SPECIFICS OF PRESCRIBING ANTIRETROVIRAL DRUGS IN THE TREATMENT OF HIV INFECTION.

HIV infection is one of the most acute problems of our time, characterized by slow development, prolonged course, and numerous clinical manifestations. Currently, there is a large number of drugs acting on different processes of human immunodeficiency virus replication, which constitute the group of highly active antiretroviral therapy (HAART). This article shows a theoretical review of modern HAART and analyzes the prescribed treatment regimens for patients with HIV infection. The study revealed two most common combinations: nucleoside reverse transcriptase inhibitors + protease inhibitors; nucleoside + non-nucleoside reverse transcriptase inhibitors.

[The structure of pathogenic germline variants in colorectal cancer in Moscow patients]. / Struktura patogennykh germinal'nykh variantov pri kolorektal'nom rake v vyborke patsientov Moskvy.

OBJECTIVE: Describe the structure of pathogenic germline variants and clinical and anatomical features in colorectal cancer patients in Moscow. MATERIAL AND METHODS: The whole genome sequencing results of patients with suspected hereditary cancer syndrome were evaluated. All identified genetic variants were validated using Sanger sequencing. RESULTS: The study included 238 patients with colorectal cancer, 41/238 (17.2%) patients have pathogenic germline variants associated with hereditary cancer syndromes or increased cancer risk. Lynch syndrome accounts for 8% of all colorectal cancer cases (19/238), and familial adenomatous polyposis - 1.7% (4/238). 5 new genetic variants were described for the first time in a Russian colorectal cancer patients: MLH1 c.1921dup (p.Leu641fs), APC c.2929C>T (p.Gln977Ter), PMS2 c.327del (p.Ala110LeufsTer2), MSH2 c.1857dup (p. Val620CysfsTer24), ATM c.895G>T (p.Glu299Ter). In 197 of 238 patients, no significant variants were identified or variants with an uncertain clinical underlying cause were identified. CONCLUSION: According to the results of the study, an earlier manifestation of a malignant neoplasm and a more frequent occurrence of high-grade carcinomas in the presence of pathogenic germline mutations were noted compared to the group of patients without clinically significant varianrs, while in the group with identified mutations, the frequency of regional and distant metastasis was not increased.

[Prevalence and risk factors of delirium in COVID-19]. / Rasprostranennost' i faktory riska deliriya pri COVID-19.

OBJECTIVE: To assess the frequency and risk factors of delirium in patients hospitalized with COVID-19. MATERIAL AND METHODS: Four hundred and forty patients admitted to the Infectious Diseases Hospital of the University Clinical Hospital No.3 of Sechenov University were included in the study. The Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Screening Questionnaire-7 (GAD-7), the Insomnia Severity Index (ISI), the Delirium severity rating scale (DRS-R-98) were administered. RESULTS: Delirium was detected in 27.8% of patients. Significant risk factors were age (p=0.002), severity of respiratory failure (p=0.005), concomitant somatic disease (p=0.003), and respiratory therapy (p<0.001). There was an association between severe anxiety (p<0.001) and insomnia (p=0.07) observed at admission with the risk of developing delirium during the hospital stay. CONCLUSION: The study reveals a high prevalence of delirium in patients with COVID-19. In order to prevent delirium and/or reduce the risk, early diagnosis and identification of preclinical forms are of particular importance.

Characterization of the C6D7-RBD Human Monoclonal Antibody Specific to the SARS-CoV-2 S Protein Receptor-Binding Domain.

The new coronavirus infection COVID-19 is an acute viral disease that affects primarily the upper respiratory tract. The etiological agent of COVID-19 is the SARS-CoV-2 RNA virus (Coronaviridae family, Betacoronavirus genus, Sarbecovirus subgenus). We have developed a high-affinity human monoclonal antibody, called C6D7-RBD, which is specific to the S protein receptor-binding domain (RBD) from the SARS-CoV-2 Wuhan-Hu-1 strain and exhibits virus-neutralizing activity in a test with recombinant antigens: angiotensin-converting enzyme 2 (ACE2) and RBD.

[Physical therapy - the main focus of modern ophthalmic rehabilitation]. / Fizioterapiya ­ osnovnoe napravlenie sovremennoi oftal'moreabilitatsii.

