Репозиторий Университета

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA). Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies. Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded. Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early.

© 2018 Bentham Science Publishers. Background: This study discusses the crucial factors responsible for the progression of atherosclerotic cardiovascular disease (CVD). The interaction between the gut microbiota, heart and vessels in CVD pathogenesis is extremely complex and includes components such as direct bacterial translocation from the gut to vessels and metabolitemediated damage. To a greater extent, CVD seems to be entangled with a subtle immune system-to-microbiota interface. From among the most significant advances in recent years in this area, it is necessary to highlight the discovery of the pro-atherogenic effect of trimethylamine-N-oxide (TMAO) and changes in the activity of effector T-cells in the settings of dysbiosis. Currently, we are witnessing an explosive growth in interest in using the microbiota and interlinked cascades as a target for therapeutic interventions, including direct microbiome targeting, the attenuation of toxic metabolite-induced damage, the modulation of intestinal immunity, and downstream inhibition of systemic inflammatory pathways. Objective: In this brief review, modern strategies of microbiome-based therapies for the prevention and treatment of CVD are classified and discussed from the perspective of personalized medicine.

© 2018 Russian Transplant Society. All rights reserved. Aim. To evaluate the functioning of an implantable pediatric axial pump «DON-3» for bypassing the left ventricle of the heart in experiments on sheep. Materials and methods. Five sheeps at the age of 12–18 months performed paracorporeal installation of the children’s axial pump «DON-3» according to the scheme «left ventricle – aorta». Results. A technique was developed and 5 chronic experiments were conducted on sheep to assess the model of the children’s axial pump «DON-3». The duration of the experiments in this series averaged 9 ± 5 days. The main indicators of hemodynamics, acid-base balance were within the norm. Conducted morphological and histological studies of the kidneys, liver and lungs did not reveal the presence of zones of ischemia and thromboembolism. Conclusion. The results of this series of experiments showed satisfactory results, suggesting further research on the development of prototypes of a pediatric pump for clinical practice.

© 2018 Russian Transplant Society. All rights reserved. Tricuspid valve insufficiency is one of the most common variants of valve pathology of transplanted heart. The review is sanctified to the analysis of modern looks to on causes, potentially influencing on development of tricuspid valve insufficiency of transplanted heart, and also methods sent to declines risk his development.

© 2018 Media Sphera Publishing Group. All rights reserved. Objectives: This article reports 1-year clinical outcomes of patients with rheumatoid arthritis (RA) receiving abatacept (ABA) therapy. Materials and methods: Patients (n=91) with high RA activity (DAS28 = 5.1 ± 1.0) and an inadequate response on synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α inhibitors, 93%) were included in the study. The majority of patients were middle- Aged (49 ± 13.5) womens, RF (72.5%) and ACPA (77%) positive, with moderate functional impairment - HAQ = 1.4 (0.9-2). ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR / ACR 2011 criteria using SDAI, CDAI, HAQ and the intention to treat approach. Results: ABA led to a significant (p <0.05) decrease activity of RA. Clinical improvement according to EULAR criteria after 6 months of treatment was registered in 70.9%, after 12 months 63%. Almost a third of patients (28.7%) achieved a good response after 3 months of therapy, 39,2% - After 6 months and 39% - After 12 months. The retention rate of ABA therapy after 6 months was 77%, after 12 months - 60%. There were no significant differences between "bio-naive", 1 Bio and ≥2 Bio groups in achieving EULAR response. A good response was achieved in 38%, 38% and 43%, respectively, but the lowest number of non-responders was registered in ≥2 Bio - 38%, 36% and 43%. ABA significantly improved functional status of patients, after 12 months a marked and moderate improvement in the HAQ was achieved in 39% and 21% of patients, respectively. Adverse events (AE) were registered in 22 patients. The most frequent AE were upper respiratory tract infections - 11 (12%) patients. Conclusion: Abatacept was effective in the overall population, and in all subgroups of patients. It has shown significant improvement of clinical and functional status in patients who had an inadequate response to previous therapy. ABA has a good safety profile. AE were registered only in a small number of patients.

