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Background. The increased antiretroviral therapy (ART) coverage of patients in the absence of routine drug resistance (DR) tests highlight the importance of HIV-1 drug resistance surveillance in Armenia. Aim. The aim of this study was a determination of the prevalence of HIV-1 DR on a large-scale cohort of HIV-infected citizens of the Republic of Armenia who had no experience of taking antiretroviral drugs. Materials and methods. The study was carried out on a cohort of more than 20% of PLHIV in the Republic of Armenia. The resulting 982 nucleotide sequences of the HIV-1 pol gene fragment, encoding the protease and reverse transcriptase region, as well as 367 sequences of the integrase gene, were analyzed using the Stanford University database and the CPR tool for the presence of drug resistance mutations and determination of the resistance level to ARV drugs. The HIV-1 subtype was determined using the Stanford University database and confirmed by phylogenetic analysis. Results. The overall prevalence of HIV DR to ARV drugs in naïve patients was 13.8%. Resistance to non-nucleoside reverse transcriptase inhibitors was 11.2%, nucleotide reverse transcriptase inhibitors — 1.4%, protease inhibitors — 2.0% and integrase inhibitors — 0.5%. The predominant genetic variant among viruses containing DR mutations was subtype B. Resistance was most often recorded among men who have sex with men living in Yerevan. Conclusion. In our study, prevalence of DR was high only for the NNRTI drugs. The results show that the first-line ARV drugs recommended in current national guidelines are highly likely to be effective. The analysis was carried out on a significant proportion of HIV-infected citizens of the Republic of Armenia, which increases the reliability and accuracy of the data obtained.

From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.

The development of sequencing technologies and bioinformatic analysis made it possible to conduct molecular and epidemiological studies, in which nucleotide sequences of the human immunodeficiency virus (HIV) are used as information added to the patient profile. From a practical perspective, studies of prevalence of HIV drug resistance (HIVDR) are of the highest significance. To promote such studies, different countries use databases that serve as repositories of genetic and epidemiological information. The Russian HIVDR database (https://hivresist.ru/) was created in 2009. Nevertheless, it was characterized by limited applicability for a long time. Since 2021, after the regulatory documents had been revised and updated, the entry of HIVDR research results into the Russian HIVDR database has been mandatory. Therefore, the priority attention has been given to upgrading the database and improving its functional capabilities. Different methods have been developed to enter clinical, epidemiological and genetic data. At the time of this study, the Russian database HIVDR contained 10,626 unique records about patients and 13,126 nucleotide sequences deposited by 10 institutions. The following functions have been provided for data analysis: quality control of the epidemiological and clinical information about a patient, quality control of nucleotide sequences, contamination check, subtyping, detection of DR mutations, identification of viral tropism and generation of standardized reports. The efforts toward further development of the Russian HIVDR database will be focused on designing tools for detection and analysis of molecular clusters, adaptation to routine application for epidemiological surveillance of HIV infection.

α-synuclein is one of the key molecular links in the pathogenesis of Parkinson’s disease. The accumulated data indicate that pathogenic mutations in the Snca gene are associated with the development of neurodegenerative brain damage, indicating the relevance of studying the synuclein neurobiological role.The aim of the study was to create a genetically modified clone of mouse stem cells with a conditional knockout of humanized α-synuclein, which can be used for the reinjection into mouse blastocysts, as well as for basic and applied in vitro research in the field of pathophysiology and neuropharmacology.Materials and methods. To create mouse stem cells with a conditional knockout of the humanized Snca gene, a previously obtained clone with the first Snca exon flanked by LoxP sites, was used. The CRISPR/Cas9-mediated homologous recombination system with donor DNA oligonucleotides of the human sites of the corresponding gene sites was used to humanize the fourth and fifth exons. Cas9 nuclease, single guide RNA, and donor DNA were transfected into mouse cells.Results. An approach to obtaining clones of mouse genetically modified stem cells expressing pathological humanized α-synuclein, has been proposed and implemented. The resulting clones were plated on Petri dishes for propagation and a further genetic analysis. Clone 126-2F4 was found out carrying the necessary genetic modifications. The results obtained are fundamentally important not only for understanding the development of the pathological process in α-synucleinopathies, but which is more important, for the development of new therapeutic approaches that will stop the extension of the human α-synuclein aggregation pathology throughout the nervous system, and the validation of these approaches in preclinical trials.Conclusion. As a result of the study, a strategy for CRISPR/Cas9-assisted homologous recombination in the genome of mouse embryonic stem cells has been developed to create a fully humanized Snca gene encoding α-synuclein, and the clone genome of mouse embryonic stem cells has been edited using a CRISPR technology. The RNA and DNA oligonucleotides necessary for the creation of RNP complexes that carry out a directed homologous recombination in the Snca locus of the mouse genome have been synthesized. The developed cell clone can serve to create a line of genetically modified mice that serve as a test system for pathophysiological and neuropharmacological studies associated with synucleinopathies. Herewith, before the induction of the Cre-dependent recombination, this line is a representative model for studying a biological role of mutant Snca. At the same time, after a Cre-dependent knockout activation, it is possible to imitate the pharmacological inhibition of α-synuclein, which is of particular interest for applied research in neuropharmacology.

