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Aim. To determine the incidence of premature ovarian failure (POF) and early menopause with regard to reproductive status in carriers of the pathogenic variant of the BRCA1 gene. Materials and methods. According to the inclusion and exclusion criteria, out of 90 carriers of pathogenic variants of the BRCA1 gene, 38 females were included in the study group, and 110 females without these pathogenic variants were included in the control group. The reproductive status, age of menopause onset, history of pelvic surgeries, and palliative care were evaluated in the study groups. Results. The incidence of POF in the group of carriers of pathogenic variants of the BRCA1 gene was significantly higher compared to the control group (p0.004), while the incidence of early menopause showed no significant differences in the studied groups (13.2% vs. 4.5%, respectively; p0,069). No significant differences were found in the analysis of reproductive status. Conclusions. Females with and without pathogenic variants of the BRCA1 gene did not differ significantly by the main indices of reproductive status. Carriers of pathogenic BRCA1 gene variants have a significantly higher incidence of POF vs. controls. Adverse effects of pathogenic BRCA gene variants on women's ovarian reserve and reproductive potential cannot be excluded. Healthy carriers of pathogenic variants of the BRCA1/2 gene are recommended to plan pregnancy in the early reproductive period.

Currently, cervicitis of nonspecific etiology is one of the urgent problems of modern gynecology due to the extremely high frequency of their occurrence, a tendency to a chronic relapsing course, a negative impact on reproductive health, and the risk of developing a number of complications. The role of violations of vaginal microbiocenosis and local immune status in the development of CNC has been convincingly shown. The replacement of lactobacilli with predominantly anaerobic microorganisms (Ureaplasma, Mycoplasma, Gardnerella vaginalis, Prevotella, Peptostreptococcus spp. and Bacteroides spp.), characteristic of bacterial vaginosis, is extremely often detected in patients with CNC. Of particular importance from the point of view of clarifying the pathophysiological mechanisms of development and the development of new diagnostic and prognostic markers, as well as the personalization of CNC therapy, is the study of the cytokine status. Cervicitis and other inflammatory diseases of the lower genital tract are characterized by an increase in the expression of pro-inflammatory cytokines with simultaneous inhibition of the formation of anti-inflammatory cytokines. Significant multidirectional changes in the balance of pro- and anti-inflammatory cytokines were revealed in active and chronic sluggish cervicitis. It should be noted that, despite the variety of proposed approaches to CNC therapy, this problem is still far from being solved to date. One of the promising directions is the personalization of CNC therapy based on molecular genetic markers (polymorphisms of cytokine genes, Toll-like receptors, genes of the detoxification system). The use of such a personalized approach can significantly increase the effectiveness of CNC treatment and reduce the risk of disease recurrence.

Relevance. Acute respiratory infections (ARI) are a serious health problem not only because of the high frequency of their occurrence, but also because of the economic damage they cause both in the form of direct costs (the cost of diagnosis and treatment) and indirect costs (disability, reduced labor productivity, etc.). Pregnant women and children under 5 years of age are included in the group of patients with risk factors for complications of influenza and other ARI, therefore, an analysis of the etiological structure of ARI and influenza in obstetric hospitals is an urgent task. In recent years, there has been an urgent need to create a national complex diagnostic test system based on molecular genetic methods for detecting infectious agents that cause ARI. Aims. The aim of the study is to analyze the etiological structure of ARI and influenza in patients with clinical symptoms and to develop and implement a new test system for rapid screening and diagnosis of infections that cause ARI. Materials & methods. When studying the etiological structure of ARI and influenza, cultural studies of the nasal and pharyngeal mucosa were carried out, followed by identification of microorganisms using MALDI-TOF mass spectrometry and molecular genetic study (real-time PCR) using an experimental test panel containing primers that allow detecting the following viruses: influenza A, B viruses, parainfluenza viruses of the 1st, 2nd, 3rd and 4th types, coronaviruses OS43, HKU1, NL63, E229, respiratory syncytial virus, metapneumovirus, rhinovirus and adenovirus, as well as bacterial pathogens of ARI: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa. The test system was developed using the following methods: real-time PCR, a combination of reverse transcription and real-time PCR (RT-PCR) and the next generation sequencing (NGS) method. Results. The etiological structure of ARI and influenza was analyzed in patients with clinical manifestations (cough, tickling/sore throat/hyperemia of the mucous membrane of the palate and the back wall of the pharynx, shortness of breath/difficulty breathing, acute runny nose/nasal congestion). The species spectrum of bacterial and viral pathogens was revealed. A new test system based on PCR, real-time RT-PCR and NGS has been created for complex diagnostics of both viral and bacterial pathogens of ARI, consisting of three separate components: the main test system «ARI», which detects the main viral and bacterial pathogens of ARI, and two additional sets of reagents: «Oseltamivir resistance» and «Oseltamivir/ Zanamivir resistance». Conclusions. The new test system can be used to detect and differentiate nucleic acids of pathogens of ARI of humans. The test system seems to us promising for further use. As a result of the analysis of the etiological structure of acute respiratory infections and influenza, attention is drawn to a significantly smaller variety of identified pathogens in 2020 and a much more pronounced dominance of rhinovirus infection compared to our previous study in 2019.

Aim. To analyze the outcomes of assisted reproductive technology (ART) cycles in patients with different levels of vitamin D. Materials and methods. The study included 100 infertile patients who applied for ART. Vitamin D levels were determined by mass spectrometry. The VDR polymorphism was evaluated using real-time PCR. Results. 50% of patients (n=50) had a sufficient level of vitamin D (group 3), 36% of patients (n=36) had an insufficient level of vitamin D (group 2), 14% of patients (n=14) had a deficiency of vitamin D (group 1). The level of vitamin D was not associated neither with baseline patients characteristics nor with embryological stage of the cycle. The clinical pregnancy rate was lower in the group 1 (vitamin D deficiency), but the difference was not significant. There was a trend to an increase of miscarriage rate in the groups of patients with vitamin D insufficiency and deficiency: 66.7% in group 1, 26.3% in group 2, and 13.6% in group 3. The live birth rate was higher in the groups of patients with normal and insufficient levels of vitamin D compared with the group of vitamin D deficiency: 46.0 and 38.9% compared to 7.1%, p=0.0821. In multivariate analysis clinical pregnancy rate was influenced by vitamin D deficiency and the genetic characteristics of the VDR gene: the presence of the G allele (FOKI-rs2228570). Conclusion. The vitamin D deficiency impairs the effectiveness of ART cycles.

