Репозиторий Университета

© 2018 Russian Transplant Society. All Rights Reserved. Blood level of transforming growth factor beta 1 (TGF-β1) is associated with liver function and immune homeostasis, which suggests it as a potential biomarker for immunosuppressant tacrolimus dose requirement at liver transplantation (LT). Aim. To evaluate diagnostic efficacy of TGF-β1 blood level at determination of individual tacrolimus dose requirement in children at LT. Materials and methods. 89 children with end stage liver disease aged from 3 to 73 months were examined. Children underwent living related LT, then the recipients received 2–3 component immunosuppressive therapy, including tacrolimus. Blood concentration of tacrolimus and TGF-β1 was measured by ELISA. Results. TGF-β1 blood level in children before LT was significantly lower than in healthy children: 3.7 (1.3–8.4) and 19.3 (12.6–25.5) ng/ml, p = 0.001. A month after LT, its concentration increased to 8.1 (1.8–15.3) ng/ml (p = 0.02). A year after LT, the cytokine level remained higher than before transplantation: 6.6 (1.9–12.6) ng/ml, p = 0.01. TGF-β1 level did not correlate with tacrolimus blood concentration, determined 12 hours after the last administration of the drug, neither a month, nor a year after transplantation. At the same time, the cytokine level one month after LT was associated with a tacrolimus daily dose one year after the operation (r = –0.23, p = 0.04). In the recipients, who received smaller daily doses (0.4–2.5 mg) of tacrolimus, TGF-β1 level was higher than in those receiving large doses (3.0–6.0 mg) of the drug: 9.1 (2.6–16.2) ng/ml vs. 4.2 (1.3–9.2) ng/ ml, p = 0.04. Evaluation of diagnostic efficacy of the TGF-β1 level as a test for the detection of tacrolimus dose requirement showed that the area under the ROC curve (AUC) was 0.66 ± 0.07; 95% CI [0.53–0.79], the sensitivity and specificity of the test were 60 and 74% at threshold value 6.7 ng/ml. Relative risk of higher tacrolimus dose requirement was 3.14 ± 0.48; 95% CI [1.24–7.96]. Conclusion. TGF-β1 blood level in one month after LT less than 6.7 ng/ml is 3 times higher risk factor of tacrolimus dose requirement more than 3.0 mg per day. The likehood of the test is 66%, the sensitivity and specificity – 60 and 74%.

© 2018 Park-media, Ltd. In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. The second one is characterized by a significantly worse estimated binding affinity and is reactive. Thus, echothiophate combines the features of two types of inhibitors: competitive and suicidal. This observation will help clarify the kinetic reaction scheme in order to accurately assess the kinetic constants, which is especially important when designing new butyrylcholinesterase variants capable of full-cycle hydrolysis of organophosphorus compounds.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To estimate a clinical picture of the pertussis-like illnesses caused by Bordetella holmesii. Patients and methods. The research is conducted in Infectious diseases clinical hospital No 1 of the Moscow Department of Healthcare. Under observation there were 7 children (from 1 month to 15 years). Examination is conducted by means of PCR-RT with the primers the IS481, ptxA, IS1001 and hIS1001 for identification of fragments of genomes of B. holmesii, B. pertussis and B. parapertussis, and by means of the AmplySens® Bordetella Multi-FL test system for identification of B. pertussis, B. parapertussis and B. bronchiseptica DNA. Results. At 6 children the disease proceeded an easy form, from them in five children in clinical samples DNA of B. holmesii also is found in one child – B. holmesii and B. parapertussis DNA; at 1 child (1 month) the disease proceeded in a medium-weight form, and B. holmesii and DNA of B. pertussis is found in him in a sample. In a clinical picture of the pertussis-like illnesses caused by B. holmesii at all children the symptoms characteristic of the course of the whooping cough caused by B. pertussis were observed: whooping cough, with office of a transparent phlegm, with hyperaemia of the person. But the disease proceeded in easier form, the health of the child didn't suffer, respiratory frustration weren't observed, duration of a disease was much shorter. Conclusion. The research demonstrates circulation of B. holmesii in the territory of the Russian Federation. At allocation of B. holmesii pertussis-like symptoms are noted, however easier current including at children of early age is registered.

