Репозиторий Университета

© 2018 Izdatel'stvo Meditsina. All rights reserved. Introduction of amendments to the registration dossier is the responsibility of the marketing application holder (MAH). Increased knowledge on pharmaceuticals, its manufacturing and control processes can reduce the number of documents submitted to the regulatory authorities. The existing requirements establishing the procedure for the introduction of amendments differ in terms of change classification, period of notification of regulatory authorities, ways of conformity validation of pharmaceutical properties, etc. ICH proposed draft guideline Q12 «Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management» which covers the problem of harmonization of regulatory approaches to the changes provided in the «Quality» section of CTD during the commercial phase of drug life cycle. The new guideline can be considered as the continuation and elaboration of previous ICH documents. The article provides explanations on the main provisions and regulatory mechanisms introduced by the draft guideline ICH Q12: categorization of post-approval changes, established conditions, post-approval change management protocol, and drug product lifecycle management.

© 2018 Media Sphera Publishing Group. All rights reserved. Aim of the study was to explore the role of the FGF-23/sKlotho/sclerostin ratio disturbance in the determining of cardiovascular risk in end stage renal disease (ESRD) patients, receiving treatment with regular hemodialysis (ÍD) or hemodiafiltration (ÍDF) online in Russia. Materials and methods. 42 patients with ESRD, at the age of 18-55 years, treated with HD or HDF on line for at least 6 months, were examined. 22 (52.3%) patients received traditional HD, the remaining 20 (47.7%) - HDF online. In all the patients, in addition to a general examination, the serum levels of FGF-23, sKlotho, sclerostine (by ELISA), their associations with cardiovascular risk factors (left ventricular hypertrophy (LVH), acute coronary syndrome (ACS), serum troponin I levels) with the numbers of techniques (ECG; Eho-CGF (with calculation of left ventricular myocardium mass index (LVMMI), as well as the relative thickness of the walls of the left ventricle (RWT); sphygmography (central (aortal) blood pressure (CBP), subendocardial blood flow (SBF) - by Sphygmocor), and the effect of regular HD and HDF on serum levels of the studied markers, were assessed. Results and discussion. An independent effect of FGF-23 on the risk of LVH, as well as on the increase of serum troponin I in the studied ESRD patients [β=3.576 p<0.01, and β=1.115, p<0.05, respectively] was found. Serum Klotho was the factor most associated with the CBP [β=-0.023; p<0.001]. The increased serum sclerostin was correlated with a lower incidence of both reduced SBF [r=0.492; p<0.05], symptoms of coronary heart disease [r=-0.449; p<0.05] and rhythm disturbances [r=-0.446; p<0.05]. In addition, in HD patients higher FGF-23 and lower Klotho and sclerostine serum levels were associated with: inadequate dialysis syndrome (Kt/V <1.1; r=0.463; p<0.05), chronic inflammation (C-reactive protein >10 mg/L; r=0.612; p<0.01), and with a decrease in serum albumin level (<35 g/l; r=0.459; p<0.05). The FGF-23/sKlotho/sclerostin ratio disturbance was more pronounced in patients treated with traditional HD then HDF online. A direct correlation (r=0.445; p<0.05) was established between FGF-23 serum levels and serum phosphorus, which was more pronounced in HD patients (r=0.545; p<0.01). Conclusion. In HD and HDF ESRD patients, higher serum FGF-23 and lower sKlotho and sclerostin levels were associated with a chronic inflammation, malnutrition, secondary hyperparathyroidism, and may considered as predictors of cardiovascular complications such as LVH, ACS, rhythm disturbances, persisting of subincreased serum troponin I.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This research was aimed at the pharmacological analysis of dermotropic activity ofCaragana jubata (Pall.) poiraqueous extract on the model of atopic contact dermatitis induced by 2,4-dinitrochlorobenzene in male rats. It was found that the aqueous C. jubata extract exhibited expressed dermotropic activity as manifested by reducing thickness of the skin fold by 47% (p = 0.05) and decreasing severity of the onset of contact dermatitis on the average by 38% (p = 0.05). Histological examination showed positive trends in the regeneration of skin lesion. Hematologic examination showed normalization of peripheral blood parameters in animals affected by contact dermatitis. Calculations of the index of inhibition of the inflammatory response confirmed anti-inflammatory effect of the aqueous C. jubata extract.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II - 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7-10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II - 5.5±0.06 years and 2.4±0.07 years, respectively (p<0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p<0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p<0.001). Immunohistochemical analysis of the endometrium on the 18th-24th day of the cycle established high expression of CD16, CD20, CD56, and HLADRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p<0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p<0, 05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16, CD20, CD56 and HLA-DRII .