© 2018 ABC-press Publishing House. All rights reserved. The review is devoted to loop-mediated isothermal amplification (LAMP) - a novel molecular diagnostic method that has recently become increasingly popular. Unlike polymerase chain reaction, LAMP does not require thermal cycling; DNA or RNA amplification occurs at a constant temperature (about 65 °C) with 4 or 6 primers. This is a fast, highly-sensitive, and highly specific method, which does not require expensive equipment, where visual detection of the reaction products is performed by the unaided eye. LAMP is successfully used for the diagnosis of multiple viruses, bacteria, and other pathogens (including those in food). Moreover, it can be applied for the detection of single-nucleotide polymorphisms. Recently, a modified LAMP assay - one-step nucleic acid amplification (OSNA) - was validated for metastasis detection. OSNA was demonstrated to have almost the same sensitivity and specificity as standard diagnostic methods (sometimes even higher). Particular attention is paid to the mechanism of LAMP, primer design, and diagnostics of cancer using OSNA.

© 2018 Media Sphera Publishing Group. All rights reserved. Stomach's output part and small intestine, combining with damaging of the urinary tract is a rare systemic lupus eritematosus (SLE's) manifestation. The patient is 32 years old, suffering from SLE with damaged join, blood system, secondary antiphospholipid syndrome with pulmonary embolism in the history and formation of high postembolic pulmonary hypertension on therapy with hydroxychloroquine and low doses of corticosteroids, was hospitalized because of persistent nausea, vomiting, loss of more than 10 kg body weight 1.5 months. The research have shown the obstruction's formation of the stomach's output part, small bowel obstruction at several levels, as well as thickening of the bladder wall and the unilateral expansion of the ureter. Against the backdrop of strengthening of immunosuppressive therapy these lesions completely regressed.

© Russian Journal of Cardiology. In the article, an analysis provided of recent views on the overtraining syndrome by the data from local and foreign publications. The witness of the problem actuality is also an existence of controversial opinions and absence of clear definitions on properties of the condition. It has been revealed that the main role in pathogenesis of the overtraining syndrome do play the changes of cardiovascular, endocrine and central nervous systems. These changes are complicated and ambiguous, depend upon multiple factors, as the type of sport, specifics of exertion and loads, stage of pathophysiological process. Entraining effect of exertion, if incorrectly utilized, underestimation of current condition of a sportsman, might not lead to expected results. Moreover, non-rational application of exertion might lead to opposite effect, that is, to decrease adaptation potential and reserves, towards the edge of the condition as an overtraining syndrome, which shows phasic, progressing character, starting from fatigue and mild disorders, to persistent, rigidly reversible processes. Due to controversy, multiple stages and multifactorial of the overtraining syndrome, by now there is no unified approach to its definition, as no unified standards to its diagnostics, treatment and prevention.

© 2018 Stolichnaya Izdatelskaya Kompaniya. In the article, with regard to current clinical recommendations, the place of combined antihypertensive therapy, especially triple drugs regimens, is considered in the treatment of patients with arterial hypertension. Special focus is given to the body of evidence for the efficacy of valsartan and amlodipine, as the reference drug of angiotensin II receptor blockers and calcium channel blockers, respectively. Not only their high antihypertensive properties are demonstrated, but also a favorable effect on target-organ protection and prognosis is described. In particular, the possibilities of valsartan in reducing the severity of left ventricular hypertrophy and microalbuminuria are described, and its unique properties in the class of sartans that allow the use of this drug in patients with ischemic heart disease and chronic heart failure are emphasized. Data on the antiatherosclerotic effects of amlodipine and its proven ability to reduce cardiovascular risk are presented. Current data are presented about their use in a fixed-dose combination with hydrochlorothiazide, including real clinical practice settings. The evidence base of high clinical efficacy, safety and metabolic neutrality of the triple combination of antihypertensive drugs valsartan, amlodipine and hydrochorothiazide is presented. The issues of increasing adherence of patients to treatment when prescribing fixed-dose combinations are considered. An algorithm for the selection of antihypertensive drugs in the form of monotherapy and combination therapy of two or three drugs depending on the clinical situation (the presence of certain target-organs damages and associated clinical conditions, primarily ischemic heart disease, atherosclerosis of carotid arteries and chronic heart failure) and the severity of the additional risk of cardiovascular complications..