Relevance.Infections of the lower genital tract are one of the most common reasons for women to visit a gynecologist. According to various authors, among all vulvovaginitis, the highest percentage of patients visiting a doctor is bacterial vaginosis (2050%), vulvovaginal candidiasis (1739%), trichomoniasis (10%) and other genital infections (10%). In the management of patients with infectious processes of the genitals, the choice of the method of therapy is of great importance, which allows not only to influence the microbes-associates, detected in high concentrations in the womans vagina during the initial episode of the disease, but also to prevent the development of relapses. Aim.To evaluate the clinical and laboratory efficacy, adherence and long-term results of benzydamine use in patients with vulvovaginal candidiasis, aerobic vaginitis and bacterial vaginosis Materials and methods.The study included 31 women aged 18 to 49 years, who complained of abundant discharge from the genital tract, itching, burning, dyspareunia. A comprehensive clinical and laboratory examination was carried out, including the collection of anamnestic data, general and special gynecological examination, microscopy of vaginal smears, KOH test, determination of the pH of the vaginal environment, assessment of vaginal microbiocenosis by quantitative PCR in real time. All patients were prescribed benzydamine hydrochloride, which was used as monotherapy in the form of a vaginal solution according to the recommended treatment regimen specified in the instructions for medical use of the drug TantumRosa 1 (irrigation 2 times a day for 10 days). Results.In 1219 days after beginning treatment, 25 (80.6%) of 31 patients with laboratory signs of vaginal microflora alterations showed restoration of the normal vaginal biocenosis laboratory parameters. Of them, 8 patients initially had dysbiosis, 12 patients yeast-like fungi, 4 patients aerobic vaginitis and 1 patient a combination of dysbiosis and fungi. Herewith, all patients also noted clinical signs of improvement. In 1219 days after beginning treatment, 6 (1.4%) of 31 patients with laboratory signs of vaginal biocenosis alterations had unsatisfactory laboratory parameters; that is vaginal biocenosis alterations (a decrease in Lactobacillus spp. percentage). At the same time, there were no clinical signs of pronounced inflammation such as pathological discharge, hyperemia, vaginal swelling. Conclusion.Benzydamine hydrochloride can be widely used in gynecological practice due to its combined effects on inflammation of the vagina, good clinical and microbiological results. It is important to note that additional therapy with drugs which contain lactobacilli is required only in 19.4% of cases. The clinical and laboratory effectiveness of benzydamine hydrochloride (TantumRosa) was 96.8%, since the relapse rate after 3060 days of the study did not exceed 3.2%.

It is a common fact that children are less susceptible to COVID-19 than adults, and they usually have milder forms often without symptoms, due to the age-related characteristics of their immune response and the features of the renin-angiotensin system (RAS). The recent studies have shown that the RAS elements are widely represented in the lungs, and they actively participate in the inflammation process in addition to their main vasoregulatory function. The cascade of RAS reactions is one of the key links in the pathogenesis of COVID-19, and it is analyzed from two positions: expression of ACE2 receptors and polymorphisms of certain genes of this system. The studies have demonstrated that the ACE2 transmembrane protein is both the “entry gate” for the virus, and it also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1—7) with vasodilating properties. A higher content of ACE2 in children as compared to that in adults maintains the RAS system balance and prevents the development of complications. It has been also found that certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) can cause the imbalance of RAS components, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift of the vasoconstrictor, proliferative and profibrotic mechanisms. The patients with certain genetic polymorphisms of NOS genes regulating vascular tone, cell growth and proliferation may have a genetic predisposition to the development of severe forms of COVID-19.

Aim: the study was aimed to develop a reagent kit for the real-time RT-PCR diagnostics of virus causing COVID-19.Materials and Methods.Three target sites were chosen in the genome SARS-CoV-2. The testing included 220 samples, 48 artificially created positive samples (made from patients’ biomaterial) and 172 clinical samples (scrapes from nasal and pharyngeal cavities, bronchoalveolar lavage, expectoration, endotracheal/nasopharyngeal aspirate, feces, post-mortem material), obtained from two medical centers. Preliminary, the obtained biomaterial was analyzed with a reagent kit of comparison. The evaluation was performed with a confidential interval CI 95%. The calculation of CI for the sensitivity and specificity was made based on the distribution of χ2.Results.The authors developed a technology of novel coronavirus infection (COVID-19) real-time RT-PCR diagnostics for the application in practical healthcare and proposed the variants of testing at all the stages (preanalytical, analytical, and post-analytical, including automated results processing). The proposed reagent kit meets the requirements of the World Health Organization and the Ministry of Healthcare of the Russian Federation. The study results demonstrated high sensitivity and specificity. The sensitivity was 100% (95% CI) 95.6–100%; the specificity was 100% (95% CI) 96.7–100%.Conclusion.The proposed reagent kit was registered in the RF as a medical product; the registration certificate No. RZN 2020/9948 dated 01.04.2020. The application of the reagent kit in network laboratories will provide patients with access to testing for the virus causing COVID-19 and contribute to quick differential diagnostics, improvement of pandemic control, and accurate statistics on the spread of the virus.

Uterine leiomyomas are a worrying reproductive health issue that has serious social implications. The aim of this study was to conduct a search for marker single nucleotide polymorphisms (SNPs) associated with uterine leiomyoma. To test the hypothesis about the contribution of genetic predisposition to the pathogenesis of myomas, the initial group of 100 patients with a verified diagnosis of uterine leiomyoma was divided into 2 subgroups: subgroup Ia (women with a family history of the disease) and subgroup 1b (women with no family history of the disease). The control group consisted of 30 postmenopausal patients who did not have a medical history of uterine fibroids and denied uterine fibroids in their close female relatives. DNA sequences were read using Sanger sequencing. Statistically significant differences (p < 0.05) were discovered between the analyzed groups in terms of genotype frequencies for rs12637801 and rs12457644. Also, previously unknown protective SNPs were identified whose rare alleles could predict the reduced risk of uterine leiomyomas.

Infectious process even at the initial stage after aerosol infection with Mycobacterium tuberculosis induced rapid changes in vaginal microbiota in mice. Rapid decrease in both the quantity and diversity of microbiota was noted, and then, partial recovery of normal flora was observed. Changes in vaginal microbiota was detected as soon as in 3-7 days after lung infection, while inflammatory changes appeared by day 35. At the early stage of infection, no signs of inflammation were observed, neither M. tuberculosis nor its DNA were detected in mouse genital organs.

The aim of the study was to determine the clinical and genetic features of the syndrome of undifferentiated connective tissue dysplasia (CTD) in cystic fibrosis (CF) children and the possible modifying effect of polymorphisms of connective tissue genes on the development of severe pathology of the bronchopulmonary system in CF cases. 188 patients with the moderate to severe course of СF, aged from 3 to 17 years were examined. In СF patients significant associations have been established between polymorphisms of matrix metalloproteinase 3, the phenotypic signs of CTD and severe clinical signs of respiratory disorders.

