An attempt to identify the peptide structure of bovine prostate extract using water/vinegar technology followed by tangential ultrafiltration is described. Protein-peptide components with known functional activity were revealed. A new previously unknown peptide, a fragment of bovine chemokine MCP-1, was selected from the discovered regulatory peptide fragments, synthesized, and tested in three biological assays. The ability of the peptide to suppress the in vitro migration of monocytic cells and platelet aggregation was demonstrated. The newly identified peptide fragment was evaluated as promising for developing a synthetic analog of prostate extract to be used in the treatment of diseases of autoimmune and pseudo-allergenic nature.

В статье описываются особенности разных технологий производства активной фармацевтической субстанции простаты экстракта, обеспечивающие различные качественные характеристики конечного продукта. Приводятся данные, характеризующие субстанцию простаты экстракта с точки зрения ее физико-химических и биологических свойств при использовании для производства готовой лекарственной формы. Проводится сравнительный анализ ключевых показателей качества субстанций, произведенных по разным технологиям.

Введение. Адекватный контроль функциональной активности тромбоцитов, в том числе при воздействии антиагре­гантных препаратов, является нерешенной проблемой лабораторной диагностики. К наиболее часто используемым методам определения функциональной активности тромбоцитов относятся оптическая агрегатометрия и проточная цитометрия. Цель исследования: оценить изменения функциональной активности тромбоцитов под влиянием антиагрегантных препаратов, используя методы оптической агрегатометрии и проточной цитометрии. Материалы и методы. В проспективном исследовании приняли участие 22 здоровые женщины фертильного возраста (26,0 ± 4,7 лет). Кровь отбирали из локтевой вены в вакутейнер с антикоагулянтом – цитратом натрия в соотношении кровь: антикоагулянт = 9:1. В качестве антиагрегантов использовали ацетилсалициловую кислоту (АСК) и эптифибатид. С помощью метода оптической агрегатометрии оцени­вали степень и скорость агрегации тромбоцитов (АТ). Методом проточной цитометрии оценивали экспрессию P-селектина (CD62P), гликопротеина GPIIb/IIIa (CD41а) и образование тромбоцитарно-лейкоцитарных комплексов. Результаты. Определение функциональной активности АДФ-индуцированных тромбоцитов под действием АСК выявило снижение скорости и степени их агрегационной активности и снижение уровня экспрессии CD41a и CD62P. При обработке тромбоцитов препаратом эптифибатид установлено увеличение экспрессии CD62P и CD41a и выраженное подавление скорости и степени АТ. Добавление АСК не оказывало заметного влияния на АДФ-индуцированное образование комплексов тромбоцитов с лейко­цитами. Напротив, в присутствии эптифибатида наблюдали более интенсивную АТ с лейкоцитами. Заключение. Оценку функциональной активности тромбоцитарного звена гемостаза необходимо проводить с учетом всех этапов активации тромбоцитов и их участия в межклеточных взаимодействиях. Расширение подходов к оценке эффективности антиагрегантной терапии лабораторными методами имеет большое значение для поиска безопасных и эффективных методов лечения пациентов с тромбофилическими состояниями на различных этапах их развития. Background. Adequate control of platelet functional activity, including exposure to antiplatelet drugs, is an unresolved problem in laboratory diagnostics. Optical aggregation and flow cytometry are the most commonly used methods for determining of platelet functional activity. Objective: to assess changes in platelet functional activity under the influence of antiplatelet drugs using optical aggregation and flow cytometry methods. Patients/Methods. The prospective study involved 22 healthy women of fertile age (26.0 ± 4.7 years). Blood was taken from the cubital vein into a vacutainer with an anticoagulant – sodium citrate in ratio blood: anticoagulant = 9:1. Acetylsalicylic acid (ASA) and eptifibatide were used as antiplatelet agents. The degree and rate of platelet aggregation (РA) were accessed by optical aggregation. Flow cytometry was used to assess the expression of P-selectin (CD62P), glycoprotein GPIIb/IIIa (CD41a) and the formation of platelet-leukocyte complexes. Results. Determination of the functional activity of ADP-induced platelets under ASA action revealed a decrease in the rate and degree of РA activity and a decrease in the level of CD41a and CD62P expression. Platelet processing with eptifibatide caused an increase of CD62P and CD41a expression anda pronounced suppression of РA rate and degree. ASA addition had no significant effect on ADP-induced formation of platelet-leukocyte complexes. On the contrary, more intense РA with leukocytes was observed in the presence of eptifibatide. Conclusions. Assessment of platelet functional activity should take into account all stages of platelet activation and their participation in intercellular interactions. Expansion of approaches for assessing of antiplatelet therapy effectiveness by laboratory methods is of great importance for searching safe and effective methods of treating patients with thrombophilic conditions at various stages of their development.

