Репозиторий Университета

© 2017 Elsevier Inc. A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-D-Arg-Phe-Gly-NH2 was modified with the inclusion of a (D-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (D-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32–1 mg/kg) and TDP (0.32–1.8 mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10 mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7 days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.

© Springer Science+Business Media New York 2016. A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

© 2018 Ima-Press Publishing House. All Rights Reserved. The paper presents the proceedings of the Round Table with the participation of leading neurologists, which is devoted to chronic cerebrovascular diseases. It is noted that chronic cerebral ischemia (CCI), or dyscirculatory encephalopathy (DEP), is one of the most common neurological diagnoses in our country. The pathogenesis, clinical presentations, diagnosis and treatment of CCI (DEP) and its matching with vascular cognitive impairment (CI), which is regarded in foreign literature as the main manifestation of chronic cerebrovascular disease (CVD) were considered. The authors analyze clinical trials evaluating the efficacy of vinpocetine (Cavinton) in chronic CVD, dizziness, Cl, as well as the use of new vinpocetine formulations, such as Cavinton Comforte, in various neurological diseases, dysphagia in particular, in poststroke patients.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. agnetic iron oxide nanoparticles (MNP) show great potential as the contrast agent for magnetic resonance imaging (MRI). Purpose. To evaluate the efficiency and safety of the contrast agent based on HSA-coated MNP on the model of the C6 glioma. Materials and methods. Extensive preclinical research of specific activity has been performed. Studies were conducted on the model of the orthotopic C6 glioma. Results. In the preclinical studies, it was demonstrated that HSA-coated magnetic iron oxide nanoparticles (MNP-HSA) accumulate in the tumor and its large vessels. Conclusion. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.

© 2018 Nailya Kubysheva et al.  Soluble molecules of the major histocompatibility complex play an important role in the development of various immune-mediated diseases. However, there is not much information on the participation of these proteins in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of our work was to determine the content of soluble molecules of the major histocompatibility complex of classes I and II (sHLA-I and sHLA-II) in the exhaled breath condensate (EBC) and in the blood serum in patients with moderate to severe COPD during the exacerbation and stable phase. We investigated 105 patients (male) with COPD aged 46-67 and 21 healthy nonsmoking volunteers (male) comparable in age. The content of sHLA-I and sHLA-II molecules was studied using ELISA. We found an increase in the level of sHLA-I and sHLA-II molecules in EBC, as well as an enhancement in the serum content of sHLA-II in all the examined COPD patients compared to healthy nonsmoking volunteers. The revealed negative correlation between the serum concentration of sHLA-II and values of FEV 1 and FEV 1 /FVC in all examined patients with COPD gives a possibility to consider the content of these proteins as an additional systemic marker of disease severity. The maximum endobronchial and serum concentrations of sHLA-I and sHLA-II were detected in patients with severe COPD during the exacerbation. The negative associations between the content of these molecules in EBC and serum and the parameters of lung function in patients with severe COPD were established. These findings suggest a pathogenetic role of sHLA-I and sHLA-II molecules in the mechanisms of the development and progression of local and systemic inflammation in COPD.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Specific features of the mental state of women during pregnancy have been attracting the attention of specialists for many years. The article is aimed at describing an empirical study of the identification of specific features of emotional states and self-esteem of working women during pregnancy. Method: The leading method to investigate this problem is diagnostic and static methods, which allow one to reveal the presence of significant differences in the emotional states of pregnant women, the psychological component of the gestational dominant and self-esteem. Results: According to the results of the empirical study, it was found that in employed women, in comparison with unemployed pregnant women, the optimal and hypogestognosic type of attitude to pregnancy is more pronounced, an average level of self-esteem is observed with a tendency to high. In non-working women, it was found that, in comparison with working pregnant women, an alarming type of attitude towards pregnancy was revealed, an obsession with oneself and one’s own negative experiences; uncertainty and negative emotional background were revealed in relation to the role of the mother, low self-esteem was identified. Conclusion: In employed women, in comparison with unemployed pregnant women: 1) the optimal and hypogestognosic type of attitude towards pregnancy is more pronounced-that is, employed women have an emotionally positive sentiment, they are joyful, active and goal-oriented; 2) they like the way of life that they lead, which forms their positive mood; 3) there is a lack of support for their lifestyle from relatives and people around, which leads to the dominance of low spirits; 4) there is an average level of self-esteem with a tendency to high. It was found that in non-working women, in comparison with working pregnant women: 1) an alarming type of attitude towards pregnancy was found, an obsession with oneself and one’s own negative experiences; 2) uncertainty and negative emotional sentiment in relation to the role of the mother have been found; 3) low self-esteem has been revealed. The results of the study can be used in practical work of maternity homes, counseling, as well as in assessing the emotional state of pregnant women.

