Структура и биологическое действие аналогов и производных биогенных полиаминов

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.Цели. Биогенные полиамины широко представлены в живой природе. Они характерны как для клеток простейших, так и для многоклеточных организмов. Данные соединения обладают широким спектром биологической активности и необходимы для нормального роста и развития клеток. Нарушение гомеостаза полиаминов может вызывать существенные отклонения в функционировании клетки, провоцируя протекание патологических процессов различного рода, включая онкологические и психоневрологические заболевания. Воздействие на «полиаминовый путь» является привлекательным базисом для создания ряда фармакологически активных веществ с различным спектром действия. Целью данного обзора является обобщение результатов исследований, посвященных изучению биологической активности соединений полиаминового ряда; сопоставление биологического действия с воздействием на определенные молекулярные мишени. В виду структурного многообразия данной группы веществ невозможно в полной мере отразить имеющиеся на сегодняшний момент данные в одном обзоре. Поэтому в настоящей работе основное внимание уделено производным насыщенных полиаминов ациклического строения.Результаты. В общем виде рассмотрены следующие аспекты: биологическая активность, биосинтез и катаболизм, клеточный транспорт и локализация биогенных полиаминов в живых системах. Представлены структурные аналоги и производные биогенных полиаминов, обладающие противоопухолевой, нейропротекторной, антиаритмической, противопаразитарной, антибактериальной и некоторыми другими видам биологической активности; отражена взаимосвязь между биологической активностью и мишенями воздействия. Установлено, что на характер воздействия большое влияние оказывает природа заместителя, количество катионных центров, а также длина полиаминовой цепи.Выводы. В настоящее время применение структур полиаминового ряда сдерживается наличием цитотоксичности, а также неспецифического токсического воздействия на ЦНС. Дальнейшие исследования в области биохимии, клеточного транспорта, а также более глубокое понимание механизмов рецепторного взаимодействия позволят использовать полиамины в качестве основы для создания потенциальных лекарственных препаратов

FEATURES OF GENOTYPiNG VARIABILITY OF STRAINS OF BORDETELLA PERTUSSIS ALLOCATED FROM PATIENTS WITH WHOOPING COUGH IN RUSSIA

On the basis of studying of features of structure of 7 genes determining major factors of pathogenicity of the causative agent of whooping cough - ptxA, ptxB, ptxC, ptxD, ptxE, ptxP and prn, features of genotyping variability of strains of B.pertussis allocated from patients with whooping cough in Russia are shown. Dynamics of formation of population of strains of the causative agent of whooping cough is tracked and is established that population of strains of B.pertussis is formed by clonal expansion of strains with, new genetic structure of major factors of pathogenicity - pertussis toxin and. pertactin. The structure of population of strains of B.pertussis causing a disease by whooping cough, at the present stage of epidemic process of a pertussis infection - domination. of strains with new «non-vaccine» alleles genes - ptxA1 (97,7 %), ptxC2 (87,4 %), prn2 (89,5 %) and. ptxP3 (93,3 %), in 2,2 % cases with ptxB2 allele and. in 1,3 % cases with. prn9 allele circulate

Microstructural changes in cast martensitic steel after creep at 620°C

Microstructural changes in the cast steel GX12CrMoWVNbN10-1-1 (Fe-0.11 C-0.31 Si-0.89 Mn-9.57 Cr-0.66 Ni-1.01 Mo-1.00 W-0.21 V-0.06 Nb-0.05 Cu-0.05 N in wt %) have been investigated after tests for long-term strength at a temperature of 620°C in the range of stresses of 120-160 MP

The significance of retained austenite in the high strength and plasticity of medium carbon Q&P steel

The Fe-0.44%C-1.8%Si-1.3%Mn-0.82%Cr-0.28%Mo steel treated by the quenching-partitioning partitioning process showed a product of strength and elongation of 30 GPa % with yield stress of 1350 MPa. Such a combination of high ultimate tensile strength and good ductility is attributed to a high portion of retained austenite (≥20%) transforming to martensite under tension. The high yield stress is provided by carbon supersaturation of austenite and a high dislocation density in this phas

Optimization of the Conditions for Cultivation of Yersinia pseudotuberculosis in the Process of Obtaining Cell Mass

Objective of the study was to optimize the conditions of submerged recurrent cultivation and the composition of the nutrient medium for obtaining the cell mass of Yersinia pseudotuberculosis strains, used as an adsorbent in the preparation of diagnostic plague immunoglobulins. Materials and methods. We utilized Y. pseudotuberculosis adsorbent strains 6; 31; 68; 69; and 70 belonging to V, I, III, IV, and V serotypes, respectively, received from the State Collection of Pathogenic Bacteria at the premises of the RusRAPI “Microbe”. The cultivation process was carried out on an incubator-shaker, laboratory and pilot fermenters with variation of the process parameters, different options for feeding and nutrient media. Results and discussion. In the course of work, the optimal parameters of recurring submerged cultivation have been established. It was found that the highest biomass yield is provided by a combination of a nutrient medium – a carbon substrate in the form of a broth, based on an enzymatic fibrin hydrolysate, with the addition of galactose as a substrate feeding. Thereat, the morphology and immunochemical properties of microbial cells obtained through modified preparation process do not differ from those produced in the control run. The optimization of the parameters for Y. pseudotuberculosis cell mass cultivation with subsequent upscaling has been performed

Characteristics of erythropoietin antibodies in patients treated with recombinant human erythropoietin