Ophthalmic rehabilitation consists of improving or maintaining the functions of the visual analyzer within the possibilities of the "therapeutic window". Ophthalmic rehabilitation involves physiotherapeutic methods, as well as additional ones that improve the condition of the body and indirectly affect the organ of vision. This article presents schematic algorithms of physiotherapeutic ophthalmic stimulation in neurodystrophic diseases of the visual organ and the main results of their multifactorial objective and subjective analysis. It was shown that even with the consistent visual resolution, treatment courses can help get positive changes at the level of nerve structures lasting for three to six months. This allows us to recommend physiotherapeutic ophthalmic stimulation for maintaining the therapeutic effects obtained after the main medical or surgical treatment.

Ex Vivo Production of IL-1ß and IL-10 by Activated Blood Cells of Wistar Rats with Different Resistance to Hypoxia after Systemic Inflammatory Response Syndrome.

We studied spontaneous and ex vivo activated cytokine production by blood cells of male Wistar rats with different resistance to hypoxia against the background of an LPS-induced systemic inflammatory response. In rats with low (LR) and high resistance (HR) to hypoxia, the number of leukocytes, granulocytes, and peripheral blood lymphocytes was determined, the levels of spontaneous and stimulated production of IL-1ß and IL-10 and their ratio were assessed ex vivo. Against the background of a systemic inflammatory response, only HR animals showed a decrease in spontaneous and stimulated production of IL-1ß and spontaneous production of IL-10. The IL-1ß/IL-10 ratio decreased only in LR rats during the development of a systemic inflammatory response, while in HR animals, no changes in this indicator were observed. The obtained data suggest a high proinflammatory potential of blood cells in LR rats, which apparently determines the development of a more severe course of the systemic inflammatory response.

[Comparative evaluation of the results of one- and two-piece mushroom keratoplasty]. / Sravnitel'naya otsenka rezul'tatov mono- i dvukhkomponentnoi modifikatsii gribovidnoi keratoplastiki.

PURPOSE: To compare and evaluate the outcomes of one- and two-piece mushroom keratoplasty configurations for various corneal pathologies. MATERIAL AND METHODS: A total of 32 patients (32 eyes) with corneal perforations, descemetocele and deep corneal opacities underwent surgery. Depending on the surgery technique, the patients were divided into 2 groups: group I (17 eyes) underwent manual one-piece mushroom keratoplasty according to our own technique; group II (15 eyes) underwent modified two-piece microkeratome-assisted mushroom keratoplasty according to the technique by M. Busin. All patients underwent clinical and functional studies before surgery and in the course of a 1-year follow-up. RESULTS: Transparent engraftment of the cornea was achieved in 82 and 80% of cases; best corrected visual acuity (BCVA) averaged 0.57±0.19 and 0.53±0.17; spherical component of refraction varied from 1.25 to +5.5 and from 1.25 to 6.0 diopters; mean corneal astigmatism was 3.15±1.73 and 3.21±1.89 diopters in groups I and II, respectively. At 6 months after surgery, the mean endothelial cell density (ECD) was 2336±198 and 2291±175 cells/mm2, at 1 year - 2041±189 and 1955±161 cells/mm2 in groups I and II, respectively. CONCLUSION: One- and two-piece mushroom keratoplasty is effective in surgical treatment of various corneal pathologies ensuring a high rate of transparent corneal engraftment. The revealed risk of false chambers formation between separate parts of the graft after the two-piece method could in most cases be eliminated by re-injecting air into the anterior eye chamber.

[Diagnosis and treatment of adenoviral keratoconjunctivitis]. / Diagnostika i lechenie adenovirusnogo keratokon"yunktivita.