© 2018 Bentham Science Publishers. Introduction: One promising target for novel psychotropic drugs is the 5-HT6 receptor, G-Protein-Coupled Receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked procognitive effects. Methods: An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models. The present study is devoted to a detailed QSAR analysis of 61 drugs (26 agonists and 35 antagonists) acting on the 5-HT6 receptor (rattus norvegicus and homo sapiens). Five classification methods were used: k-Nearest Neighbors (k-NN), Logistic Regression (LG), Linear Discriminant Analysis (LDA), Random Forest (RF), and Support Vector Machine (SVM). Multiple Regression Analysis (MRA) was involved also for regression analysis. Spectra of Inter Atomic Interactions (SIAI) were applied in the search for ligand centres interacting with the 5-HT6 receptor. Results & Conclusion: SAR and QSAR models based on the use of HYBOT, MOLTRA, VolSurf+, and SYBYL programs, and having cross-validated coefficients of determination of at least 0.80, show a predominant influence of H-bond acceptor ability and hydrophobicity on the type of ligand activity and degree of inhibition.

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. We have developed cryo-applicators based on the sapphire shaped crystals fabricated using the edge-defined film-fed growth (EFG) and noncapillary shaping (NCS) techniques. Due to the unique physical properties of sapphire: i.e. high thermal, mechanical, and chemical strength, impressive thermal conductivity and optical transparency, these cryo-applicators yield combination of the tissue cryo-destruction with its exposure to laser radiation for controlling the thermal regimes of cryosurgery, and with the optical diagnosis of tissue freezing. We have applied the proposed sapphire cryo-applicators for the destruction of tissues in vitro. The observed results highlight the prospectives of the sapphire cryo-applicators in cryosurgery.

© 2018 Medical Education. All rights reserved. Mild asthma is characterized by infrequent and slight clinical manifestations and, therefore, is paid lack of attention both from patients and physicians. Physicians tend to underestimate risk of severe exacerbations including asthmatic status in patients with mild asthma. Patients with mild asthma are often poorly adherent to treatment. Also, certain difficulties are related to timely and correct diagnosis and the choice of the optimal treatment by primary care physicians who are first physicians encountering such patients. The paradoxus of asthma and use of short-acting β2-agonists (SABA) to treat chronic airway inflammation lead to excessive dependence on rescue inhalers and insufficient adherence to maintenance anti-inflammatory therapy. This could trigger acute exacerbations and even fatal outcomes in patients with mild asthma. Therefore, SABA monotherapy has to be limited. Easy-to-use questionnaires, algorithms and treatment protocols accessible for primary care physicians could improve detection of mild asthma. Favorable results of clinical trials on as-needed use of budesonide/formoterol Turbuhaler® could change the management paradigm for mild asthma regarding risk of exacerbations, control of asthma symptoms, airway inflammation, and cost-efficacy.

© 2018 Elsevier Inc. Immunoglobulin E (IgE)-associated allergy is the most common immune disorder. More than 30% of the population suffer from symptoms of allergy which are often severe, disabling, and life threatening such as asthma and anaphylaxis. Population-based birth cohort studies show that up to 60% of the world population exhibit IgE sensitization to allergens, of which most are protein antigens. Thirty years ago the first allergen-encoding cDNAs have been isolated. In the meantime, the structures of most of the allergens relevant for disease in humans have been solved. Here we provide an update regarding what has been learned through the use of defined allergen molecules (i.e., molecular allergology) and about mechanisms of allergic disease in humans. We focus on new insights gained regarding the process of sensitization to allergens, allergen-specific secondary immune responses, and mechanisms underlying allergic inflammation and discuss open questions. We then show how molecular forms of diagnosis and specific immunotherapy are currently revolutionizing diagnosis and treatment of allergic patients and how allergen-specific approaches may be used for the preventive eradication of allergy.