The aim of the work was to analyze the available therapeutic options for the conventional therapy of hereditary myopathies.Materials and methods. When searching for the material for writing a review article, such abstract databases as PubMed and Google Scholar were used. The search was carried out on the publications during the period from 1980 to September 2022. The following words and their combinations were selected as parameters for the literature selection: “myopathy”, “Duchenne”, “myodystrophy”, “metabolic”, “mitochondrial”, “congenital”, “symptoms”, “replacement”, “recombinant”, “corticosteroids”, “vitamins”, “tirasemtiv”, “therapy”, “treatment”, “evidence”, “clinical trials”, “patients”, “dichloracetate”.Results. Congenital myopathies are a heterogeneous group of pathologies that are caused by atrophy and degeneration of muscle fibers due to mutations in genes. Based on a number of clinical and pathogenetic features, hereditary myopathies are divided into: 1) congenital myopathies; 2) muscular dystrophy; 3) mitochondrial and 4) metabolic myopathies. At the same time, treatment approaches vary significantly depending on the type of myopathy and can be based on 1) substitution of the mutant protein; 2) an increase in its expression; 3) stimulation of the internal compensatory pathways expression; 4) restoration of the compounds balance associated with the mutant protein function (for enzymes); 5) impact on the mitochondrial function (with metabolic and mitochondrial myopathies); 6) reduction of inflammation and fibrosis (with muscular dystrophies); as well as 7) an increase in muscle mass and strength. The current review presents current data on each of the listed approaches, as well as specific pharmacological agents with a description of their action mechanisms.Conclusion. Currently, the following pharmacological groups are used or undergoing clinical trials for the treatment of various myopathies types: inotropic, anti-inflammatory and antifibrotic drugs, antimyostatin therapy and the drugs that promote translation through stop codons (applicable for nonsense mutations). In addition, metabolic drugs, metabolic enzyme cofactors, mitochondrial biogenesis stimulators, and antioxidants can be used to treat myopathies. Finally, the recombinant drugs alglucosidase and avalglucosidase have been clinically approved for the replacement therapy of metabolic myopathies (Pompe’s disease).

The article contains information on the problem of the combined course of HIV infection and leishmaniasis: a number of statistical and overview data in the world. It also presents a brief description of known cases of HIV patients with leishmaniasis in the Russian Federation. In all cases the diagnostics of leishmaniasis was difficult due to the lack of alertness of physicians to this illness, as well as poor knowledge of epidemiological situation of leishmaniasis. All patients with visceral leishmaniasis but one caught it during their stay in Crimea. Cutaneous leishmaniasis was described in HIV infection in the Russian Federation for the second time and is associated with the patient's residence in the Chechen Republic.

Introduction. Overactive bladder (OAB) with or without urgent incontinence tends to progress with age and occurs in both men and women. However, the frequency of occurrence in the female population averages about 25%.Purpose of the study. To assess the effectiveness and safety of the drug Diunorm® (in caps.) in the prevention and treatment of OAB in women.Materials and methods. The statistical analysis includes the results of a survey of 28 women with symptoms of OAB, whose average age was 35.3 years. The drug Diunorm® was used for treatment in dosage 400 mg QD for 90 days. Patients completed the Overactive Bladder Awareness Tool and a urination diary. Additionally, urinalysis, bacteriological examination of urine, uroflowmetry, bladder ultrasound and cystoscopy were performed.Results. All women throughout the study had negative urine cultures and no pyuria in urinalysis, which excluded an infectious etiology of urinary dysfunction. During therapy, a statistically significant decrease in irritative symptoms was recorded according to the Overactive Bladder Awareness Tool questionnaire. The sum of points after 1 and 3 mo decreased by 3.0 and 4.3 points, respectively (p < 0.05). Positive dynamics in terms of the points' sum was noted in 75%, in relation to nocturia in 82% of patients (p < 0.01). The average urination rate increased from 13.3 ± 0.7 ml/s to 15.1 ± 0.7 ml/s and 15.4 ± 0.5 ml/s after 1.5 and 3 months, respectively (p < 0,0001). A similar trend was observed for maximum urine flow and residual urine volume. The maximum urine flow when taking Diunorm® increased from 15.9 ± 0.6 ml/s to 17.4 ± 0.5 ml/s and 18.1 ± 0.4 ml/s (p < 0.001). Residual urine volume decreased throughout the study. When included in the study, after 1,5 and 3 mo, this indicator was 19.9 ± 1.4; 12.2 ± 1.6 and 6.4 ± 1.1 ml, respectively (p < 0.001).Conclusion. Diunorm® can become a worthy alternative to traditional first-line OAB therapy. Comparative studies are required to obtain a high-level evidence base.

Bacterial purulent meningitis (BPM) is one of the most severe infectious and inflammatory diseases of the nervous system, which is characterized by high mortality and frequent development of residual neurological deficits. Edema and swelling of the brain is the most common cause of death in patients with neuroinfections. Most often, brain edema develops in pneumococcal meningitis (PM), which has the highest mortality rate among all bacterial meningitis. The aim of our work was to study the effect of new derivatives of 3-hydroxypyridine, 2-ethyl-6-methyl-3-hydroxypyridinium 2.6-dichlorophenyl (amino)phenylethanoic acid (EMHDA) and bis(2-ethyl-6-methyl-3-hydroxypyridinium) 2.6-dichlo-rophenyl (amino)phenylethanoic acid (B-EMHDA), on the degree of brain edema in the simulation of BPM in experimental conditions.Material and methods. BPM was modeled by injecting a suspension containing Streptococcus pneumoniae at a concentration of 5 x 109 CFU/ml into the subarachnoid space of the brain. The degree of severity of cerebral edema in rats was assessed by determining the content of total water, free and bound fractions in the brain tissue, as well as the hydration coefficient. The lower the hydration coefficient, the more pronounced the cerebral edema. Determination of the content of water fractions in brain tissue and blood was carried out by the thermogravimetric method.Results and discussion. 24 hours after the induction of meningitis, the free water content increases and the amount of bound water decreases. That testifies to the development of cerebral edema. Hydration coefficient in the group treated with EMHDA at a dose of 50 mg/kg, increased by 11.5 % relative to the control group; in the group receiving EMHDA at a dose of 25 mg/kg, increased by 15.3 % compared to the control group (p