© 2018, Dynasty Publishing House. All rights reserved. Objective: to assess diagnostic value of serological tests for Helicobacter pylori detection and to evaluate its feasibility in pediatric gastroenterology. Patients and methods. This study included 850 children aged between 2 and 17 years undergoing inpatient treatment in the Department of Gastroenterology. Participants were diagnosed with chronic gastritis, duodenitis, or esophagitis. All patients underwent a comprehensive examination that included standard blood tests, urine tests, stool tests, fibroesophago and abdominal ultrasonography. H. pylori infection was diagnosed using both invasive and non-invasive methods. Results. Stool tests for H. pylori were positive in 43% of children, which is lower than the estimated infection rate in the Russian population (60%–80%). Analyzing the sensitivity and specificity of various methods for H. pylori detection, we found that the HELPIL test, based on determinig urease activity in the gastric biopsy, was the most accurate one among those evaluated. Serological detection of H. pylori-specific IgM antibodies demonstrated low sensitivity and specificity (32%). However, the analysis of the test results in various age groups showed that this test is highly-sensitive (97%) in children under the age of 6 years. Conclusion. Our findings can be explained by age-related characteristics of the immune response and by the fact that colonization of the gastrointestinal mucosa by H. pylori in children occurs during the development of immunological tolerance to microbiota, which limits inflammatory responses to H. pylori and promotes long-term persistence of bacteria in mucous membranes resulting in chronic inflammation. We recommend paying attention to age-related characteristics of the immune response when choosing a diagnostic option.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Steady increase in the prevalence of chronic kidney disease (CKD) is a serious public health problem, since CKD potentially leads to the development of end-stage renal disease (ESRD) that requires high-cost replacement therapy and is closely associated with increased risk of developing cardiovascular diseases (CVD), which are the cause of death in most patients. Progression of renal dysfunction and development of CVD are significantly affected by hyper- and dyslipidemia. This review contains results of studies evaluating the effect of hypolipidemic therapy on reduction of cardiovascular risk and slowdown of renal dysfunction in patients with CKD at pre-dialysis and dialysis stages of renal failure, as well as in patients with kidney transplant. In addition, recommendations on nutrition and new therapeutic approaches to lipid-lowering therapy in patients with CKD, as well as prospects for the usage of new hypolipidemic drugs are also presented.

© 2018 Izdatel'stvo Meditsina. All Rights Reserved. Introduction. Alzheimer's disease (AD) is the most common neurodegenerathe disease in the population. Often, patients with AD have a combined brain lesion of vascular etiology (cerebral microangiopathy). Arterial blood spin labeling (ASL - Arterial spin labeling) is one of the most modem and promising methods for quantifying cerebral perfusion in patients with AD. Objective. To assess regional cerebral blood flow (CBF) using the ASL method in patients with AD with chronic cerebral ischemia - cerebral microangiopathy (CMA) and without it. Material and methods. A group of 20patients (mean age 66 ± 10 years), consisting of 11 patients with AD without CAIA and 9patients with AD with CMA, was examined. The study was conducted on a Siemens Magnetom Skyra magnetic resonance imaging scanner with a magnetic field induction of3T. The examination protocol included an impulse sequence of arterial blood spin labeling. Using the software for postprocessing data processing Olea Medical Sphere 3.0, the indicators of regional cerebral blood flow in various parts of the gray matter of the brain were measured in a manual mode. A neuro-psychological study was performed, confirming a presence of mild to moderate dementia in all patients. Results. A decrease of CBF was revealed in AD patients with CAIA in comparison with AD patients without CMA. The lowest CBF were found in the upper temporal; middle temporal; occipital-temporal; upper frontal and angular gyrus. No correlation was found between CBF measures and neuropsychological results. C onclusion. ASL is a sensitive method in assessing cerebral perfusion in AD patients.

© 2018 Ima-Press Publishing House. All Rights Reserved. Daytime sleepiness is one of the clinically significant non-motor manifestations of Parkinson's disease (PD). One of its insufficiently studied aspects is a relationship between daytime sleepiness and nighttime sleep disorders. Objective: to clarify the clinical characteristics of PD in patients with different types of daytime sleepiness and to estimate of the ratio of daytime sleepiness to clinical and polysomnographic characteristics of nighttime sleep in patients with advanced stages of PD. Patients and methods: The investigation included 110 patients (56 men and 54 women) (mean age, 63.78±0.6 years) with PD (Hoehn and Yahr stage 2.6±0.2; disease duration, 6.3±3.2 years) without dementia. All the patients received therapy with levodopa at a mean daily dose of 667.8 mg; 98 of them had the drug in combination with dopamine receptor agonists at a stable dose. The unified PD rating scale, the PD sleep scale (PDSS), and the Epworth sleepiness scale (ESS) were applied. Nocturnal polysomnography (PSG) and the multiple sleep latency test (MSLT) were performed. Results and discussion: There was daytime sleepiness in 44% of the patients: permanent sleepiness in 15%, sudden daytime sleep attacks (along with low daytime sleepiness (ESS) in 14%, and permanent drowsiness concurrent with sleep attacks in 15%. The PSG findings showed a decrease in sleep efficiency, an increase in the duration of the first stage of sleep, a reduction in the duration of the second and third sleep stages, an extension of rapid eye movement (REM) sleep latency, and frequent awakenings (sleep fragmentation). PSG also demonstrated REM sleep behavior disorders (RBD) in half of the examinees. Patients with sleep attacks differed from those with permanent drowsiness without sleep attacks with more severe sleep disorders (PDSS) and shorter sleep latency (MSLT). Patients with the RBD phenomenon had shorter sleep latency (MTLS) than those without this parasomnia. Patients with moderate or severe sleepiness (ESS scores of >10) differed from those with milder drowsiness (ESS scores of =10) and a lower representation of the third sleep stage. Conclusion: There is evidence for the association of daytime sleepiness in PD with reduced efficiency, changes in the nighttime sleep pattern, and RBD.