Aim. To analyze an efficacy of monotherapy and combined therapy (an immunomodulator + radio wave ablation) in patients with low-grade squamous intraepithelial lesion (L-SIL) caused by HPV infection. Materials and methods. The study included 210 women with human papillomavirus infection which was identified using real-time polymerase chain reaction (PCR). All women underwent a comprehensive examination which included history taking, general and gynecological examinations, extended colposcopy and a bacterioscopy of Gram-stained vaginal smears. A quantitative determination of vaginal microflora composition by PCR was carried out. Conclusion on either inflammatory response is present or absent was made on the basis of an inflammation index magnitude: with a value of more than 60% indicating a presence of local inflammation signs. Based on cervical cytology data a group consisting of 79 women who had L-SIL was formed. Patients were divided into 2 subgroups: the main one (n=45) who received combined treatment with radio wave ablation + an immunomodulator and a control one (n=34) who received only local monodestruction of L-SIL foci followed etiotropic treatment. Results and discussion. An efficacy of combined treatment which included radio wave ablation + an immunomodulator was higher compared to monodestruction only - 86.7% vs 64,7% respectively. It is important that by 6th month of follow-up a relapse of human papillomavirus infection occurred in 4.5 and 23.5% of patients of main and control groups respectively. Local inflammation was assessed as positive with an inflammation index of more than 60%. So after 6 months of follow-up this indicator decreased by 83.3 and 54.2% in the 1st and 2nd groups respectively. Clinical manifestations of an inflammatory process in the cervix was observed only with CIN recurrence. In addition, combined therapy provides a higher rate of human papillomavirus elimination at 6 months and faster cervix epithelization followed treatment by ablation.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR). Differences in the level of mRNA expression of all the studied genes in the receptive endometrium were found in comparison to the prereceptive one, which allowed us to classify two functional states of the endometrium. The results of histological examination responded to the stage of maturation of the endometrium in 78.7% of cases. Receptive endometrial status can be determined based on the integral evaluation of mRNA expression level of 4 PAEP, DPP4, MSX1, and HLA-DOB genes. The model for determining a personalized `window implantation' is offered for practical application in ART.

To investigate whether intravenous contrast-enhanced multislice spiral computed tomography (computed tomography) (MSCT) versus myocardial morphological examination can diagnose myocarditis and the non-inflammatory causes of dilated cardiomyopathy (DCM) and evaluate prognosis in patients with the latter.A study group consisted of 130 patients, including 95 men (46.8±11.9 years), with DCM (mean left ventricular (LV) end-diastolic dimension (EDD), 6.6±0.8 cm; mean LV ejection fraction (EF), 29.8±9.3%; NYHA functional class (FC) III (II; III)). All the patients underwent intravenous contrast-enhanced 320-slice CT of the heart; myocardial morphological examination was made in 48 patients (endomyocardial biopsy in 29 patients, intraoperative biopsy in 7, and autopsy in 9, and study of the explanted heart in 3). In addition, cardiotropic viral DNA in the blood and myocardium and the level of anticardiolipin antibodies were determined; echocardiography (in all the patients), scintigraphy (n = 45), magnetic resonance imaging (MRI) (n = 21), and coronary angiography (CG) (n = 46), and a genetic consultation were performed. A comparison group comprised 20 patients, including 14 men (69.3±9.2 years), with coronary atherosclerosis (40% or more stenoses) according to MSCT findings in the absence of criteria for DCM (mean LV EDD, 4.8±0.5 cm; mean LV EF, 59.4±4.6%).Morphological/comprehensive examination showed that myocarditis as a cause of DCM was diagnosed in 76 (65%) patients; its concurrence with genetic cardiomyopathies was in 17 more patients (17%). MSCT of the heart revealed lower accumulation areas in 2 (1.5%) patients (type 1 based on the proposed rating scale), delayed myocardial contrast agent accumulation (DMCAA) in 81 (62.3%): subendocardial accumulation (type 2) in 8, intramyocardial accumulation in 4 (type 3), subepicardial accumulation in 52 (type 4), and transmural accumulation in 15 (type 5); DMCAA was not noted in 49 patients. DMCAA was not found in the comparison group. As compared with biopsy, the sensitivity, specificity, predictive value of positive and negative results of the tests in detecting active myocarditis for all the types of DMCAA were 77.4, 47.1, 72.7, and 53.3%, respectively; those for types 3-5 of DMCAA were 77.4, 52.9, 75.0, and 56.3%; those in detecting all the morphological types of myocarditis were 68.3, 28.6, 84.8, and 13.3%, and those for types 3-5 were 65.9, 28.6, 84.4, and 12.5%, respectively. Comparison of the data of MSCT and those of comprehensive examination in all the patients with DCM, the diagnostic significance in detecting myocarditis for all the types of DMCAA was 70.6, 67.9, 88.9 and 38.8%, respectively; that for DMCAA types 3-5 was 60.8, 67.9, 87.3, and 32.3%. In the study group, MSCT also identified the non-compacted myocardium (n = 31 (23.8%)), coronary atherosclerosis (n = 31 (23%)), which is confirmed by CG findings in 15 patients. The patients with DMCAA significantly more frequently showed a relationship with previous infection, acute onset, significantly higher NYHA FCs, end-diastolic and end-systolic LV volumes, and insignificantly lower LV EF. During a mean follow-up periods of 12 (6; 37.25) months, the overall mortality rate was 17.7% (23 deaths); the death + transplantation index was 20% (n = 26). All the types of DMCAA were found to be significantly related to prognosis: in the DMCAA group, the mortality rate was 21.5% versus 7.8% in the non-DMCAA group (odds ratio 3.22; 95% confidence interval, 1.02 to 10.21; p0.05).MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.Цель исследования. Изучение возможности мультиспиральной компьютерной томографии (МСКТ) сердца с внутривенным контрастированием у больных с синдромом дилатационной кардиомиопатии (ДКМП) в диагностике миокардита (в сопоставлении с морфологическим исследованием миокарда), невоспалительных причин ДКМП и оценке прогноза. Материалы и методы. В основную группу вошли 130 пациентов (95 мужчин, средний возраст 46,8±11,9 года) с синдромом ДКМП: средний конечный диастолический размер (КДР) левого желудочка (ЛЖ) 6,6±0,8 см, средняя фракция выброса (ФВ) 29,8±9,3%; III (II; III) функциональный класс (ФК) по классификации NYHA. Всем проведена 320-срезовая МСКТ сердца с внутривенным контрастированием; 48 пациентам выполнено морфологическое исследование миокарда (эндомиокардиальная биопсия у 29, интраоперационная у 7, аутопсия у 9, исследование эксплантированного сердца у 3). Кроме того, определяли ДНК кардиотропных вирусов в крови и миокарде, уровень антикардиальных антител, проводили эхокардиографию (всем пациентам), сцинтиграфию (у 45), магнитно-резонансную томографию - МРТ (у 21), коронарографию - КГ (у 46), консультацию генетика. Группу сравнения составили 20 пациентов (14 мужчин, средний возраст 69,3±9,2 года) с коронарным атеросклерозом (стенозы 40% и более) по данным МСКТ в отсутствие критериев ДКМП (средний КДР ЛЖ 4,8±0,5 см, средняя ФВ 59,4±4,6%). Результаты. По данным морфологического комплексного обследования, миокардит как причина синдрома ДКМП диагностирован у 76 (65%) пациентов, его сочетание с генетическими кардиомиопатиями - у 17 (17%). При МСКТ сердца участки пониженного накопления выявлены у 2 (1,5%) больных (1-й тип по предложенной шкале оценки), отсроченное накопление контрастного препарата (ОНКП) в миокарде - у 81 (62,3%): у 8 субэндокардиальное (2-й тип), у 4 интрамиокардиальное (3-й тип), у 52 субэпикардиальное (4-й тип), у 15 трансмуральное (5-й тип); у 49 больных ОНКП не отмечено. В группе сравнения ОНКП не выявлено. В сопоставлении с биопсией чувствительность, специфичность, прогностическая ценность положительного и отрицательного результатов тестов всех типов ОНКП в выявлении активного миокардита составили 77,4, 47,1, 72,7 и 53,3%, 3-5-го типа ОНКП - 77,4, 52,9, 75 и 56,3%, в выявлении всех морфологических типов миокардита - 68,3, 28,6, 84,8 и 13,3%, 3-5-го типов 65,9, 28,6, 84,4 и 12,5% соответственно. При сопоставлении данных МСКТ и комплексного обследования у всех больных с ДКМП диагностическая значимость всех типов ОНКП в выявлении миокардита составила 70,6, 67,9, 88,9 и 38,8%, 3-5-го типа ОНКП - 60,8, 67,9, 87,3 и 32,3%. При МСКТ в основной группе выявлены также некомпактный миокард (n=31, или 23,8%), коронарный атеросклероз (n=31, или 23%), который подтвержден данными КГ у 15 пациентов. У больных с ОНКП достоверно чаще определялись связь дебюта с перенесенной инфекцией, острое начало, достоверно более высокие ФК по классификации NYHA, конечный диастолический и конечный систолический объемы ЛЖ, недостоверно более низкая ФВ ЛЖ. Общая летальность при среднем сроке наблюдения 12 (6; 37,25) мес составила 17,7% (умерли 23 больных), показатель смерть + трансплантация - 20% (26 больных). Выявлена достоверная связь всех типов ОНКП с прогнозом: в группе ОНКП летальность составила 21,5% по сравнению с 7,8% в группе без ОНКП (отношение шансов 3,22 при 95% доверительном интервале от 1,02 до 10,21; p0,05). Заключение. МСКТ с оценкой отсроченного контрастирования (и одновременной КТ-ангиографией коронарных артерий) может использоваться для неинвазивной диагностики миокардита у пациентов с синдромом ДКМП, в том числе при наличии противопоказаний к проведению МРТ. ОНКП в миокарде коррелирует с наличием миокардита, его активностью, степенью функциональных нарушений и прогнозом.