The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p

The aim of the experiment was to determine the effectiveness of the combined use of trimetazidine and a purified micronized flavonoid fraction, as well as their combinations with methyldopa, in comparison with monotherapy with the same drugs in the correction of morphofunctional disorders arising in the conditions of experimental preeclampsia. An integrated/multimethodology approach is the most effective way of treatment for preeclampsia. Therefore, an urgent task of modern pharmacology is to study the effectiveness of new drugs when used in combinations, as well as the drugs included in the standards for treatment.Materials and methods. The study was carried out at the Research Institute of Pharmacology of Living Systems of Belgorod State National Research University. The experiment was performed on 200 female Wistar rats, weighing 250–300 g, in which an ADMA-like model of preeclampsia had been reproduced. To assess the degree of correction of emerging morphological and functional disorders, the following parameters were involved: blood pressure, a coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid contents in the greater omentum, morphometric indicators of placental tissues and fetal height and weight parameters.Results. The combined use of trimetazidine (Preductal® MB) 6 mg/kg and a purified micronized flavonoid fraction (Detralex®) 260 mg/kg, as well as their combination with methyldopa (Dopegit®) 86 mg/kg, leads to a more pronounced decrease in the blood pressure, compared with a decrease in the coefficient of endothelial dysfunction by 2.22, 2.19 and 1.94 times, respectively, in relation to “untreated” animals. There was an increase in microcirculation indices in the placenta by 2.35, 2.21 and 2.03 times, respectively. In addition, there was an improvement in morphological parameters in the placenta and fetuses.Conclusion. The results of the study showed a greater effectiveness of the combined use of the studied drugs in experimental preeclampsia compared to their monotherapy. This indicates the prospects for the use of trimetazidine and purified micronized flavonoid fraction in the complex therapy for preeclampsia and the need for further research in this direction.

The aim of the study: to analyze the prevalence of resistance mutations to elsulfavirine and to evaluate the effectiveness of it among HIV-infected treatment-naïve patients in real clinical practice.Materials and methods. The study included 578 patients with HIV infection, which divided into 3 groups. The first group is 354 HIV-infected treatment-naïve patients for whom HIV-1 nucleotide sequences were obtained as part of routine drug resistance testing. The second study group included 111 HIV-infected treatment-naïve patients, tested for drug resistance before the antiretroviral therapy containing elsulfavirine. The third study group included 113 HIV-infected treatment-naïve patients, each of whom was assigned a treatment regimen containing elsulfavirine without prior drug resistance testing. The observation period for patients of the second and third groups who received treatment was 24 weeks. To assess the effectiveness of antiretroviral therapy in patients, viral load, CD4+ T-cell counts, and adherence to therapy were assessed. HIV-1 subtypes and drug resistance mutations were determined using the Stanford HIV Resistance Database (v. 8.9-1). To clarify the results of subtyping, phylogenetic analysis of nucleotide sequences was carried out using the MEGA program (v. 6.0).Results. The prevalence of mutations associated with decreased susceptibility to elsulfavirine among HIV-infected treatment-naïve patients was 1.7% and 4.5% for the first and second groups of patients, respectively. All of the patients have only single resistance mutations which, according to the results of preclinical studies, cannot cause drug resistance. The use of elsulfavirine in real clinical practice among treatment-naïve patients has demonstrated good virological and immunological efficacy of the drug. As a result of 24 weeks of therapy in patients of the second group, no treatment ineffectiveness, and the development of drug resistance were observed. Among the patients of the third group, 6 patients (5.3%) have the virological failure of therapy associated with the resistance to the used drugs. All patients with virological failure had a resistance mutation profile associated with a high level of drug resistance to one of the drugs in the treatment regimen, lamivudine. Additionally, 1 patient had a combination of mutations that reduce susceptibility to elsulfavirine, and 4 patients had mutations that can reduce susceptibility to elsulfavirine in combination with other mutations.Conclusion. The low prevalence of mutations associated with a decrease in susceptibility to elsulfavirine and the absence of combinations of mutations make it possible to predict the successful use of this drug for Russian treatment-naïve patients. Reported cases of virological failure of antiretroviral therapy are difficult to interpret in the context of elsulfavirine due to the lack of an exact list of mutations and their combinations, and associations with the degree of resistance to it. This study describes for the first time the mutation profiles in patients with virological failure of therapy containing elsulfavirine and demonstrates the necessity of the further study of drug resistance profile to drug in vitro and in vivo.

The aim of the wok is to assess the efficiency of hormone-regulating synchronization of ovulation in female mice, to increase the number of simultaneously fertilized individuals and obtain their offspring in the planned time frame.Materials and methods. The study was carried out on 180 female mice of three lines – CBA/lac, C57BL/6, BALB/c (n = 60), divided into three subgroups: intact (mating without confirmation of the estrous phase) (n = 20), cytological examination of vaginal secretions before mating with the determination of the estrous phase (n = 20), hormone-regulating synchronization of the estrous cycle with the introduction of progesterone (4.5 mg/100 g) on the 1st and prostaglandin F2α (0.083 mg/100 g) on the 7th day, once from the beginning of the experiment followed by immediate mating (n = 20). The planned date of delivery was considered the 22nd day from the moment of mating. The ovulation synchronization index (OSI) was assessed on the 14th day after mating.Results. On the 14th day from the beginning of the experiment, the ovulation synchronization index in the intact groups of the CBA/lac, C57BL/6, BALB / c lines, was 25%, 25%, 40%, respectively. On the 14th day, the number of pregnant individuals admitted to mating after the established estrus by the method of cytological assessment of vaginal secretions according to OSI, was 65%, 60%, 75%, respectively. In the experimental groups, OSI was 80%, 75%, 100%, respectively. On the 22nd day, the number of delivered females of CBA/lac, C57BL/6, BALB/c lines in the intact group, was 3, 1, 3 individuals; in the control group – 10, 6, 9, and in the experimental group – 16, 15, 17, which is significantly higher than in the control and intact groups (p˂0.05).Conclusion. Hormone-regulating synchronization of ovulation in female mice significantly increases the number of delivered individuals on the 22nd day, relative to those synchronized by estrus by 53%, and to intact groups by 85.5%. It has been revealed that an additional effect of hormonal synchronization of ovulation is an increase in the number of offspring by 120% in comparison with the control groups and by 390% in comparison with the intact groups. This method of timing planning of the offspring birth of the experimental animals reduces the time spent on preclinical studies of drugs for the following types of assessment of toxic effects: reproductive toxicity, embryotoxicity, teratogenicity, effects on fertility.

