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In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women’s reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the “Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age.The prospective study included 120 women who were vaccinated against COVID-19 with the “Gam-COVIDVac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies.The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response.Vaccination with “Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response.

Prerequisites, creation, place and role of vertically integrated medical information system “Obstetrics and gynecology” and “Neonatoloy” (VIMIS “AKiNEO”, System) the purpose of which is to increase the efficiency of managing the vertical of medical care organization by providing prompt and comprehensive analysis of information, improving the qualifications of medical workers, as well as improving the quality of medical care to patients by improving information support at all levels in the digital transformation are considered in the article. VIMIS “AKiNEO” receives in the form of structured electronic medical documents, processes and aggregates primary data from external medical information systems. Thus, the principle of a single input of information and its further multiple use is observed. Components, working principles and current state of the System are described in details, including the results using the severe maternal morbidity register. Examples of clinical situations in which the registry played a significant role in saving life and health of patients are given. Positive effects of the System influence on the obstetric services both at the regional level and at the level of the whole Russian Federation are shown. The problems encountered during creation and implementation VIMIS “AKiNEO” in Russian digital healthcare system are presented.

The study was performed in 48 rabbits. After 1 cm resection of central part of radius diaphysis the defect was substituted with fragments of fetal tissue. Sixteen rabbits made up a control group. It was shown that fetal bone tissue stimulated reparative bone regeneration. Its fragments were not the centers of osteogenesis but bone development started within preserved periosteum and endosteum, i.e. in the location of cambial cells of osteodifferone. There were several stages of damaged bone full value structure restoration: 1) filling of the defect with fibrillar connective tissue surrounding the fragments of fetal bone tissue; 2) development of reticulo-fibrotic bone regenerate with fragments of fetal bone tissue; 3) remodeling and formation of laminar bone regenerate; 4) restoration of medullar canal with bone marrow. Restoration of damaged radius structure was accompanied by periosteal reaction and focal resorption of undamaged ulnar both at the defect level and outside the defect. In control group full value restoration of damaged bone was observed in no case

It is given in an article the obtained investigation results in studying antiphospholipid antibodies contains and combined pathology of small pelvis organs in 32 women with tumors and timorous ovary formations, who suffered with infertility. Analysis of anamnesis and clinic-laboratorial data, echography, operative laparoscopy and histological investigation is presented.

Relevance. There is limited evidence on the effect of various vaccines on the human reproductive system. Potential adverse effects of vaccines on fertility are associated with autoimmune disorders, which might cause gonadal damage. Currently, several studies are underway investigating the impact of COVID-19 vaccines on human fertility. To our best knowledge, there is only one study published which demonstrated no adverse effects of the COVID-19 vaccine on assisted reproductive technology outcomes. Aim. To investigate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on ovarian reserve and antiphospholipid antibody level in reproductive-age women. Materials and methods. The prospective study included 51 women vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V) vaccine. The inclusion criteria were age from 18 to 45, preserved menstrual function, normal ovarian reserve, no history of COVID-19, negative PCR test result for SARS-CoV-2 and negative SARS-CoV-2 IgG antibody test before vaccination, no pregnancy, and no history of serious illnesses. Clinical evaluation was carried out twice-immediately before immunization and 90 days after the first vaccine component administration. The antral follicle count was measured by pelvic ultrasound. Serum levels of AMH, FSH, TSH, estradiol, antiphospholipid antibodies (aPL) M and G isotypes against cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP-1), annexin V (aAn V), phosphatidylserine (aPS), and IgG antibodies against SARS-CoV-2 were measured by enzyme immunoassay. Results. There were no significant changes in hormones levels and antral follicle counts before and after vaccination, including in women of advanced reproductive age (≥37 years). After immunization, aPL antibody levels did not differ significantly from the baseline. There was no correlation between aPL antibody level dynamics and level of FSH and AMH, which indirectly demonstrates no possible autoimmune effect of vaccination on women's fertility. Conclusion. This is the first study investigating the effect of the Gam-COVID-Vac vaccine on ovarian reserve parameters and aPL antibody levels. The preliminary results prove that the Gam-COVID-Vac vaccine in women of reproductive age does not adversely impact ovarian reserve.