Aim. To study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis in comparison with a standard combination of corticosteroids and azathioprine.Material and methods. The study included 46 patients aged 18 years and older with severe and moderate lymphocytic myocarditis (men, 34; women 12; mean age, 53,5±13,0 years). The diagnosis was verified using endomyocardial biopsy. Symptom duration averaged 9,5 [4; 20.25] months. All patients had class 3 [2,75; 3] heart failure (HF). The main group included 29 patients who received MM 2 g/day, including six patients — instead of azathioprine, which was canceled due to cytopenia (n=3) or insufficient effect (n=3). The comparison group included 17 patients who received azathioprine 150 [100; 150] mg/day. Patients of both groups also received methylprednisolone at a starting dose of 24 [24; 32] and 24 [24; 24] mg/day and standard HF therapy. In 7/2 patients, the parvovirus B19 genome was detected in the myocardium. In all cases, an increase in anticardiac antibody titers was evidence of immune activity. The average follow-up period was 24 [12; 54] months (at least 6 months).Results. The groups were completely comparable in age, initial characteristics and standard drug therapy. In both groups, a comparable significant increase in the ejection fraction (EF) was noted as follows: from 31,2±7,6 to 44,7±8,3% and from 29±9,1 to 46±11,9% (pConclusion. In patients with moderate and severe virus-negative (except for parvovirus B19) lymphocytic myocarditis, the combination of moderate-dose corticosteroids with mycophenolate mofetil 2 g/day is at least no less effective than the standard regimen of immunosuppressive therapy. There was a tendency towards a more pronounced decrease in anticardiac antibody titers in combination with better tolerance (no cases of cytopenia) in MM group. MM in combination with corticosteroids can be recommended as an alternative treatment regimen for lymphocytic myocarditis.

Vulvovaginal candidiasis (VVC) frequently occur in women of childbearing age. 5-10% of these women experience recurrent vulvovaginal candidiasis (RVVC), which is characterized by at least 4 episodes of infection in 12 months. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and antifungal immune response play a substantial role in the pathogenesis of RVVC. The aim of this study was to identify a molecular-genetic factors of recurrence of VVC. Our results shows that single nucleotide polymorphisms (SNP) in cytokine genes such as IL4, IL1b and CCL2 were associated with recurrent vulvovaginal candidiasis and effect on susceptibility to disease.

The article is devoted to the outstanding Hungarian doctor - Andrew Czeizel, his biography and achievements in the Enforcement Network for the improvement of the Health of Children - the future of humanity.

The expression of immune response gene mRNA in the umbilical and venous blood were compared in newborns of the first day of life with and without signs of infection. The expression of il1b, il6, il8, il10, il12a, il15, il18, tnfa, tgfb1, tbx21, gata3, foxp3, rorc2, cd45, cd68, cd69, tlr2, tlr4, tlr9, and mmp8 mRNA was evaluated in umbilical and venous blood cells of newborns by reverse transcription real time PCR. In full-term newborns without signs of infection, the expression of il8, tlr2, tlr4, and mmp8 in venous blood was higher than in umbilical blood, while in preterm newborns, the levels of mmp8 transcript were elevated while the levels of tlr9, cd45, and gata3 were reduced. The expression of some markers differed in the umbilical and venous blood and in newborns with congenital infectious disease and without signs of infection.

Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

to study the renin-angiotensin-aldosterone-system (RAAS) in patients with polymorphic variants of the vitamin D receptor gene (VDR), arterial hypertension (AH) and obesity.We included in this study 98 patients with stage II-III AH and obesity (33 men, 65 women, mean age 61.1±9.9 years and BMI 43.3±5.0 kg/m2). The VDR gene study included genotypes TaqI, BsmI, FokI. After identification of TaqI, BsmI, FokI VDR gene sites we carried out measurements of levels of RAAS markers.We revealed an associative relationship between the presence of allele G of the BsmI site, C/C homozygosity of FokI site of VDR gene and presence of AH in patients with obesity. An increase of renin level was noted only in the homozygous T/T genotype of FokI, no differences in the concentration of aldosterone and angiotensin were detected between any of the studied genotypes.Polymorphic alleles and genotypes of the VDR gene can be used as predictors of AH development in obese patients with subsequent characterization of the state of the RAAS system.