Our aim was to characterize anti-EPO antibodies in serum samples of the patients treated with erythropoietin. 106 serum samples from the patients treated with erythropoietin (EPO) were collected and assayed. 134 serum samples of patients who did not receive EPO were taken for comparative analysis. The anti-EPO antibody detection was performed in ELISA test with rhEPO, by passive capture on ELISA plates, using steptavidin-biotin immunochemical system. Mouse monoclonal antibodies to human IgG, IgG1, IgG2, IgG3 and IgG4 conjugated to horseradish peroxidase were used to detect anti-EPO antibodies, and protein-A peroxidase conjugate was used for quantitative assays. Rabbit anti-human EPO polyclonal antibodies at known concentrations were used as a calibration standard. Six calibration samples at the concentration range of 16-1000 ng/ml were used to plot calibration curves. The lower detection limit was 12 ng/mL, and the quantitative detection limit was 31 ng/ml. Immunochemical capturing led to increasing of total IgG antibody detection by 3.2 times, IgG1 – by 1.1 times IgG2 – by 1.25 times, IgG3 – by 1.5 times, IgG4 – by 1.7 times. Antibodies of mixed isotype were found in most patients. IgG1 or IgG4 antibodies to EPO were determined only in 3 samples. Specific IgM was not detectable among 106 sera samples, whereas total IgG antibodies were detected in 36.8 % of cases. In 34% of sera, their presence was confirmed by detection of at least one of the subclasses. IgG1 antibody was detected in 83.3%; IgG4, in 80.6% of the samples positive for total IgG antibodies. In all cases, IgG2 and/or IgG3 were detected in presence of IgG1 or IgG4 antibodies. The antibody concentration was 3.2 to 35.5 µg/mL in sera from 28 patients, in 8 cases the level of antibodies was > 50 µg/ml, however, being below the limit of quantitative detection in 3 patients. Only 6 samples contained antibodies with avidity index of > 50%. Immunochemical capturing of the antigen led to increased sensitivity for detecting all subclasses of specific antibodies. The specific IgG antibodies to EPO were found in more than 1/3 of serum samples from the patients treated with erythropoietin. Low-avidity antibodies of IgG1 and IgG4 subclasses were determined in most cases

APPLICATION OF MATHEMATICAL METHOD PREDICTIONS FOR IDENTIFICATION OF PATTERNS RELATIONS MUTATIONS IN PROTEINS ENCEPHALITIS VIRUS AND A MANIFESTATION OF ITS PHENOTYPIC TRAITS

We studied the natural connections between the amino acid sequences of proteins C, prM, E and NS1 virus strains of tick-borne encephalitis (TBE) and their three phenotypic traits -neuroinvasiveness, thermal stability and thermoresistance. Coupling strength is assessed using measures of competitive sequence similarity of each strain with reference strains. For such purposes subsets of strain sections are chosen amino acid composition specifics of which can predict the value of a phenotypic trait of interest. The possibility to predict missing elements in data both in amino acid composition, and in target properties is demonstrated. The relationships between pairs of phenotypic traits of strains were evaluated

Кафедра патологической анатомии Сибирского государственного медицинского университета. И.В. Торопцев (1907—1985). К 95-летию со дня рождения

Biography of the great scientist-pathologist, professor of Tomsk medical institute (Siberian State Medical University at present) I.V. Toroptsev — one of the founders of radio- and magnetobiology.Представлена биография крупного ученого-патологоанатома, профессора Томского медицинского института (ныне СГМУ) И.В. Торопцева — одного из основателей отечественной радио- и магнитобиологии

Characterization of toxigenic Corynebacterium diphtheriae strains isolated in Russia

The aim of the study was to characterize toxigenic strains of Corynebacterium diphtheriae by examining 12 toxigenic strains of C. diphtheriae isolated in Russia between January, 2017 to June, 2019. The morphological, toxigenic and biochemical properties of C. diphtheriae was studied. Genotyping of C. diphtheriae strains was performed using MLST and dtxR gene sequencing with subsequent phylogenetic analysis. Results. Toxigenic strains of C. diphtheriae were isolated in the Novosibirsk, Samara and Chelyabinsk Regions, the Khanty-Mansi Autonomous Okrug — Yugra as well as the Republic of Northern Ossetia — Alania. Among these strains, 5 were isolated from diphtheria patients (moderate disease found in one case, mild course — remaining patients) and 7 strains were isolated from bacterial carriers. In two cases C. diphtheriae from diphtheria patients were identified as ST25 sequence type, gravis variant; in one case — ST8 type, gravis variant; two cases — ST67 sequence type, mitis variant. In asymptomatic carriers of tox-positive C. diphtheriae strains they belonged to ST25 sequence type, gravis variant — in two cases, ST67 type, mitis variant — in four cases. A sequencing type was not identified in one case. All sequence types were widespread globally being presented by a large number of isolates in the PubMLST and characterized by a substantial amount of derivative sequence types. At the same time, they belonged to different clonal complexes and differed markedly from each other contributing to their reliable difference as assessed by MLST. Study of gene dtxR sequence diversity showed that all allelic variants were typical for the representatives of these sequence types. New alleles of gene dtxR were not revealed in strains examined. It was shown that non-synonymous substitution C440T leading to A147V amino acid substitution was found solely in one allele distributed in ST8, ST185, ST195 and ST451 types suggesting at late mutation. In contrast, the polymorphism C640A resulting in the amino acid substitution L214I was found not only in the same allele, but also in the basal tree branches indicating that isoleucine was in the ancestral sequence of the protein