New prognostic criterion for the outcome of pregnancy in patients with threatening preterm birth.

To identify new criteria for predicting the outcome of pregnancy in women with threatened preterm labor based on the establishment of the characteristics of differentiation and functional activity of memory T-cells in the population of CD8 + T-lymphocytes. The study involved 56 women with threatened preterm labor at 22-34 weeks of pregnancy. Depending on the outcome of pregnancy, patients were divided into 3 groups: Group I included 22 women by premature labor; group II - 34 women whose pregnancy ended by deliver at term. By tricolor flow cytofluorometry method the content of peripheral Tn, Tcm, Tem and Temra cells in CD8+ population was studied. Statistical analysis was carried out using programs «Statistica for Windows 13.0¼, «Microsoft Excel 2019¼ and «MedCalc 19.3¼. Patients with the threat of preterm birth were characterized by a significant increase in the relative content of CD8+ T-lymphocytes in the peripheral blood compared to the control group (p=0.001). When comparing this indicator in the subgroups of women with the threat of preterm birth, it was found that preterm birth was associated with significantly higher relative CD8 + lymphocyte counts (p=0.03) compared to the indicators of the subgroup of women who gave birth on time. When evaluating the results obtained, it was found that the percentage of CD8+Temra GranzymeB-producing cells in the group of patients with threatened preterm birth, whose pregnancy ended in preterm birth, was significantly lower than in the group of women who gave birth on time (p=0.003). The content of Tcm, Tem memory cells producing GranzymeB in the subgroups of women with pregnancy outcomes of timely and preterm birth did not have significant differences compared to the control group. Thus, the prediction of preterm birth is possible with a value of GranzymeB-producing CD8 + Tem equal to 8.2% or less (sensitivity-87.9%, specificity-85%, accuracy-87.9%). Thus, the identification of a new criterion will make it possible to predict preterm birth in a timely manner and promote the choice of optimal pregnancy management tactics, reasonable prevention of fetal respiratory distress syndrome and transfer of a woman to an obstetric hospital designed to provide high-tech care to premature newborns.

Ð rediction of the outcome of pregnancy in women with reccurent miscarriage.

To determine the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, to identify new criteria for predicting abortion before 22 weeks of gestation in women with the threat of early termination and recurrent miscarriage. Materials and methods. A survey of 91 women in the gestation period of 5-12 weeks was carried out. The main group consisted of 59 women with recurrent miscarriage and the threat of early termination at the time of the study. Depending on the outcome of pregnancy, the main group was subdivided into 3 subgroups: subgroup I - 44 women whose pregnancy ended in timely delivery, II - 8 women who had preterm labor, III - 8 women with termination of pregnancy up to 22 weeks ( missed pregnancy or spontaneous miscarriage). The control group consisted of 32 women with uncomplicated pregnancy. The relative content of IL-4 +, IL-6 +, IL-10 +, IFNγ + monocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). In women with threatened early miscarriage and recurrent miscarriage, the percentage of IL-4 + and IL-10 + cells in the population of peripheral monocytes is significantly lower, while IL-6 + cells are higher compared to the control group (p = 0.0001 in in all cases), no statistically significant differences were found in the percentage of IFNγ + cells (p = 0.076). A retrospective analysis revealed that in the group of women with termination of pregnancy up to 22 weeks, there was a significant decrease in IL-10 + monocytes in the peripheral venous blood. Prediction of termination of pregnancy before 22 weeks of gestation is possible with a relative content of IL-10 + monocytes equal to 27.0% or less (sensitivity 87.5%, specificity 95.2%, accuracy 93.1%).

Role of CD20 + IL-10 + B-lymphocytes in immunoregulatory processes in women with reccurent miscarriage.

To determine the level of CD20 + IL-10 + B-lymphocytes in pregnant women with the threat of termination of pregnancy at 5-12 weeks and recurrent miscarriage in history and compare the data obtained with the end of gestation. A survey of 65 women at a gestational age of 5-12 weeks was carried out. The main group consisted of 33 women with a threatening recurrent miscarriage at the time of the examination, the comparison group consisted of 10 pre-pregnant women with a threatening sporadic miscarriage at the time of the examination, the control group consisted of 22 pregnant women without signs of a threatening miscarriage. The main group, depending on the outcomes of pregnancy, is divided into 2 subgroups: subgroup A - pregnancy ended in undeveloped pregnancy or miscarriage (9 women), subgroup B - pregnancy ended in childbirth (24 women). The relative content of CD20 + IL-10 + B-lymphocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). Women in the main group had a significantly lower level of CD20 + IL-10 + B-lymphocytes in comparison with the rest of the surveyed. A retrospective analysis revealed that among women of subgroup A there was a sharp decrease in CD20 + IL-10 + cells compared with subgroup B. Prediction of a non-developing pregnancy and spontaneous miscarriage up to 22 weeks of gestation in pregnant women with threatened spontaneous miscarriage and a history of recurrent miscarriage is possible with the relative content of CD20 + IL-10 + equal to or less than 4.5% (sensitivity 100%, specificity 82.6%, accuracy 87.9%).