PURPOSE: To improve the treatment of adenoviral lesions of the eye based on express diagnostics by the fluorescent antibody technique (FAT) and the use of modern drugs. MATERIAL AND METHODS: The study included 184 patients (333 eyes) with various manifestations of adenoviral lesions of the ocular surface, who were divided into two groups: group 1 (149 patients, 196 eyes) - acute form, and group 2 (76 patients, 137 eyes) - long lasting form. Effectiveness of the proposed treatment was evaluated against separate group 3 (controls) consisting of 28 people (46 eyes) with completed acute adenovirus infection, who had previously received antibiotic and corticosteroid therapy in other clinics. Conjunctival scrapings of study patients were examined with FAT in our proposed modification. Study patients received local therapy with modern drugs (Okomistin, Aktipol). RESULTS: FAT detected the adenovirus antigen in 169 cases in group 1 (86%) and in 99 cases in group 2 (72%). Treatment duration amounted to 12±6 days in group 1, 18±8 days in group 2, and 29±7 days in controls. In both study groups, the duration of treatment was significantly reduced in comparison with the controls (p<0.01). Stable clinical effect and complete restoration of visual acuity have been achieved in most cases. There were no allergic and side effects from the therapy. CONCLUSION: Fluorescent antibody technique is a fast and effective way to diagnose adenovirus infection in ophthalmology. In terms of therapy, the use of an antiseptic, an antiviral drug and diluted corticosteroids is the most rational approach.

[Results of the application of complex physiotherapeutic neurostimulation in optical neuropathies of various genesis]. / Rezul'taty primeneniya kompleksnoi fizioterapevticheskoi neirostimulyatsii pri opticheskikh neiropatiyakh sosudistogo geneza.

Optical neuropathies (ON) are the outcome of many diseases of various origins. The main ones are classified as inflammatory, vascular and traumatic ON. ON lead to subatrophy of the optic nerve, but even after the completion of treatment, it is possible to improve visual functions by using physiotherapeutic means of ophthalmic rehabilitation. OBJECTIVE: To evaluate the effectiveness of complex physiotherapeutic neuro-ophthalmostimulation in case of ON of vascular origin. MATERIAL AND METHODS: The study included 60 patients (120 eyes) with a verified diagnosis of optic neuropathy of vascular origin, who were divided into 2 groups comparable in age, gender and anatomical and functional characteristics: the main group of 30 patients (60 eyes) and the control group - 30 patients (60 eyes), including 24 men and 36 women, mean age was 66.2±4.1 years, disease duration was 4.1±1.7 years. All patients underwent courses of conservative treatment with vitamins according to the available ophthalmological standards, repeating them 1-2 times a year, the last of which was six months before the present study. Physiotherapy courses and patients did not pass. 20 healthy volunteers were taken to create basic indicators of the «norm¼ of the applied research methods. Patients of the main group used a set of procedures: transcranial magnetic electrical stimulation, endonasal electrophoresis with the drug neuroprotector Semax 0.1%, oxybaric chamber and acupuncture. Patients in the control group were prescribed basic therapy, including taking the vitamin complex BEROCCA for 3 months. Breakpoints: before treatment and at times: 1st week, 12 weeks and 24 weeks after the course of treatment, according to the standard recommendations for international multicenter studies. The following were assessed: visual field boundaries (dilation meridians; in deg.), light sensitivity (MS, MD; in dB), indicators of the state of the retinal ganglion layer (GCS thickness, volume loss): Avg CCG (in µm), FLV, GLV (in %). RESULTS: When evaluating the results in patients of the main group who received complex neurostimulation, the therapeutic efficacy in a week after the end of treatment was 94%, in 12 weeks - in 88% and in 24 weeks - 83%, while in patients of the control group for all studied indicators showed only a positive trend and therapeutic efficacy did not exceed 30-42%. CONCLUSION: Under the influence of the developed neurostimulating complex, the activity of nerve cells objectively increases, leading to a significant increase in the boundaries of the field of view and light sensitivity and a decrease in global losses of the retinal ganglion complex and optic nerve.

[Modern capabilities of ophthalmic tonometry in pathologically altered corneas]. / Sovremennye vozmozhnosti oftal'motonometrii pri patologicheskikh izmeneniyakh rogovitsy.

Changes in intraocular pressure have great influence on the course of various processes in ocular tissues. Presently, the scientific discussion has returned to the theoretical issues of tonometry and the creation of models that would allow assessing the influence of various ocular parameters on IOP values. Some of the modern tonometers (Icare, Tono-Pen) are convenient and effective when measuring IOP in eyes with damaged, uneven or edematous cornea. It is necessary to analyze the results of ophthalmic tonometry by modern methods in accordance with the data of direct intracameral manometry in pathological conditions of the cornea and after keratoplasty.

[Features of pathological anatomy of COVID-19 according to autopsy results in the Volgograd Region]. / Osobennosti patologicheskoi anatomii COVID-19 po rezul'tatam autopsii v Volgogradskoi oblasti.