Relevance. During the pandemic and large-scale vaccination against COVID-19, studies of the effect of various types of vaccines on human reproductive function have become particularly important. Vaccination may have a negative impact on the reproductive organs and tissues due to the development of an autoimmune process involving the gonads. Currently, there are some studies on the effect of vaccination against coronavirus infection caused by SARS-CoV2 on the male and female reproductive function. The absence of a negative effect of vaccination on spermatogenesis in men has already been demonstrated in the results of three studies. Objective. To evaluate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on spermatogenesis and the level of antiphospholipid antibodies in men. Materials and methods. The prospective study included 45 men who were vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V). The criteria for inclusion in the study were the age from 18 to 55 years, the absence of a previous history of COVID-19, a negative RT-PCR result in SARS-CoV-2 testing, negative SARS-CoV-2 IgG results prior to vaccination, and the absence of severe somatic diseases. The patients were examined twice: immediately before vaccination and 90 days after the first dose was injected. We evaluated spermogram parameters, determined the levels of FSH, LH, TSH and total testosterone, and analyzed blood for IgM and IgG antiphospholipid antibodies (aPL) to cardiolipin (aCL), β2-glycoprotein-1 (as2-GP1), annexin V (aAnV), phosphatidylserine (aPS), as well as IgG antibodies to SARS-CoV-2 using enzyme immunoassay. Results. There were no significant changes in the parameters of spermogram and hormone levels before and after vaccination;men with moderate impairment of spermatogenesis (oligoasteno-and/or teratozoospermia) did not show considerable changes either. The level of aPL after vaccination did not increase compared to the baseline level. Besides, there was no correlation between the dynamics of the level of antisperm antibodies, aPL and spermogram parameters. These findings indirectly indicate that there are no changes in the reproductive function associated with this autoimmune factor after vaccination in men. Conclusion. This is one of the first studies that has revealed the effect of the Gam-COVID-Vac vaccine on spermatogenesis, hormonal profile and aPL level in men. The obtained results demonstrate that the Gam-COVID-Vac vaccine does not have a negative effect on the reproductive function in men.

Aim To investigate the impact of patient immune status on the severity of COVID-19 Materials and methods The prospective study included 63 employees of the V I Kulakov NMRC for OG&P of Minzdrav of Russia with confirmed COVID-19 The patients were stratified into three groups based on the disease severity, including asymptomatic (group 1, n=17), mild (group 2, n=29), and moderate (group 3, n=17) form of COVID-19 On days 3–7 from the onset of the disease, peripheral venous blood samples were collected from the study subjects and tested for serum levels of anti-SARS-CoV-2 IgG antibodies and immune profile by ELISA After day 20+, testing for serum levels of anti-SARS-CoV-2 IgG antibodies was repeated using ELISA Results Patients who had a higher BMI, blood group A(II), lower leukocyte and lymphocyte counts, higher relative monocyte count, changes in the immune profile in the form of a lower number of CD3+, CD3+ CD8+, СD19+, CD19+ CD5+, and phagocytic activity of neutrophils, developed more severe forms of COVID-19 They had severe clinical manifestations of the disease, and 100% of them developed antiviral immunity Conclusion This study identified several clinical, laboratory, and immune profile features that may be considered as predictive factors of severe COVID-19 and can be used in clinical practice to predict the clinical course of the disease

We studied the association of polymorphic markers of cell cycle control genes (Arg72Pro of the TP53 gene, T(-410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene) in ovarian cancer and progression-free survival following platinum-based chemotherapy. Tumor tissue samples obtained from 49 patients who had undergone chemotherapy were examined. Patients received standard platinum-based chemotherapy and were observed until disease progression. Polymorphic markers of genes were evaluated by PCR-RFLP and real-time PCR. In patients carrying the G allele of the T(-410)G marker of the MDM2 gene, a decreasing trend was observed in median progression-free survival. An increase in the median progression-free survival was observed in carriers of the Pro allele of the TP53 gene (p=0.045). Furthermore, a stronger association was noted with carriers of the minor Pro/Pro homozygous genotype relative to the Arg/Arg genotype (p=0.007). In the subgroup of patients who underwent optimal or complete cytoreductive surgery, carriage of the minor Arg allele of the Ser31Arg marker (CDN1A gene) was associated with a decrease in the median progression-free survival time (p=0.004).