The aim of the study is to search compounds with neuroprotective properties among new ethylthiadiazole derivatives in simulated traumatic brain injury.Materials and methods. The experiment was carried out on 78 white male rats 270±20 g line “Wistar” 5–6 months of age and 120 outbred sexually mature mice weighing 20±2 grams. The article describes the search for compounds with neuroprotective properties among new ethylthiadiazole derivatives under the codes LKHT 4–15, LKHT 10–18, LKHT 11–18, and LKHT 12–18 in experimental traumatic brain injury in rats. Acute toxicity of the compounds was studied. Pharmacological screening was performed using behavioral and neurological research methods. The McGraw stroke score scale modified by I.V. Gannushkina and the mNSS psychometric scale were used in the study. The open field and Rota-rod tests were used to assess the behavioral status of the animals.Results. The compound-LKHT 12–18 at a dose of 50 mg/kg was detected as a leader. In pharmacological correction of pathology, this compound had the lowest percentage of fatality among the studied compounds (8%), the severity of neurological deficit was significantly reduced, the lowest scores and a higher level of motor activity of the limbs were registered. The number of rearing in the group of animals receiving the compound LKHT 12–18 at the dose of 50 mg/kg increased by 1.5 times, statistically significant (p

Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol — MMP-1 decreased by 35% (p

Aim. To study neurological disorders in rats when modeling purulent bacterial meningitis (PBM) on the example of pneumococcal meningitis under experimental conditions.Materials and methods. Pneumococcal meningitis was modeled by injecting a suspension containing Streptococcus pneumoniae at a concentration of 5×109 CFU/ml into the subarachnoid space. The degree of neurological disorders was determined by clinical assessment of rat health status, the degree of neurological defi cit, specifi c strength, “Infrared activity monitor”, “Object recognition task” tests.Results. When modeling pneumococcal meningitis in rats, the sum of points of clinical assessment of their health in the 1st day after modeling the pathology is 34.2 % less than the initial, on the 5th — less than 3.4 %, on the 8th day returns to the primary indicator, 5 points. The maximum degree of severity of neurological defi cit was observed in the fi rst four days after meningitis modeling; it was in the 1st day 34 % less than the same indicator in the group of intact animals, on the 2nd day 32.7 % less, on the 3rd day — 30.7 % and on the 4th day — 30.1 %. In the meningitis group on day 10, the distribution of neurological defi cit by severity was as follows: mild — 32 %, medium — 20 %, severe — 16 %, without residual neurological defi cit — 32 %. The specifi c strength of rats in the group of meningitis on the 1st, 5th and 10th day after the development of the pathology was 48.7, 64, and 67.4 % of the baseline specifi c strength. In relation to intact animals, the index of recognition of short-term memory in rats of the meningitis group is 2.3 times greater, and the index of recognition of long-term memory is 1.7 times greater.Conclusion. The dynamics of neurological disorders in rats in the simulation of PBM can be determined using the methods of assessing behavioural and cognitive status. In rats, when modeling pneumococcal meningitis, neurological disorders are maximally expressed on the 1st day of the disease. Then there is a distinct positive dynamic up to 5 days of the disease. From 6 to 10 days positive dynamics is present, but insignifi cant.

The treatment of coronary artery disease (CAD) in patients with combined pathology of peripheral arteries who are to perform endovascular or surgical interventions is a difficult task. The most important issues are the adequate diagnostics of artery systems’ lesions, determining the most optimal strategy and stages of treatment. This makes a multidisciplinary approach with the involvement of various specialists the most optimal.Aim. Based on multidisciplinary approach, to determine the prevalence of CAD and treatment strategy in patients with lesions of the aorta and peripheral arteries.8Material and methods. The study included 693 patients with pathology of the aorta and peripheral arteries: 171 (32,5%) were female, and 522 (75,3%) were male. The age of patients ranged from 29 to 93 years, an average — 67,2+8,8 years. Also 32,5% of patients (n=223) were older than 71 years. Cardiac complaints were present only in 203 (29,3%) patients, while 490 (70,7%) were asymptomatic. The majority of 693 patients had an isolated lesion of the internal carotid artery (ICA) (n=196, 28,3%), a combined lesion of the ICA and lower limb arteries (n=93, 13,4%), a combined lesion of the iliac and superficial femoral arteries (n=70, 10,1%) and femoral arteries lesions (n=60, 8,6%).Results. Finally, 554 (79,9%) of 693 patients had lesions of at least one coronary artery more than 50%, while 368 (66,4%) of them were clinically asymptomatic. By the decision of the multidisciplinary heart team, 316 (57,0%) patients underwent myocardial revascularization operations: 21 (6,7%) — coronary artery bypass grafting and 295 (50,3%) — percutaneous coronary intervention. Surgical and endovascular operations for pathology of the aorta and peripheral arteries were performed in 486 (70,1%) of 693 patients. Unlike with 260 (53,5%) patients, in 226 (46,5%) patients, in addition to vascular surgery, myocardial revascularization was performed. As a result of 923 (564 endovascular and 359 surgical) operations performed in 580 patients at the hospital stage, 3 (0,51%) of them had a fatal outcome. In other 2 (0,56%) cases, there was stroke: in one case after ICA prosthetics, in the other case — thrombosis of the ICA after the carotid endarterectomy. Acute myocardial infarction at the hospital stage was not detected in any of the patients.Conclusion. In 79,9% of patients with atherosclerosis of the aorta and peripheral arteries, at least one coronary artery lesion of more than 50% is detected. In 66,4% of patients with pathology of the aorta and peripheral arteries and with lesions of the coronary arteries of more than 50%, there are no cardiac complaints. In 45,6% of patients hospitalized with a diagnosis of atherosclerotic lesions of the aorta and peripheral arteries, myocardial revascularization is required. A multidisciplinary approach is an effective and safe treatment strategy for patients with pathology of the aorta and peripheral arteries of atherosclerotic origin and concomitant CAD.