In connection with the ongoing pandemic of the novel coronavirus infection, the study of its morphopathology and the analysis of autopsy data are relevant. At the same time, attention should be paid to thromboses that play a significant role in the development of fatal outcomes in COVID-19, even taking into account the prescription of anticoagulant therapy to most patients. OBJECTIVE: To make an assessment of morphological changes and a statistical analysis of the structure of mortality in COVID-19 on the basis of autopsy results in the Volgograd Region in 2020. MATERIAL AND METHODS: The study was based on data from «The system for information on the work of the Volgograd Regional Autopsy Bureau¼ with a search for cases according to U07.1 code (the COVID-19 virus was identified) in January 1, 2020, to December 31, 2020, as well as on the autopsy materials of the Volgograd Regional Autopsy Bureau, and microscopic examination with photo fixation. Statistical processing was performed using the R programming language. RESULTS: During the above period, 1119 deaths were identified with a confirmed diagnosis of COVID-19. Anatomopathological examination of the autopsy material showed that 77.54% of cases had blood clots mainly in the vessels of the pulmonary microvasculature, often only in the single veins during the applied anticoagulant therapy.Analysis of variance indicated that the obtained result statistically significantly differed from the random distribution, and the probability of the presence of blood clots of specified localization was 3.17 times higher (CI 2.3-4.4; p<0.05) than their absence, as evidenced by logistic regression. In addition, perivascular and intra-alveolar diapedesis hemorrhages were noted in most fatal cases. CONCLUSION: Thus, this investigation has revealed that the high frequency of thrombosis detected in the presence of perivascular and intra-alveolar diapedesis hemorrhages in COVID-19 confirms the tendency of patients with a severe course of the disease to manifest hemostatic disorders, significant blood vascular endothelial injury, and obvious vascular impermeability.

[Anterior eye segment damage in coronavirus infection (COVID-19)]. / Porazhenie perednego segmenta glaza pri koronavirusnoi infektsii (COVID-19).

Conjunctivitis may appear as the first symptom of the coronavirus infection (COVID-19). In isolated cases, the lesion of the conjunctiva evokes a systemic infectious process. Currently, the conjunctiva is not considered as an area of long-term reproduction of coronavirus, and its damage is caused by hyperproduction of pro-inflammatory cytokines (especially IL-6); development of iridocyclitis and keratoconjunctivitis is also possible. Most often, local corticosteroids are used to treat these processes, although their use requires caution due to the risk of activating secondary infection (herpetic bacterial, fungal), which often develops as a result of immunodeficiency caused both by COVID-19 and the massive corticosteroid and antibiotic therapy employed when the course of the disease is severe. The severe condition of patients, the lung ventilation, and the prone position all contribute to corneal erosions, exposure keratopathy, pseudomonas aeruginosa keratitis and angle-closure glaucoma attacks. The risk of transmission of coronavirus infection during keratoplasty is estimated as minimal.

[Unipolar depression: a gender-based comparative analysis]. / Depressivnye rasstroistva s monopolyarnym techeniem: sravnitel'nyi analiz po gendernomu priznaku.

OBJECTIVE: To compare socio-demographic and clinical characteristics in men and women with depression. MATERIAL AND METHODS: We studied 388 patients with unipolar depression, 74 men and 314 women. The survey was carried out using the clinical-psychopathological method and psychometric scales for depression. RESULTS AND CONCLUSION: Gender differences are identified for several parameters. Women are older, more often had comorbid somatic and organic disorders; men have personality disorders and chronic depression. The severity of depression in women was higher due to symptoms such as reported sadness, anxiety, reduced sleep and appetite, concentration difficulties, and suicidal thoughts. Apparent sadness did not significantly differ in men and women. Anhedonia was more pronounced in men.

[Differential diagnosis of chylothorax in therapeutic practice].

The article is devoted to the differential diagnosis of chylous pleural effusion. The spectrum of traumatic and non-traumatic causes of chylothorax is discussed in detail. Examples of necessary diagnostic measures are given for the accumulation of milky fluid in the pleural cavity in order to verify chylothorax.

Genetic diversity of enteroaggregative Escherichia coli.