© Izdatel'stvo Meditsina. All rights reserved. In the article, an overview of the information on the method and application technology of SWOT (Strengths, Weaknesses Opportunities, Threats) analysis is presented. The specific characters of the method, the object domain of its application, the task, the methodology are disclosed. An interesting idea is the scheme of the options used to achieve more complete benefit from the method. The strengths and the shortcomings of the SWOT analysis noted by experts in the field of its application are given. Further on, the authors propose an innovative technology for using the SWOT model to develop personalized forecasting, preservation, development, and management of health, based on the provisions of the functional direction of genetics - phenomics. The advantages of technology, the urgency of its application are revealed. The new technology is based on provisions of the development of the theory of the essential adaptation. To ensure the state of health the functioning level of the body's systems must be consistent with the optimality, namely with their response norms, which determine the individual phenotype. In the process of the organism adaptation to the conditions of the external environment, the central nervous system (it's a known fact) and the significant body system (the system with the maximum response norm), determining, respectively, the specific and nonspecific responses of the organism will be released by their activity. In the interaction of body systems, it is important to take the ordering into consideration. Dominant systems can actively involve other systems of the body to the process of adaptation according to the principle of the interaction with them, by strengthening or decreasing their activity. Taking into account the direction of interaction (inhibition, toning), this fact becomes important for understanding the pathogenesis of diseases, their targeted prevention, and treatment. A comprehensive record of the mechanisms of the formation of a specific and nonspecific reaction is used in the interest of identifying and effectively preventing functional disorders in the body. The SWOT analysis technology of personalized forecasting, preservation, development and health management eliminates the main drawbacks of SWOT analysis. On the other hand, the SWOT analysis technology helps to expand the range of application of phenomics, depending on the opportunities and threats of the environment.

© 2018 Bentham Science Publishers. Atherothrombosis-related diseases are one of the world’s leading causes of mortality, and thus the search for new therapeutic approaches in this area remains a very urgent task. Modern pharmacogenomic technologies make it possible to obtain valuable data on disease pathogenesis and optimal therapeutic approaches. One promising research direction is the study of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis. This review summarizes the recent evidence and suggests that systematic works in this area are creating new and promising opportunities in the treatment of patients with cardiovascular diseases.

© 2018 Media Sphera Publishing Group. All rights reserved. Chronic obstructive pulmonary disease (COPD) and its exacerbations remain an important problem of clinical medicine. Aim. To assess the quality of medical care provided in large Russian hospitals to patients with COPD exacerbation. Materials and methods. The study included patients with acute exacerbations of COPD hospitalized into three large clinical hospitals in Moscow. The diagnosis of "COPD exacerbation" was established in accordance with current clinical recommendations. We collected the data about patients’ demography, clinical signs and symptoms, blood gas analysis, chest radiography, drug therapy, oxygen therapy and respiratory support. The follow-up period was 90 days. The obtained data were compared with the data of patients from the multicenter study "European COPD Audit". Results and discussion. The leading clinical symptoms in COPD exacerbation were dyspnea (95.4%) and sputum production (60.7%). The majority of patients with COPD received short-acting β2-agonists (77.4%), systemic steroids (85.1%), antibiotics (79.0%) and theophyllines (48.1%). Noninvasive ventilation was performed in 8.6% of patients, oxygen therapy – in 23,8% of patients, pulmonary rehabilitation – in only 6,2% of patients. Chest radiography was performed in 97.9% of patients, pulmonary function tests – in 79.8%, blood gases analysis – in 19.3% of patients. The mean duration of hospitalization was 18.2±3.9 days, repeated hospitalization within 90 days occurs in 36.2% of patients. In-hospital mortality was 3.3%. Conclusion. Based on the results of the study practical recommendations for improving the quality of medical care in acute exacerbations of COPD are proposed.