This article describes a hybrid surgical technique for high-risk patients with thoraco-abdominal aortic dissections and aneurysms. The technical aspects of the first stage of surgical treatment - visceral and brachiocephalic debranching are described in detail. 17 surgical interventions for chronic dissection and aneurysm in the thoracic and thoracoabdominal aortas were performed at the Vishnevsky National Medical Research Center of Surgery of Ministry of Health of the Russian Federation in the period from 2014 to 2019. In two cases, we observed postoperative pancreatitis after surgical treatment of the abdominal aorta branches, which we managed using conservative therapy. After open surgery, all patients were discharged in a satisfactory condition. The selected technique made it possible to prepare patients for the following stage of treatment - endografting of the aorta - without developing serious complications.

Abstract Background Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from the paraganglion at the bifurcation of the carotid artery and are responsible for approximately 65% of all head and neck paragangliomas. CPGLs can occur sporadically or along with different hereditary tumor syndromes. Approximately 30 genes are known to be associated with CPGLs. However, the genetic basis behind the development of these tumors is not fully elucidated, and the molecular mechanisms underlying CPGL pathogenesis remain unclear. Methods Whole exome and transcriptome high-throughput sequencing of CPGLs was performed on an Illumina platform. Exome libraries were prepared using a Nextera Rapid Capture Exome Kit (Illumina) and were sequenced under 75 bp paired-end model. For cDNA library preparation, a TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold (Illumina) was used; transcriptome sequencing was carried out with 100 bp paired-end read length. Obtained data were analyzed using xseq which estimates the influence of mutations on gene expression profiles allowing to identify potential causative genes. Results We identified a total of 16 candidate genes (MYH15, CSP1, MYH3, PTGES3L, CSGALNACT2, NMD3, IFI44, GMCL1, LSP1, PPFIBP2, RBL2, MAGED1, CNIH3, STRA6, SLC6A13, and ATM) whose variants potentially influence their expression (cis-effect). The strongest cis-effect of loss-of-function variants was found in MYH15, CSP1, and MYH3, and several likely pathogenic variants in these genes associated with CPGLs were predicted. Conclusions Using the xseq probabilistic model, three novel potential causative genes, namely MYH15, CSP1, and MYH3, were identified in carotid paragangliomas.

Abstract Background Carotid body tumor (CBT) is a rare neoplasm arising from paraganglion located near the bifurcation of the carotid artery. There is great intra-tumor heterogeneity, and CBT development could be associated with both germline and somatic allelic variants. Studies on the molecular genetics of CBT are limited, and the molecular mechanisms of its pathogenesis are not fully understood. This work is focused on the estimation of mutational load (ML) in CBT. Methods Using the NextSeq 500 platform, we performed exome sequencing of tumors with matched lymph node tissues and peripheral blood obtained from six patients with CBT. To obtain reliable results in tumors with low ML, we developed and successfully applied a complex approach for the analysis of sequencing data. ML was evaluated as the number of somatic variants per megabase (Mb) of the target regions covered by the Illumina TruSeq Exome Library Prep Kit. Results The ML in CBT varied in the range of 0.09–0.28/Mb. Additionally, we identified several pathogenic/likely pathogenic somatic and germline allelic variants across six patients studied (including TP53 variants). Conclusions Using the developed approach, we estimated the ML in CBT, which is much lower than in common malignant tumors. Identified variants in known paraganglioma/pheochromocytoma-causative genes and novel genes could be associated with the pathogenesis of CBT. The obtained results expand our knowledge of the mutation process in CBT as well as the biology of tumor development.

This article provides indications for and description of surgical technique of carotid endarterectomy with the formation of a new bifurcation. It also presents the results of observations in the immediate postoperative period based on the findings of this surgery among patients of Vishnevsky National Medical Research Center of Surgery.

Aim. The research was designed to study the renoprotective properties of erythropoietin derivatives on the kidney ischemiareperfusion experimental model.Materials and methods. The renoprotective properties of asialo erythropoietin (0.4 μg/kg and 2.4 μg/kg 30 minutes before the induction of ischemia) and carbamylated darbepoetin (50 μg/kg 24 hours before the ischemic stimulus) were studied in comparison with erythropoietin and darbepoetin in a series of experiments on male Wistar rats on a 40-minute bilateral model of renal ischemia-reperfusion. The renoprotective properties were evaluated by the results of biochemical markers of acute kidney injury, the dynamics of glomerular filtration rate and fractional sodium excretion, as well as the severity of microcirculatory disorders.Results. It was found that the prophylactic use of asialo erythropoietin (dose-dependent) and carbamylated darbepoetin leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders.Conclusion. Asialo erythropoietin and carbamylated darbepoetin have the pronounced renoprotective properties and are the promising agents for the prevention and treatment of acute kidney injury.