© 2017 Astro Ltd. A two-photon laser femtosecond crosslinking process at the wavelength of 525 nm was studied in a human donor cornea in the presence of riboflavin using two-photon optical microscopy and nanoindentation. It was shown that such an approach results in efficient crosslinking of the corneal collagen and a significant (three-fold) increase in the Young's modulus of the corneal structure. Application of a femtosecond laser with the wavelength of 525 nm allows a drastic enhancement of efficiency in the presence of riboflavin on human corneas and a 50-fold reduction of the laser treatment duration in comparison with the use of a femtosecond laser with the wavelength of 760 nm. We relate this effect to a significant growth in the coefficient of two-photon absorption due to the laser wavelength falling within the edge of the photoinitiator (riboflavin) absorption band. Our studies on a donor human cornea demonstrate the good potential for the clinical application of a femtosecond laser with the wavelength of 525 nm for increasing the cornea rigidity using the two-photon laser femtosecond crosslinking technique.

© 2017 Elsevier Inc. Rabies virus is endemic to Russia, among other countries. It is therefore critical to develop a high-quality and high-precision diagnostic procedure for the control and prevention of infection. The main objective of the research presented here was to develop a reliable RT-qPCR assay for rabies diagnostics. For this purpose, a RABV strains from various biological and geographical origins were used. In addition, rabies-positive and rabies-negative samples, as well as nucleic acids from other viruses and DNA extracted from the brain tissues of mice, dogs, cats, bats and humans, were studied using the developed assay. The analytical sensitivity of the assay, as assessed using armored recombinant positive control dilutions, was 103 copies/ml, and the sensitivity measured using characterized strains was between 0.1 LD50/ml and 1.0 LD50/ml. A broad range of RNA from RABV strains circulating in different regions of Russia, as well as RNA from RABV-positive primary brain samples from 81 animals and two humans, was detected using the developed assay. No false-positive or false-negative results were obtained. Given that high analytical and diagnostic sensitivities and a high specificity were verified for this assay, it has high potential as a screening test that may be suitable for the epizootiological monitoring of animals and for the fast postmortem diagnosis of rabies.

© 2018 by the MediaSphere. The materials of the National Consensus reflect the modern domestic and international experience on this issue. Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation. A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child's height is < –2.0 SDS, if the difference between the child's height SDS and child's midparental height SDS exceeds 1.5 SDS and/or a low growth velocity. The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation. The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day. With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum. GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphy-seal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient's desire and his parents / legal representatives satisfied with the achieved result of the final height. Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation. If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

© 2018 Park-media, Ltd.  Common marmosets are small New World primates that have been increasingly used in biomedical research. This report presents efficient protocols for assessment of the parameters of adaptive cell-mediated immunity in common marmosets, including the major subpopulations of lymphocytes and main markers of T- and B-cell maturation and activation using flow cytometry with a multicolor panel of fluorescently labelled antibodies. Blood samples from eight common marmosets were stained with fluorescently labeled monoclonal antibodies against their population markers (CD45, CD3, CD20, CD4, CD8) and lymphocyte maturation and activation markers (CD69, CD62L, CD45RO, CD107a and CD27) and analyzed by flow cytometry. Within the CD45 + population, 22.7±5.5% cells were CD3 - CD20 + and 67.6±6.3% were CD3 + CD20 - . The CD3 + subpopulation included 55.7±5.5% CD3 + CD4 + CD8 - and 34.3±3.7% CD3 + CD4 - CD8 + cells. Activation and maturation markers were expressed in the following lymphocyte proportions: CD62L on 54.0±10.7% of CD3 + CD4 + cells and 74.4±12.1% of CD3 + CD8 + cells; CD69 on 2.7±1.2% of CD3 + CD4 + cells and 1.2±0.5% of CD3 + CD8 + cells; CD45RO on 1.6±0.6% of CD3 + CD4 + cells and 1.8±0.7% of CD3 + CD8 + cells; CD107a on 0.7±0.5% of CD3 + CD4 + cells and 0.5±0.3% of CD3 + CD8 + cells; CD27 on 94.6±2.1% of CD3 + cells and 8.9±3.9% CD20 + cells. Female and male subjects differed in the percentage of CD3 + CD4 + CD45RO + cells (1.9±0.5 in females vs 1.1±0.2 in males; p < 0.05). The percentage of CD20 + CD27 + cells was found to highly correlate with animals' age (r = 0.923, p < 0.005). The basal parameters of adaptive cell-mediated immunity in naïve healthy marmosets without markers of systemic immune activation were obtained. These parameters and the described procedures are crucial in documenting the changes induced in common marmosets by prophylactic and therapeutic immune interventions.