© Russian Association of Endocrinologists, 2018. Background: As in many other developed nations, the problem of obesity and type 2 diabetes is acute in Russia. In Russia, the only combination of sibutramine and metformine (Reduxin®Met) is authorized to reduce body mass and prevention development of type 2 diabetes mellitus or its complication. The article presents the results of the observational program “AVRORA”. Aim: Evaluation of the effectiveness and safety of Reduxin®Met (sibutramine + microcrystalline cellulose + Metformin) in patients with type 2 diabetes and alimentary obesity in routine clinical practice. Materials & methods: The observational program “AVRORA” was conducted from September 2016 to October 2017 under the auspices of the Endocrinological Scientific Center and the Russian Association of Endocrinologists. The “AVRORA” program was a multicenter, non-interventional study of patients to whom the attending physicians prescribed Reduxin®Met, a set (tablets + capsules), in accordance with the instruction for medical use as part of routine clinical practice. The treated group included patients of both sexes, aged 18–65 years, with an established diagnosis of obesity in combination with type 2 diabetes. The duration of the drug usage was determined by the attending physician and was up to 6 months. Reduxine®Met was prescribed in addition to the existing glucose-lowering therapy, the dose of metformin was adjusted to the patient's needs. Results: The “AVRORA” study was attended by 259 doctors and 5,812 patients in 240 medical institutions from 12 cities of the Russian Federation. The average age of patients was 46.6 ± 10.5 years, the ratio of male / female -24% / 76%. The decreasing of BMI during 6 months of the therapy amounted to 5.4 ± 2.3 kg / m2 (on average, 15.1 ± 6.4 kg). After 3 months of the therapy 81.6% of patients achieved clinically significant weight loss of 10.6% or more. The average decrease in waist circumference during 6 months of therapy was 13.8 ± 7.4 cm. A decrease of indicators of glycemic control and lipid metabolism right up to the target values was observed. Conclusions: In “AVRORA” study it was shown that addition of Reduxine®Met (sibutramine+ microcrystalline cellulose+met-formine) to the complex therapy of the diabetes in combination with obesity according to approved indications is safe and effective for long-term treatment in regards to weight loss, regulation of lipemic index, glucose profile and quality of life.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. The article discusses various mechanisms of developmentt and progression of arterial hypertension in young and middle aged adults. It emphasizes the predominant role of hypersympathicotonia in the development of the disease in this category of patients. Various mechanisms are considered, by means of which the increase of activity of the sympathetic nervous system leads to elevation of arterial pressure and potentiates early damage of target organs, first of all, damage of the heart. The data of numerous studies demonstrating pronounced cardioprotective effects of a highly selective representative of the class of β-blockers bisoprolol in young and middle aged hypertensive patients are presented.

© 2018 Brovko et al. Purpose: Experimental studies suggest that the nephrotic syndrome is associated with “vasopressin escape”, characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome. Patients and methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA. Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all P<0.05). In patients with nephrotic syndrome and a partial remission of nephrotic syndrome combined, there was more than a ten-fold decrease in the median urinary AQP2 excretion (0.03 ng/mL) compared with healthy volunteers (0.41 ng/mL; P<0.001) and more than a five-fold decrease compared with patients with minimal proteinuria (0.21 ng/mL; P<0.05). Unlike copeptin levels, the median urinary AQP2 excretion in patients with minimal proteinuria also decreased but less significantly than in those with nephrotic syndrome. There was a negative correlation between the urinary AQP2 excretion and daily proteinuria (R=−0.41; P=0.005). Conclusion: Our clinical study was the first to demonstrate low AQP2 excretion in nephrotic syndrome that may indicate an escape from the vasopressin regulating effect.

© 2018 Media Sphera Publishing Group. All rights reserved. Àim. To compare the efficacy of prophylactic administration of mineral-vitamin complexes "Feroglobin-B12" and "Complivit iron" with different degrees of Fe valence. Materials and methods. 120 female subjects were examined. To determine the quality of life, the SF-36 questionnaire was used. The presence of anxiety was determined on the Spielberger-Khanin Alarm Scale. 30 women with a deficit of Fe were divided into 2 groups of 15 people each. The first group received "Ferroglobin-B12", the second – "Complivit iron" for a month. Results. In a month after the initiation of preventive therapy in women of the 1 group the content of Fe serum was normalized. In the second group, its concentration approached the control values. The difference in Fe content in the 1 and 2 groups was of a reliable nature. Conclusion. The intake of "Ferroglobin-B12" was not accompanied by side effects, and performance indicators, social activity and mental health reached control values, unlike the group of patients taking Complivit iron.