Important peculiarities of various technologies used for manufacturing the API of prostate extract that determine different qualitative characteristics of the final product are described. Data on the physicochemical and biological properties of APIs essential for the production of finished dosage forms possessing the desired safety and efficacy indices are presented. The key quality parameters of APIs produced by various technologies are comparatively analyzed.

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough. AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age. MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed. RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications. CONCLUSIONS: D iabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough. AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age. MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed. RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications. CONCLUSIONS: D iabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

Hypothesis/Aims of study: The prevalence of diabetes mellitus in pregnant women is increasing. Physiological hyperlipidemia is usually developed during the last third of gestation, increases during pregnancies complicated by diabetes mellitus. Abnormal lipid profiles are associated with adverse perinatal outcomes. However, the associations between maternal dyslipidemia and pregnancy complications in women with different diabetes mellitus types remain unclear. The aim of this study was to assess the lipid profile in women with different types of diabetes mellitus (Type 1, Type 2, and gestational diabetes) based on the therapy in the third trimester of pregnancy, to investigate the associations between serum lipid profile and perinatal complications, and to determine possible prognostic value of lipids in the development of adverse pregnancy outcomes. Study design, materials and methods: The study included 277 women who were divided into several groups depending on the type of diabetes mellitus and its therapy method, a group of patients with preeclampsia, and the control group. We analyzed the clinical and laboratory data of outpatient and inpatient cards of pregnant women in the period between 2010 and 2017. Maternal blood samples were collected between 28 and 32 weeks of gestation. The samples were assayed for fasting triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol concentrations, as well as the atherogenic index of plasma. We also assessed the incidence of gestational arterial hypertension, preeclampsia, intrauterine growth restriction, and preterm birth. Results: Pregnant women with various types of diabetes mellitus were characterized by a significant rise in serum triglycerides and very-low-density lipoprotein cholesterol levels, an increase in the atherogenic index of plasma, and a significant decrease in antiatherogenic, high-density lipoprotein cholesterol levels. These changes were most pronounced in pregnant women with pregestational diabetes mellitus types and in groups receiving insulin therapy. Correlation analysis revealed weak positive correlations between serum triglycerides concentrations and macrosomia (r = 0.26) and between the atherogenic index of plasma and severe preeclampsia (r = 0.26). The analysis of the ROC curve showed that triglycerides, very-low-density lipoprotein cholesterol, and the atherogenic index of plasma are predictors of severe preeclampsia. Conclusion: Diabetic pregnancies are associated with increased dyslipidemia, which plays an essential role in the pathogenesis of perinatal complications. Evaluating lipid profile markers in the third trimester of diabetic pregnancy may be valid predictors of severe preeclampsia.