Epithelial ovarian cancer (OC) ranks first in the number of deaths among diseases of the female reproductive organs. Identification of OC at early stages is highly beneficial for the treatment but is highly challenging due to the asymptomatic or low-symptom disease development. In this study, lipid extracts of venous blood samples from 41 female volunteers, including 28 therapy-naive patients with histologically verified high-grade serous ovarian cancer at different stages (5 patients with I-II stages; 23 patients with III-IV stages) and 13 apparently healthy women of reproductive age, were profiled by high-performance liquid chromatography mass spectrometry (HPLC-MS). Based on MS signals of 128 differential lipid species with statistically significant level variation between the OC patients and control group, an OPLS-DA model was developed for the recognition of OC with 100% sensitivity and specificity R2 = 0.87 and Q2 = 0.80. The second OPLS-DA model was developed for the differentiation between I-II OC stages and control group with R2 = 0.97 and Q2 = 0.86 based on the signal levels of 108 differential lipid species. The third OPLS-DA model was developed for the differentiation between I-II OC stages and III-IV stages based on the signal levels of 99 differential lipid species. Various lipid classes (diglycerides, triglycerides, phosphatidylchlorines, ethanolamines, sphingomyelins, ceramides, phosphatidylcholines and phosphoinositols) in blood plasma samples display distinctly characteristic profiles in I-II OC, which indicates the possibility of their use as marker oncolipids in diagnostic molecular panels of early OC stages. Our results suggest that lipid profiling by HPLC-MS can improve identification of early-stage OC and thus increase the efficiency of treatment.

We compared the expression profiles of α2,3- and α2,6-sialoglycans in the glycocalyx of the placental barrier structures in early and late forms of preeclampsia and fetal growth restriction using the method of lectin histochemistry. It was found that the expression of α2,3-sialoglycans in the syncytiotrophoblast and fetal endothelium of the terminal villi of the placenta was reduced in preeclampsia in comparison with normal placenta and, on the contrary, was increased in fetal growth restriction. Significant differences were found in both clinical phenotypes of preeclampsia and fetal growth restriction. Changes in the expression pattern of α2,6-sialoglycans in the endothelium of terminal villi were more pronounced than in syncytiotrophoblast. In early and late-onset preeclampsia, a significant increase in the expression of α2,6-sialoglycans was revealed only in the fetal endothelium; in early fetal growth restriction, the expression of α2,6-sialoglycans was reduced in the endothelium, but increased in syncytiotrophoblast in late fetal growth restriction. The features of the expression of sialoglycans in structures of the placental barrier in preeclampsia and fetal growth restriction were revealed, which may indicate the pathogenetic involvement of sialoglycans in the inflammatory activation cascade in fetal growth restriction, and in preeclampsia, apparently, they are associated with impaired fetal tolerance.

Aim. To study long-term results of surgical treatment of patients with familial adenomatous polyposis (FAP) with the cell reconstruction of the rectal mucosa.Materials and methods. 57 FAP patients were subjected to treatment, which involved colproctectomy, the preservation of the lower rectal ampulla, mucosectomy and the reconstruction of the mucosa by cell transplantation. Endoscopic monitoring was carried out, with the endoscopic observation covering the period of 19–120 months (median — 44.3 months). Morphological and immunohistochemical studies were conducted. The long-term functional results of treatment (anorectal manometry (profilometry)) were studied. The patients were surveyed using the SF-36 questionnaire to monitor the quality of their life.Results. Our results show that the use of cell transplantation leads to the reconstruction of the rectal mucosa over a fairly short time: in 44/57 (77.2 %) patients, the endoscopic picture corresponded to the unchanged rectal mucosa 4 weeks after the surgery. In 13/57 (22.8 %) patients, a complete mucosal reconstruction was achieved 8–12 weeks after the surgery. The absence of polyp growth in the preserved part of the rectum was observed. Late complications developed only in 5 (9.4 %) patients. Good functional results (acceptable frequency of defecation, lack of signs of anal incontinence and nocturnal defecation) were observed in 48/53 (90.6 %) patients. The quality of life was at a fairly high level in 90.6 % of patients.Conclusion. The proposed method of FAP treatment allowed the immediate and long-term treatment results to be improved significantly.