© 2018 Maik Nauka-Interperiodica Publishing. All rights reserved. Changes in the power and coherence of the EEG theta-1 (4-6 Hz) and theta-2 (6-8 Hz) activity were studied in subjects (31 males, 18-21 years old) with different performance levels in logical tasks. EEG was recorded to the International 10-20 System from the occipital (O2, O1), parietal (PA, P3), central (C4, C3), frontal (FA, F3), and temporal (T4, 73) leads. The achievement of better performance during the tests based on logical reasoning positively correlated with higher spectral power of theta-1 band potentials in the left cortical areas. The theta-1 band potential power increased during testing and compared to the previous period in the left occipital, parietal, central and temporal cortical areas. The simultaneous increasing in intrahemispheric coherence of theta-1 band potentials was observed in the left frontal and central areas, as well as in the left frontal and parietal cortical areas. The spectral power of theta-2 band potentials decreased during testing and compared to the previous period in the right central frontal and temporal cortical areas. The inter- and intrahemispheric coherence of the EEG theta-2 band potentials decreased during testing in the system of relationships with the focus in the left and right occipital and right parietal cortical areas. The desynchronization in the EEG theta 2 band in all cortical areas was observed at transition from a state of quiet wakefulness with eyes closed to a state with eyes open. The conclusion is made about the different functional significance of the electrical activity of the low and high frequency theta EEG bands under cognitive activity.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. Determination of desialized apolipoprotein-B-100 (apoB-100) and lipoprotein-containing circulating immune complexes in patients with chronic kidney disease (CKD) in program hemodialysis with type 2 diabetes mellitus. Materials and methods. We examined 81 patients with CKD (50 men / 31 women) treated with program hemodialysis, of which 36 (17/19) with type 2 diabetes mellitus, 45 (33/12) non-diabetic patients. The levels of total cholesterol, triglycerides and desialylated apoB-100 in blood plasma and lipoprotein-containing circulating immune complexes. A color duplex scan of brachiocephalic arteries was used to assess the extent of development of atherosclerosis with the determination of the thickness of the intima-medial complex. Results and discussion. Patients with diabetes had high values of total cholesterol, triglycerides (p<0.05). Duplex scan of brachiocephalic arteries showed an increase in the thickness of intima-medial complex in all patients for program hemodialysis, however, in patients with diabetes, the thickness was 13% higher (p<0.05). In patients with diabetes, plaques with stenosis up to 50% prevail, compared with non-diabetic patients, p<0.05. The incidence was significantly higher for desialized apoB-100 by 46% in patients with diabetes on hemodialysis compared non-diabetic patients (p<0.05). An increase in the level of lipoprotein-containing circulating immune complexes by 39%, (p<0.05) in patients with diabetes mellitus was observed, compared with patients non-diabetic patients. The correlation between desialized apoB-100 and duplex scan of brachiocephalic arteries parameters (r=0.325), as well as between the cholesterol level and stenosis up to 50% (r=0.465) in patients with diabetes mellitus, was found to be of medium strength. The patients with diabetes and CKD, myocardial infarction developed 79% more often than in patients without diabetes (p<0.05). Thus, immunogenic lipid markers of atherosclerosis can be considered both as mechanical factors of atherogenesis and diagnostic and prognostic characteristics in type 2 diabetic patients with impaired renal function and chronic renal insufficiency. The conclusion. Accelerated development of atherosclerosis with diabetes and CKD, confirmed with the help of duplex scan of brachiocephalic arteries, may be associated with an increase in the level of modified low density lipoprotein.