Golovatyuk K. P., Nosenko O. M., Makshayeva E. T., Trofimov D. Yu., Donnikov A. E., Kolin V. V. Molecular-genetic aspects of the endometrium state on the day of the tentative implantation window in women with recurrent miscarriage in the programs of assisted reproductive technologies. Journal of Education, Health and Sport. 2017;7(9):621-626. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.1068361 http://ojs.ukw.edu.pl/index.php/johs/article/view/5076 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 1223 (26.01.2017). 1223 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Authors 2017; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 15.08.2017. Revised: 20.09.2017. Accepted: 29.09.2017. MOLECULAR-GENETIC ASPECTS OF THE ENDOMETRIUM STATE ON THE DAY OF THE tentative IMPLANTATION WINDOW INWOMEN WITH recurrent miscarriage IN THE PROGRAMS OF ASSISTED REPRODUCTIVE TECHNOLOGIES 1K. P. Golovatyuk, 2O. M. Nosenko, 1E. T. Makshayeva, 3D. Yu. Trofimov, 4A. E. Donnikov, 3V. V. Kolin 1Limited Liability Company Medical Center for Reproductive Health "Gameta", Odessa, Ukraine; 2Odessa National Medical University, Ukraine; 3Limited Liability Company "NPF DNA-Technology", Moscow, Russia; 4FGBU Scientific Center for Obstetrics, Gynecology and Perinatology. named after acad. V.I. Kulakov Ministry of Health care and Social Development of Russia, Moscow, Russia; e-mail: nosenko.olena@gmail.com Abstract More than 50% of pregnant women after the programs of assisted reproductive technologies (ART) face the problem of recurrent miscarriage (RMC), especially in the first trimester. Significant role in the development of RMC has infectious factor and chronic inflammation in the endometrium. The aim: to reveal the peculiarities of immune response mRNA genes of the inflammatory component expression in the period of the tentative implantation window (TIW) in women with RMC in ART programs. Material and methods. The main group consisted of 240 patients with RMC in ART programs; the control group included 100 conditionally healthy fertile women. On the ground of PCR reverse transcription, the mRNA of the IL-1β, IL-2, IL-10, Foxp3, TLR9, IL-2Rα cytokine genes was examined in endometrial samples obtained with the help of biopsy on the TIW day. Results. Analysis of the transcriptional profile of the immune response genes in the endometrium on TIW day revealed that the relative level of mRNA expression of the IL-1β, IL-2, Foxp3, TLR9, IL-2Rα genes did not differ significantly in the main and control groups. Statistically significant decrease in mRNA expression of IL-10 gene was observed in women with RPL. Conclusions. A feature of mRNA expression of the inflammatory component of the immune response in TIW period in women with RMC in ART programs is a decrease in the expression level of the IL-10 gene mRNA, which may be one of the reasons for the unfavorable outcomes of the onset pregnancy. Key words: recurrent miscarriage, assisted reproductive technologies, immune response, reverse transcription-polymerase chain reaction, tentative implantation window.

Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events. © 2014 Informa UK, Ltd.

UNLABELLED α-Actinin-3 (ACTN3) has been proposed to regulate skeletal muscle differentiation and hypertrophy through its interaction with the signalling protein calcineurin. Since the inhibition of calcineurin potentiates the production of testosterone, we hypothesized that α-actinin-3 deficiency (predicted from the ACTN3 XX genotype) may influence serum levels of testosterone of athletes. OBJECTIVE To investigate the association of ACTN3 gene R577X polymorphism with resting testosterone levels in athletes. METHODS A total of 209 elite Russian athletes from different sports (119 males, 90 females) were genotyped for ACTN3 gene R577X polymorphism by real-time PCR. Resting testosterone was examined in serum of athletes using enzyme immunoassay. RESULTS The mean testosterone levels were significantly higher in both males and females with the ACTN3 R allele than in XX homozygotes (males: RR: 24.9 (5.7), RX: 21.8 (5.5), XX: 18.6 (4.9) ng · mL(-1), P = 0.0071; females: RR: 1.43 (0.6), RX: 1.21 (0.71), XX: 0.79 (0.66) ng · mL(-1), P = 0.0167). CONCLUSIONS We found that the ACTN3 R allele was associated with high levels of testosterone in athletes, and this may explain, in part, the association between the ACTN3 RR genotype, skeletal muscle hypertrophy and power athlete status.

AIM of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of complex clinical-morphological examination and to assess efficacy of differentiated (including etiotropic and pathogenetic) treatment. MATERIAL AND METHODS We examined 190 patients (117 women, mean age 45.33 ± 14.84 years) with "idiopathic" arrhythmias: atrial fibrillation (38.9%) (AF,) and flutter (11.1%), supraventricular (44.7%) and ventricular (55.3%) extrasystoles (SVE and VE), bouts of ventricular tachycardia (15.8%), atrioventricular block (22,6%) et al. Mean number of antiarrhythmic drugs per patient was 3 (from 1 to 8). Examination included Holter ECG monitoring, echocardiography, determination of anticardiac antibodies (97.4%) and markers of cardiotropic viruses (87.4%), treadmill test (26.3%), transesophageal cardiac pacing (12.1%), electrophysiological investigation (10%), multispiral computed tomography (22.1%), magnetic resonance tomography (21.6%), scintigraphy (27.4%), coronary angiography (10.0%), endomyocardial biopsy (EMB) (10.0%), DNA diagnostics (8.9%). RESULTS EMB revealed immune-inflammatory (myo/endocarditis, systemic/myocardial vasculitis) or genetic pathology in 78.9 and 21.1% of cases, respectively. Level of anticardiac antibodies (including specific antinuclear factor) most closely correlated with EMB findings. On the basis of comparison of EMB data with data of complex examination we created algorithm of nosological diagnostics in "idiopathic" arrhythmias. According to nosology all patients were distributed in the following way: 1) chronic infectious-immune myocarditis (n=144, 75.7%), morphologically verified in 14, viral in 27 patients; 2) genetic cardiomyopathy (n=15, 7.9%), morphologically verified in 4, virus positive in 1 (arrhythmogenic right ventricular dysplasia, non-compaction myocardium, Fabri disease, Brugada syndrome, undetermined); in 4 patients mutations in plakophilin 2, desmoglein, desmin, -galactosidase A genes were found; 3) combination of genetic diseases with myocarditis (n=18; 9.5%) including viral (n=3); 4) isolated myocardiodystrophy (tonsillogenic< dyshormonal, n=3, 1.6%); 5) proper idiopathic arrhythmias (n=10, 5.3%). Therapy of myocarditis included antiviral (43.2%) and immunosuppressive (76.3%) drugs. Cardiotropic and antiarrhythmic therapy was also administered. Only in patients with myocarditis it was possible to withdraw effective antiarrhythmic (16.7%) and to improve effect of previously ineffective drugs. Surgical treatment (implantation of pacemaker or cardioverter-defibrillator, radiofrequency ablation) was more frequently used in patients with genetic (39.4%) and idiopathic arrhythmias (53.8%) than in patients with myocarditis (16.0%). CONCLUSION Etiology of idiopathic arrhythmias can be established in most cases. Their main causes are immune-inflammatory diseases, genetic cardiomyopathies and their combination. Therapy of myocarditis improves antiarrhythmic activity of treatment, in some patients allows to withdraw antiarrhythmic drugs, decrease requirements in surgical treatment and to optimally prepare patients to radiofrequency ablation.