Objective. To assess the efficacy and safety of low molecular weight sugar solution as a hepatoprotector in the first trimester of pregnancy in patients with liver functional disorders against the background of early toxicosis and / or hepatotoxicity. Patients and methods. The study included 70 patients: the main group (n = 30) – pregnant women with functional hepatopathies who received therapy with drug Heptrong; the control group (n = 30) – pregnant women who received standard treatment, of which 15 patients had hepatotoxicity (essential phospholipid therapy) and 15 patients with early toxicosis (intravenous saline fluid therapy, Cerucal), as well as 10 pregnant women with early toxicosis who were treated without drugs (the placebo group). Results. Pregnant women with early toxicosis noted a decrease in its clinical manifestations against the use of the drug Heptrong after 2.3 ± 0.8 days from the onset of therapy; by the end of therapy, all patients had no vomiting, and nausea stopped in 80%, which was not observed in comparison groups. The normalization of alanine aminotransferase (≤40 U/L) occurred in 80% of pregnant women in the main group (p < 0.01) and in 66% (p < 0.01) when treating with essential phospholipids. The normalization of alanine aminotransferase (≤40 U/L) occurred in 90% (p < 0.01) and 33.3% (p = 0.03), respectively. A significant decrease in the level of bile acids (from 8.49 ± 2.1 μmol/L to 2.74 ± 1.1 μmol/L; p < 0.05) and improvement in the indicators of the antioxidant system – an increase in total antiradical activity (from 804.0.0 ± 10.5 μmol/L to 839.0 ± 11.0 μmol/L; p < 0.05) and a decrease in the level of conjugated dienes (from 3.77 ± 0.2 μmol/L to 3.26 ± ± 0.1 μmol/L; p < 0.05) – were observed only in the main group. A number of other indicators of the “liver panel” tended to improve only in the main group. Conclusion. Heptrong is an effective hepatoprotective drug, which considerably improves the state of pregnant women during early toxicosis and helps to reduce liver transaminases and bile acids in pregnant women with hepatotoxicity. Due to the antiinflammatory and pronounced antioxidant effect, which is not observed in standard pharmacological treatment, Heptrong can be used to prevent late obstetric complications. Key words: Heptrong, drug-induced hepatopathies, “liver panel” indicators, early toxicosis

Fetal adrenal cortex glucocorticoid andfetal hypophysial adrenocorticotropic function in normal pregnancy and pregnancy, complicated with maternal insulin dependent diabetes mellitus were examined in the present study. Statistically significant feta l hypercortisolemia was observed in pregnancies, complicated by insulin-dependent diabetes mellitus. Correlations between vascular complications o f maternal insulin-dependent diabetes mellitus and fetal cortisol andACTG levels were revealed during the investigation. Severe vascular lesions o f maternal diabetes have been associated with delayed feta l lung maturity. Fetal pulmonary maturity was significantly associated with fe ta l cortisol levels.

We tested the effect of low temperature (18-20 °C) applied at the 13-22 days of imago life. We detected prolongation of individual life span. The effect is due to prolongation of the first phase of the annuity curve and thus to further delay of the next ones. This may lead to delay of mature pathology and prolongation of maximal life span. The effect is not dependent on sample size.

The rearing of Drosophila fruit flies at a temperature 5–7°C lower than the standard level until day 13 (or day 22) of the imaginal period enabled an increase of the individual insect lifespan. The positive effect of the longest exposure was evident in all age groups. This effect was due to prolongation of the initial period of the individuals’ lives and the subsequent delay of the onset of later developmental stages. The observed phenomenon may result in delayed development of aging-related pathology and a significant increase in the object’s maximal lifespan. The effect was independent of sample size (in samples of 100 to 1200 flies) and the interval between the experiments. All individuals of the cohort are assumed to contribute to the phenomenon.

Analysis of male imago mortality in Drosophila melanogaster Canton-S strain demonstrated deviation from Gompertz law. Annuity curves were composed of five phases divided by sharp bends. All the phases seemed to be linear. We discuss the hypotheses of strict genetic determination of the phenomenon.