© Ima-Press Publishing House. All rights reserved. Stroke is one of the leading causes of death and disability in the population, has a complex multifactorial nature and develops through the interaction of environmental factors and genetic predisposition, the pattern and mechanisms of which have been insufficiently studied. Ischemic stroke (IS) is most commonly encountered. Objective: to investigate the differential expression of microRNAs (miRNAs) in the plasma of patients in the acute and subacute stages of stroke. Patients and methods. The investigation enrolled 10 patients (5 men and 5 women; mean age, 64.5 years) with IS and 10 gender- and age-matched volunteers (a control group). A real-time polymerase chain reaction (PCR) was used to analyze the expression of 45 miRNAs isolated from the plasma samples of the patients on days 1 and 8 after onset of IS and isolated once from those of the controls. Results. A list of 45 miRNAs, that might be potential biomarkers and/or prognostic factors of stroke, was compiled. The investigation showed a decrease in let-7i-3p and miR-23a-3p miRNA expression in patients on the first day after onset of IS compared to the control group. The expression of miR-23a-3p increased in the patients at 8 days after IS. The patients with IS and the controls both showed gender differences in the expression of let-7i-5p and miR-92b-3p. Conclusion. The in-silico analysis revealed specific miRNA clusters associated with the peculiarities of clinical manifestations of IS. This may suggest that the patients with the favorable and unfavorable course of stroke may have its different molecular basis. In addition, it is necessary to take into account gender differences in the expression of individual miRNAs in assessing their significance in the pathogenesis and prognosis of IS.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Vitamin D deficiency is widespread worldwide and present in about 30-50% of population. In most cases, this problem is associated with musculoskeletal system pathology: Rickets in children, and osteomalacia or osteoporosis in adults. However, in recent years, convincing data was obtained on the links between Vitamin D deficiency and cardiovascular pathology. Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe cardiovascular diseases, including strokes and infarctions. It has been demonstrated that Vitamin D has a strong vasoptotective effect via endothelial dysfunction improvement, prevents blood vessels and myocardium remodeling, improves blood pressure parameters, reduces the risk of development of left ventricular hypertrophy, slows down fibrosis, reduces the risk of atherosclerosis, reduces insulin resistance, and also affects inflammation and immunity. This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic heart failure.

© 2018 Media Sphera Publishing Group. All rights reserved. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

© 2018 Izdatel'stvo Meditsina. All rights reserved. There were studied the impact of selective antagonist of the mitochondrial translocator protein (TSPO 18 kDa) PK11195 (N-butan-2-yl-l-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide; 1 or 3 mg/kg, i.p.) and 5α-reductase inhibitor finasteride (1.25; 2.5; 5 mg/kg, i.p.) on anticonvulsive effect of pyrazole[c]pyridine derivative GIZH-72 (4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-l//-pyrazolo[4,3-c]pyridin-3-one chloralhydrate, 20 mg/kg, i.p.) in marble burying test in C57BL/6 mice. It is established that PK11195 (1 or 3 mg/kg, i.p.) had no effects on both compulsive behavior of mice and anticompulsive effect of GIZH-72 (20 mg/kg, i.p.). Finasteride (2.5 or 5.0 mg/kg) decreased of compulsive behavior in the dose-dependent manner in C57BL/6 mice. Pretreatment with finasteride (2.5 or 5.0 mg/kg, i.p.) led to completely reduction of anticompulsive effect of GIZH-72 (20 mg/kg, i.p.). Thus, anticompulsive effect of GIZH-72 may depend on activity of 5α-reductase, but not TSPO 18 kDa.

© Russian Association of Endocrinologists, 2018. This review examined the current problem of low adherence to treatment in patients with chronic diseases, particularly type 2 diabetes mellitus. According to the definition of the World Health Organization, 'adherence to treatment' is the degree to which a patient's behaviour corresponds to the doctor's recommendations with respect to medications and implementation of dietary advice and/or lifestyle changes. The current medical literature includes a large number of scientific publications devoted to the study of various factors that lead to low adherence to treatment. The term 'barriers' is most often used to designate these factors. The first part of this work contains an analysis of the main factors that impede compliance to the doctor's recommendations, such as socioeconomic and psychological (personal) barriers related to the disease itself, the peculiarities of its treatment and the organisation of medical care (the health care system). The second part of this review examines the different theoretical models of patient behaviour and strategies that improve adherence to treatment. Most researchers believe that there is an unsatisfactory (low) adherence to treatment and that none of the existing intervention strategies can improve adherence to treatment among all patients. The cornerstone of the entire diabetes management system is the training of patients within the framework of developed structured programmes. Conversely, success depends on the individual approach, the course of the disease and the mandatory consideration of the individual psychological characteristics of each person. Establishment of a partnership built on trust between a doctor and a patient contributes to greater patient satisfaction with treatment and improved adherence, and this relationship ultimately affects the treatment efficacy and clinical outcomes.