We examined 179 patients with and without preterm rupture of fetal membranes. The mothers and their newborns have been genotyped by two polymorphic loci of estrogen receptor α (ESR1) gene: -397T > C[PvuII] (rs2234693) and -351A > G[XbaI] (rs9340799). The CG haplotype of the fetus should be regarded as a risk factor of preterm rupture of fetal membranes, while haplotype TA as a protective factor. Genotype -351A/A is a marker of the protective haplotype in the fetus, while genotype -397C/C is a marker of the risk haplotype, which can be used in combined analysis of both markers. These data attest to an important role of fetal genotype in the formation of genetic predisposition to preterm rupture of fetal membranes.

Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy.The study involved 119 patients (72 men) aged 60.9 ± 9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 ± 3.4 years. All bleedings were categorized as 1) single bleeding with INR4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP2C9 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (3 points of HAS-BLED scale, n = 58;4 points of HEMORR2HAGES scale, n = 109) and high (3 points of HAS-BLED scale, n = 61, ≥ 4 points of HEMORR2HAGES scale, n = 10) bleeding risk groups.There was no relationship between total HAS-BLED, HEMORR2HAGES scores and numbers of all as well as category 1 and 2 bleedings. The difference in bleeding frequency between high and low risk groups was significant only for recurrent bleedings. There were 22 (36.1%) and 5 (8.6%) recurrent bleedings among 61 and 58 patients with high and low-risk HAS-BLED score, respectively (p = 0.0048). Recurrent bleedings also occurred more frequently among patients with high risk (7/10, 70%) compared with low risk (20/109, 18.35%) HEMORR2HAGES score (p = 0.018). Subgroups of high and low bleeding risk according to HAS-BLED and HEMORR2HAGES scores differed only by proportion of patients with recurrent bleedings. High W sensitivity represented by 2*/2*, 2*/3*, 3*/3* CYP2C9 and/or AA VKORC1 homozygosis was detected in 25 of 119 patients. Six of 8 patients (75%) with category 1 bleedings were carriers of any polymorpism.HAS-BLED and HEMORR2HAGES scales performed best in predicting recurrent bleedings in patients on long term W therapy. Single bleedings with INR4.0 during 1st month of W therapy were associated with reduced W metabolism (AA VKORC1 or/and CYP2C9 allelic variants 2*/2*, 2*/3*, 3*/3*).

An increasing number of hormonal contraceptives and their varying system effects on the body of a woman makes it necessary to personify their prescription and search for means of predicting their safety and tolerability. The article presents the research data and shows the various informative clinical predictors in the development of adverse reactions in the background. It was found that the most significant clinical predictors of occurrence of side effects and complications on the background of the use of the HC are the existence of gynecological diseases associated with menstrual cycles and poor portability of HC in history; an independent predictor of adverse effects on the background of the COC are chronic cholecystitis and dysfunction of the sphincter of Oddi; dynamics of lipid parameters, biochemical blood spectrum, as well as some parameters of hemostasis with the use of different variants of HC; genotype women polymorphic locus rs2414096 aromatase gene (CYP19A1) is a significant predictor of complications and side effects when using HC.

We studied the relationship between the levels of protamines 1 and 2 (PRM1 and PRM2) and fertilin-β (ADAM-2) mRNA expression and outcomes of infertility treatment using assisted reproductive technologies was studied. Analysis of the relationships between the outcomes of in vitro fertilization and embryo transfer and profiles of the expression of seminal genes PRM1, PRM2, ADAM-2 mRNA, evaluated by reverse transcription quantitative PCR was carried out in 79 couples. Significant differences in the expression of seminal PRM1, PRM2, ADAM-2 mRNA were detected in couples with different outcomes of in vitro fertilization and embryo transfer. The levels of seminal gene expression are potential predictors of the efficiency of in vitro fertilization and embryo transfer.

The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Signifi cant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1β, il8, il18, tnfα, il10, tgfβ, igfbp2, etc.

Studies of collagen gene polymorphisms associated with predisposition to early recurrent miscarriages revealed significant differences in the distribution of COL1A1 C-1997A C>A (rs1107946) genotypes and alleles in the group of pregnant patients with early miscarriages in comparison with controls (normal pregnancy). Identification of COL1A1 C-1997A C>A (rs1107946) collagen gene polymorphisms at the stage of pregnancy planning will make it possible to form early miscarriage risk groups for more thorough preparation to gestation and optimization of follow up of this patient population.

We present here analysis of surgical treatment of 24 patients (5 women, 19 men, age 20-75, mean age 50.7 +/- 2.5 years) with dilated cardiomyopathy (DCM) operated during the period from 2008 to 2013. Duration of the disease ranged from 4 months to 12 years (mean 49.4 +/- 7.5 months). According to symptoms and results of 6-minute walk test 3 patients (13%) had heart failure NYHA class III and 21 patients (87%)--NYHA class IV. Average end-diastolic left ventricular size was 7.4 +/- 0.18 cm (6.0-9.2 cm), ejection fraction--26.7 +/- 2.1% (13-47%), mean pulmonary artery pressure 54.9 +/- 2.9 mm Hg (35-80 mmHg). All patients underwent organ-conserving surgery aimed at reverse remodeling of the heart. Surgery was accompanied with implantation of implantable cardioverter defibrillator in 3 patients and/or cardiac resynchronization therapy device in 6 patients. Two patients (8.3%) died during hospitalization of hemodynamically significant ventricular arrhythmias; seven patients (29.2%) died in the late postoperative period. The results of the analysis indicate that reverse-remodeling surgery may be effective in patients with DCM of any age group with preserved reserves of the liver, kidney, and lung function in the absence of active myocarditis. Further observations are needed to determine the place of this operation in the protocol of treatment of patients with DCM.