© 2018 Media Sphera Publishing Group. All rights reserved. Scleromyxedema is a rare mucinosis with a primary skin lesion due to diffuse mucin deposition, sclerosis, and lichenoid eruptions in the absence of hypothyroidism. The paper describes scleromyxedema cases and gives recommendations for the histological diagnosis of the disease by histochemical reactions to detect acid and neutral glycosaminoglycans.

© 2018 Media Sphera Publishing Group. All rights reserved. Objective - to study endometrial receptivity in infertile women with external genital endometriosis (EGE). Subject and methods. Clinical, morphological, immunohistochemical, and molecular genetic examinations of endometrial aspiration pipelle biopsy specimens obtained on days 22-24 of the menstrual cycle from 94 infertile women with endometriosis: 50 women with Stage I-II EGE and 44 women with ovarian endometrioid cysts (OEC). A control group consisted of 54 women with tubal peritoneal factor of infertility (TPFI) and a successful attempt at IVF. Hematoxylin and eosin-stained sections were found to contain a number of endometrial surface epithelial cells containing mature pinopods. The expression levels of leukemia inhibitory factor (LIF), HOXA-10, glycodelin A, avβ3 integrin, estrogen receptors (ER) and progesterone receptors (PR), aromatase in the superficial epithelium, glandular epithelium and endometrial stroma were immunohistochemically revealed. Forty-four patients, including 17 with Stage I-II EGE and 27 with TPFI, showed mRNA expression levels of leukemia inhibitory factor receptor (LIFR), LIF, ER1, PgR, HOXA-10, and PTEN by real-time quantitative polymerase chain reaction (PCR) with a preliminary reverse transcription PCR assay. Results. It was established that in the infertile women with Stage I-II EGE and those with OEC, endometrial receptivity was impaired, which was manifested by a decline in the number of superficial epithelial cells containing mature pinopods, as well as a decrease in the endometrial level of the key receptivity markers: αvβ3 integrin, LIF, glycodelin A, and HOXA10 and increases in the synthesis of aromatase and in the imbalance of endometrial stromal expression of ER and PR detected by immunohisto chemistry (IHC). Molecular genetic study showed lower mRNA expression levels of the HOXA-10, LIFR, and PgR genes, which confirms the data obtained by IHC. Conclusion. To assess the role of the endometrium in the development of infertility in women with EGE, it is necessary to conduct morphological and IHC studies of the molecular markers of receptivity, by determining the status of pinopods of the endometrial surface epithelium during the window of implantation.

© 2018 Saint Petersburg Pasteur Institute. All rights reserved. Nowadays sepsis is grave complication of infection end the cause of death reanimation. In this survey, we would like to emphasize the importance of the control over the activation over the compliment system. It has been proved of animal model a complement one of the key role in the development of hyperactive immunity response, later resulting in violation of immunity homeostasis. Mice which had C3-/-, C4-/-deficit, aft receiving a LPS dose intraperitoneallis showed a better survival to compare with the control group of animals. There exist clinical data which confirm active participation of the compliment in the chain of the septic process. The research showed the patient affected by sepsis, had protein C3 and C4 concentration correlating which mortality at the time of diagnosis. The is chemoattractants, protein C3a and C5a, turn tube the result of complements pathway activation. The chemoattractants, provoke the extraction a big number of cytokines. Vessels permeability increase and DIC-syndrome activation wis it, multiple organ dysfunction develops. Ishemiareperfusion launch triggers aseptic inflammation, which appears decentralization and DIC-syndrome. C1-INH controls the work of classical way complement and Hemostasis System. Researchers the deficit in C1-INH animals and patients affected bay sepsis, which is proved in laboratory and clinics. The remedy C1-INH (Berinert, CSL Behring) appeared over 25 years ago and was used and therapy hereditary angioedema. For the lasted years we accumulated a considerable quantity of fasts of C1-INH use which after pathologies: heart attack, Ischemia-reperfusion injury, trauma provoked by cardiopulmonary bypass. The use of C1-INH on animal models septic in clinical research their efficacy and safety.

