Integrative Modeling of Electrical Properties of Pacemaker Cardiac Cells

This work represents modeling of electrical properties of pacemaker (sinus) cardiac cells. Special attention is paid to electrical potential arising from transmembrane current of Na{+}, K{+} and Ca{2+} ions. This potential is calculated using the NaCaX model. In this respect, molar concentration of ions in the intercellular space which is calculated on the basis of the GENTEX model is essential. Combined use of two different models allows referring this approach to integrative modeling

Pharmacokinetic studies of new antiparkinsonian drug Rapitalam

The aim of this study was to investigate the pharmacokinetic parameters of the mGluR4 receptor blocker Rapitalam on rabbits. There was developed the method of the quantitative determination of Rapitalam in the blood plasma of rabbits using high performance liquid chromatography with tandem mass spectrometric detection. The study was performed on 12 rabbits (males, weighing between 3,300 to 3,500 g). In intragastric dosing of the substance was administered using a gastric tube in the form of suspension in water 0.9 mg/ml, 9 mg/ml, and 90 mg/ml at a dose of 0.3 mg/kg, 3 mg/kg and 30 mg/kg. The main pharmacokinetic parameters of the substance was established on rabbits that allow you to optimize the future use of it's as a potential drug for the treatment of Parkinson's diseas

Effects of bariatric surgery on bone metabolism: focusing on vitamin D

The main goal of bariatric surgery is weight loss due to fundamental differential changes in the anatomical and physiological characteristics of the gastrointestinal tract. At the same time, one of the most frequent complications of obesity surgery, especially operations associated with malabsorption, is vitamin D deficiency. Patients with obesity initially have a wide range of predisposing factors for metabolic diseases of the skeleton due to lifestyle problems. Nutrient deficiencies with high-calorie diets and a sedentary lifestyle with a tendency to wear clothing that covers most of the skin — reduces serum 25 (OH) D levels. In addition, the situation is aggravated by a decrease in the bioavailability of 25 (OH) D due to its sequestration in adipose tissue and its complete inaccessibility to the central blood flow. The consequences of bariatric surgery — a decrease in the amount of skin and malabsorption can aggravate the existing deficiency. As a result of a decrease in the level of 25 (OH) D and subsequent hypocalcemia and secondary hyperparathyroidism, negatively affect the state of bone health. The presented literature review is devoted to the problems of obesity surgery and vitamin D deficiency. The main focus is on bone metabolism associated with bariatric surgery, the causes of pre and postoperative vitamin D deficiency are discussed, and recommendations for its treatment after obesity surgery are given

To the question of the pathogenetic mechanisms of the influence of obesity on the level of vitamin D

The influence of obesity on human health, as a multifactorial and multigenic disorder, is a rather complex, interdisciplinary and at the same time extremely urgent problem of modern society. Vitamin D deficiency is one of the consequences of obesity that negatively affects a person’s life expectancy. Vitamin D deficiency is rightfully considered a silent, non-infectious metabolic pandemic of the 21st century. Its significant role in the functioning of the human body is deep and multifaceted, since vitamin D is an integral regulator of the transcriptional activity of genes that control 3–5% of the human genome. There are ongoing discussions among experts in the medical community about the negative impact of obesity on 25 (OH) D levels, and the opposite hypothesis is also being discussed, where vitamin D deficiency is considered an independent risk factor for obesity. Both external causes of the formation of vitamin D deficiency against the background of excessive deposition of adipose tissue and internal metabolic processes underlying the pathogenetic association are analyzed two pathological conditions

Evaluation of denitration of nitrocellulose by microbiological treatment for industrial waste effluents using calorimetry analysis

© 2018, Akadémiai Kiadó, Budapest, Hungary. The problem of utilization of the compounds present in the effluents of the production of cellulose nitrates (NC) is very important and complicated, and its decision is inextricably related to the environment. The process of heat release in the samples of nitrocellulose subjected to biological processing of different types was studied. Biological processing was conducted by incubation with sulfate-reducing bacteria Desulfovibrio desulfuricans BКMB-1388, microscopic fungi Fusarium solani BKM F-819, and their mixed culture. The studies were carried out on the native NC (13.38% nitrogen) and the NC processed (NCproc) using ultraviolet radiation and ozone (UV + ozone). It has been shown that the pretreatment of the NC by UV + ozone significantly increases the degree of decomposition of the NC during its subsequent biodegradation assisted by symbiotic microorganisms of D. desulfuricans and F. solani. A substantial result was achieved on the fifth day of NCproc incubation, which is promising from the viewpoint of practical applications