Aim of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of right ventricular endomyocardial biopsy (EMB) and to assess effect of etiotropic and pathogenetic treatment.We included into this study 19 patients (mean age 42.6 +/-11.3 years, 9 women) with atrial fibrillation (AF, n = 16), supraventricular (n = 10) and ventricular (n = 4) extrasystoles (SVE and VE), supraventricular (n = 2) and ventricular (n = 1) tachycardia (SVT and VT), left bundle branch block (LBBB, n = 2), atrioventricular block (n = 2) without structural changes of the heart. In addition to standard examination we performed the following tests: determination of IgG to herpes and Coxsackie B virus, polymerase chain reaction (PCR) for DNA detection of human herpesviruses 1, 2, and 6, Epstein-Barr virus, Varicellae-zoster virus (human herpesvirus 3) and cytomegalovirus in blood; determination of anticardiac antibodies; EMB with subsequent PCR-diagnostics including that of parvovirus B19 and pathomorphological study. DNA diagnostics (n = 4), coronary angiography (n = 6), skin biopsy (n = 1) and some other studies were also performed when indicated.Histological picture was abnormal in all cases. Nosological diagnosis was established in all patients: infectious-immune myocarditis (n = 11), parvovirus positive endomyocarditis (n = 1); systemic vasculitis (n = 2); myocardial vasculitis (n = 1), Fabri disease (n = 1), arrhythmogenic right ventricular dysplasia (ARVD, n = 1), undetermined genetic cardiomyopathy (n = 2). Level of various anticardiac antibodies including antinuclear factor with bovine heart antigen was most valuable for diagnosis of myocarditis (sensitivity 78.6%, prognostic value of positive result 91.7%). The following therapy was used in patients with myocarditis/vasculitis: intravenous or oral acyclovir (n = 10), gabreglobine (n = 2), meloxicam (n = 12), hydroxychloroquine (n = 15 for 15 [7.0; 24.] months), glucocorticosteroids (n = 14 for 18 [4.0; 25.5] months), azathioprine (n = 2). Mean duration of follow up was 4 years (48 [31; 62] months). At baseline 62.5% of patients with AF were resistant to all antiarrhythmic drugs. Treatment of myocarditis resulted in significant reduction of mean frequency of attacks of AF from 8 to 3 points, more than in 40% of patients AF emerged less than once a month and 1 patient had no attacks at all. Disappearance of tachycardia dependent LBBB was also noted. Cardioverter defibrillator and cardiac pacemaker were implanted to patients with ARVD and Fabri disease, respectively. EMB helped to establish immunoinflammatory and genetic diseases as causes of idiopathic arrhythmias (in 78.9 and 21.1% of patients, respectively). Antiviral immunosuppressive therapy of myocarditis allowed to increase efficacy of antiarrhythmic therapy in resistant patients and when necessary to optimize their preparedness to interventional treatment.

Conclusion. 1. There were no significant differences in the occurrence frequency of allele and genotypes of C1444 locus of CRP gene in patient with osteoporosis. 2. It was founded that T allele and TT genotype of C1846T locus of CRP gene were more common in women with osteoporosis. 3. The determination of gene CRP polymorphism gives a responsibility to realize individual prognosis and to take preventive measures. Цель исследования. Определить полиморфизмы генов OPG, RANKL, VDR, SOST и оценить их взаимосвязь с минеральной плотностью кости (МПК) и переломами для последующей оптимизации диагностики и лечения постменопаузального остеопороза. Материал и методы. В исследование вошли 236 женщин в постменопаузе, проживающих в Москве и Московской области. Основную группу составили 174 пациентки, в возрасте от 50 до 83 лет, с показателями минеральной плотности кости (МПК) < - 2,5 SD по Т-критерию. Группу сравнения составили 62 женщины в постменопаузе с показателями МПК в пределах нормальных значений и отсутствием переломов в анамнезе, в возрасте от 50 до 77 лет. В нашем исследовании всем испытуемым с постменопаузальным остеопорозом и группы контроля с помощью полимеразной цепной реакции проводили молекулярногенетическое проводили с определением полиморфизмов генов VDR(rs10735810, rs1544410), RANKL (rs9594738, rs9594759) и OPG (rs3102735, rs3102735 и rs4355801), SOST (rs1230399). Результаты. При наличии Т аллелей гена RANKL по полиморфизмам rs9594759 и rs9594738 риск снижения МПК в поясничном отделе позвоночника увеличивается в 2 раза. У женщин с гомозиготным генотипом С/С по полиморфизму rs3102735 гена OPG риск развития переломов дистального отдела лучевой кости повышается в 17 раз вне зависимости от показателей МПК. Наличие генотипа G/G по полиморфизму rs1544410 гена VDR у пациенток с постменопаузальным остеопорозом ассоциировано с повышением риска переломов дистального отдела лучевой кости в 3 раза. У пациенток с ПМО гомозиготный генотип С/С по полиморфизму rs1230399 гена SOST обуславливают только различия в индексе массы тела. Заключение. Полиморфизмы генов RANKL (rs9594759 и rs9594738), OPG (rs 3102735) и гена VDR(rs1544410) ассоциированы с риском развития постменопаузального остеопороза и переломов. Ген SOST(rs1230399) не оказывает статистически значимого влияния на МПК и риск переломов.

Oral cavity is inhabited by microbial communities which vary in composition. These include normal microflora as well as opportunistic microorganisms which may cause periodontitis. Quantitative and qualitative detection of major opportunistic microorganisms DNA serves as a useful tool for dysbiosis assessment, proper treatment choice and outcome appraisal.

To study possibility of nosological diagnosis in patients with dilated cardiomyopathy (DCMP) with use of myocardial biopsy.The trial enrolled 62 patients (23 females) with DCMP syndrome (end diastolic left ventricular size5.5 cm, ejection fraction55%). Mean age of the patients was 46.0 +/- 12.8 years. The examination included diagnosis of viral infections (Herpes virus, parvovirus B19), measurement of anticardial antibodies titer, 99Tc-MIBI single photon emission computed tomography of the myocardium, multislice computed tomography, MRT of the heart, coronarography, morphological study of the myocardium (n=20) with application of polymerase chain reaction (PCR) for H.simplex viruses of types 1, 2 and 6, herpes zoster, Epstein-Barr, cytomegalovirus, parvovirus B-19, adenoviruses. The control group (20 operated patients with valvular heart disease and coronary heart disease) was examined for viral genome in the blood and myocardium.Complex examination of DCMP patients showed the following distribution by nosological entuities: myocarditis (n=41, 66.1%) including virus-positive (n=14), primary DCMP (n=16, 25.9%) including with non-compact myocarditis (NCM) in 3, with debute at delivery of the child--in 3. Arrhythmogenic right ventricular dysplasia combined with viral myocarditis (n=2), genetic myopathy (n=1) and Takayasu disease (n=1) combined with NCM, isolated NCM (n=1) were diagnosed in the rest cases. Morphological investigation of the myocardium was made in 20 patients: diagnosis of myocarditis and primary DCMP were made in 70% (including in 2 patients with CHD) and 20%. Detection of viral genome was 20 and 15% in the study and control group, respectively, in the myocardium--in 57.9 (test for parvovirus B19 was not made in 26%) and 65.0% (complete diagnosis). All the virus-positive patients with DCMP were diagnosed to have signs of active/borderline myocarditis. Diagnostic criteria and poor prognosis factors were defined.The nosological diagnosis of DCMP was made in all the examinees basing on the complex of clinical, case history and device evidence. The diagnosis was morphologically verified in 33.9% patients. Treatment approaches are developed.