The article presents the results of intravenous transplantation of allogeneic multipotent mesenchymal stromal cells, derived from a human umbilical cord, to a child with Crigler–Najjarsyndrome type I during the first 2 years of life. The therapy is aimed at reduction of the duration of phototherapy while maintaining a safe level of serum bilirubin.In this study, a five-day-old child with the bilirubin level of 340 µmol/l was treated with phototherapy for 16–18 hours daily in the neonatal period. Then, phototherapy was reduced to 14–16 hours. The level of bilirubin varied from 329 to 407 μmol/l. At the age of 2 months, it was decided to use multipotent mesenchymal stromal cells with a significant decrease in the duration of phototherapy up to 2 hours a day. During the observation period (2 years at the time of writing this article) the child received 6 injections of multipotent mesenchymal stromal cells. A positive effect developed within 4–7 days after administration and persisted for 2–3 months. There were no side effects or complications during and after transplantation.Thus, intravenous transplantation of multipotent mesenchymal stromal cells is an effective treatment of Crigler–Najjar syndrome type I; it reducesthe need for phototherapy,significantly improvesthe quality of life of the patients and prolongstheir life with native liver.

We studied the effect of extracellular vesicles of the follicular fluid on morphofunctional characteristics of human spermatozoa using CASA (computer-assisted sperm analysis) analytical system. The vesicles were obtained by sequential centrifugation at different rotational speeds and frozen at -80°C in the Sydney IVF Gamete Buffer medium. The sperm fraction was isolated from the seminal fluid of 21 patients aged 27-36 years by differential centrifugation in a density gradient. The precipitate was suspended in Sydney IVF Gamete Buffer to a concentration of 10

We performed a comparative analysis of the expression of fucosylated glycans and morphometric characteristics of the terminal villi of the placenta, depending on the severity of preeclampsia (PE). Similar patterns of the expression of fucosylated glycans in the syncytiotrophoblast glycocalyx were revealed in the placental tissue of patients with normal pregnancy and with mild and severe PE: predominance of glycans with α1,6-fucose in the core, clustered fucose residues, and LeX glycan over α1,2-fucose-containing glycans. The expression pattern of fucosylated glycans and the composition of the endothelial glycocalyx are normally close to the expression pattern and composition of the syncytiotrophoblast glycocalyx; in case of mild and severe PE, the expression pattern of fucosylated glycans was changed uniformly, and α1,2-fucose-containing glycans significantly prevailed in the endothelial glycocalyx. According to the results of Fisher's LSD test, in patients with severe PE, the total vascular area in the villus prevailed over the indices established during physiological course of pregnancy (p=0.04) and mild PE (p=0.04). Correlation analysis revealed direct and reciprocal relationships between the morphometric characteristics of the terminal villi of the placenta and the expression of fucosylated glycans in the syncytiotrophoblast and endothelium in PE. Our results indicate a changed expression of fucosylated glycans in the glycocalyx of placental barrier structures and the morphometric parameters of villi in PE of different severity, which can affect the function of the placental barrier.

Using a non-invasive approach, quantitative laser scanning microtomography (QLSM), the morphology of human oocyte was studied layer-by-layer. Then, the cell volume was computed based on 3D reconstruction of a stack of optical sections obtained by QLSM. The integrity of oocyte membrane after cryopreservation was assessed by measuring the changes in oocyte volume in response to hypotonic shock.

A system analysis of the published data on antiendothelial cell antibodies (AECAs) was performed. The AECAs target antigens on endothelial cells are characterized, the methodology of revealing AECAs is described, and the role of antibodies in the pathogenesis of processes caused by the activation/dysfunction of endothelium is considered. The review summarizes the present-day results of Russian and international studies published in the last 25 years in the Pubmed, High Wire, and e-Library databases. The characteristics of natural and disease-associated AECAs (related to pathology) and mechanisms of their influence on cells in different pathologies are presented.