The Determinants of the 13-Year Risk of Incident Atrial Fibrillation in a Russian Population Cohort of Middle and Elderly Age

Atrial fibrillation (AF) is the most common arrhythmia and a predictor of the complications of atherosclerotic cardiovascular diseases (ASCVDs), particularly thromboembolic events and the progression of heart failure. We analyzed the determinants of the 13-year risk of incident AF in a Russian population cohort of middle and elderly age. A random population sample (n = 9360, age 45–69 years) was examined at baseline in 2003–2005 and reexamined in 2006–2008 and 2015–2017 in Novosibirsk (the HAPIEE study). Incident AF was being registered during the average follow-up of 13 years. The final analysis included 3871 participants free from baseline AF and cardiovascular disease (CVD) who participated in all three data collections. In a multivariable-adjusted Cox regression model, the 13-year risk of AF was positively associated with the male sex (hazard ratio (HR) = 2.20; 95% confidence interval (CI) 1.26–3.87); age (HR = 1.10 per year; 95% CI 1.07–1.14); body mass index (BMI), (HR = 1.11 per unit; 95% CI 1.07–1.15); systolic blood pressure (SBP), (HR = 1.02 per 1 mmHg; 95% CI 1.01–1.02), and it was negatively associated with total cholesterol (TC), (HR = 0.79 per 1 mmol/L; 95% CI 0.66–0.94). In women, the risk of AF was more strongly associated with hypertension (HT) and was also negatively related to total cholesterol (TC) level (HR = 0.74 per 1 mmol/L; 95% CI 0.56–0.96). No independent association was found with mean alcohol intake per drinking occasion. These results in a Russian cohort have an implication for the prediction of AF and ASCVD complications in the general population

Экспрессия интерферон-стимулированных генов у пациентов с ревматоидным артритом на фоне анти-В-клеточной терапии (предварительные результаты)