The considered clinical case of combination of multifocal atherosclerotic vascular lesion with type 2 diabetes mellitus and liver fibrosis demonstrates a combination of polyvalent risk factors for resistance to antiplatelet therapy with clopidogrel. The decrease in the effectiveness of prolonged therapy with P2Y12 inhibitor was clinically manifested by repeated thrombotic events and was confirmed by laboratorial VerifyNow P2Y12 Assay test system as a low percentage of inhibition of ADP-induced platelet aggregation. We established probable genetic predictors of the decrease in the effectiveness of antiplatelet therapy in this patient, namely, the carriage of polymorphic markers of the ABCB1 CT, CES1 CA and CYP3A4*22 CT genes that determine the decrease in absorption, excessive hydrolysis of the drug and reduced activity of isoenzymes and transporters, that leads to disorders of active clopidogrel metabolite formation. A potential contribution of hepatic dysfunction to reduction in antiaggregant effect of P2Y12 inhibitor was demonstrated. Variant of drug interaction of clopidogrel and an inhibitor/substrate of P450 CYP2C19 – omeprazole, accompanied by a decrease in the effectiveness of antiplatelet therapy, was also considered.

Aim. Lipoproteide (a) (Lpa) is a pathogenetic risk factor of cardiovascular atherosclerotic disease. On the role of Lpa in the development of cardiovascular complications (CVC) after lower limbs arteries revascularization, there is lack of data. The aim of the study was assessment of Lpa relation to CVC occurrence after revascularization of lower extremities during 1 year follow-up.Material and methods. In the study, 111 patients were included (97 males, 14 females, mean age 66±9 y.o.), who had undergone revascularization of lower libms arteries due to atherosclerosis. As CVC during 1 year follow-up, the following were taken: recurrent intermittent claudication, lower extremity amputation, ischemic stroke, transient cerebral ischemia, non-fatal myocardial infarction, unstable angina, repeat revascularization and cardiovascular death. In all patients, in the blood serum, there were measured lipids and Lpa.Results. Within 1 year after revascularization there were 45 (41%) CVC. In the group with raised Lpa ≥30 mg/dL there were more CVC than in Lpa

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from paraganglionic tissue of the carotid body localizing at the bifurcation of carotid artery. These tumors are slowly growing, but occasionally they become aggressive and metastatic. Surgical treatment remains high-risk and extremely challenging; radiation and chemotherapy are poorly effective. The study of molecular pathogenesis of CPGLs will allow developing novel therapeutic approaches and revealing biomarkers. Previously, we performed the exome sequencing of 52 CPGLs and estimated mutational load (ML). Paired histologically normal tissues or blood were unavailable, so potentially germline mutations were excluded from the analysis with strong filtering conditions using 1000 Genomes Project and ExAC databases. In this work, ten genes (ZNF717, CDC27, FRG2C, FAM104B, CTBP2, HLA-DRB1, HYDIN, KMT5A, MUC3A, and PRSS3) characterized by the highest level of mutational load were analyzed. Using several prediction algorithms (SIFT, PolyPhen-2, MutationTaster, and LRT), potentially pathogenic mutations were identified in four genes (CDC27, CTBP2, HYDIN, and KMT5A). Many of these mutations occurred in the majority of cases, and their mutation type was checked using exome sequencing data of blood prepared with the same exome enrichment kit that was used for preparation of exome libraries from CPGLs. The majority of the mutations were germline that can apparently be associated with annotation errors in 1000 Genomes Pro ject and ExAC. However, part of the mutations identified in CDC27, CTBP2, HYDIN, and KMT5A remain potentially pathogenic, and there is a large body of data on the involvement of these genes in the formation and progression of other tumors. This allows considering CDC27, CTBP2, HYDIN, and KMT5A genes as potentially associated with CPGL pathogenesis and requires taking them into account in further investigations. Thus, there is a necessity to improve the methods for identification of cancer-asso ciated genes as well as pathogenic mutations.

A randomized multicenter 96-week study of an elsulfavirine (ESV), non-nucleoside reverse transcriptase inhibitor (NNRTI) of novel generation, in combination with 2 nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs) was conducted in naive HIV adult patients, divided by 2 parts: 1) partially blind comparative to efavirenz (EFV) 48-week study, 2) open-label observational study during additional 48 weeks. High virological and immunological effectiveness maintained during the study: proportion of patients with HIV RNA

Abstract Background Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated. Methods Exome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina). Results Exome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6–8 mutations per megabase (Mb). Genes with the highest mutation rate were identified. Conclusions Exome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.

Preeclampsia is a frequent and dangerous disease in pregnancy which has shown no decrease in incidence. The article describes preeclampsia pathogenesis as reported in recent studies. A promising trend in the development of new medicines aimed at prevention and treatment of preeclampsia is the activation of biological processes of cytoprotection which arise during ischemic preconditioning. The article cites experimental and clinical data that help to justify the good potential of this area of research.

RETRACTED ARTICLEThe article describes arginase’s role in pathogenesis of endothelial dysfunction and a number of cardio-vascular diseases. Arginase catalyzes the hydrolysis of L-arginine, the substrate for nitric oxide synthesis, to L-ornithine and urea. Two isoforms of arginase were found in the human organism. Arginase I is located in the cells cytoplasm and is predominantly expressed in the liver. Arginase II is a mitochondrial protein that is expressed in the kidney, prostatic gland and vascular wall. Arginase II hydrolyzes L-arginine, thereby reducing the synthesis of nitric oxide and leading to the development of endothelial dysfunction and a number of cardio-vascular disorders. Arginase is a promising pharmacological target in the treatment of endothelial dysfunction and a number of cardio-vascular diseases, though the development of highly-selective arginase II inhibitors is still a difficult task.