© 2018 ABV-Press Publishing House. All rights reserved. Bruxism is stereotypical movements of the mandibula accompanied by grinding or clenching of teeth. Bruxism has 2 circadian manifestations: during sleep (nocturnal bruxism) and during wakefulness (diurnal bruxism). Etiology of the disease is unclear but occlusal disharmony, stress management, basal ganglia dysfunction, and genetic factors are being discussed. An association between bruxism and other motor disorders such as Parkinson's disease, oromandibular dystonia, Huntington's disease, as well as some drugs, is observed. For bruxism diagnosis, questionnaires, clinical examination, polysomnography, electromyography, and brux checkers are used. The leading treatment method for bruxism and accompanying dysfunction of the temporomandibular joint is local administration of botulinum neuroprotein into the temporal, masseter, and lateral pterygoid muscles.

© 2018 Slovak Academy of Sciences. All rights reserved. Given the fact that oxidative stress response induced by training/detraining has still not been clarified and may be influenced by gender, the aim of our investigation was to compare the effects of swimming training and detraining on oxidative and antioxidative parameters in rats, with a special focus on sex differences. Wistar albino rats (n = 64) were divided into 4 groups: control, trained group, groups exposed to 2 and 4 weeks of detraining. Each group included two subgroups: males and females. After sacrificing, hearts were isolated and retrogradely perfused according to Langendorff technique. Levels of superoxide anion radical, hydrogen peroxide, nitrites and thiobarbituric acid reactive substances were measured in plasma and coronary venous effluent, while reduced glutathione, activities of superoxide dismutase and catalase were measured in erythrocytes. Our results indicate that swimming training doesn't promote oxidative damage, nor act protectively within the heart. However, 2 and 4 weeks of detraining led to a partial lost in exercise-induced adaptation. It seems that moderate-intensity physical exercise of sufficient duration leads to beneficial adaptations, which may be partially lost during detraining period. Positive antioxidative effects of training remained longer in males. Findings of present study may help in elucidation of training and detraining effects on modulation of redox homeostasis, especially from aspect of gender differences.

© 2018 Lippincott Williams and Wilkins. All rights reserved. The application of the screening techniques for the purpose of chemical toxicological and forensic chemical analysis has the objective to detect and identify the life-threatening substances within the shortest possible time period for distinguishing them from a large number of other chemical compounds amenable to the toxicological evaluation. Such methods acquire special importance for forensic chemical expertise in the cases of a negative result of the primary examination. The present article provides information about the history of development of the screening techniques.

© 2018, Media Sphera Publishing Group. All Rights Reserved. Mutant forms of the gene IDH1 progress significantly slower, have a lower risk of neoplastic transformation, and generally, mutations of this gene have a pronounced anti-oncogenic effect. At the same time, almost all mutations are quite stereotyped (98,9%) and occur in the same region of the gene — R132H mutations. IDH1 gene mutations is a complex multi-layered process, which is a completely new, not previously described anti-oncogene activation mechanism of intracellular protection. The reason that there is a mutation in the tumor cells is associated with de novo blocking differentiation processes and development of brain cells in the development process, as evidenced by severe cerebral hypoplasia in patients with congenital forms of this mutation. A completely new mechanism of antitumor protection has been described — stereotypical IDH1 gene mutation is a gene, in fact, is a key event, causing a cascade of further anti-oncogenic mechanisms in brain gliomas.

© 2018 by the Serbian Biological Society. The aim of present study was to investigate the difference between α-linolenic acid (ALA, omega-3) and linoleic acid (LA, n-6) on the redox status and cardiac function of the isolated rat heart. ALA or LA were administered for 6 weeks by gavage to all animals, which were randomly divided into 4 groups: male rats treated with a linoleic acid (M-LA), dose of 7.3 mg/kg/day; female rats treated with a linoleic acid (F-LA), dose of 7.3 mg/kg/day; male rats treated with an α-linolenic acid (M-ALA), dose of 165 mg/kg/day; female rats treated with α-linolenic acid (F-ALA), dose of 165 mg/kg/day. Using the Langendorff technique, markers of heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dp/dt max, dp/dt min), systolic and diastolic left ventricle pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). We measured the concentrations of prooxidative markers: nitrites (NO2-), superoxide anion radicals (O2-) and hydrogen peroxide (H2O2), as well as the index of lipid peroxidation (TBARS) in the plasma and effluent. In the lysate, we measured the concentrations of reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). ALA more negatively influenced the isolated rat heart, especially in females. In contrast, the administration of LA was linked to more prominent oxidative stress, while the application of ALA was associated with improved activity of the antioxidative defense system (with better values in males).