[New early prognostic criteria for pregnancy outcome in women with recurrent miscarriage.]

To determine the new criteria for predicting the outcome of pregnancy in women with habitual abortion based on features of differentiation of naive T cells and memory cells in a population of T-helper (CD4+) and cytotoxic T lymphocytes (CD8+). The study involved 61 women with threatened and habitual abortion in the first trimester of gestation. Depending on the outcome of pregnancy was allocated to 3 groups: I went to 39 women whose pregnancy ended in timely delivery; in II - 10 women whose pregnancies ended in premature birth; in III - 11 patients in whom there was a spontaneous miscarriage. Using three-color flow cytometry as peripheral venous blood in populations of CD8+ and CD4+ determined by the content Tn, Tcm, Tem and Temra cells. Statistical analysis was carried out in the program «MicrosoftOffice 2010¼, «Statistica for Windows 6.0¼ and MedCalc¼. When conducting a retrospective assessment, it was found that in the group of patients whose pregnancy ended in preterm delivery, the percentage of CD4+ Tem memory cells was significantly higher and CD4+ Tn lower than in the subgroup with timely delivery (p = 0.013 and p = 0.025, respectively ) In patients with early spontaneous miscarriage, the level of CD8+ Tn significantly decreased against the background of the growth of CD8+ Tem memory cells compared with the same parameters in patients with timely delivery (p = 0.040 and p = 0.014, respectively). Prediction of spontaneous abortion is possible up to CD4+ Tn equal to 34.2% or less (sensitivity - 100.0%, specificity - 56.4%, accuracy - 63.8%), premature birth - if the CD4+ Tn equal to 35, 2% or less (sensitivity - 66.7%, specificity - 74.4% accuracy - 72.9%). Thus, the new criteria will allow additional time to identify risk and assign adequate treatment aimed at prolonging the desired pregnancy.

[Peculiarities of the content of peripheral blood cytokines in pregnant women with a habitual miscarriage.]

A lot of research nowadays is dedicated to the problem of habitual pregnancy loss, and this attention is dictated by the continued high frequency of this condition. The pathogenesis of habitual pregnancy loss is very complicated and includes many factors, at present especially close attention is paid to immune aspects. It is considered, that cytokine imbalance might play a key role in the pathogenesis of habitual pregnancy loss. Examination of 38 pregnant women was carried out at 5-12 weeks of gestation. The main group consisted of 17 women with habitual miscarriage and the threat of interruption at the time of the examination, the control group consisted of 21 women with uncomplicated pregnancy and a favorable obstetric history. As the material for investigation peripheral blood was used. Serum level of a complex of cytokines IL-ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IFNγ, TNFα, GM-CSF was assessed on the Luminex 200 multiplex fluorescence analyzer (Luminex Corporation, USA). The significant differences in the serum level of IL-1ß, IL-22, IL-23 и IL-27 were observed between the groups, in the main group their level was higher comparing to that of healthy pregnant women. When evaluating the cytokines serum level, fairly high values of IL-27 (in 25%of cases) (p<0,05), TNFα - (in 18% of cases) (p>0,05) were found in the main group, while in the control group they were not registered. Significant differences in the serum level of IL-2, IL-4, IL-9, IL-12p70, IL-18 and IFNγ were not noted in the compared groups (p>0,05). The simultaneous increase in the serum level of pro- and anti-inflammatory cytokines observed in our study can be explained by both an increase in the immune response and triggering of fetoprotection mechanisms. Inadequate cytokine regulation may be a prerequisite for the development of conditions for the development of a threat of termination of a real pregnancy in women with habitual miscarriage.

[Method for predicting perinatal hypoxic lesions of the central nervous system in newborns.]

Perinatal lesions of the Central nervous system (CNS) in newborns occupy a leading place in the structure of perinatal morbidity and subsequent disability of children. To identify the features of the content of sRAGE in pregnant women with threatening preterm labor (UPR) in the period of 22-27 weeks, who subsequently gave birth to children with perinatal CNS lesion. Serum of venous blood of pregnant women with UPR at the term of 22-27 weeks was determined by ELISA once the content of sRAGE. If the value of sRAGE in pregnant women is 659.5 PG/ml or less, perinatal hypoxic lesions of the Central nervous system in newborns are predicted with an accuracy of 75.8% (sensitivity of 82.6%, specificity of 66.7%).

[Relationship between activation of endometrial CD56+ natural killers and the character of leiomyoma nodules growth in patients with uterine leiomyoma.]