Aim of the study was to elucidate genetic and drug factors affecting efficacy of clopidogrel in patients with ischemic heart disease - inhabitants of central region of Russian Federation. We included 399 patients with IHD (79% men, mean age 58.3+/-9 years) receiving long term therapy with clopidogrel 75 mg/day (during stable manifestations of the disease) or 75-150 mg/day in combination with aspirin (in relation with recent elective percutaneous interventions). We studied carriage of polymorphisms of genes controlling intestinal absorption of clopidogrel (ABCB1 C3435T), activation of clopidogrel in the liver (CYP2C19 *1 *2), and also registered concomitant administration of proton pump inhibitors (PPI). Then we determined relationship of these factors to development of vascular complications (vascular death/myocardial infarction/requirement in revascularization) during 18 months followup. Among studied genetic factors carriage of allele variants CYP2C19 *1/*2 and *2/* (found in 25.5 and 1.8% of patients, respectively), possessed prognostic significance. In the group of clopidogrel monotherapy carriage of at least one *2 allele was associated with increased rate of vascular complications (33.3% vs. 11.3%) including thrombotic complications (27.7% vs. 3.2%; =0.01). In patients receiving 75 mg/day of clopidogrel in combination with aspirin total rate of thrombotic complications as well as of all adverse unfavorable outcomes was higher in *2 carriers compared with wild type homozygotes (14.0% vs.8.7% and 21.0% vs. 15.8%, respectively). In patients receiving double dose clopidogrel in combination with aspirin we found no worsening of outcomes associated with CYP2C19*2 carriage. In the multifactorial risk model independent predictors of vascular complications turned out to be CYP2C19 *2/*2 homozygosity (RR 4.9; =0.02) and concomitant PPI administration ( 1.8; p=0.05).

The main parameters of humoral immunity during medium intensity exercise were studied in oarsmen with high and low cardiovascular adaptation. A relationship between high cardiovascular adaptation to exercise and immune response polarization by the Th2 mechanism was demonstrated. Increased production of IL-10 in response to physical stress plays a key role in this relationship.

A 4-week study of adaptation reserves of the body was carried out during medium intensive exercise (medium intensive training: 60-80% threshold anaerobic metabolism). Two groups of athletes were singled out by the results of pulsometry analysis: with less than 20% work duration at the level above the 80% threshold anaerobic metabolism and with more than 20% work duration at the level above 80% threshold anaerobic metabolism. No appreciable differences between the concentrations of total testosterone, growth hormone, and cortisol before and after exercise in the groups with different percentage of anaerobic work duration were detected. In group 1 the concentrations of free testosterone did not change throughout the period of observation in comparison with the levels before training. In group 2, the level of free testosterone increased in comparison with the basal level: from 0.61+/-0.12 nmol/liter at the end of week 1 to 0.98+/-0.11 nmol/liter at the end of week 4 (p

Purpose: To perform morphologic study of dilated cardiomyopathy's etiology and estimate the diagnostic value of other instrumental methods. Methods: 42 patients (30 men, 45.0±13.9 years) with dilated cardiomyopathy syndrome (average left ventricle diastolic diameter 6.8±0.9 cm, EF 25.9±11.1%) have undergone endomyocardial/intraoperative biopsy, autopsy or explanted heart examination with virus detection (PCR); anti-heart antibodies were also measured as well as EchoCG, myocardial scintigraphy (n=9), CT (n=21), MRI (n=13), coronary angiography (n=21). The control group included 20 patients with ischemic heart disease. Results: Morphologic study allowed to diagnose: 1) isolated myocarditis in 28 patients (19 – viral, 1 – bacterial, 1 – hypersensitive). In 7 patients productive vasculitis prevailed (none with systemic); in 4 patients myocarditis was combined with severe coronary atherosclerosis, in 2 – with bicuspid aortic valve; 2) ARVD + viral myocarditis in 2 patients (1 case also with noncompaction of the myocardium, NCM); 3) desminopathy + acute fatal myocarditis in 1 case; 4) TTR-amyloidosis in 1 case; 5) unverified storage disease with viral myocarditis and NCM in 1 case; 6) NCM in 5 patients (with myocarditis in 4 cases and viral genome in 2 cases); 7) unverified primary dilated cardiomyopathy in 4 patients (with viral genome in 2 cases). Viral genome in the myocardium (including mixt infection) was detected in 26 patients (61.9%): parvovirus B19 in 16 cases, herpes virus type 6 in 12 cases, Epstein-Barr virus in 9 cases, cytomegalovirus in 4 cases, and herpes simplex virus type 1/2 in 4 patients. Only 2 virus-positive patients (with primary cardiomyopathy) had no signs of myocarditis. In control group, the viral genome in the myocardium was found in 85% of patients but myocarditis was confirmed only in 25%. The most useful methods of diagnostics (in addition to history) were: specific antinuclear antibodies, high level of antibodies to conduction system (sensitivity for diagnostics of myocarditis was 52.9% and 85.3%, specificity and positive predictive value 100%) and general level of anti-heart antibodies, viral genome in the blood, late enhancement (CT), diffuse/local defects of perfusion by scintigraphy, pathologic Q/QS (for genetic diseases). Conclusions: Morphologic study revealed the immune-inflammatory nature of dilated cardiomyopathy in 66.7% of patients, isolated genetic cardiomyopathy in 14.3%, and their combination in 19.0%. We have developed an algorithm for nosologic diagnostics of dilated cardiomyopathy on the basis of combination of clinic, laboratory and instrumental signs.

The effects of 6-h marathon ultra-race (long aerobic work below the lactate threshold level) on the levels of IL-6, leukemia inhibiting factor (LIF), and stem cell growth factor (SCF) were studied. The athletes participating in the study had different endurance levels evaluated by the distance covered over 6 h. The level of IL-6 sharply increased after exercise. The degree of IL-6 increase correlated with the length of the distance covered (r=0.83, p=0.042). The concentration of LIF after exercise inversely correlated with the distance covered (r= -0.75), but this correlation was statistically insignificant. The IL-6/LIF proportion exhibited the highest correlation with the result in the marathon ultra-race. This parameter most fully characterized athlete endurance (r=0.92, p=0.009). Hence, the relationship of LIF with physical endurance was demonstrated. Involvement of LIF in antibody production processes can be responsible for it.