I n t r o d u c t i o n . The search for new pharmacological agents is justified by the need for drugs with high efficiency along with low toxicity. The substances with minimal side effects, which include herbal remedies, are of particular interest. The assessment of safety, and study of toxicity of new medicines in particular, is a necessary stage of their preclinical development.
A i m . To determine the toxicity of Thymus marschallianus Willd. extracts and study their effect on the biochemical parameters of the blood of mice with repeated administration.
M a t e r i a l s a n d m e t h o d s . The toxicity of Thymus marschallianus Willd. extracts was determined by probit analysis. The experiment was carried out on 24 female mice: three experimental groups and a control group (intact). The animals of experimental groups got a single intraperitoneal injection with Thymus marschallianus Willd. extracts at doses of 1000, 3000, 5000 mg/kg (in terms of thick extract) respectfully. The study of the effect of Thymus marschallianus Willd. extracts on blood biochemical parameters was carried out on 24 male mice: three experimental groups and a control group (intact). The experimental groups received drinking water, ethanol and aqueous extracts of Thymys marschallianus Willd. intragastrically at a dose of 100 mg/kg daily for 21 days of the experiment. The content of glucose, cholesterol, urea, total bilirubin, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) in blood samples was determined.
R e s u l t s . According to the classification of toxicity of chemicals, an ethanol extraction of Thymus marschallianus Willd. belongs to low-toxic substances. The administration of an aqueous extract of Thymus marschallianus Willd. led to a significant decrease in glucose, albumin, total bilirubin and urea, as well as a decrease in ALT activity. The content of cholesterol, total protein, creatinine, as well as the activity of ALP and LDH did not significantly differ from the indicators of the control group. With the administration of an ethanol extraction of Thymus marschallianus Willd., there was an increase in the total protein content and activity of ALT, AST, ALP and a decrease in the level of total bilirubin and urea compared with the control group. The content of glucose, cholesterol, albumin, creatinine and LDH activity remained within the control group values.
C o n c l u s i o n . The results of the study did not reveal significant changes in the biochemical parameters of the blood of mice with the administration of Thymus marschallianus Willd. extracts, which confirms the safety of the use of extracts from this type of plant raw materials. 

I n t r o d u c t i o n . Anticipating regulatory mechanisms allow a person to more effectively adapt to the impact of environmental factors with the formation of an optimal response structure.
A i m . To reveal the features of the antedating response of the autonomic nervous system under conditions of cognitive load in apparently healthy students.

M a t e r i a l s  a n d  m e t h o d s . The study involved 30 medical university students aged 18–19 years. The partici- pants were divided into two groups (15 people in each). In group 1, the semantic verbal fl uency test was used as a load, in group 2 – the Intelligence Structure Test (IST) by Amthauer. RR intervals in the examined young men were recorded under control and load conditions. The indicators of heart rate variability (HRV) were assessed – RRNN, TP, HF, LF, VLF.

R e s u l t s . Analysis of HRV in group 1 revealed that after exercise, RRNN, TP, HF, and LF indicators signifi cantly decreased; in group 2, after exercise, TP and LF indicators signifi cantly increased relative to control values. Using correlation analysis, we revealed diff erences between the HRV indicators at the time of preparation for the cognitive test between the studied groups. In group 1, unlike group 2, there was no correlation between RRNN and HF, TP and LF, HF and LF, LF and VLF. After the test in group 1, a signifi cant positive correlation was found between RRNN and HF. In group 2, the correlation relationships between the RRNN and LF indicators were determined, the interaction between HF and LF increased, there were no correlation between the LF and VLF indicators. Diff erences between the HRV indicators at the time of preparation for the cognitive test showed that the anticipation of the upcoming examination determines the response of the HRV regulatory mechanisms to the action of the load.

C o n c l u s i o n . Diff erent variants of cognitive loads contribute to changes in the activity of the autonomic nervous system in the regulation of HRV. The nature of these changes depends on the initial level of regulatory capabilities of HRV, which determine the antedating response to the cognitive load. 