Light luminescent microscopy was used to study the distribution of extracellular microvesicles with PKH26-stained membranes secreted by placenta-derived mesenchymal stromal cells in the uterine tissues at different terms after injections to intact rats and after abdominal delivery (a model of cesarian section). Microvesicles migrated through the uterine tissues and were detected for at least 8 days after injection. In some cases, microvesicles were more numerous in the uterus after cesarian section modeling, which can be related to blockade of microcirculation and lymph flow due to inflammation accompanying surgical intervention. The content of microvesicles in the uterine tissues gradually declined due to macrophage phagocytosis and, probably, due to their migration into the vascular bed. Despite their size, properly stained extracellular microvesicles can be detected by light microscopy in tissues after injections.

The title of the article should be «KrioBlast

General discussion on priority: speachs of academicians I.I. Dedov, G.T. Sukhikh, E.L. Choynzonov, Yu.V. Gulyaev

Here, the possibility of proteomic and metabolomic analysis of the composition of exhaled breath condensate of neonates with respiratory support. The developed method allows non-invasive collecting sufficient amount of the material for identification of disease-specific biomarkers. Samples were collected by using a condensing device that was incorporated into the ventilation system. The collected condensate was analyzed by liquid chromatography coupled with high resolution mass spectrometry and tandem mass spectrometry. The isolated substances were identified with a use of databases for proteins and metabolites. As a result, a number of compounds that compose the exhaled breath condensate was determined and can be considered as possible biomarkers of newborn diseases or stage of development.

Purpose. To study the presence of carotenoids in the tissues of prenatal human eye in the course of its development. Material and methods. The eyes were obtained from abortive human fetuses of 12-28 weeks of pregnancy. The fetuses were brought to the Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, the Russian Academy of Medical Sciences, from licensed institutions of the Ministry of Public Health, working under the Russian Federation legislation on citizen health protection, and in accordance with the approved list of medical indications. The ages of the fetuses were determined by an obstetrician. Totally, 49 samples of eye tissues from human fetuses at different pregnancy ages were used. The content of carotenoids and their oxidized forms was measured by high-performance liquid chromatography (HPLC) technique. Results. The presence of lutein and/or its oxidized forms was estimated by HPLC in the tissues of prenatal human eyes (cornea, sclera, optic nerve, retinal pigment epithelium with choroid, ciliary body with iris, vitreous body). Conclusion. The finding of lutein or oxidized forms of lutein in tissues of the human eye in the course of prenatal development is of essential interests for understanding physiology of the prenatal and postnatal eye.

Pilot experiments on kinetic vitrification of human pluripotent stem cells and spermatozoa using a KrioBlast

The autoimmune reactions against sperm, which are accompanied by the elaboration of antisperm antibodies (AsAb), are one of the causes of male infertility.Objective: to specify the role of different factors (other than obstruction) in the etiology of male immune infertility.Subjects and methods. Clinical and laboratory studies were made in 536 males from infertile couples (their age 18–45 years); a control group comprised fertile men whose wives were 8–16 weeks pregnant (n = 82). Their sperms were examined in accordance with the WHO recommendations. AsAbs in the sperm were determined by a MAR test. Oxidative stress was estimated using luminol-dependent chemiluminescence. Chromosome damage was identified from DNA fragmentation by chromatin dispersion in an inert agarose gel, by making a microscopic examination of halo formation after acid DNA denaturation and nuclear protein lysis. The blood levels of interferons (IFN) and their natural and in vitro induced production were determined by the Campbell method. Reproductive tract infections were diagnosed by polymerase chain reaction.Results. There is a high significant correlation between the quantity of AsAb, on the one hand, and previous orchitis, as well as subclinical testicular injury, on the other hand. There was no correlation between varicocele and AsAb, but in the former, the risk of immune infertility and orchitis increases after injury; varicocelectomy promotes a reduction in AsAb with the higher degree of varicocele and a less marked autoimmune process. AsAbs are observed during Chlamydia infection with the increased production of IFN-γ. Cryptorchidism and orchiopexy, parotitis, epididymitis, herniotomy, chronic bacterial prostatitis, and other potential risk factors for decreased male fertility had no significant impacts on an odds ratio for developing immune infertility. In the majority (41 %) of cases, immune infertility seems to be idiopathic, but it is accompanied by the hyperproduction of reactive oxygen species and DNA damage (fragmentation).Conclusion. Male immune infertility is multietiological: blood-testis barrier damage, cross reactions with microorganisms, and immunopathological reactions. Autoimmune reactions against sperm can be considered to be both a cause and a sequence of the bad semen quality caused by genetic and different endo- and exogenous factors.