The present article describes the stages of the development of the test-system that allows to research the potency of GSK-3 inhibitors to induce endothelial progenitor differentiation and to increase cell survival in hypoxia in vitro. β4-thymosin, which shows anti-ischemic and angiogenic activity, has been used a reference preparation. The proposed experimental cell model can be useful in the preliminary testing of new chemical compounds in terms of their ability to treat ischemic disorders and it can be used as an alternative for procedures involving animal testing.

The article discusses the results of analysis a number of candidate molecules for TRPA1 ion channel selective antagonists using molecular modeling methods of high throughput screening. The study determined their mechanisms of action and specific activity in cells with overexpression of TRPA1 ion channel. It demonstrated antagonistic activity of test substances in relation to TRPA1 ion channel based on the results of molecular screening of biologically active molecules and their comparison with the reference antagonist. The highest activity was demonstrated by the substance with the ZC02-0012 code which was regarded as the main candidate that could be recommended for use in further safety and selectivity studies using in vitro tests and subsequent in vivo experiments aimed at determining its activity and safety in relation to living systems.

Aim. To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. Subjects and methods. The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987—2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. Results. The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988—1989. Conclusion. The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

In 2015, the infection caused by human immunodeficiency virus (HIV) (HIV infection) dominated among life-threatening infections in Russians: it was first diagnosed in 98,177 Russians and 15,530 citizens of the Russian Federation died from HIV/AIDS, amounting to 45% of all deaths from infectious diseases in Russia. By the mid-2016, there were a total of 1,062,476 identified HIV-positive Russians, of whom 225,992 people died. The estimated number of HIV-infected patients in Russia approximated to 1% of the population, the highest prevalence of HIV being found in the age group of 30—40 years. The most active and expensive measures against HIV/AIDS in Russia are to examine the population for anti-HIV antibodies (29 million screenings per year) and to use in HIV-positive people antiretroviral therapy that was free of charge to more than 200,000 patients, i.e. nearly 25% of the registered Russians living with the HIV-infected. However, treatment coverage and quality are far from the target indicators that the international experts consider needed to reduce HIV prevalence and mortality. A wider program on HIV/AIDS, which includes a number of preventive measures with proven efficiency, as well as a program of promising researches and developments should be introduced in Russia.

Aim. To study the sociodemographic data of people living with HIV who visit AIDS centers. Subjects and methods. A multicenter open-label study was conducted, which included the retrospective model “A patient’s portrait”. Outpatient records and questionnaires were analyzed in 7,000 patients older than 18 years of age who had visited AIDS centers in 27 regions of Russia from 1 April to 31 July 2014 and signed their informed consent form to participate in the study. Results. There were women accounting for 49% of the study participants, including one transgender. Their mean age was 35.6 years; the median age was 34 (18-79) years. 77.4% of the women were infected sexually; 57.4% of the men were infected parenterally; the men who had sex with men accounted for 2.5% of the whole group (4.7% among the men). Only 9.8% of the respondents reported that they had used intravenous drugs in the past 6 months. 87.8% of the respondents had secondary and higher education; 68.6% of the patients (73% were male and 64% were female) were employed; 59.3% of the respondents were married or cohabited; 66.2% of the patients reported that they had had sexual contacts with one partner, 14.2% had not had sexual intercourses. 38.3% of the women and 48.8% of the men had a permanent HIV-negative sexual partner. 46% of the study participants had dependent minor children. 30% of the women had given birth to at least one child after the diagnosis of HIV infection. Conclusion. People living with HIV in Russia and visiting AIDS centers do not differ in main social and demographic indicators from the Russian Federation citizens of the same age who do not have HIV. They represent an economically and socially active population and participate in demographic processes so one of the public health priorities is to maintain and improve their quality of life.

Using the combined of L-arginine with inhibitors of HMG-Co-A reductase simvastatin, atorvastatin, rosuvastatin and rosuvastatin nanopartikulirovannym on background modeling endotoxin-induced disease, the introduction of strain 603 Staphylococcusaureus shows endotelio- and cardioprotective effects, manifested in preventing the proliferation coefficient of endothelial dysfunction (CED), adrenoreactivity, maintaining myocardial reserve and the normalization of the values of biochemical markers (Total NO, expression of eNOS, C-reactive protein, IL-6, TNF). Thus, combination therapy was so effective, that the values obtained in the combination therapy did not differ from those derived from control animals.

Using of the combined use of non-selective inhibitor of arginase L-norvaline with simvastatin, atorvastatin, rosuvastatin and rosuvastatin nanopartikulirovanny on background modeling endotoxin-induced disease, the introduction of strain 603 Staphylococcusaureus shows ekdotelio- and cardioprotective effects, manifested in preventing the proliferation of coefficient of endothelial dysfunction (CED), adrenoreactivity, maintaining myocardial reserve and normalization values of biochemical markers (Total NO, Expression of eNOS, C-reactive protein, IL-6, TNF). Thus, combination therapy found no additive effect of drugs.

Methylated analogs of L-arginine - asymmetric dimetilarginin (ADMA) and monometilarginin (L-NMMA) - are endogenous inhibitors of endothelial NO-synthase (eNOS). ADMA level in maternal plasma is increased in women with preeclampsia. The high level of ADMA is one of the predictors of preeclampsia. L-arginine increases the activity of eNOS and production of nitric oxide in the ADMA-similar model of L-NAME-induced endothelial dysfunction. ENOS activator (resveratrol), antioxidants, potentiated polyclonal antibodies to eNOS and others agents have been effective in this model. Studies of endotelioprotective activity in other «ADMA-eNOS-associated" experimental models of metabolic syndrome and homocysteine-induced, gipoestrogen-induced sepsis-induced endothelial dysfunction and endothelial dysfunction in postvaccinal vasculitis have been developed.