I n t r o d u c t i o n . Amidines have a fairly high biological activity. One aspect of their therapeutic action is the antiinflammatory effect. Therefore, the development of a granulate technology based on amidines with anti-inflammatory activity for subsequent dosing into enteric capsules is an issue of interest today.
A i m . To develop a granulate based on amidines with anti-inflammatory activity for subsequent dosing into enteric capsules.
M a t e r i a l s  a n d  m e t h o d s . An experimentally synthesized substance N-(naphthalene-2-yl)benzene carboximidamide and excipients: lactose monohydrate, sodium starch glycolate (Explotab®), povidone (Plasdone™ K-29/32) were used as the active substance. The granulate was obtained by pressing wet masses through. The resulting granulate was dosed into enteric capsules. The technological properties of the substance and the quality attributes of the granulate and capsules were determined according to the methods described in the State Pharmacopoeia of the Russian Federation, edition XIV (SP XIV).
R e s u l t s . According to the results of the study of technological properties, it was found that the substance has poor flowability, is quite light and bulky, the main fraction of the powder is particles up to 0.1 mm in size. To improve the flowability and reduce the hygroscopicity of the granulated material, lactose monohydrate was used as a filler. A 5% solution of Plasdone K-29/32 was chosen as a binder, which improves the dissolution and bioavailability of drugs due to the formation of water-soluble complexes. Sodium starch glycolate was used as a disintegrant. The resulting granulate was dosed into enteric capsules that meet the SP XIV requirements.
C o n c l u s i o n . A synthesis method was proposed and a substance of N-(naphthalene-2-yl)benzene carboximidamide with pharmacological activity was synthesized. Excipients were selected taking into account the properties of the substance, composition and technology of the granulate based on the previously synthesized substance N-(naphthalene-2-yl) benzene carboximidamide was developed, followed by dosing into enteric capsules, a draft specification for enteric capsules was proposed in accordance with the SP XIV requirements.

I n t r o d u c t i o n . The decrease in physical health parameters of children and adolescents in our country justifies the need to develop programs aimed at correcting this situation, in particular, conducting research in the field of anthropology, studying the autonomic balance and the influence of the body’s individual morphological features on it.
A i m . Identification of the relationship between autonomic status and morphofunctional parameters of the cardiovascular system depending on the somatotype in adolescent girls of the city of Krasnoyarsk.
M a t e r i a l s  a n d  m e t h o d s . The study involved 158 adolescent girls (from 13 to 15 years old) living in Krasnoyarsk. An anthropometric examination was carried out with the further determination of the somatotype according to the Rees-Eysenck body index. Some indicators of the cardiovascular system (systolic and diastolic blood pressure (SBP and DBP), heart rate (HR)) and the tone of the autonomic nervous system were assessed according to the Kerdo’s index.
R e s u l t s . According to the results of anthropometry, the participants were distributed as follows: ectomorphy – 65 people, mesomorphy – 51 people, endomorphy – 42 people. A statistically significant increase in SBP and DBP was found as body strength increased in all three groups. In ectomorphic body type girls, there was a decrease in SBP values in combination with higher HR. The predominance of sympathicotonia was found in the ectomorphy and endomorphy groups (65.2 and 52.8%, respectively). The largest number of girls with the excitation-inhibition balance of the autonomic nervous system was among mesomorphy (53.3%) and slightly less among endomophy girls (39.6%), both of these indicators were significantly higher than among the ectomorphic body type girls (30.4%). At the same time, in the latter, the parasympathicotonia predominates less often (4.3%) than in mesomorphy (6.7%) and endomorphy (7.5%) (p < 0.05).
C o n c l u s i o n . The obtained data on the difference in hemodynamic parameters and autonomic status in girls aged 13–15, depending on the body type, must be considered when choosing sports activities and realization of medical and preventive work in a secondary school.

I n t r o d u c t i o n . Antiphospholipid syndrome (APS) is an autoimmune thrombophilia in which patients with clinical criteria for recurrent arterial and venous thrombosis and/or pregnancy failure show positive laboratory results for the presence of antiphospholipid antibodies (aPL). The genetic predisposition to non-infectious endocarditis (NIE) in patients with APS remains a complex and poorly understood problem.
A i m . Revealing of possible associations between polymorphisms of candidate genes and non-infectious endocarditis in patients with APS, as well as the development of possible thromboembolic complications.
M a t e r i a l s  a n d  m e t h o d s . The study involved 35 patients aged 43.0 ± 13.9 years. At the same time, the main signs characterizing NIE in APS were negative blood culture, normothermia, and the absence of obvious echoscopic signs of infection (thickening and induration calcification of the valve leaflets, minimal regurgitation). Polymorphisms of 18 genes were studied as possible molecular genetic markers for the development and/or protection of NIE in 35 patients with APS: the primary disorder was diagnosed in 15 patients (18.5%), secondary – in 20 patients with autoimmune pathology (24.7%).
R e s u l t s . For the first time, for polymorphisms rs6025 (1691 G>A) of the F5 gene, 4а/4b of the NOS3 gene, rs1800795 of the IL6 gene, rs1805087 (2756 A>G) of the MTR gene, a significant association with the development of vegetations on the valvular heart apparatus in APS was revealed. Two polymorphisms, rs1126643 (807 C>T) of the ITGA2 gene and rs1799889 (-675 5G>4G) of the PAI1 gene (SERPINE1), were found to be associated with thromboembolic complications (acute cerebrovascular accident) in NIE.
C o n c l u s i o n . It is reasonable to perform genotyping of some single nucleotide polymorphisms in patients with APS.