In patients with different clinical variants of uterine leiomyoma (large or small size, presence or absence of intensive proliferation of tumor cells) the comparative analysis of endometrial CD56+ natural killers (NK) activation was carried out. The relative content of CD56+ cells, expressing of CD158a and CD158i molecules from KIR (killer immunoglobuline-like receptors) family, interferon γ (IFNγ) and transforming growth factor ß1 (TGFß1), was estimated by flow cytometry method. It was found that in the endometrium of all patients with uterine leiomyoma independently of tumor size the content of CD56+ cells and the amount of NK, expressing both activating (CD158i) and inhibitory (CD158a) receptors, were increased. In group of women with stably small uterine leiomyoma the amount of CD56+IFNγ+ lymphocytes was increased, and in women with rapidly growing tumor the elevation of NK, expressing TGFß1, was noted. Differential analysis of data in patients with large leiomyoma in dependence of type of leiomyoma growth was shown that in patients with the high level of tumor cells proliferation the amount of CD56+ NK and the ratio of NK with activating and inhibitory receptors were lower and the content of CD56+TGFß1+ lymphocytes was higher than that in women with leiomyoma, which grew due to accumulation of the extracellular matrix components. Received results showed on the suppression of cytotoxic activity of endometrial NK in patients with uterine leiomyoma with increased proliferation. These changes can be used as additional diagnostic criteria of type of leiomyoma growth.

[Comorbid states in Parkinson's disease: an effect of MAO-B inhibitors].

The comorbidity in Parkinson's disease (PD), which is closely related to the tolerability of antiparkinsonian drugs, is-'analyzed. The authors present the results of the studies that have confirmed the greater safety of rasagiline compared to dopamine receptor agonists in elderly patients. The effects of rasagiline, including combinations of this drug with antidepressants, on-depression in PD and the low risk,of the serotonin -syndrome caused by these combinations are considered. The studies demonstrated the effect of rasagiline on fatigue and cognitive functions in PD patients are described. Single cases of the development of impulsive compulsive disorders:in patients treated with- rasagiline are presented.

Interaction of decidual CD56+ NK with trophoblast cells during normal pregnancy and recurrent spontaneous abortion at early term of gestation.

The immunological paradox of pregnancy, when maternal immune system recognizes but does not reject the semiallogenic foetus, is not yet fully understood. The aim of this work was to detail the mechanisms of the interaction of decidual CD56+ NK, infiltrating the maternal part of placenta, and trophoblast cells of foetal origin. Samples of the endometrial tissue from 13 healthy non-pregnant women, 37 placentas, obtained after medical abortion of viable pregnancy at 7-10 weeks of gestation, and 26 samples of placentas from first-trimester recurrent spontaneous abortion (RSA) were used as the material for investigation. Phenotype of NK was assessed by flow cytometry. The influence of trophoblast cells upon IFNγ and GrB mRNAs expression by dNK was investigated by RT-PCR. The influence of dNK upon trophoblast cells migration and invasion was studied using collagen and Matrigel systems. In RSA group comparing to the normal pregnancy, the decrease of dNK with inhibitory receptors (NKG2A) and elevation of activated dNK were seen. In normal pregnancy, but not in RSA, trophoblast cells increased the expression of IFNγ and GrB mRNAs by CD56+ dNK. Both in normal and RSA pregnancy, dNK inhibited the migration and invasion of trophoblast cells. Initially, low invasive and migration capacities of trophoblast cells were seen during RSA. Thus, unbalanced activation of dNK can lead to the impairment of dNK and trophoblast cells interaction during RSA.

[Cerebrolysin alleviates perinatal CNS disorders through the autoimmune modulation and antioxidant protection].

We investigated the effects of the neuroprotective drug cerebrolysin on the autoimmune parameters (FasL, Fas and metallotionein-1) in 20 newborns with perinatal ischemic CNS damage and 20 healthy newborns. The treatment with cerebrolysin in dosage of 0,1 ml per 1 kg of body mass, 10 injections every other day, resulted in the normalization (p<0,001) of the T-lymphocyte apoptosis (the increase of Fas and decrease of FasL) and activation of antioxidant protection through the increase of metallotionein-1 expression. The normalization of the autoimmunity was found to reduce edema and improve the circulation of the brain sites affected with ischemia.

Stem cells in experimental chronic hepatitis.

We studied the state of the pools of mesenchymal precursor cells in the bone marrow and peripheral blood and the dynamics of regional precursor cells in the liver in experimental chronic hepatitis. We showed that bone marrow mesenchymal stem cells are involved in liver regeneration in its chronic disease. Our results suggest that these mechanisms are insufficient for the recovery of liver tissue.

Effect of granulocyte colony-stimulating factor on myocardium recovery in postinfarction period.