Poster presentada en el 50th ERA-EDTA Congress (European Renal Association - European Dialysis Transplant Association), celebrado del 18 al 21 de mayo de 2013 en Estambul (Turquia)

This document is the consensus of the experts of the Russian Association of Endocrinologists and those of the Russian Association of Obstetricians and Gynecologists on diagnostic criteria for gestational diabetes mellitus and other carbohydrate metabolic disturbances during pregnancy. The consensus is based on the analysis of the results of the largest multinational Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study of more than 23 thousand pregnant women. The draft was repeatedly considered at the meetings of the working group and presented as oral reports at the 6th All-Russian Congress of Endocrinologists with international participation on Current Technologies in Endocrinology and at the All-Russian Interdisciplinary Educational Congress on Complicated Pregnancy and Premature Birth: from the Summit of Science to Everyday Practice in May 2012.

Aneuploidies as quantitative chromosome abnormalities are a main cause of failed development of morphologically normal embryos, implantation failures, and early reproductive losses. Preimplantation genetic screening (PGS) allows a preselection of embryos with a normal karyotype, thus increasing the implantation rate and reducing the frequency of early pregnancy loss after IVF. Modern PGS technologies are based on a genome-wide analysis of the embryo. The first pilot study in Russia was performed to assess the possibility of using semiconductor new-generation sequencing (NGS) as a PGS method. NGS data were collected for 38 biopsied embryos and compared with the data from array comparative genomic hybridization (array-CGH). The concordance between the NGS and array-CGH data was 94.8%. Two samples showed the karyotype 47,XXY by array-CGH and a normal karyotype by NGS. The discrepancies may be explained by loss of efficiency of array-CGH amplicon labeling.

In open prospective study we determine the efficacy of zoledronic and ibandronic acids on bone metabolism markers and bone mineral density in women with postmenopausal osteoporosis. 225 women with postmenopausal osteoporosis treated with zoledronic acid in dose 5 mg, intravenously, once a year and 64 women treated ibandronic acid were followed up. The investigators assessed clinical and medical history data, evaluated the gynecological and somatic statuses, and made laboratory and instrumental studies: clinical, biochemical blood tests, general urinalysis, determination of serum bone metabolism markers (B-Crosslaps, osteocalcin), osteodensitometry and electrocardiography, therapist ’s examination if needed. Therapy with zoledronic acid 5 mg once a year and ibandronic acid 150 mg once a month was followed by a significant reduction in resorption markers (B-Crosslaps) just following one month. Formation markers decreased to a lesser degree, which was indicative of preserved positive bone remodeling balance during the therapy. Determination of biochemical markers of bone remodeling permits assessment of an individual patient response to antiresorbtive therapy just in the first month after infusion. Zoledronic acid or ibandronic acid therapy exerts a rapid and potent effect on bone metabolism, mainly by inhibiting the resorption processes.

Дидрогестерон – высокоселективный прогестаген, использующийся при широком спектре гинекологических заболеваний. Из всех стероидных рецепторов дидрогестерон значительно взаимодействует только с прогестерон-рецепторами. Результаты проведенного нами ранее исследования моделей структур комплекса прогестин–рецептор позволяют предположить, что ключевым моментом высокой селективности и специфичности дидрогестерона является уникальное для этой молекулы позиционирование метильной группы С19. Некоторые другие препараты прогестинов взаимодействуют и с другими типами рецепторов и как следствие приводят к нежелательным побочным эффектам. Побочными эффектами применения некоторых прогестинов являются вирилизация, являющаяся результатом активации андрогенных рецепторов, а также нежелательная активация эстрогеновых рецепторов. В настоящей работе мы приводим результаты полногеномного исследования транскрипционных эффектов активации прогестероновых, андрогенных и эстрогеновых рецепторов. Результаты показывают, что эти три типа рецепторов активируют существенно разные группы генов. Путем анализа функционального связывания установлены гены, предположительно влияющие на вирилизацию или феминизацию плода. Результаты исследования подчеркивают, что использование разновидностей прогестинов, побочно активирующих эстрогеновые или андрогеновые рецепторы, нежелательно при беременности и вмешивается в гормональные процессы развития плода. И, наоборот, применение во время беременности высокоселективных прогестинов (например, дидрогестерона) является безопасным для правильного развития плода как женского, так и мужского пола.