In t r o d u c t i o n . Tubercular granulomatosis in newborns and children is much less common than in adults, and especially its visceral forms, including hepatic lesion. Oxidized dextran enhances the production of oxygen radicals, cytotoxic and bactericidal potential of phagocytes, accelerates the process of phagolysosomal fusion and elimination of the pathogen, reducing the granulomatous infl ammatory process in organs.
A i m . To study morphological changes in the liver of mice from the neonatal period to adulthood with the BCG vaccine administration and use of oxidized dextran.
Ma t e r i a l s  a n d  m e t h o d s . Mice of the C57B1/6 line (200 animals in total) were divided into 4 groups: mice from the 1st (intact) group were injected with 0.02 ml/kg of 0.9% sodium chloride solution on the fi rst day after birth. Mice from the 2nd group on the 2nd day after birth were injected with a solution of oxidized dextran with a molecular mass of 40 kDa. Mice from the 3rd group were injected with a solution of the BCG vaccine of 0.02 ml/kg on the fi rst day after birth. Mice of the 4th group were injected with a solution of the BCG vaccine of 0.02 ml/kg, on the second day after birth – a solution of oxidized dextran with a molecular mass of 40 kDa.
R e s u l t s . The numerical density (Nai) of granulomas in the liver progressively increased from 28th to 56th day of the experiment in mice of the 3rd and 4th groups by 13.5 times. However, in mice of the 4th group, the number of granulomas was 1.4 times less than in mice of the 3rd group. The diameter of granulomas in the liver in mice of the 4th group was smaller on the 28th and 56th days in comparison with the same indicator in mice of the 3rd group by 2 times and 1.3 times, respectively. In mice of the 4th group, the volume density (Vv) of degenerated hepatocytes from 3rd to 5th day was 8 times lower compared to the same indicator in mice of the 3rd group, on the 10th and 28th days – 1.7 and 1.2 times, respectively. Vv of foci of hepatocyte necrosis in mice of the 4th group did not diff er from that in mice of the 1st (intact) and 2nd (control) groups in all periods of observation, and was less on the 3rd and 56th days in comparison with the same indicator in mice of the 3rd (BCG) group by 3 times. On the 28th and 56th days of the experiment, mice from the 3rd and 4th groups showed an increase in the Nai of binuclear hepatocytes and hepatocytes with mitoses in comparison with the same indicator in mice of the 1st and 2nd groups. In mice of the 4th group, the number of binuclear hepatocytes, refl ecting the reparative regeneration of hepatocytes, was 1.8 times greater than in mice of the 3rd group on the 28th and 56th days.
Co n c l u s i o n . Granulomas formation (the number and diameter of granulomas) in the liver of mice with the admin-istration of the BCG vaccine and use of oxidized dextran was less marked in comparison with animals not treated with oxidized dextran, which indicates the eff ective elimination of the pathogen in phagocytes. Destructive changes (degeneration and necrosis of hepatocytes) in the liver parenchyma of mice with the injection of the BCG vaccine and subsequent use of oxidized dextran are signifi cantly reduced, while the processes of reparative regeneration in the liver parenchyma of mice are activated, which is due to the hepatotropic action of oxidized dextran.