© Rational Pharmacotherapy in Cardiology 2018. Background. Carriership of CYP4F2*3 (rs2108622, Val433Met) allelic variant can affect antiplatelet effect of clopidogrel, thus changing efficacy and safety of its standard dose. Aim. To study the impact of carriership of at least one CYP4F2*3 allele on the risk of resistance to clopidogrel in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Material and methods. The study enrolled 81 patients with ACS and PCI: 64 males and 17 females, mean age 63.9±10.9 years. CYP4F2 allelic variants were detected by the method of real-time polymerase chain reaction. Platelet functional activity was evaluated by a portative aggregometer - the VerifyNow P2Y12 assay. Results. Pharmacogenetic testing showed that 40 (49.4%) of ACS patients had normal genotype (CC), 38 (46.9%) patients were carriers of one associated with reduced drug metabolism allele (CT genotype), and 3 (3.7%) patients were homozygotes for T (TT genotype). Genotype and allele distribution was in the Hardy-Weinberg equilibrium (χ2=2.79; p=0.095). There were no statistically significant differences in CYP4F2*3 allele frequency between patients that are resistant to clopidogrel (PRU > 208) and in patients with a normal response to clopidogrel (PRU < 208): 36.8% vs 54.8% (p=0.17). Average platelet reactivity units (PRU) and average platelet inhibition (%) in patients with and without T allelic variant of CYP4F2 also were not significantly different: 165.34±51.03 PRU vs 174.8±51.06 PRU (p=0.407), respectively, and 29.51±21.59% vs 27.72±18.35%, respectively (p=0.69). Conclusion. Carriership of CYP4F2*3 allelic variant does not affect antiplatelet effect of clopidogrel in ACS patients. Further research on larger samples is needed to determine the role of CYP4F2 polymorphisms in personalization of clopidogrel antiplatelet therapy.

to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. Subjects and methods. The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. Results. According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. Conclusion. Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

© AUTHORS, 2018. The area of invasive species Aedes albopictus and Aedes aegypti is expanding. Precise identification and understanding of the genetic diversity of invasive mosquito populations allows us to develop appropriate control methods. Endosymbiotic bacterium Wolbachia pipientis has different effects on their arthropod hosts and can influence the transmission and spread of the pathogens. The objective of the presented study was molecular-genetic identification of the Aedes mosquitoes collected in sampling sites on the Black Sea coast from 2007 to 2017; determination of genetic variability of Ae. aegypti, Ae. albopictus and their symbiotic bacteria Wolbachia; assessment of mosquitoes ability to be infected and to spread parasitic Dirofilaria. Another objective was obtaining the genetic characteristic of laboratory strain Ae. aegypti IMPITM. We investigated two markers of nuclear and mitochondrial DNA from Ae. albopictus and Ae. aegypti and compared them to DNA from Ae. cretinus and Ae. koreiсus sympatrically inhabiting the territory, as well as to one of Ae. aegypti from a laboratory line. The study of nuclear and mitochondrial DNA revealed a low level of variability in the invasive mosquitoes Ae. albopictus and Ae. aegypti collected at different collection sites and in different years. More than a half of Ae. albopictus were infected with Wolbachia, two strains of bacteria, wAlbA and wAlbB, occur in the Ae. albopictus population on the Black Sea coast. Total infection of Ae. aegypti and Ae. albopictus with dirofilariae was 1.8 %. Dirofilaria immitis was found only in mosquito abdomen, larvae of infective stage L3 were not found. D. repens larvae developed to the infective stage in the mosquitoes of both species.

© 2018 Ima-Press Publishing House. All rights reserved. The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- A nd anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1â (IL-1â), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: Nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment. Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®). Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI - 27.1 [23.0; 39.9], and CDAI - 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p<0.01). At week 12, the frequencies of ACR 20%, 50%, 70% improvements were 70, 55, and 5%; at week 24, these were 75, 45, and 15%, respectively. A good or moderate EULAR response at week 24 was observed in 25 and 60% of patients, respectively. At week 24, DAS28, SDAI, and CDAI remissions were achieved by 4 (20%), 2 (10%), and 1 (5%); low disease activity - by 4 (20%), 5 (25%), and 6 (30%) patients, respectively; high disease activity as measured by SDAI and CDAI remained in 3 (15%) patients. Two patients (10%) met the 2011 ACR/EULAR remission criteria at 24 weeks. Conclusion. The rituximab biosimilar Acellbia® 600 mg used in patients with active seropositive RA is clinically effective and comparable in the safety profile as shown in investigations of the brand-name MabThera® (F. Hoffman-La Roche Ltd., Switzerland) at a low dose (500 mg), as well as the first BA.