The paper considers the late sequels of preeclampsia that is one of the main causes of poor perinatal outcomes. The idea that this gestational complication shows no noticeable impact on the female health status in the late postpartum periods has long been prevalent. At the same time, recent studies suggest that this cohort of women will have a high cardiovascular risk in future life, which requires the formulation of their management strategy. Epidemiological data are given on late female morbidity and mortality due to coronary heart disease, stroke, and renal failure.

Mutations in the C-terminal domain of tissue inhibitor of metalloproteinases-3 (TIMP-3) lead to autosomal dominant hereditary disease of the retina (Sorsby fundus dystrophy). Mouse knock-out and heterozygous knock-in fibroblasts and fibroblasts from patients with Sorsby fundus dystrophy exhibit some characteristics of myofibroblasts. Genetic changes in the timp-3 gene (TIMP-3) lead to a shift towards the myofibroblast phenotype in the fibroblast culture. It is hypothesized that Timp-3 (TIMP-3) plays a role of antitransformation agent preventing myofibroblast transformation in vivo and that the pathogenesis of Sorsby fundus dystrophy is associated with the loss of the antitransformation function by the mutant protein.

Here, the possibility of proteomic and metabolomic analysis of the composition of exhaled breath condensate of neonates with respiratory support. The developed method allows non-invasive collecting sufficient amount of the material for identification of disease-specific biomarkers. Samples were collected by using a condensing device that was incorporated into the ventilation system. The collected condensate was analyzed by liquid chromatography coupled with high resolution mass spectrometry and tandem mass spectrometry. The isolated substances were identified with a use of databases for proteins and metabolites. As a result, a number of compounds that compose the exhaled breath condensate was determined and can be considered as possible biomarkers of newborn diseases or stage of development.

Пациентки, страдающие привычным невынашиванием беременности, составляют группу риска по реализации нарушений имплантации и плацентации в I триместре беременности. Подобные нарушения чаще всего обусловлены иммунными взаимодействиями между эндометрием и клетками развивающегося трофобласта [1–3]. Женщины, которым проводится экстракорпоральное оплодотворение (ЭКО), как правило, имеют гормональные проблемы, страдают хроническими воспалительными заболеваниями и как следствие – спаечными процессами в области малого таза, нередко перенесли одно или несколько оперативных вмешательств на матке, яичниках и трубах. При этом трудности с наступлением беременности, решаемые благодаря использованию вспомогательных репродуктивных технологий, сочетаются с иммунологическими проблемами, что в ряде случаев ведет к повторным ранним репродуктивным потерям. У пациенток с повторными потерями плода формируется так называемый порочный круг, когда иммунопатологический процесс активируется с самых ранних этапов развития беременности

In order to study the potentiality of spinal cord reconstruction the experimental work (65 rats) on the selection of the combined biologic graft for stimulation of optimum vascularization, elimination of nerve tissue deficit, restoration of neurologic function and survival rate of animals after dosed contusion of spinal cord was performed. In experimental group (41 rats) suspension of cultured neural stem cells was administered. Control group included 24 animals. For stimulation of compensative restorative processes in the injured spinal cord of adult rats combined grafts with use of either vascularized omentum by Goldsmith or alloaorta (adventitia turned to the spinal cord) with simultaneous of neural stem cells are the most appropriate.

Changes in cell composition and viability as well as the content and functional activity of hemopoietic progenitor cells were analyzed during long-term (up to 1 month at 4°C) storage of human umbilical cord blood cells. No significant quantitative changes in erythrocytes were found during this period. The total content and viability of leukocytes changed, which resulted in the prevalence of mononuclear cells (lymphocytes and monocytes). Analysis of functional activity of hemopoietic stem cells in semisolid culture revealed a decrease in the relative content of CFU during the first week of storage [corrected] and inability of cells to colony formation after 2 weeks.