I n t r o d u c t i o n . The proportion of pure alcohol (PA) per capita in the Russian Federation (RF) is high, and moderate alcohol consumption is important for elderly  Russians. In 2008, the Ministry of Health, Labor and Welfare of Japan (the Japanese are considered one of the healthiest nations in the world) recommended a daily moderate consumption of less than 20 g/day of PA. In the Russian Federation, recommendations on daily moderate alcohol consumption  for elderly persons have not yet been introduced.
A i m . To clarify the factors associated with the daily moderate PA consumption and its physical and social eff ects on the elderly people, using in reference the recommendations for the Japanese population, in order to consider the possibility of their adaptation among the Russian population.
M a t e r i a l s  a n d  m e t h o d s . A cross-sectional study was conducted among 770 elderly Russians aged 60 years and older. Methods of descriptive statistics were used to process the obtained data. Odds ratio (OR) and 95% confi dence interval (CI) were calculated. A logistic regression analysis was performed, with a sample stratifi ed by gender.
R e s u l t s . The logistic regression analysis among drinking participants found correlations between consumption of more than 20 g of PA per day with gender (OR = 0.582; 95% CI: 0.351–0.966), hypertension (OR = 0.384; 95% CI: 0.223– 0.661), living alone (OR = 0.453; 95% CI: 0.256–0.803), the reason for alcohol intake – stress relief (OR = 4.580; 95% CI: 2.313–9.069), enjoyment of life (OR = 3.015; 95% CI : 1.207–7.531), drinking alone (OR = 2.480; 95% CI: 1.079–5.703) and with the family (OR = 2.586; 95% CI: 1.506–4.439). As a result of the stratifi ed analysis, it was found that among male participants, alcohol consumption signifi cantly correlated with hypertension (OR = 0.216; 95% CI: 0.090–0.521), the desire to reduce stress (OR = 2.530; 95% CI: 1.043–6.136), drinking alone (OR = 5.454; 95% CI: 1.699–17.510) and with the family (OR = 4.934; 95% CI: 2.003–12.154). Among women, alcohol consumption signifi cantly associated with living alone (OR = 0.455; 95% CI: 0.228–0.907), the desire to reduce stress (OR = 5.274; 95% CI: 2.092–13.299), and enjoy life (OR = 4.669; 95% CI: 1.218–17.899) and drinking alcohol in the family (OR = 2.077; 95% CI: 1.069–4.033).
C o n c l u s i o n . The introduction of daily moderate alcohol consumption is crucial for improving the health and life expectancy of elderly Russians. However, the attempt to adapt the Japanese health policy for the Russian Federation showed no signifi cant diff erence in the health characteristics of elderly people, indicating the need to introduce other possible cutoff s for daily moderate alcohol consumption. Excessive alcohol consumption occurred among Russian older people drinking alone and to relieve stress, which indicates a risk of social isolation and misunderstanding of doses for alcohol’s sedative eff ects. Family drinking may result in higher daily alcohol consumption among elderly people, whereas gender diff erences in alcohol consumption with a cutoff  of 20 g per day need to be considered, especially among women. The eff ect of moderate alcohol consumption on hypertension requires further study.

I n t r o d u c t i o n . Immobilized subtilisins are currently used as a fibrinolytic agent in antithrombotic drugs. The effect of immobilized subtilisins (ISs) on the contractile function of the heart has not been previously studied.
A i m . To study the effect of coronary perfusion with immobilized subtilisins (ISs) on the contractile function of an isolated rat heart in an experiment.
M a t e r i a l s a n d m e t h o d s . The study used a Langendorff model of coronary retrograde perfusion of an isolated rat heart with solutions of ISs at different concentrations. The experiment included 50 male rats. The animals were divided into 5 groups: group 1 – control (hearts perfused only with Krebs-Henseleit solution) and 4 experimental groups – hearts perfused with a solution of ISs at concentrations of 170, 340, 510 and 1020 IU/l, respectively. The contractile function (inotropic effect) of the isolated rat heart was assessed in terms of the pressure developed by the left ventricle (LVP).
R e s u l t s . Perfusion of an isolated rat heart with a solution of ISs for 40 min causes a positive inotropic effect in all experimental groups. At a concentration of 170 IU/l, the effect is observed from the 10th minute, at higher concentrations – from the 5th minute. The duration of the effect’s rising when using ISs in the dose range of 170–510 U/l manifests itself up to the 20th minute, and when using a dose of 1020 U/l – up to the 30th minute. Then there is a weakening of the inotropic effect. In groups of animals with the introduction of immobilized subtilisins at a concentration of 340–1020 U/l, there is a decrease of LVP by the 40th minute, but the values of this indicator remain higher compared to the control group.
C o n c l u s i o n . Perfusion of the isolated heart with a solution of ISs increases the contractile activity of the isolated heart. When the heart is perfused with ISs, there is an increase of LVP. The inotropic effect is dose-dependent at various time points

