasive cervical cancer in pregnancy. Russian Journal of Woman and Child Health. 2019;2(2):135–138.<br

Long-term outcomes of cytokine therapy in pregnant women with cervical intraepithelial neoplasia

Yu.E. Dobrokhotova1, E.I. Borovkova1, V.V. Romanovskaya1, I.V. Stepanyants2 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Maternity Hospital of the City Clinical Hospital No. 40, Moscow, Russian Federation Aim: to assess long-term outcomes of exogenous cytokine therapy in pregnant women with cervical intraepithelial neoplasia (CIN). Patients and Methods: this prospective study included 50 pregnant women with CIN. Women were randomized into two groups. Group 1 women (n=30, mean age 31.6±1.7 years) received vaginal suppositories with Superlymph 25 U. Group 2 women (n=20, mean age 29.8±1.4 years) received rectal suppositories with Superlymph 25 U. Cervical smear cytology (at baseline, 22 days after starting treatment, and 6 weeks after delivery), colposcopy, and cervical biopsy (at baseline and 6 weeks after delivery) were performed. Results: in group 1, cytology revealed high-grade squamous intraepithelial lesion (HSIL) in 43.3%, atypical squamous cells-cannot exclude a high-grade lesion (ASC-H) in 6.7%, and atypical squamous cells of undetermined significance (ASCUS) in 10%. In group 2, cytology revealed low-grade squamous intraepithelial lesion (LSIL) in 25%, HSIL in 45%, ASC-H in 10%, and ASCUS in 20%. After the treatment course, in group 1, a regress from HSIL to LSIL was detected in 6.7%, regress from LSIL to ASCUS in 3.3%, and regress from HSIL to ASC-H in 3.3%. In group 2, NILM was detected in 5%, a regress from HSIL to LSIL in 5%, and regress from LSIL to ASCUS in 5%. Histologically, LSIL was verified in 50% of women of both groups, CIN grade 2 in 36.7% (group 1) and 40% (group 2), CIN grade 3 in 13.3% (group 1) and 10% (group 2). Six weeks after delivery, cytological abnormalities were identified in 30 women of both groups (HSIL in 56.7% and LSIL in 43.3%). Histology detected&nbsp; carcinoma in situ in 3.3% and CIN grade 2–3 in 53.3%. Delivery in time (on average, at 38.4±1.1 weeks of gestation) occurred in all women. Conclusion: trend toward the improvement of cytological parameters irrespective of the mode of drug administration is reported after finishing cytokine therapy. Normalization of cytological findings was reported in 3.3% (group 1) and 5% (group 2), while improvement was reported in 6.6% (group 1) and 10% (group 2). No worsening was reported. Keywords: cytokine therapy, pregnancy, cervical intraepithelial neoplasia, cytological study, histological study. For citation: Dobrokhotova Yu.E., Borovkova E.I., Romanovskaya V.V., Stepanyants I.V. Long-term outcomes of cytokine therapy in pregnant women with cervical intraepithelial neoplasia. Russian Journal of Woman and Child Health. 2022;5(2):106–111 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-106-111. </p

Current treatment approach to allergic disorders in pregnancy

Current treatment approach to allergic disorders in pregnancy E.I. Borovkova1, I.M. Borovkov2, V.I. Koroleva1, A.A. Pashchenko3 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Sechenov University, Moscow, Russian Federation 3National Medical Research Center of Obstetrics, Gynecology and Perinatology named after V.I. Kulakov,&nbsp; Moscow, Russian Federation&nbsp; The article addresses the results of systematic review of current published data on management strategy of pregnancy associated with allergic disorders. Difficulties in the diagnosis are accounted for by physiological changes and failure to perform standard testing. All diagnostic procedures aimed at identifying allergic diseases should be carried out at the stage of pregnancy planning, which is associated with an increased risk of using skin tests and stress tests. Vasomotor rhinitis of pregnancy, allergic rhinitis, sinusitis, and rhinitis medicamentosa are the most common conditions during pregnancy. Their treatment should be started with non-medical therapies, i.e., nasal lavage with salt solutions, inhalations of cromolyn sodium preparations, corticosteroids, and H1 blockers. Treatment for atopic dermatitis includes emollients and oral antihistamines. Topical hydrocortisone formulations (2C) are additional therapies. Allergic reactions do not directly affect the risk of obstetric complications. Keywords: allergy, vasomotor rhinitis, allergic rhinitis, sinusitis, urticaria, dermatosis of pregnancy, corticosteroids, histamine receptor blockers. For citation: Borovkova E.I., Borovkov I.M., Koroleva V.I., Pashchenko A.A. Current treatment approach to allergic disorders in pregnancy. Russian Journal of Woman and Child Health. 2020;3(2):70–76. DOI: 10.32364/2618-8430-2020-3-2-70-76. </p