Objective: to evaluate the expression of interferon-stimulated genes (ISG) – interferon (IFN) signature – in patients with rheumatoid arthritis (RA) and its dynamics during anti-B-cell therapy.Patients and methods.We examined 20 patients with RA who received two infusions of the biosimilar rituximab (RTM) Acellbia® in a total dose of 1200 mg. Five genes were selected to evaluate IFN signature: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. The expression of IFI44L and IFIT1 could not be determined for technical reasons, and further analysis included three genes – MX1, EPSTI1, RSAD2. IFN signature was calculated as the average value of the expression of three selected genes (IFN-score).Results and discussion. The initial expression level of MX1 was 11.48 (5.45–19.38), EPSTI1 – 12.83 (5.62–19.64), RSAD2 – 5.16 (2.73–10.4) and IFN-score –10.3 (5.18–17.12), in patients with RA it was statistically significantly higher than in healthy donors: 1.26 (0.73–1.6); 1.06 (0.81–1.48); 0.93 (0.72–1.19) and 1.09 (0.92–1.42), respectively (p<0.05). The IFN-score was high in 15 (75%) patients, low in 5 (15%). The use of RTM was accompanied by a statistically significant decrease in disease activity and the level of acute phase parameters (ESR, CRP) after 12 and 24 weeks of therapy (p<0.05). In the group as a whole, as well as in patients with a moderate effect of therapy or its absence, by the 24th week of treatment, an increase in the expression of RSAD2 (p<0.05) and a tendency to an increase in the IFN-score level (p=0.06) were observed.Conclusion. In patients with RA, an increased expression of ISH was found compared to healthy donors. An increase in the expression of RSAD2 and IFN-score is observed both in patients with a satisfactory effect of RTM and with no effect. The obtained results can be important for predicting the course of the disease and personalizing therapy.Цель исследования – оценить экспрессию интерферон-стимулированных генов (ИСГ) – интерфероновый (ИФН) «автограф» – у пациентов с ревматоидным артритом (РА) и ее динамику на фоне анти-В-клеточной терапии.Пациенты и методы. Обследовано 20 больных РА, получивших две инфузии биоаналога ритуксимаба (РТМ) Ацеллбия® в суммарной дозе 1200 мг. Для оценки ИФН-«автографа» были отобраны пять генов: IFI44L, MX1, IFIT1, RSAD2, EPSTI1. Экспрессию IFI44L и IFIT1 определить не удалось по техническим причинам и в дальнейшем анализе учитывали три гена – MX1, EPSTI1, RSAD2. ИФН-«автограф» был рассчитан как среднее значение экспрессии трех выбранных генов (ИФН-score).Результаты и обсуждение. Исходный уровень экспрессии MX1 – 11,48 (5,45–19,38), EPSTI1 – 12,83 (5,62–19,64), RSAD2 – 5,16 (2,73–10,4) и ИФН- score – 10,3 (5,18–17,12) у пациентов с РА были статистически значимо выше, чем у здоровых доноров: 1,26 (0,73–1,6); 1,06 (0,81–1,48); 0,93 (0,72–1,19) и 1,09 (0,92–1,42) соответственно (р<0,05). Показатель ИФН-score был высоким у 15 (75%) больных, низким – у 5 (15%). Применение РТМ сопровождалось статистически значимым снижением активности заболевания и уровня острофазовых показателей (СОЭ, СРБ) через 12 и 24 нед терапии (p<0,05). В группе в целом, а также у пациентов с умеренным эффектом терапии или его отсутствием к 24-й неделе лечения отмечались повышение экспрессии RSAD2 (p<0,05) и тенденция к повышению уровня ИФН-score (р=0,06).Заключение. У пациентов с РА выявлена повышенная экспрессия ИСГ по сравнению со здоровыми донорами. При удовлетворительном эффекте РТМ или его отсутствии наблюдается повышение экспрессии RSAD2 и ИФН-score. Полученные результаты могут иметь значение для прогнозирования течения заболевания и персонификации терапии

Improving Methodological Approach to Measures Planning for Hydraulic Fracturing in Oil Fields

Goal of the research is development of an integrated approach to the planning of hydraulic fracturing (HF) treatment taking into account geo-technical, hydrodynamic, technological and economic criteria for the selection of wells for inclusion in the programs of HF with increasing importance of economic criteria. Stages of formation of the program for HF of the oil company are selected, systematized and analyzed. It is shown that high potential effectiveness of enhanced oil recovery method in fields with hard-to-recover reserves, on the one hand, and the complexity and high cost of application, on the other, determine the need to optimize the parameters of this business process at all stages of implementation and improve its planning methods. The priority directions for improving the hydraulic fracturing planning were justified: a clear definition of the criterion for the payback period of hydraulic fracturing activities, taking into account their technological features, improving the procedure for calculating the costs of implementing this technology and improving the reasonableness of selecting candidate wells for inclusion in the hydraulic fracturing program. Feasibility of using an additional criterion in the formation of hydraulic fracturing programs – marginal minimum cost-effective wall capacity – has been shown and a method for calculating it has been developed. The use of this criterion will allow to take into account not only technological limitations, but also limits of economic efficiency of conducting hydraulic fracturing at each specific well and, at the preliminary selection of candidate wells, exclude a priori unprofitable measures. It is advisable to take into account proposed directions for improving planning of hydraulic fracturing in the development of corporate regulatory documents, which will help to improve the quality of planning geological and technical measures, minimize investment risks, make more rational use of oil companies' resources for improving oil recovery, choosing the best management decision

CLINICAL AND IMMUNOLOGICAL FEATURES OF KIDNEY TRANSPLANT RECIPIENTS WITH CYTOMEGALOVIRUS INFECTION MANIFESTATION IN THE EARLY POSTOPERATIVE PERIOD