© 2018 Media Sphera Publishing Group. All rights reserved. Cornea verticillata is the typical sign of ocular involvement in Fabry disease and manifests by the whorl-like, linear opacities in the inferior part of the cornea. Aim. To study the frequency of cornea verticillata in patients with Fabry disease and it’s relation to the severity of the disease and the types of mutation in the GLA gene. Materials and methods. We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (<20), moderate (20–40), and severe (>40) clinical categories. Results and discussion. At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. Conclusion. Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Nowadays an invasive evaluation of fractional flow reserve (FFR) is one of the main methods used for detecting lesions that cause ischemia. Invasively obtained FFR <0.75 has the specificity of 100%, and FFR >0.80 has the sensitivity >90%. Recent achievements in computational fluid dynamics and computer simulations allow noninvasive assessment of FFR using data obtained by CT angiography performed according to standard protocol at rest without additional radiation, modification of image acquisition protocols, or added medications for vasodilatation. The present review covers the results of the DISCOVER, the NXT, the DEFACTO and the PLATFORM randomized multicenter studies as well as the prospects of using a noninvasive method for measuring FFR developed by specialists of the Institute of Numerical Mathematics in collaboration with specialists of the I. M. Sechenov First Moscow State Medical University.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review summarizes the state-of-the-art in the problem of assessment of the safety of domperidone - a prokinetic and anti-emetic drug belonging to those most widely used in clinical practice. Special attention is devoted to the potential cardiotoxicity of domperidone, mechanisms of adverse effects development, and risk factors. For reducing the risk of development of dose-dependent side effects, new drugs have been created and used so as to maintain the active agent concentration in the blood plasma within the therapeutic range. Another method of increasing the efficacy and safety of domperidone treatment is based on the potentiation effect. An example is the use of domperidone in a fixed combination with omeprazole (Omez-DSR), in which a the prokinetic is present in a modified release form, which ensures uniform delivery of the acting agent into blood flow (without drug concentration +AJM-peaks+AJQ-related to increased risk of dose-dependent adverse drug reactions.

© 2018, ABV-Press Publishing House. Attention deficit hyperactivity disorder (ADHD) is the most common cause of behavioral disorders and learning difficulties in preschool and school-age children. Patients with ADHD are often diagnosed with concomitant diseases, which creates additional diagnostic and therapeutic challenges and leads to a more significant reduction in the quality of life. ADHD is often associated with epilepsy: ADHD manifestations are more common in individuals with epilepsy, and vice versa, patients with ADHD are more likely to have epilepsy. The estimated prevalence of ADHD in children is 7-9 %, whereas in children with epilepsy, it reaches 20-50 %. Epilepsy is also one of the most common diseases in children (affecting approximately 1 % of the pediatric population), which is often aggravated by concomitant diseases, including cognitive, behavioral and emotional disorders. Various factors, such as characteristics of epileptic process and lesions in particular portions of the brain, can underlie the development of ADHD in epilepsy. Epileptiform activity and adverse effects of antiepileptic drugs can also play an important etiological role. Some antiepileptic drugs (such as barbiturates) may cause symptoms similar to those in ADHD (in this case, inattentiveness and hyperactivity shall be considered as adverse events that can be reduced or eliminated after cessation of the drug) or exacerbate ADHD symptoms in patients with these disorders. Therefore, the drugs with no negative impact on concomitant diseases or with a positive therapeutic effect for both diseases are preferable in these cases. High prevalence of the ADHD/epilepsy combination leads to a greater reduction in the quality of life, suggesting high relevance of this problem and requiring a revision of therapeutic approaches.

© 2017 Izdatel'stvo Meditsina. All rights reserved. Chronic hepatitis B is caused by a persistent form of hepatitis B virus, covalentiy closed circular DNA (cccDNA). Stability of cccDNA is associated with intracellular localization of cccDNA and formation of minichromosome, regu-lated by epigenetic mechanisms. One of the key mechanisms in epigenetics is methylation of DNA on CpG islands. Expression levels of DNA-methyltransferases (DNMTs) in chronic hepatitis B patients were shown to be upregu-lated. Nevertheless, the role of DNMTs in the life cycle of HBV and their effects on the cell remain elusive. In this review, we discuss latest achievements on the role of DNMTs in chronic hepatitis B and HBV in vitro models.