Studied 74 E. coli strains isolated from stool samples (60) and urine samples (14) of patients examined for clinical indications. Molecular methods included: PCR with electrophoretic detection of genes associated with diarrheal E. coli pathogroup EAgEC (aggR, aaf, aap, aatA, pet, ast, aai) and ExPEC pathogroup UPEC (pap, sfa, afa, kpsMT II, iutA, hlyA, cnf), MLST typing, whole genome sequencing. Strains isolated from stool samples were significantly more likely (88.3%, p > 0.05) to be typical EAgECaggR+ compared to atypical EAgECaggR-. Strains isolated from urine samples, significant differences between typical and atypical EAgEC were not detected (p > 0.05). Genes associated with ExPEC were present in all strains isolated from urine samples and in 45 strains (75%) isolated from stool samples. Coproisolates belonged to 10 serogroups and 13 serovars: O3:H2, O11:H10, O16:H48, O51:H30, O55:H21, O73:H18, O73:H33, O86:H2, O86:H10, O92:H33, O140:H2, O159:H10. Two strains had unique nucleotide sequences of genes encoding O-antigens that were missing from the SerotypeFinder database. 80% of EAgEC isolated from feces and urine was characterized by an enteroaggregative/uropathogenic genotype (EAgEC/UPEC). Most of the strains isolated from urine belonged to the virulent clone of high-risk epidemic spread ST 38 associated with hybrid strains of UPEC / EAgEC.

[Laboratory errors for identification of the escherichia coli strains of the serological groups O6 and O25 as acute intestinal infections.]

Were studied the genes encoding the virulence factors of 221 strains: E. coli O6:H1 (194) and E. coli O25:H4 (27), isolated in 2014-2018 from stool samples of children and adults examined according to epidemic indications. Molecular methods included PCR with hybridization-fluorescence and electrophoresis detection of amplified products. The strains did not have virulence genes for diarrheagenic E. coli (DEC) pathogroups EPEC, ETEC, EIEC, EHEC, EAggEC, and belonged to the phylogenetic group B2. They contained from four to eight genes encoding virulence factors of ExPEC: E. coli O6:H1 - pap (68,6%), sfa (87,6%), fimH (96,4%), hly (62,4%), cnf (74,7%), iutA (97,9%), fyuA (95,9%), chu (100%); E. coli O25:H4 - pap (66,7%), afa (22,2%), fimH (100%), hly (44,4%), cnf (44,4%), iutA (100%) , fyuA (100%), chu (100%). The antimicrobial susceptibility testing to 6 classes of antimicrobials (beta-lactams, fluoroquinolones, aminoglycosides, nitrofurantoin, sulfanilamide, trimethoprim / sulfamethoxazole) according the EUCAST. 60,3% of E. coli O6:H1 were sensitive to antibiotics, E. coli O25:H4 remained sensitive to carbapenems and nitrofurans. Extended-spectrum cephalosporins resistance was due to the production ESBL (CTX-M). The 57,1% resistant strains of E. coli O6:H1 and 100% of E. coli O25:H4 strains belonged to the MDR phenotype. The XDR phenotype had one in five MDR strains of E. coli O6:H1 and E. coli O25:H4. All strains of E. coli O25:H4 belonged to ST131. Given the important role of E. coli in human pathology, detection of virulence genes should be performed to confirm the etiological significance of the isolated strain.

[Phylogenetic groups and virulence genes of Escherichia coli strains isolated from the children gut microbiota.]

Escherichia coli is characterized by a wide intraspecific diversity. The species includes both commensals and pathogens that cause diarrhea and extra-intestinal diseases. Pathogenic strains differ from non-pathogenic ones by the presence of virulence factors and their genes. The phylogenetic structure of the species is represented by four main groups (A, B1, B2, D), which differ in their prevalence among residents of different geographical regions. Pathogenic members of the species have been studied in detail, while non-pathogenic strains have not received such attention. This report presents the results of a study of 511 E. coli strains isolated from the gut microbiota of children without diarrhea and urinary tract infections, aged from 1 month to 17 years, living in St. Petersburg. The main phylogenetic groups were determined by PCR, and E. coli virulence genes associated with diarrhea and extra-intestinal diseases were identified. Results: population structure of E. coli is represented by the following groups: A-33.3%, B1-6.7%, B2-34.0%, D-26%. In the studied population 2.5% of strains belonded to EPEC and 4.5% to EAggEC. EPEC virulence genes were more often detected in strains of phylogroup B1, and EAggEC virulence genes in isolates of phylogroup D. The prevalence of extra - intestinal virulence genes was as follows: pap - 29.5%; sfa - 19.8%; afa - 3.3%; hly - 20.9%; cnf - 17.4%; aer-20.0%. The pap, sfa, hly, and cnf genes were detected mostly in the B2 phylogenetic group. Obtained data shows the similarity of E. coli phylogenetic groups structure in St. Petersburg with E. coli populations isolated from residents of Paris and Sydney. Analysis of the virulence genes prevalence showed the dependence of their presence on the genetic background bacteria.

