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CELL SURFACE AMYLOID PROTEINS OF MICROORGANISMS: STRUCTURE, PROPERTIES AND SIGNIFICANCE IN MEDICINE
стр.4-12
Rekstina V.V., Gorkovskii A.A., Bezsonov E.E., Kalebina T.S.
This review summarizes data which describe properties of microbial cell surface amyloids proteins. Definitions of amyloids and microbial functional amyloids are given. The review provides numerous examples of research in which the presence of amyloid-like properties in microbial cell surface proteins is demonstrated convincingly. Studies of the important role of pili, curii, tafi and some other bacterial fibrillar proteins in host colonization are reviewed. Data on amyloid proteins of yeast cell surface, their properties and potential association with candidiasis development are summarized. This review also appeals to experts in biology and medicine in an attempt to draw their attention to the issue which is increasingly discussed in scientific work at present, namely to a possible role of bacterial extracellular matrix amyloids and amyloid proteins of eukaryotic microorganism surface, yeast in the first place, in the development of amyloidosis in animals and humans.
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NEURODEGENERATIVE CHANGES INDUCED BY INJECTION OF β-AMYLOID PEPTIDE FRAGMENT (25-35) IN HIPPOCAMPUS ARE ASSOCIATED WITH NGF-SIGNALLING ACTIVATION
стр.13-18
Stepanichev M.Yu., Ivanov A.D., Lazareva N.A., Moiseeva Yu.V., Gulyaeva N.V.
β-amyloid peptide (Ap) is an important component of the neurodegeneration mechanism in Alzheimer's disease. This work investigates the effect of intrahippocampal injection of Aβ(25-35) fragment on nerve growth factor (NGF) signalling. Aggregated Aβ(25-35) was injected into rat dorsal hippocampus. Rats in the control group received injections of the peptide with an inverted amino acid sequence and a solvent. It was shown that Aβ(25-35) induces neuron death in rat hippocampus. Neurodegeneration was accompanied by a statistically significant increase (p
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CLARIFICATION OF THE STATUS OF SOME MUTATIONS CONSIDERED PATHOGENIC, BY HARMLESS MUTATIONS ATTRIBUTES
стр.19-22
Borisevich D.I., Shatalova L.V., Korostin D.O., Minsky V.V.
Prediction of mutation pathogenicity and its effect on the phenotype is an important task of modern bioinformatics. This task is particularly difficult in regard to single nucleotide polymorphisms, as their effect is very hard to predict. Information on pathogenic mutations is provided by curated databases such as Online Mendelian Inheritance in Man (OMIM) and The Human Gene Mutation Database (HGMD) which include data from experimental works. However, as different authors interpret the term “mutation pathogenicity” differently, it is necessary to double-check data before using them. We have assessed HGMD database quality using the most common bioinformatic tools, namely, snpEff, polyphen2 and SIFT. Our study relied on the characteristics specific for harmless mutations: high frequency in a population, weak effect on amino acid sequence of a protein, low pathogenicity as computed by the utilities used in the study. As a result, we have identified clearly harmless variants among those in the mutation database, as well as ambiguous ones in which a mutation type depends on characteristics and tools used for the analysis.
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T-CADHERIN GENE POLYMORPHISM IS ASSOCIATED WITH CORONARY HEART DISEASE MANIFESTATIONS
стр.23-29
Balatskiy A.V., Chotchaeva F.R., Pinevich Yu.S., Samokhodskaya L.M., Tkachuk V.A.
A number of studies have shown that a -encoded T-cadherin protein, which is a receptor for low density lipoproteins and adiponectin, an adipocyte hormone, is associated with atherosclerosis and coronary heart disease (CHD) development. Some single nucleotide polymorphisms in gene affect the expression of T-cadherin and the levels of adiponectin and blood plasma lipids, but the connection between these polymorphisms and CHD development has not been studied yet. In this work the role of and single nucleotide polymorphisms in CHD development and its manifestations was investigated. The study enrolled men under 55 years of age: 79 patients with stable effort angina with no prior myocardial infarction, 107 patients with prior myocardial infarction being the first manifestation of CHD, and 99 healthy subjects. All subjects were clinically examined; laboratory tests and genotyping were conducted. The results of genotyping were evaluated using SNPStats on-line software. This study has not found a connection between gene polymorphisms and CHD development. However, it was shown that polymorphism is associated with the specifics of the disease onset: GT genotype was detected in 13 (16.5 %) patients with stabile effort angina and only in 3 (2.8 %) patients with myocardial infarction (odd ratio of 7.54; 95 % confidence interval of 2.01-28.35). Thus, the study demonstrates that gene polymorphism can affect atherogenesis and CHD manifestations.