I n t r o d u c t i o n . In assisted reproductive technology pregnancy (ARTP), the most unfavorable factor aff ecting perinatal outcomes is iatrogenic multiple gestation. Active introduction into practice of techniques that reduce the risk of multiple pregnancy, on the one hand, and management of ARTP in specialized medical centers with experience in working with this category of patients, on the other, can improve perinatal outcomes.
A i m . Analysis of perinatal outcomes in assisted singleton and multiple pregnancies in order to assess the contribution of the multiple gestation factor to adverse health outcomes for newborns, and its relevance for improving of assisted reproductive technology.
M a t e r i a l s  a n d  m e t h o d s . A retrospective study of the ante-, intra- and early neonatal period was carried out in 672 infants born at the Medical Center AVICENNA (Novosibirsk) for the period from 2006 to 2015. The total sample was divided into 3 groups: 1st – infants from singleton ARTP (n = 345); 2nd – infants from multiple ARTP (n = 177); 3rd – infants from singleton spontaneous pregnancy (SSP) (n = 150) without infertility in the parental history, gravidity and parity were equal. A clinical and anamnestic method was used, with an assessment of the main parameters of the health status of infants and parents.
R e s u l t s . It was revealed that complications such as threatened miscarriage and preterm labor, cervical insuffi  ciency, preeclampsia, and placental disorders are diagnosed signifi cantly more often in multiple ARTP (p < 0.001) compared with singleton ARTP. At the same time, in the setting of a specialized center, the majority of infants from ARTP were full-term, both in singleton (94.5% of cases) and in multiple (52.5% of cases) pregnancies. Any assisted reproductive technology pregnancy belongs to the group of high obstetric risk, but timely correction of complications signifi cantly improves perinatal outcomes.
C o n c l u s i o n . ARTP belongs to the group of high obstetric risk, which increases signifi cantly with multiple gestation. Management of an infertile couple in a specialized center with continuity at all stages from the moment of contacting the clinic to the birth of a child allows, despite the development of complications, to ensure the birth of full-term infants (both in singleton and multiple pregnancies), and in singleton pregnancies it leads to the birth of children, in main health indicators similar to those from a spontaneous pregnancy.

I n t r o d u c t i o n . The development of methods for determining the concentration of antimicrobial drugs used in various pathological conditions of the body is of great interest.
A i m . Development of a technique for quantitative determination of amphotericin B in blood serum.
M a t e r i a l s  a n d  m e t h o d s . The drug amphotericin B was used for the preparation of solutions. The optical density of the solutions was determined by the spectrophotometric method.
R e s u l t s . The method of quantitative determination of amphotericin B in sodium chloride solution, which is the closest in composition to biological fl uids, has been tested. Statistical analysis showed that the error of the method for determining
Co n c l u s i o n . A unifi ed method of spectrophotometric determination of amphotericin B in blood serum has been developed. The optimal conditions for the determination of amphotericin in biological fl uids were found: the solvent – 0.9% sodium chloride solution, wavelengths – 363, 383 and 406 nm, t – 3^–6°C, detectable concentrations – from 1.0 · 10^–2 to 1.0 · 10^–5 mg/l. 

The review summarizes modern researches about the role of the blood-brain barrier (BBB) in the development of lymphomas of the central nervous system (CNS). Currently, it has been established that the BBB is a highly active structure. On the one hand, it protects the brain tissue from chemical, physical and other infl uences, and on the other hand, it is uniquely adapted for transmitting signals between the CNS and other parts of the body. BBB cells respond to signals from the CNS or blood compartments that can stimulate changes in their barrier, transport, and secretory functions. The immune privilege of the CNS is not absolute. Normally, extravasation of lymphocytes through the BBB is crucial for immune surveillance in nervous tissue, although it is tightly regulated.

Damage to the BBB is one of the central links in the pathogenesis of many diseases of the nervous system, and the nonspecifi c permeability of the BBB can increase signifi cantly in various somatic pathologies. In general, immunological dysfunction and infl ammation are the main factors in the violation of the BBB integrity. The mechanisms of metastasis of malignant lymphomas in the CNS remain poorly understood, although it is already clear that their implementation requires interactions between circulating tumor cells and BBB components, while some cytokines can act as attractants for metastatic cells, and the process of tumor development includes several stages from extravasation to local proliferation and activation of neoangiogenesis.