The multifactorial correlative analysis showed the tightness and correlative connection between the time after one time irradiation of experimental animals, breathing and redistribution of hepatocytes' mitochondria dimensions. It has been established that the velocity of mitochondrial breathing can be described by linear correlative dependences from time and area, negative coefficients in equations shows that the velocity of breathing decrease when time and mitochondrial area increase. This equations let to estimate mitochondrial population state, depending on time and their dimensions and show that big mitochondria perish in a more brief time. It was assumed that the velocity of destruction is depend on irradiation dose and it leads to the change of equation coefficients.

The present investigation was undertaken to study the detection rate of herpes simplex virus (HSV) and cytomegalovirus (CMV) in the ejaculates of males with infertility and to evaluate the impact of virus infection on the major parameters of sperm. Ejaculates from 808 patients were studied. As compared with apparently healthy individuals, the coupled males with primary infertility were found to have HSV more frequently in both the whole ejaculate (31% versus 17%; p = 0.049) and the fraction of actively motile spermatozoa (30% versus 8%; p = 0.016). Ejaculate HSV detection directly correlated with the reduced amount of actively motile spermatozoa (p = 0.0001) and the smaller proportion of morphologically normal forms of germ cells (p = 0.002). CMV was found to have no impact on the motility and morphology of spermatozoids in the ejaculate. Both HSV and CMV in the male ejaculate were significantly more frequently detectable in winter months. The findings lead to the conclusion that HSV is one of the factors for male infertility and can negatively affect the results of assisted reproductive technologies.

Mutations in the C-terminal domain of tissue inhibitor of metalloproteinases-3 (TIMP-3) are linked with Sorsby fundus dystrophy (autosomal dominant retinal dystrophy). Experiments on timp-3 gene knock-out and knock-in mice, carriers of dystrophy-linked Timp-3S156C mutation, showed that expression of mutant Timp-3S156C, in contrast to the normal one, is not regulated by phorbol-myristate-12-acetate and is retained at a high level in a medium without FCS. The mutant protein is not transported into the nucleus, while fibroblasts expressing it survive without FCS and other growth factors. It is hypothesized that normal Timp-3 is involved in the regulation of expression of its own timp-3 gene and, probably, other genes associated with growth and proliferation. The absence of this characteristic in mutant Timp-3S156C is presumably responsible for its accumulation in the extracellular matrix.

We studied expression of genes of interleukins, interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta(2) in adhesions on uterine tubes. In tubal adhesions the intensity of production of mRNA for proinflammatory cytokines, antiinflammatory cytokine interleukin-10, and regulator of cell proliferation surpassed that in normal tissues by 2.5-7.4, 2.2, and 50.2 times, respectively. Correlations were found between production of mRNA for tumor necrosis factor-alpha and transforming growth factor-beta(2), interleukin-12, and interferon-gamma and interleukin-12 and transforming growth factor-beta(2). Our results suggest that expression of these genes during adhesion formation is regulated by the feedback mechanism.

Production of interleukin, interferon-gamma, and transforming growth beta(2)-factor mRNA in peripheral blood mononuclear cells was studied in women with pyoinflammatory diseases of adnexa uteri. Predominant expression of Th1 proinflammatory cytokine genes in patients was demonstrated. Production of interleukins 4 and 8 mRNA decreased 200- and 60-fold, respectively, in comparison with that in healthy women. One month and a half after extirpation of fallopian tubes the cytokine production in blood mononuclear cells shifted towards antiinflammatory cytokines, expression of interleukin-8 gene returned to normal, and expression of interleukin-4 gene increased.

The interferon system was studied in women with genital papillomavirus infection. In most patients the interferon system was activated, while the ability of lymphocytes to respond to inductors decreased. Laserotherapy and immunomodulatory therapy with larifan, ridostin, and viferon for 1 month normalized blood interferon concentration (39.4% patients) and interferon-gamma production by lymphocytes in response to inductors (87.9% patients). After laser monotherapy these parameters returned to normal only in 13.2 and 7.6% patients, respectively. Correlation and regression analyses showed that changes in the interferon system were synchronized after immunomodulatory therapy. These data indicate that immunomodulatory therapy produces a complex effect on the interferon system. Measurements of blood interferon level can be used to predict the effect of further treatment with interferon-gamma inductors.