Possibilities of preserving reproductive function in female patients with atypical hyperplasia and endometrial cancer at an early stage

O.F. Serova1, Yu.E. Dobrokhotova2, E.I. Borovkova2, A.V. Charkhifalakyan3 1Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation 2Pirogov Russian National Research Medical University, Moscow, Russian Federation 3European Medical Center, Moscow, Russian Federation Due to the childbearing shift to the fourth decade of life, the probability of detecting endometrial cancer (EС) in female patients who did not have time to realize their reproductive life plan increases. If cancer is detected in female patients of reproductive age and they want to realize their fertility in the future, this option should be considered at the stage of treatment planning. Discussion concerning the admissibility and safety of conservative EC treatment is extremely relevant in the current demographic conditions. The article considers the decision-making algorithm on the conservative therapy indication in the cancer manifestation in a female patient of reproductive age with unrealized fertility, as well as the protocol when making such a decision. Data on the frequency of pregnancy in female patients after conservative treatment of EC are given. The accumulated experience showed that drug treatment of atypical hyperplasia and initial EC is effective, and upon condition of subsequent pregnancy does not aggravate the oncological prognosis. Keywords: endometrial cancer, uterine cancer, atypical hyperplasia, pregnancy, assisted reproductive technologies, conservative therapy. For citation: Serova O.F., Dobrokhotova Yu.E., Borovkova E.I., Charkhifalakyan A.V. Possibilities of preserving reproductive function in female patients with atypical hyperplasia and endometrial cancer at an early stage. Russian Journal of Woman and Child Health. 2023;6(4):–361 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-5. </p

Chronic endometritis. Towards the improvement of diagnostic methods

A.M. Shamilova, I.Yu. Il’ina, E.I. Borovkova, Yu.E. Dobrokhotova Pirogov Russian National Research Medical University, Moscow, Russian Federation This paper reviews an important issue that significantly affects female fertility, chronic endometritis. This condition is characterized by&nbsp;clinical presentations of various severity and abnormalities of endometrial morphology. The rate of chronic endometritis varies greatly, mainly due to&nbsp;predominantly asymptomatic course and imperfect diagnostics. Pathogenic mechanisms of endometrial inflammation and different views on its effects on female reproductive potential are addressed. Further search for endometrial receptivity markers is needed as these markers will allow for assessing the severity of endometrial damage to develop the algorithm of preconception care. The authors focus on&nbsp;diagnostic techniques for chronic endometritis and their value. Immunohistochemistry of endometrium is a promising tool to be applied to diagnose endometrial inflammation and monitor treatment efficacy. A complex diagnostic approach to chronic endometritis that includes pelvic ultrasound, 20 Doppler ultrasound, assessment of endometrial microbiota, diagnostic hysteroscopy and endometrial histopathology, and&nbsp;evaluation of endometrial receptivity is useful. Keywords: chronic endometritis, termination of pregnancy, infertility, autoimmune processes, chronic inflammation, endometrial structure, immunohistochemistry. For citation: Shamilova A.M., Il’ina I.Yu., Borovkova E.I., Dobrokhotova Yu.E. Chronic endometritis. Towards the improvement&nbsp; of diagnostic methods. Russian Journal of Woman and Child Health. 2021;4(3):243–249 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-243-249. </p