The effect of Neutrostim (preparation of granulocytic colony-stimulating factor) on recovery of myocardial tissue after acute myocardial infarction was studied in rats. A course of Neutrostim after ligation of the left coronary artery led to normalization of electrocardiographic and morphological parameters of the myocardium after one month.

Mechanisms of psychopharmacological effects of granulocytic colony-stimulating factor during severe hypoxia.

Granulocytic colony-stimulating factor produced a strong therapeutic effect during encephalopathy of different genesis. The preparation improved the psychoneurological status and increased the number of neural precursors in the paraventricular area of cerebral hemispheres in animals.

[Antimicrobial action of Lentinus edodes juice on human microflora].

The action of the juice of Shiitake mushroom (L. edodes) on pathogenic and opportunistic microorganisms, detected in cases of considerable dysbiotic changes (Escherichia coli O-114, Staphylococcus aureus, Enterococcus faecalis, Candida albicans), as well as on some bacterial eubiotic producer strains (Escherichia coli M-17, Bifidobacterium spp., Lactobacillus spp.). The juice of this mushroom at a concentration of 5% from the volume of the nutrient medium was found to produce a pronounced antimicrobial effect with respect to C. albicans, S. aureus, E. faecalis, E. coli O-114 and to stimulate the growth of E. coli M-17. Bifidobacteria and lactobacteria exhibited resistance to the action of L. edodes juice.

Pharmacological regulation of functional activity of stem cells in restoration of the myocardium during the postinfarction period.

The effect of granulocytic CSF on myocardial tissue recovery after acute myocardial infarction was studied on rats. A course of granulocytic CSF after ligation of the left coronary artery normalized ECG parameters and morphological picture of the myocardium 1 month after treatment. It was shown on mouse model of myocardial infarction that this process was associated with more intensive mobilization and homing of mesenchymal stem cells in the heart.

Mechanisms of hepatoprotective effect of preparation containing superlow doses of antibodies to granulocytic colony-stimulating factor.

The hepatoprotective effects of superlow dose preparation of antibodies to granulocytic CSF were studied on a model of CCl4-induced hepatitis. The preparation exhibited high antiinflammatory and antisclerotic activities determined by stimulation, mobilization, and determined homing of mesenchymal stem cells into damaged liver with subsequent differentiation of these cells into mature hepatocytes.

Dynamics of functioning of thyroid gland transplant under conditions of stimulation with autologous adherent bone marrow cells.

The efficiency of thyroid tissue autotransplantation was studied in 150 male Wistar rats for 3 months. Comparative analysis of functional competence of the thyroid tissue transplanted into the great omentum showed restoration of the thyroid hormonal activity in animals receiving cell suspension of autologous adherent bone marrow cells.

Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver.

Hepatoprotective effects of granulocytic CSF were studied using experimental model of CCl4-induced hepatitis. It was found that treatment with granulocytic CSF increased the content of stromal precursors and mesenchymal stem cells in the bone marrow and peripheral blood with subsequent increase in the number of hepatic precursor cells in the liver. These findings attest to mobilization of progenitor mesenchymal cells and their migration into damages liver tissue, which accelerates its regeneration related to changes in the parenchyma, but not connective tissue development.

Cytokine production by immunocompetent cells of peritoneal fluid in women with external genital endometriosis.

The content of some cytokines in the peritoneal fluid and the level of their in vitro production by peritoneal macrophages and lymphocytes were evaluated in women with external endometriosis. The ratio of peritoneal lymphocytes and macrophages in the peritoneal fluid was changed in endometriosis because of increased percentage of lymphoid cells and decreased content of macrophages, in the presence of high absolute counts of both types of cells. The cytokine status of women with endometriosis was characterized by higher levels of IL-1beta, TNF-alpha, and epidermal growth factors both in the peritoneal fluid and supernatants of 24-h cultures of peritoneal macrophages; the content of IFN-alpha remained unchanged. The concentrations of IFN-gamma in the peritoneal fluid did not change in endometriosis, but increased in the supernatants of peritoneal lymphocyte cultures.

[Immunity status in early postoperative complications in children with anomalies of kidneys and upper urinary tract]. / Sostoianie immuniteta pri razvitii rannikh posleoperatsionnykh oslozhnenii u detei s anomaliiami pochek i verkhnikh mochevykh putei.

31 children aged 1 to 9 years with malformations of the kidneys and upper urinary tracts were preoperatively examined for immune status. After plastic operation 14 children developed early postoperative infectious-inflammatory complications. It is suggested that early postoperative complications in some children with renal and upper urinary tract maldevelopments may arise because of weak compensatory abilities and immunodeficiency resultant from the operative stress. These created favourable conditions for activation of latent infection. Immunological assessment of the patient prior to surgery predicts early postoperative complications and thus enables proper preventive measures.