© Bionika Media Ltd. Objective. To assess the immediate results of laparoscopic radical hysterectomy for Stages IB2 and IIB cervical cancer (after neoadjuvant chemotherapy) and for the early stages of the disease. Material and methods. The paper presents the results of treating 59 patients with cervical cancer who have undergone Piver type III laparoscopic radical hysterectomy, including 33 patients with early stages (IA2, IB1, IIA1) of the disease and 26 patients with its locally advanced forms (IB2, IIA2, IIB) after neoadjuvant chemotherapy. Results. The histopathological parameters of radical surgery (the number of lymph nodes, the level of removal of the parametrium and a vaginal cuff) did not differ at the early and locally advanced stages of cervical cancer. Conclusion. Laparoscopic radical hysterectomy after neoadjuvant chemotherapy for Stages IB2–IIB cervical cancer is an effective method for the surgical treatment of patients.

© 2018, Peter the Great St. Petersburg Polytechnic University. Nanocomposite layers consisting of an acrylic paint and single-walled carbon nanotubes (∼1.5 wt.%) have been investigated. The investigated samples had a disk shape with a diameter of 20-30 mm and a thickness of 2-50 μm. After exposure in water for 350 h, the layer mass remained almost invariable (a mass loss of ≤ 1.5%) and the layer samples exhibited high adhesion to glass substrates and a conductivity of ∼ 40 S/m. The layers consisting of the nanotubes and acrylic paint exfoliated from the substrates for ∼1 h. After heat treatment at a temperature of 140 °C, all the layers exhibited a semiconductor-type temperature dependence of the resistance. The prospects of using these layers in various medical products, e.g. implants for wireless energy transmission, have been discussed.

© 2018 Nutritec. All rights reserved. Specialized sports nutrition is one of the most important factors in the extension of the functional potential of athletes, providing adaptive resistance to physical stress, which determines the high physical performance and prolongs athletic longevity of the athletes. The study involved 30 skiers-racers (the average age of 19.5±1.8 years). 12 skiers of the main group within 21 days consumed a specialized food product, obtained on the basis of fermented milk whey containing amino acids, several vitamins, minerals and trace elements, live culture of lactic acid bacteria: L. lactis, L. thermophilus, L. bulgaricus (1.2 × 10s CFU/cm3). The control group consisted of 18 skiers, those taking the placebo (food starch of the same consistency). After a course of product intake, blood level of hemoglobin increased by 6%, of leukocytes - by 10% due to an increase in the number of granulocytes by 32%, and segmented neutrophils by 16% (p<0.05), there was a tendency to increase the number of red blood cells by 7% with a significant decrease in lymphocyte count by 19%. Erythrocyte sedimentation rate in blood of the skiers from the comparison group increased by 41% (p<0.05), while in the athletes of the main group it decreased by 16% (p>0.05). After product intake it has been established by the method of laser Dopplerflowmetry that there was a tendency to increase blood perfusion by 15%, a statistically reliable increase in the flux by 53%, which is based on the improvement of the internal mechanisms of microcirculation regulation. According to the mathematical analysis of cardiac rhythm, centralization of regulation decreased while the activity of an autonomous mechanism for controlling the work of the heart increased. The revealed functional changes ensured an increase of absolute (by 31%, p<0.05) and relative (by 33%, p<0.05) physical performance and aerobic endurance of skiers, contributed to the improvement of short-Term memory. The conclusion is made about the expediency of the intake of the specialized food product to enhance the adaptive capacity of athletes under the influence of systematic physical loads.