[Methods of preserving donor corneas]. / Metody konservatsii donorskikh rogovits.

Corneal transplantation is the most successful and frequently performed allotransplantation procedure. Benign outcome of penetrating and posterior keratoplasty depends on viability of the corneal tissue and presence of the proper endothelial layer, which retaining is one of the main objectives of preservation of donor material. Methods designed to reach this goal may be classified according to storage duration as short-term (storage in a moist chamber), medium-term (hypothermia), long-term (organ cultivation) and unlimited (cryopreservation). While there are reports of successful application of cryo-conserved corneas for penetrating keratoplasty, its use for this type of transplantation is limited due to complexity of the method and very high requirements for the quality of donor material. However, being a method of unlimited storage, it still attracts the attention of researchers. Taking into account the ongoing development of innovative keratoplasty technologies and the tendency for predominant use of layered grafts that in some cases do not need viable endothelium, methods of preservation of such material for anterior lamellar and intralamellar keratoplasties become relevant. In this context, cryopreservation without the use of cryoprotective agents is promising because it allows simple and fast accumulation of large amount of material with long storage time. Further research on the development of preservation methods of the corneal endothelial layer at sub-zero temperatures may allow storing the material by cryopreservation that will be suitable for penetrating and posterior keratoplasty.

[Evaluation of the cardioprotective effect of ubiquinol on the model of reperfusion injury of rat myocardium]. / Otsenka kardioprotektornogo deistviia ubikhinola na modeli reperfuzionnogo povrezhdeniia miokarda krys.

The cardioprotective effect of ubiquinol on the model of myocardium reperfusion injury in rats was investigated. The study was carried out using mature males of outbred rats. Myocardial ischemia-reperfusion injury was performed after 30-minute ligation of the left coronary artery followed by reperfusion. The main criteria for assessing the development of pathology included the results of electrocardiography, biochemical analysis of blood plasma, histological and histochemical study of the myocardium. Development of the reperfusion damage of the myocardium caused specific changes in non-treated animals. The best therapeutic effect on biochemical indices was provided by a drug with the known cardioprotective activity - Mexidolâ and the tested object ubiquinol at doses of 2-6 mg/kg. Evaluation of the results of electrocardiography allowed to confirm the development of ischemic myocardial damage in all groups. The results of histochemical and histological examination of the myocardium suggest a high cardioprotective activity of ubiquinol at a dose of 3 mg/kg and a potential cardioprotective effect of ubiquinol in doses closest to the therapeutic doses of 2 and 6 mg/kg. Ubiquinol is a dose 9 mg/kg showed signs of prooxidant activity, manifested in the form of aggravation of reperfusion injury of the myocardium. The most effective in the conditions of experimental pathology is 1% solution of ubiquinol, at a dose of 3 mg/kg, whose cardioprotective effect is comparable or higher than that for the reference drug Mexidolâ at the therapeutic dose. In doses that are greater than therapeutic ubiquinol is able to act as a pro-oxidant.

[A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats]. / Éffektivnost' kombinirovannogo primeneniia levodopy i karbidopy s tsitikolinom pri éksperimental'noi modeli bolezni Parkinsona.

AIM: To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson's disease in rats. MATERIAL AND METHODS: Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed. RESULTS AND CONCLUSION: Combined therapy led to the decrease in muscle rigidity (the decrease of gibbosity in resistance to passive flexion in the ankle joint). There was a decrease in oligokinesia that emerged in higher vertical and horizontal locomotor activity of experimental animals, decrease in the time of head turning during climbing down the pole and total time of climbing down the pole. The combination of drugs had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy.