Ectonucleotidase Activity in Smooth Muscle Tissues of Rats with a Valproate Model of Autism.

Ectonucleotidases play an important role in regulating the level of extracellular nucleotides and nucleosides and are an important part of the regulation of the effects of adenosine and ATP on adenosine and P2 receptors, respectively. We have previously established the ambiguous effect of P2 receptor agonists on the contractile activity of smooth muscle tissue in rats with the valproate model of autism. In this work, HPLC was used to evaluate the activity of ectonucleotidases in the smooth muscle tissues of the internal organs of rats with a valproate model of autism. The activity of ectonucleotidases was significantly higher in the smooth muscle tissues of the duodenum, vas deferens, and bladder, but lower in the ileum and uterus. The results obtained make it possible to compare the activity of ectonucleotidases identified here with changes in P2 receptor-mediated contractility of smooth muscle tissues revealed in our previous experiments.

Evaluation of Disorders of Contractile Activity of Smooth Muscle Tissues in 9-Month-Old Rats with a Model of Autism.

We studied the effect of carbachol, P2 receptor agonists, and electric field stimulation on mechanical activity of isolated preparations of the duodenum, ileum, bladder, and vas deferens in 9-month-old rats with the valproic acid-induced model of autism. It was found that the contractions and relaxations of the isolated intestine of the experimental rats caused by various agonists and electric field stimulation did not differ from those in control animals. Carbachol induced more significant contractions of the bladder in rats with autism model than in controls and electric field stimulation induced more significant contractions of the vas deferens. We did not find significant differences in the effect of ATP, α,ß-methylene-ATP and 2-methylthio-ATP on the contraction and relaxation of the studied smooth muscle organs of rats of the experimental and control groups. It was concluded that 9-month-old rats with an autism model retained increased contractile activity of the bladder and vas deferens, while intestinal contractions in experimental and control animals of this age did not differ significantly.

Comparative Assessment of Disturbances of Contractions of the Isolated Uterus in 3- and 9-Month-Old Rats with a Model of Autism.

We performed a comparative study of the effects of carbachol, α,ß-methylene-ATP, ß,γ-methylene-ATP, and electric field stimulation on the contractile activity of the isolated uterus from rats aged 3 and 9 months with valproic model of autism. The contractile responses of isolated rat uterine preparations induced by P2X-receptor agonists α,ß-methylene-ATP and ß,γ-methylene-ATP were significantly lower than in the control. In addition, the contractions of the isolated uterus of 9-month-old rats induced by carbachol were significantly lower than in controls. No significant differences in uterine smooth muscle contractions in both age groups of rats induced by electric field stimulation in comparison with the control were found. Thus, significant impairment of uterine contractile activity was revealed in rats with valproic model of autism, which persisted up to the age of 9 months. The absence of changes in the contractions induced by electric field stimulation suggests that the changes in the contractile activity of the uterus of the rats with modeled autism spectrum disorder are caused by the disorders occurring at the postsynaptic level.

[Surgical treatment of patients with chest malignancies in anti-tuberculosis hospital]. / Khirurgicheskoe lechenie bol'nykh zlokachestvennymi novoobrazovaniyami organov grudnoi kletki v protivotuberkuleznom statsionare.

OBJECTIVE: To evaluate the effectiveness of surgical treatment of patients with malignancies of lungs, pleura and chest wall in early and long-term follow-up period in anti-tuberculosis hospital. MATERIAL AND METHODS: There were 2139 patients between 2016 and 2020. Chest tumors were diagnosed in 290 (13.6%) patients and 210 (94.2%) ones underwent surgery. RESULTS: Surgical interventions are rare in patients with lung cancer and active tuberculosis (0.7%, n=15). Lobectomies prevailed (73.3%). All sublobar resections were performed in elderly patients with severe comorbidities and low functional reserves. Postoperative complications occurred in 9% of cases. Overall 3-year survival rate was 84.8%, overall 5-year survival rate - 70.8%. Overall survival of patients with lung cancer and tuberculosis does not depend on activity of specific process. CONCLUSION: The TRA test used in differential diagnostics of tuberculosis and lung cancer has a mediating value. Lung cancer surgery in patients with active tuberculosis has no negative effect on effectiveness of tuberculosis treatment. Surgical treatment of malignancies in anti-tuberculosis hospital can be performed in accordance with standards of specialized medical care in oncology.

[Involvement of p2 receptors in the contractile activity of the bladder in patients with benign prostatic hyperplasia].

AIM: to study the role of P2 receptors in impaired bladder contractility in patients with lower urinary tract obstruction. MATERIALS AND METHODS: in pharmacological studies, tissue samples from the bladder wall of 30 patients were used, obtained during planned surgical interventions for benign prostatic hyperplasia (transvesical simple prostatectomy without placement of cystostomy tube). Based on these tissue, isolated smooth muscle specimens were prepared. Their mechanical activity and the efficiency of ligands of purine P2 and other receptors were evaluated. With this aim, the following P2-receptor agonists were used: adenosine triphosphoric acid (ATP), adenosine diphosphoric acid (ADP), uridine-5'-triphosphoric acid (UTP), alpha, beta-methylene-ATP, 2-methylthio-ADP, as well as antagonists of P2-disulfonate receptors acid (PPADS), suramin, NF023, MRS2500. In addition, the efficiency of ligands of other receptors, including carbacholine, epinephrine, histamine, serotonin, atropine was evaluated. RESULTS: the most effective agonist was alpha-beta-methylene-ATP, while ATP and 2-methylthio-ADP were significantly less active. In our experiments, ADP and UTP did not show an effect on human bladder. The influence of P2 receptor agonists was inhibited by P2 receptor antagonists PPADS and suramin, as well as MRS2500, although to a lesser extent. Carbacholine caused a strong concentration-dependent contractile response of the bladder, which was inhibited by atropine. Histamine resulted in mild bladder contractions only at high concentrations. Epinephrine and serotonin did not cause significant changes in the contractile activity of the bladder. CONCLUSION: The main subtype of P2 receptors involved in the contractile activity of the human bladder is P2X1 receptors. P2Y1 receptors also have some influence on the contraction, while other subtypes of P2 receptors are not detected by pharmacological methods.

Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis.

Properdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients' plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.

Magnetic resonance imaging of the heart in the diagnosis of sarcoidosis.

Heart sarcoidosis diagnosis presents great difficulties due to the absence of specific clinical manifestations. Most often, the diagnosis is established during autopsy. Magnetic resonance imaging (MRI) of the heart with contrast enhancement is one of the most informative methods of intravital diagnosis of cardiac sarcoidosis. In this article, two clinical cases, shows the role of MRI of the heart with contrast enhancement in the diagnosis of cardiac sarcoidosis.

[Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts]. / Khirurgicheskoe lechenie opukholei funktsional'no znachimykh zon golovnogo mozga s primeneniem metoda neirofiziologicheskogo kartirovaniya rechevykh, motornykh zon i provodyashchikh putei.

AIM: To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). MATERIAL AND METHODS: Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. RESULTS: According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). CONCLUSION: Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.

[Malignant medulloepithelioma mimicking retinoblastoma - clinical and morphological case analysis and cell culture experience]. / . Zlokachestvennaya medulloepitelioma, simuliruyushchaya retinoblastomu ­ kliniko-gistologicheskii analiz sluchaya i opyt polucheniya kletochnoi kul'tury.

The paper presents clinical and morphological case analysis of primary intraocular malignant medulloepitelioma (medulloblastoma) of rare localization (central part of the retina with optic nerve involvement) that simulated retinoblastoma in a 2-year-old child. Histological features of the tumor are given in details (tubular and mesh structures of the tumor, rosettes, ribbons, cells with hyperchromic nuclei, and cellular polymorphism). An experience of creating a primary intraocular malignant medulloepitelioma cell culture, as yet exclusive in the Russian Federation, is described. Culture sensitivity for particular drugs (oxaliplatin, irinotecan, ifosfamide, and ascorbic acid at different concentrations) was evaluated by MTT-assay. Of the four products, IC50 (3.3 mg/ml) was obtained only for ascorbic acid. Despite the relative rarity of primary intraocular malignant medulloepitelioma, its differential diagnosis should be carried out, with retinoblastoma in mind in the first place. The obtained data on the effectiveness of ascorbic acid against intraocular malignant medulloepitelioma cells can be used to supplement the existing chemotherapeutic protocols in pediatric ocular and neuro-oncology.

Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect substantially any organ in the body. One of its most severe manifestations is lupus nephritis. Hereditary C1q deficiency is strongly related to SLE but there are very few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE. In the present study we evaluated the possible association of gene variants in complement C1q gene cluster with susceptibility to lupus nephritis in a Bulgarian population, focusing on five previously associated with SLE SNPs in other populations. MATERIALS AND METHODS: Thirty-eight patients with lupus nephritis and 185 healthy controls, all from Bulgaria, were genotyped for the five C1q SNPs, rs587585, rs292001, rs172378, rs294179 and rs631090, by quantitive real-time PCR methods. We also determined C1q serum levels of C1q and haemolytic activity of C1q in relation to C1q genotypes. RESULTS: Lupus nephritis patients and healthy controls had statistically similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, minor G allele in rs172378 was significantly overrepresented in lupus nephritis patients when compared with healthy controls (36% vs. 23%, odds ratio = 1.80, 95% confidence interval = 1.06-3.06, p = 0.029). The SNP rs292001 showed a trend towards lower serum C1q levels in healthy controls. Two SNPs - rs294179 and rs292001 - were in a linkage disequilibrium in patients and healthy controls with different power (healthy controls: r (2 )= 0.6526, D' = 0.842; lupus nephritis patients: r (2 )= 0.491, D' = 0.686). The haplotype C-A-A-T-T in the patient group was associated with lupus nephritis: 7.7% vs. 0.8%, odds ratio = 10.81, 95% confidence interval = 1.45-80.57, p = 0.002. CONCLUSIONS: These results support the implication of the G allele in rs172378 as a risk factor for lupus nephritis in a homozygous status, at least for a Bulgarian population.

[The application of the pulsed low-frequency electrostatic field for the combined treatment of the children presenting with bronchial asthma].

The objective of the present study was to develop a scientifically sound rationale for the application of the pulsed low-frequency electrostatic fields (PLIESF) for the combined treatment of the children presenting with bronchial asthma and the comparative assessment of the effectiveness of the use of this method either as monotherapy or together with therapeutic physical exercises based on the immediate and long-term results of the treatment. The dynamic clinical observations and special investigations were carried out on 101 children at the age varying from 5 to 15 years who suffered from bronchial asthma. PLIESF were shown to produce the beneficial effect on dynamics of clinical symptoms in the children manifested as the disappearance or reduced frequency of episodes of laborious respiration and the improvement of sputum discharge, auscultation picture, bronchial patency, and respiratory excursions of the chest. The application of PLIESF significantly increased the level of the general physical performance in the children with bronchial asthma, improved the functional conditions of the cardiovascular system, normalized both the cardiac rhythm and the heart rate. It was shown based on the analysis of the short-term and long-term outcomes of the treatment that the combined therapy with the use of the two physical factors, i.e. the pulsed low-frequency electrostatic fields and therapeutic physical exercises, ensures the significantly higher effectiveness of the treatment than the separate application of either of them.

[Screning study on pregnant women and neonatal infection with streptococcus agalactiae (group B streptococci)].

We report the results of a screening study on pregnant women and early onset neonatal group B streptococcal infections in Sofia, Bulgaria, July 2009-July 2010. Women were studied for risk factors at delivery, intrapartum antibiotic prophylaxis (lAP) and outcome for the newborns. All GBS positive women who had risk factors at delivery gave birth to newborns with neonatal infection despite the IAP given in 50% of the cases. The majority of the GBS positive women who had no risk factors at delivery gave birth to healthy newborns although only 32% of them received IAP However 11% of the GBS positive women without risk factors delivered children with neonatal infection. We consider that IAP should be given to all GBS positive women to prevent from neonatal infection. The dominant GBS serotypes were ll, 11 and la. The isolates were 100% susceptible to penicillin, cefazolin, cefotaxime, vancomycin and 91.66% susceptible to erythromycin and clindamycin, the resistant strains being from the MLSB phenotype.

[Physical training for the treatment of children presenting with bronchial asthma].

This paper reports the results of the treatment of 101 children presenting with bronchial asthma. The study has demonstrated the pronounced positive effect of the combined application of a pulsed low-frequency electrostatic field and therapeutic physical training on the dynamics of clinical symptoms of the disease. By the end of the treatment period, all the patients reported the disappearance of paroxysmal night-time coughing, productive cough, expectoration, and attacks of respiratory distress. Auscultation failed to reveal dry, whistling, and bubbling rales. Dynamics of the changes of the impaired airway patency was estimated from the results of computed pneumotachometry and monitoring peak expiratory flow by the peak flowmetric technique. The combined application of a pulsed low-frequency electrostatic field and therapeutic physical training significantly improved characteristics of the external expiratory function (PEF, FEV1, MEFR25, MEFR50--p < 0.02, MEFR75--p < 0.001). In the end of therapy, 96.7% of the children had normal parameters of computed flowmetry in the absence of a generalized impairment of bronchial patency while obstruction at the level of peripheral bronchi persisted only in 3.3% of the patients. The increase of PEF based on the results of peak flowmetry averaged 44.21% (p < 0.001). A rationale has been developed for the application of the proposed therapeutic strategy to the treatment of children with bronchial asthma.

[The application of the physical factors for the rehabilitation of the children presenting with bronchial asthma].

The use of anti-asthmatic preparations alone can not be considered sufficient for the rehabilitation of the children suffering from bronchial asthma. Traditional medicamental therapy does not allow mortality from asthma to be appreciably reduced. At the same time, it is known to produce serious adverse effects. The physical factors proved to be fairly well compatible with the basal treatment; specifically, their application makes it possible to decrease the amount of pharmaceutical products and the duration of therapy.

Progranulin and chemerin plasma level in obese patients with type 2 diabetes treated with a long-acting insulin analogue and premixed insulin analogue.

Diabetes, referred to as the first non-infectious epidemic, covers a heterogenous group of metabolic diseases marked by hyperglycemia resulting from a defect of insulin secretion and/or insulin resistance. Highly endocrine active adipocytes, particularly those located in white adipose tissue, constitute a source of cytokines, growth factors and complement component as well as adipocytokines including chemerin and progranulin could be the key molecules in the pathomechanism of hypertension, dyslipidemia, metabolic disorders or diabetes type 2. In this study, it was decided to verify the existence of possible relationships between the plasma concentration of progranulin and chemerin and the values of intermediate indices of insulin sensitivity and insulin resistance in patients, both before and after the 6-month insulin therapy by long-acting insulin analogue and premixed insulin analogue. The level of laboratory parameters in blood plasma collected from the control group and from obese individuals with type 2 diabetes mellitus was estimated with the test kits using enzyme-linked immunosorbent assay (ELISA): the test of Mediagnost E103 GmbH GmbH, Reutlingen, Germany for progranulin; the test of BioVendor R&D, Brno, Czech Republic for chemerin. The aim of this study was to assess the progranulin and chemerin plasma level in obese individuals with type 2 diabetes, before and after 6 months of pharmacological treatment with a long-acting analogue human insulin or premixed insulin. In the blood plasma of untreated diabetics - in contrary to progranulin plasma concentration in diabetic patients after management implementation - progranulin was found to occur in a significantly higher concentration in relation to the level of this protein in the blood plasma of control group individuals. Despite the fact that 6-month therapy, both with the insulin mixture and with the long-acting analogue in people with diabetes, does not significantly affect the plasma chemerin concentration, the high, negative correlation between the progranulin and chemerin levels in the blood of individuals of the control group, and a positive one between the levels of progranulin and chemerin in people with diabetes before and after treatment was found. The conducted studies indicated the modified, in the course of diabetes type 2, mutual quantitative relations between progranulin and chemerin - the biological mediators of systemic metabolism, reflecting their active participation in the pathogenetic changes underlying type 2 diabetes. The obtained study results indicate a modification of mutual relationships of the adipocytokines assessed in the paper - progranulin and chemerin, associated with the development of the systemic inflammatory response occurring in the course of obesity which, by inducing insulin resistance, may consequently lead to type 2 diabetes. Taking into consideration the fact that the plasma progranulin and chemerin concentrations in obese patients with type 2 diabetes subjected to pharmacotherapy have not been assessed so far, it is possible that the obtained study results may cast light on the potential influence of the applied treatment on the systemic changes of the both adipocytokines involved in the pathomechanism of the mentioned disorder and thus create the possibility of implementing new therapeutic strategies in the management of patients with diabetes, which is an increasingly common, fast-spreading metabolic disease considered as a non-infectious epidemic of the 21st century.

Biodegradation of phenol by immobilized Aspergillus awamori NRRL 3112 on modified polyacrylonitrile membrane.

Covalent immobilization of Aspergillus awamori NRRL 3112 was conducted onto modified polyacrylonitrile membrane with glutaraldehyde as a coupling agent. The polymer carrier was preliminarily modified in an aqueous solution of NaOH and 1,2-diaminoethane. The content of amino groups was determined to be 0.58 mgeq g(-1). Two ways of immobilization were used-in the presence of 0.2 g l(-1) phenol and without phenol. The capability of two immobilized system to degrade phenol (concentration-0.5 g l(-1)) as a sole carbon and energy source was investigated in batch experiments. Seven cycles of phenol biodegradation were conducted. Better results were obtained with the immobilized system prepared in the presence of phenol, regarding degradation time and phenol biodegradation rate. Scanning electron micrographs of the polyacrylonitrile membrane/immobilized Aspergillus awamori NRRL at the beginning of repeated batch cultivation and after the 7th cycle were compared. After the 7th cycle of cultivation the observations showed large groups of cells. The results from the batch experiments with immobilized system were compared to the results produced by the free strain. Phenol biodegradation experiments were carried out also in a bioreactor with spirally wound membrane with bound Aspergillus awamori NRRL 3112 in a regime of recirculation. 10 cycles of 0.5 g l(-1) phenol biodegradation were run consecutively to determine the degradation time and rate for each cycle. The design of the bioreactor appeared to be quite effective, providing large membrane surface to bind the strain.

[Cardiac damage in sarcoidosis: clinical features and impact of steroid therapy].

Twenty-seven sarcoidosis patients with signs of cardiac damage were examined to study the clinical features of cardiac sarcoidosis and the impact of systemic glucocorticosteroid (GCS) therapy on its course. ECG and echoECG changes were observed in 21 (78%) and 17 (63%) patients, respectively; abnormal perfusion was seen in 25 (93%) patients at single-photon emission myocardial computed tomography using 99mTc-MIBI. Three clusters (clinical types) of patients were identified, which differed in the pattern and degree of cardiac disorders. The use of systemic GCSs in 13 of 20 patients resulted in myocardial perfusion recovery and clinical improvement, the degree and duration of which depended on what cluster it belonged to. Seven GCS-untreated patients had progressive perfusion disorders with subsequent or synchronous clinical deterioration (p < 0.05). The degree and duration of the positive effect of a GCS differed depending on the clinical type of cardiac damage.

[Risk factors for metabolic syndrome in workers exposed to vibration].

The study covered prevalence of metabolic syndrome and its risk factors among mining and machinery industry workers. Reliably higher incidence of metabolic syndrome was revealed in workers exposed to vibration, when compared with the reference group. The authors calculated relative risk of metabolic syndrome development after exposure to the factor studied.

Extended-spectrum beta-lactamase-producing Serratia marcescens outbreak in a Bulgarian hospital.

We describe a nosocomial outbreak of extended-spectrum beta-lactamase (ESBL)-producing Serratia marcescens in a Bulgarian university hospital affecting nine patients on four wards. Phenotypic and genotypic (plasmid profile, randomly amplified polymorphic DNA analysis and amplified ribosomal DNA restriction analysis) analysis of the isolates indicated a single clone. The epidemic strain was resistant to oxyimino beta-lactams, aztreonam, aminoglycosides, tetracycline and chloramphenicol. It produced CTX-M-3 ESBL as demonstrated by isoelectric focusing, CTX-M PCR-RFLP and gene sequencing. The isolate was also found in the environment and from a nurse's hands, suggesting transmission by staff handling. The outbreak was controlled by patient isolation and intensified hand washing. This is the first report from Bulgaria describing a hospital outbreak caused by CTX-M-3 ESBL-producing S. marcescens.

[A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals]. / Sravnitel'noe issledovanie vliianiia meksidola i mildronata na fizicheskuiu rabotosposobnost' v éksperimente.

AIM: To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals. MATERIAL AND METHODS: The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice. RESULTS AND CONCLUSION: A single intraperitoneal administration of 50 and 100 mg/kg mexidolum and subchronic intraperitoneal administration of 100 mg/kg mexidolum significantly enhances the physical performance of animals in the forced swim test. Subchronic intraperitoneal administration of 100 mg/kg of the comparison drug mildronatum enhances the physical performance of animals, while intraperitoneal administration at a lower dose (50 mg/kg) has no effect. The effect of mexidolum at a dose of 50 and 100 mg/kg is comparable with the effect of mildronatum in a dose of 100 mg/kg.