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DIAGNOSTIC ADVANTAGES OF A LONG-TERM HOLTER ECG MONITORING COMPARED TO A STANDARD 24-HOUR MONITORING
стр.30-34
Longer observation periods have been proven to increase the diagnostic value of Holter ECG monitoring for paroxysmal atrial fibrillation mainly. The aim of this work was to study the diagnostic efficacy of a long-term ECG monitoring in detecting various types of arrhythmias and to assess the uneven distribution of arrhythmias over different observation days. In this study 27 patients were examined, including 13 men and 14 women with a mean age of 42.8 ± 10.8 years, their complaints suggesting various types of tachy- and bradyarrhythmias. Compact recorders and original software were used. ECG recording time was 5-7 days. Using quantity criteria characterizing the level of uneven inter-day distribution of arrhythmias, advantages of long-term observations over a 24-hour monitoring were confirmed for such arrhythmias as sinus pauses over 2.5 seconds, a second degree AV block, paroxysmal supraventricular tachycardia, single and paired ventricular extrasystoles, ventricular salvos, ventricular tachycardia.
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ECG-BASED BIOMETRIC IDENTIFICATION: SOME MODERN APPROACHES
стр.35-39
Astapov A.A., Davydov D.V., Egorov A.I., Drozdov D.V., Glukhosvkij E.M.
The uniqueness of electrical activity of every human heart prompts us to use the ECG as a biometric parameter in various security and authentication systems as it is easy and cheap to extract the signal and difficult to fake it or obtain nonconsensually. At the moment various approaches to researching a possibility of human identification by ECG are used. Identification mode includes the following stages: data collection, procession, feature extraction, classification. Researchers use different mathematical algorithms at every stage: principal component analysis, wavelets, neural networks, etc. This article reviews the most significant studies of ECG based human identification and compares their results and accuracy of conceptual approaches.
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SURFACE PHENOTYPE OF BLOOD LYMPHOCYTES IN CHILDREN WITH MEDIUM AXIAL MYOPIA IN THE PRESENCE OR ABSENCE OF SECONDARY IMMUNODEFICIENCY
стр.40-43
Khamnagdaeva N.V., Semenova L.Yu., Obrubov S.A., Salmasi J.M., Poryadin G.V., Rogozhina I.V., Kazimirskii A.N.
Investigating the role of secondary immunodeficiency in the development of myopia in children is a promising research area. We studied the surface phenotype of blood lymphocytes in healthy children and children with medium axial myopia in the presence or absence of secondary immunodeficiency clinical manifestations. The mean age of study participants was 16 ± 0.25 years. The control group and each of the two experimental subgroups included 8 children. Using indirect immunofluorescence, the expression of CD3, CD4, CD8, CD16, CD56, CD20, CD72, CD38, CD25, CD71, HLA-DR, CD95, CD54, mlgM, mlgG, ICAM-1 antigens was studied. For children with myopia and secondary immunodeficiency, only one statistically significant (p
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VITAMIN STATUS OF URBAN AND RURAL SCHOOL CHILDREN AND SPECIFICS OF FREE RADICAL REACTIONS IN THEIR BLOOD SERUM
стр.44-48
Setko N.P., Krasikov S.I., Bulycheva E.V.
The rate of free radical reactions is one of stress markers. The ability of the organism to resist oxidation is determined by various factors, including vitamin supply. Vitamins A, E, C and group В vitamins directly or indirectly affect the degree of antioxidant protection. We have studied vitamin supply in school children aged 12 to 17 in urban (n = 250) and rural areas (n = 200) and the rate of free radical reactions in their blood serum by induced chemiluminescence. Deficiency of vitamins A and E, which have antioxidant properties, was detected in both urban and rural school children; however, the former had a higher deficiency level. This corresponds to the chemiluminiscence assay data: all chemiluminescence assay values in urban school children were 2.2- 7.6 times higher than in rural school children, which indicates a higher intensity oxidation in their bodies. A deficiency of group В vitamins was also detected in rural school children, riboflavin being an exception in a subgroup of 15 tol 7 year old subjects.
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TISSUE CHEMILUMINESCENCE AS A METHOD OF EVALUATION OF SUPEROXIDE RADICAL PRODUCING ABILITY OF MITOCHONDRIA
стр.49-55
Dzhatdoeva A.A., Polimova A.M., Proskurnina E.V., Vladimirov Yu.A.
Mitochondrial dysfunctions are an underlying cause of many human diseases including degenerative diseases. One of the consequences of mitochondrial dysfunctions is apoptosis of functionally active cells. During the initial stage of apoptosis, increased production of superoxide anion-radical (SAR) is observed. A promising method of SAR detection in cells and tissues is chemiluminescence (CL), primarily, in the presence of lucigenin, a SAR specific amplifier of CL. In this study a means of improving CL was proposed, and its effectiveness in detecting SAR level in living tissues of laboratory animals in hypoxia and parkinsonism models was evaluated. Aerobic (C, - 15 %, CO, - 5 %, N, - 80 %) and anaerobic (CO - 5 %, N - 95 %) gas mixtures proposed for samples aeration, maintained a constant pH of 7.4, necessary for accurate recording of CL. Using the studied method, a statistically significant increase (1.8 and 2.0 times) in SAR production level in rat heart tissue was detected with hypoxia duration of 150 to 240 minutes. In the parkinsonian model SAR production in mouse brain tissue samples of striatum and substantia nigra was 1.7 and 1.3 times higher after administration of the final dose of proneurotoxin, as compared to the control group.