Analysis of the age-specific mortality dynamics in the male imago of the Drosophila melanogaster Canton-S strain demonstrated pronounced deviations from the Gompertz law. Four successive observations carried out in large drosophila cohorts made it possible to determine that the survival curves of the objects within the cohort lifetime consist of five discrete regions (phases) divided by sharp inflections. All of the indicated regions are linear. A rigid genetic determination for the disclosed character of the investigated curves was hypothesized.

Been analyzed and studied the characteristics of hemostasis in pregnant women with gestational diabetes mellitus. Found that for women with disorders of carbohydrate metabolism characte-rized by increased activity of procoagulant, vascular-platelet hemostasis, and decreased activity of fibrinolityc system. It is shown that the violations of the haemostatic system is directly dependent on the degree of compensation of carbohydrate metabolism and require adequate correction of glycemia. Thus, GDM is an important predictor of hemostatic disorders and possible venous thromboembolism in pregnancy.

According to the modern concepts, symphysiopathia usually occurs in the second half of pregnancy as a result of mineral metabolism violations. This complication of pregnancy mainly manifested as a pubic bone diastasis, pain in the bone of the pelvis and of the lower limbs, and cramps in the calf muscles. There are clinical manifestations of the symphysiopathia; indicators of calcium, magnesium and phosphorus in the blood and daily excretion of these minerals in the urine compared with those which have healthy pregnant women in the second and third trimesters. There is histological and immunohistochemical evaluation of placentas of patients on background treatment. The vast majority of pregnant women with symphysiopathia found increase in urinary calcium and magnesium in the urine remaining in the normal performance of mineral metabolism. According to the studies, the preparation of magnesium, calcium, and the local ultraviolet irradiation of symphysis pubis may reduce the clinical symptoms of symphysiopathia. The use of calcium supplements together with magnesium does not lead to excessive deposition of calcium salts in the placental tissue and improve metabolic function of placenta.

We studied the effects of a derivative of indole morphine (Trisan) during induction of labor on the activity of enzymes of antioxidant defense in the brains of fetuses that developed under normal (intact) and disturbed (experimental) placental blood circulation. We show that Trisan has antihypoxic and moderate antioxidant characteristics and decreased intranatal oxidative stress in the CNS of intact and experimental fetuses.

We performed comparative genetic analysis of a set of synthetic peptides effects on longevity and free-radical oxidation in Drosophila melanogaster. Strong genotype and gene-environmental interaction in determining traits value were evaluated. Mechanisms of vilon and epithalon effect on free oxygen species in mitochondria seemed to be different.

Female SHR mice received 5-days long course of delta-sleep inducing peptide preparation "Deltaran" subcutaneously in daily dose of 5 mkg/mice per 24h under standard light regime (12h light: 12 h darkness) or constant illumination. Free-radical level and antioxidative activity in brain and liver was studied by standard methods. Constant illumination increased chemiluminescence in brain by 20 % and decreased liver glutationperoxidase activity by 60 %, as compared to the mice kept in standard light regime. In conditions of standard light regime deltaran increased levels of general antioxidative activity in brain by 9%, liver superoxide dismutase by 17% and lowered levels of glutationperoxidase of liver by 82%. In conditions of constant illumination Deltaran lowered levels of chemiluminescence in liver by 23%, raised the general antioxidative activity in liver by 19% and lowered levels of glutationperoxidase of liver by 69%. It was supposed that deltaran has an antioxidant effect under constant light regime.

65535 Lipid peroxidation (LP) intencity, antiradical and total antioxidant activity (TAA) of blood from a newborn depending of duration and heaviness of hypoxia have been studied. LP intencity in case of chronic placental deficiency has been shown to stay normal within the first day after childbirth. However, in heaviest forms of intrauterine grows retardation antiradical activity decreased (with children who bore hypotrophy III) and TAA rose. An adequate increase in TAA did not occur with children born with asphyxia, while LP intencity was observed to rise. Mechanisms of fetal antioxidant defence in conditions of long-term intrauterine hypoxia are discussed.