© 2017 Izdatel'stvo Meditsina. All rights reserved. The enzyme-linked immunosorbent assay (ELISA) and the neutralization test (NT) are often used to determine the level of seropositive population and to evaluate the immunogenicity of vaccines. ELISA provides information on the total pool of antiviral antibodies, while NT allows the antiviral protection level of a person to be estimated. It is assumed that the 1: 100 titer in ELISA and the 1: 10 titer in NT are protective. Obviously, the ratio of the total pool and virus neutralizing antibodies can vary as a result of natural immunization or vaccination. In this study, two methods were used to study the blood serum samples taken in a group of inhabitants of the Sverdlovsk region aged from 1 to 60 years. The samples were collected before immunization and 30 days after two immunizations with inactivated vaccines against tick-borne encephalitis of different manufacturers. Immunizations were performed either according to a standard scheme (30-day interval between immunizations), or according to an emergency scheme (14-day interval). It was shown that the data on the presence of antiviral antibodies in protective titers obtained by ELISA and NT were consistent in more than 85% of cases. The discrepancies between the data are due, in the first place, to the difference in the sensitivities of the two methods. The proportion of seropositive people according to NT data is always greater than that according to the results of ELISA. Nevertheless, among 174 children, about 5% of recipients after a double immunization were seropositive according to ELISA, but did not have neutralizing antibodies in protective titers.

© 2019, Privolzhsky Research Medical University. All rights reserved. The aim of the study was to assess the efficiency of the method for registration of video fluorescence of 5-ALA-induced protoporphyrin IX in stomach and esophagus diseases, to adapt it for clinical conditions, i.e. for conducting differential diagnosis and detecting precancer conditions, and to formulate recommendations on the best photosensitizer doses and time of application in order to make the diagnostic procedure for these diseases more accurate. Materials and Methods. Registration of fluorescence for diagnostic purposes was performed on 57 patients with gastropathology (mainly with stomach cancer) with the help of single-channel (n=50) and dual-channel (n=7) laser video fluorescence registration systems. The study was performed using 5-aminolevulinic acid (5-ALA) (Alasens). 39 endoscopic, 18 intraoperative/laparoscopic investigations, and 7 studies on the macropreparation have been performed. Results. When both systems were used, no fluorescence was registered in cases of stomach ulcer, chronic gastritis, massive tumor necrosis and blood admixture in the stomach as well as in the patient with subcompensated stenosis and a stented output section of the stomach without serous membrane invasion and low 5-ALA concentration. In all other cases, a distinct fluorescence was recorded, the data of which may be used for establishing exact diagnosis and choosing further treatment tactics. Conclusion. Laser video fluorescence technique is a promising method for differential diagnosing and definition of the tumor extension process in the stomach and esophagus which can be used as an express method in diagnostically complex cases.

© 2018, Bionika Media Ltd.. All rights reserved. Objective. To improve cervical cancer screening programs via clinical introduction of a diagnostic vaginal swab self-sampling test for the detection of high-risk human papillomavirus (hrHPV). Subjects and methods. A total of 455 residents of the Lipetsk Region were examined; vaginal swabs tested for HPV were taken both independently by a woman with a Qvintip device and by a gynecologist with a universal urogenital probe. The women were asked whether it was convenient for them to self-collect a vaginal swab. Results. In the surveyed sample of 455 women, there were 35 (7.7%) cases of hrHPV identified on the swabs collected by the Qvintip and 38 (8.4%) women with hrHPV detected on those taken by the physician, out of them 26 (68.5%) women had atypical squamous cells of undetermined significance. 70.3% of women preferred the Qvintip self-sampling method. Conclusion. The Qvintip self-sampling method for hrHPV testing shows high diagnostic efficiency, simplicity, and ease-to-use. The method may be recommended for the detection of hrHPV to increase cervical cancer screening coverage.

© Allerton Press, Inc., 2018. A technique of extracting cotinine in urine and wastewaters, followed by its quantitative determination, using high performance liquid chromatography combined with tandem mass-spectrometric detection is presented. The method is characterized by low detection limits and high levels of efficiency and sensitivity. The optimal conditions for the solid-phase extraction of cotinine from urine and wastewaters are found. This technique makes it possible to reliably estimate the content of cotinine in the urine of active and passive smokers and in wastewaters.

© 2018 Media Sphera Publishing Group.All Rights Reserved. The article describes the clinical observation with an unfavorable outcome of the generalized form of salmonella infection caused by Salmonella typhimurium group B in a woman of 60 years without immunodeficiency, complicated by the development of multiple abscesses of the lower parts of abdominal cavity, probably of appendicular origin. In a short literary review, the pathogenetic mechanisms that contribute to the formation of generalized and extraintestinal forms of salmonella infection are discussed.