Aim. To optimize the management of postoperative renal allograft recipients through the introduction of methods for predicting risk of manifestation of cytomegalovirus infection on the basis of a comprehensive assessment of the clinical and immunological status. Materials and methods. We retrospectively analyzed the medical records of 303 patients with end-stage renal disease, among them – were the recipients of renal allograft – 136, among whom 29 within 2 months after the operation had clinical signs of CMV infection. Assessable "CMV syndrome", laboratory evidence of CMV infection, the incidence of antigens (genes) of HLA A, B and DRB *1, calculated goodness of fit χ2 and relative risk RR, changes MCP-1 in urine. Results. In renal allograft recipients with clinical and laboratory evidence of CMV infection in the early postoperative period, significantly more (χ2 > 3,8) met antigen B35. A positive association with CMV infection was detected also for DRB1 * 08, B21, B22, B41, A24 (9), B51 (5), DRB1*14 and DRB1*15. Protective effects possessed antigens / alleles of genes A26 (10), B14, B38 (16) B61 (40) and DRB1*16. MCP-1 levels in this group of recipients were raised to 2174,7 ± 296,3 pg/ml with a strong negative correlation with the levels of urea and creatinine in serum (r = 0,9, p < 0.001). Conclusion. Immunological markers of risk manifestation of CMV infection in recipients of kidneys in the early postoperative period are: the carriage of В35 и В55,56(22), В49(21), В41, DRB1*08 и DRB1*15, an increase of levels of MCP-1 in urine without increasing the levels of urea and creatinine in the serum

CHANGES OF CYTOKINE LEVELS DURING THERAPY WITH METHOTREXATE AND ADALIMUMAB IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS (REMARCA STUDY)

Objective: to estimate changes in cytokine profile versus disease activity in patients with early rheumatoid arthritis (RA) who use methotrexate (MTX) and adalimumab (ADA) in accordance with the treat-to-target concept. Subjects and methods. Forty-five patients (35 women; median age 53.5 [46; 59.5] years) with early RA (median dura- tion 7.0 [4.0; 11.5] months; DAS28 5.8 [4.9; 6.4]; rheumatoid factor positivity (RF+) 91%; anti-cyclic citrullinated peptide antibody positivity (ACCP) + 96%) were examined. In all the patients, MTX as the first agent was subcuta- neously used in a dose of 10 mg/week with its rapid escalation up to 20-25 mg/week. Serum cytokine concentrations were determined using the xMAP multiplexing technology before and 12 and 24 weeks after therapy. Results. Following 12 weeks of therapy, DAS28 mean value decreased to 4.33 [3.5; 5.2] (p < 0.05 vs baseline). Twenty- nine (64.4%) patients responded to treatment. It was decided to continue MTX monotherapy in 23 patients (a monotherapy group) and in 22 patients ADA was added to therapy due to its inadequate effect in accordance with the standard regimen (a combined therapy group). At 24 weeks, mean DAS28 was 2.9 [2.1; 3.6] and 19 (82.6%) patients responded to treatment in the monotherapy group. In the combined therapy group, DAS28 was 3.4 [3.2; 4.4]; nearly 30% of the patients achieved remission/low disease activity and the number of patients with the high activity of a pathological process also declined significantly (from 59.1 to 13.6%). At 12 weeks, the monotherapy group showed reduction of the level of proinflammatory (interleukin-6 (IL-6), IL-17, tumor necrosis factor-α (TNF-α)), anti-inflammatory (IL-4, IL-5, IL-9, IL-13) cytokines, chemokines (interferon induced protein-10 (IP-10)), and vascular endothelial growth factors (VEGF) (p<0.05); at 24 weeks, there were reductions in IL-6, IL-9, and IL-10, and transforming GF-bb and an increase in IL-10 concentration (p<0.05). At 12 weeks of MTX therapy, the combined therapy group displayed a reduction in IL-6, IL-1Pa, IP-10 (p<0.05); at 24 weeks of treatment (12-week ADA administration) there were decreases in proinflammatory (IL-12), anti-inflammatory (IL-9) cytokines, chemokines (IP-10, monocyte chemoattractant protein, and macrophageal inflammatory protein-1β), VEGF and an elevation of IL-10. Conclusion. Thus, the results of the investigation suggest the high clinical efficiency of therapy with subcutaneous MTX, which is associated with the lower levels of a number of proinflammatory cytokines, chemokines, and growth factors. ADA treatment is also accompanied by decreased disease activity and positive changes in the cytokine profile, by exerting a higher impact on the level of chemokines and growth factors