© Published under licence by IOP Publishing Ltd. Implementation of up-to-date 3D printing methods for tissue engineering applications requires synthesis of novel materials possessing both biocompatibility and processability properties. Since the hyaluronic acid is an endogenous material it represents an attractive candidate for scaffold formation. In this work, chemical modification of hyaluronic acid with glycidyl methacrylate (HAGM) was used to produce derivatives that are capable of photoinduced cross-linking. Aiming to control the degree of substitution in hyaluronic acid by glycidyl methacrylate we developed a new quantitative method based on oxidation of double bonds in HAGM by permanganate ions. HAGM hydrogel scaffolds have been produced and examined as in vitro and in vivo.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). Materials and methods: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym-oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. Results. Mean duration of follow-up was 64414.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 38956.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2-VASc, and ORACLE scores, respectively.

© 2018 SPIE. Application of terahertz (THz) spectroscopy for biological tissues is strongly limited by the extremely low penetration depth due to THz absorption by tissue water. One of the possible solution of such problem is the usage of THz wave penetration-enhancing agents (PEA) for optical clearing of tissues. In the present paper, the transmission-mode THz spectroscopy of a set of PEAs (polyethylene glycol with different molecular weight, propylene glycol, ethylene glycol, and dimethyl sulfoxide) was performed in order to reconstruct their dielectric properties and compare them with that of water. The obtained results emphasize the feasibility of using PEG to enhance the depth of THz wave penetration into tissues.

© 2018 Ima-Press Publishing House. All Rights Reserved. In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". These guidelines were drawn up to improve the use of NSAIDs, our country's most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE. Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world's leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice. The guidelines are intended for physicians of all specialties.

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. We have developed a method of the terahertz (THz) solid immersion microscopy for the reflection-mode imaging of soft biological tissues. It relies on the use of the solid immersion lens (SIL), which employs the electromagnetic wave focusing into the evanescent-field volume (i.e. at a small distance behind the medium possessing high refractive index) and yields reduction in the dimensions of the THz beam caustic. We have assembled an experimental setup using a backward-wave oscillator, as a source of the continuous-wave THz radiation featuring λ= 500 μm, a Golay cell, as a detector of the THz wave intensity, and a THz SIL comprised of a wide-aperture aspherical singlet, a truncated sphere and a thin scanning windows. The truncated sphere and the scanning window are made of high-resistivity float-zone silicon and form a unitary optical element mounted in front of the object plane for the resolution enhancement. The truncated sphere is rigidly fixed, while the scanning window moves in lateral directions, allowing for handling and visualizing the soft tissues. We have applied the experimental setup for imaging of a razor blade to demonstrate the advanced 0:2λ resolution of the proposed imaging arrangement. Finally, we have performed imaging of sub-wavelength-scale tissue spheroids to highlight potential of the THz solid immersion microscopy in biology and medicine.

© Team of authors, 2018. Objective. To investigate the efficacy of divaza in outpatients with cognitive disorders and chronic brain ischemia (CBI). Material and methods. The non-interventional observational program included the data of 2583 outpatients with CBI from 30 cities (8 federal okrugs of the Russian Federation) who were on outpatient neurological treatment and received divaza in a dose of 2 tablets three times a day from Oct 2016 to Jan 2017. Cognitive functions were evaluated using the MoCA scale before and after 3 months of treatment. Results and conclusion. Cognitive disorders were identified in 90.7% of patients (<26 МоСА scores). After treatment, the mean MoCA score increased from 19.58 ± 5.13 to 23.99 ± 4.21 (p<0.0001), the number of patients with normal cognitive functions rate (≥26 scores) increased from 9.3 to 41.3%, the number of patients with marked cognitive impairment decreased. The drug was well-tolerated by old and very old patients, adverse events were observed rarely (0.6% of cases). The majority of doctors (88.4%) noticed the effect of divaza as significant improvement or improvement, and 89.6% of patients valued the effect to be excellent or good. The use of divaza, the drug with endothelioprotective and nootropic effects, is pathogenetically justified and promising in patients with cognitive disorders of vascular etiology.