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SERUM ALBUMIN ASASOURCE OF AND ATARGET FOR FREE RADICALS IN PATHOLOGY
стр.56-61
Sozarukova M.M., Proskurnina E.V., Vladimirov Yu.A.
Oxidative stress caused by excessive accumulation of pro-oxidants and/or depletion of antioxidants, is an important pathogenic factor. Oxidative stress leads to oxidative modification of macromolecules. Proteins are a target for oxidizing agents. Of other antioxidants in human blood plasma, serum albumin is particularly interesting as a target for reactive oxygen species. In this brief review albumin is looked upon as a target for free radicals, an antioxidant, and a source of free radicals in its complexes with copper ions. Possible targets for free radicals in protein structure and the consequences of their exposure to free radicals attacks have been analyzed. The role of glycosylation in contributing to protein oxidative modification has been studied. The original experimental data on albumin structure changes in various models of oxidative stress obtained by a spectrofluorimetric method are pesented. Increased antioxidant properties of albumin modified in a physical model of oxidative stress (UV-irradiation) have been described.
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TWO HMG DOMAINS OF YEAST MITOCHONDRIAL PROTEIN ABF2P HAVE DIFFERENT AFFINITY TO DNA
стр.62-65
Kurashenko A.V., Samoilova E.O., Baleva M.V., Chicherin I.V., Petrov D.Yu., Kamenski P.A., Levitskii S.A.
Maintaining mitochondrial genome integrity is essential for the viability of the whole organism. Mitochondrial genome mutations lead to muscular dystrophies, neurodegenerative diseases, and are associated with aging. In this work a baker’s yeast () mitochondria model was used to investigate DNA-binding abilities of different domains of a mitochondrial Abf2p protein which participates in homologous recombination and reparation. A weak non-specific HMG1 binding to linear DNA and a specific HMG1 binding to a branched DNA with a dissociation constant of 510 nM have been discovered. The HMG2 domain itself does not bind to any DNA and either has other functions or demonstrates its DNA-binding activity in a full-length protein only.
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STABILITY OF GADOLINIUM-BASED CONTRAST AGENTS IN THE PRESENCE OF ZINC AND CALCIUM IONS IN DIFFERENT MEDIA
стр.66-70
Kharlamov V.G., Kulakov V.N., Lipengolts A.A., Shimanovskii N.L.
To improve the safety of Gd-based contrast agents (GBCA) in clinical practice, it is recommended to use the most stable substances and to consider conditions determining their stability. The aim of this study was to compare the stability of GBCAs for magnetic resonance imaging in the presence of zinc and calcium ions and polyvinylpyrrolidone (PVP) in water, phosphate buffer solution and blood serum using proton NMR relaxometry. The study demonstrated that macrocyclic gadobutrol is more stable than all linear contrast agents. The addition of PVP (10 mg/ml) improved the stability of linear GBCAs in phosphate buffer solution and blood serum. Calcium ions have a much weaker destabilizing effect on GBCAs than zinc ions.
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APPROACHES TO IMPROVING TUBERCULOSIS CARE IN HIV-INFECTED PATIENTS AND CRITERIA FOR ITS EVALUATION
стр.71-74
Frolova O.P., Schukina I.V., Novoselova O.A., Stakhanov V.A., Kazennyi A.B.
Despite various anti-tuberculosis measures in the setting of HIV infection, the epidemiological situation of tuberculosis in Russia is deteriorating. We have analyzed the data of statistical report form no.61 for years 2004-2014, surveillance data on individual ТВ cases with HIV coinfection for years 2004-2014 (personal data) and ТВ care arrangements for patients with HIV in 20 regions. The main causes of the deteriorating epidemiological situation are the growing immunodeficiency in patients with ТВ coinfection, unseparated epidemiologically dangerous patient flows (patients with tuberculosis and HIV-infected patients) and low quality preventative measures in special care medical facilities. Chemoprophylaxis can be an effective method of controlling the spread of tuberculosis among HIV-infected patients if it is recommended by a qualified tuberculosis therapist to patients adhering to regular drug intake under supervision of medical personnel. Otherwise a large scale chemoprophylaxis can result in an increased proportion of patients with drug-resistant tuberculosis. This works suggests criteria for the evaluation of tuberculosis care effectiveness considering the pathogenesis of the disease during late stages of HIV.
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COMPARATIVE ANALYSIS OF MODERN APPROACHES TO THE PERFORMANCE ASSESSMENT OF SCIENTIFIC MEDICAL ORGANIZATIONS IN RUSSIA AND ABROAD
стр.75-80
Aniskevich A.S., Halfin R.A., Tatarinova L.V.
The article reviews basic methods of performance assessment of scientific medical organizations in Russia. Qualitative and quantitative effectiveness criteria are provided. International practices are described; a comparative analysis of assessment methods used in Russia and abroad is carried out. Global trends in the development of approaches to analyzing the effectiveness of scientific organizations are reviewed. Based on our analysis, a compelling rationale for developing more up-to-date criteria for evaluating the performance of scientific medical organizations is given.
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