Aim. To study the effects of furostanol glycosides from cultured Dioscorea Deltoidea cells (DM-05, Institute of Plant Physiology, RAS) on physiological and biochemical markers of endothelial function in rats with hypoestrogen-induced endothelial dysfunction.Material and methods. 10 female rats of Wistar line, with body mass 200-300 g have been included in the experiment. The bilateral ovariectomy was performed in rats to produce the model of hypoestrogen-induced endothelial dysfunction. Rats were treated with the injections of DM-05 during 6 weeks. False ovariectomy was performed in rats of control group (n=10).Results. DM-05 restored the levels of stable metabolites of nitric oxide (NO) which reflex endothelial NO-synthase activity. Besides DM-05 corrected blood pressure and endothelial function. Experiments on open heart showed that DM-05 protects the cardiac tissue from hypoestrogen-induced hyperadrenoreactivity.Conclusion. Treatment with plant origin substances with estrogen-like activity can be a perspective approach to the correction of endothelial function and decrease in cardiovascular risk in menopause women.

Using the combined use of recombinant erythropoietin «Darbopoetin alpha» (500 mcg / kg) with simvastatin, atorvastatin, rosuvastatin and rosuvastatin nanopartikulirovanny on background modeling sepsis-induced disease, the introduction of strain 603 Staphylococcusaureus shows endotelio- and cardioprotective effects, manifested in preventing the proliferation of QED, adrenoreactivity, maintaining myocardial reserve and the normalization of the values of biochemical markers (Total NO, expression of eNOS, C-reactive protein, IL-6, TNF). Thus, combination therapy found an additive effect of drugs.

The article presents the results of studies of the effect of distant preconditioning by creating short-term limb ischemia and pharmacologic preconditioning of resveratrol on the size of myocardial necrosis and the level of troponin I in serum after ischemia-reperfusion. Established a comparable protective effect as distant and pharmacological preconditioning. Possible mechanisms of the protective effect of pharmacological preconditioning during ischemia/reperfusion. Preconditioning of the heart by resveratrol provides cardioprotection, as evidenced by the reduction in the size of the area of myocardial necrosis. Cardioprotection resveratrol was completely abolished as N-nitro-L-arginine methyl ester (L-NAME), and aminoguanidine (AG), which show that resveratrol provides cardioprotection type of ischemic preconditioning by nitric oxide synthase (NOS).

The work evaluated the influence of 3-(2,2,2-trimethylhydrazinium) propionate per square necrotic myocardium of the left ventricle and the level troponina I serum during acute coronary occlusion (60 minutes) followed by reperfusion (90 min) in anesthetized rabbits. It is shown that distant and pharmacological preconditioning 3 (2,2,2-trimethylhydrazinium) propionate reduce nekrooza zone 3 and 1.5 times, respectively. Found participation ATP dependent potassium channels (KATF channels) of endothelial and inducible NO-synthase in the implementation of the cytoprotective effect of distant preconditioning and 3-(2,2,2-trimethylhydrazinium) propionate, indicating that the implementation of the mechanism of pharmacological preconditioning in his kardioprotektvnom action.

Пандемия, вызванная распространением вируса иммунодефицита человека (ВИЧ), вызывающего синдром приобретенного иммунного дефицита (СПИД), начавшаяся в конце 70-х годов прошлого века и пока еще не достигшая своего апогея, создала новые серьезные проблемы, или, как теперь выражаются, «вызовы» для здравоохранения всех стран.

Experimental L-NAME-induced pre-eclampsia model in rats was achieved by L-NAME administration from 14 to 20 pregnancy days. Blood pressure elevation, gestational proteinuria, placenta microcirculation impairing, vascular tone dysregulation, and L-norvaline (10 mg/kg) and conventional medications (methyldopa 0,086 mg/kg/day & amlodipine 0,5 mg/kg) result in the evident correction of the pathological changes in pre-eclampsia model. Despite good L-norvaline with conventional pre-eclampsia medications). This might be explained by different points of applications and allows to affect many different patho-genesis chains.

Интервью с Анатолием Владимировичем Покровским — академиком РАН, доктором медицинских наук, профессором, лауреатом Государственных премий СССР и РФ, заведующим отделением сосудистой хирургии ФГБУ «Институт хирургии им. А.В. Вишневского» Минздрава России

We investigate blood flow velocity at ischemia/reperfusion early stages and at its human recombinant erythropoietin correction. Transient hyperemia absence after ischemia/reperfusion at early stages was determined. Erythropoietin administration prevents transient hyperemia development after period of ischemia in liver and small intestine but increase blood flow velocity in pancreas.

Aim. To study efficacy and safety of highly active antiretrovirus treatment (HAAT) used in the Russian Federation for development of recommendations for HIV infection treatment. Material and methods. A total of 285 patients with chronic HIV infection and 42 patients with acute HIV infection participated in investigation of efficacy and safety of different HAAT schemes in 1997-2008. Efficacy of the treatment was assessed by percentage of the patients who had HIV RNA undetectable by the test system (< 400 copy/ml) after 24-48 treatment weeks, by a mean reduction of HIV RNA in blood plasma and an increase in the number of CD4-lymphocytes in 1 mcl of blood. Results. A 12-year experience in antiretrovirus therapy administration for management of HIV infection is reviewed. Efficacy and safety of Russian antiretrovirus drug Phosphaside in HAAT schemes are shown in patients with both chronic and acute HIV infection. The model of HIV patients consulting before the treatment, psychological support during the treatment, methods of individual and group consulting, conception of the school for patients on HAAT are presented. Recommendations are proposed for administration of antiretroviral therapy and a model of calculation of the number of HIV-infected patients in need of antiretroviral therapy in Russia. Basing on the results of investigations on efficacy and safety of HAAT schemes, the physicians of the National Anti-AIDS Center have developed clinical recommendations, guidelines on the treatment of HIV infection, standards of medical care for HIV-infected patients.