Иммуномодулирующая терапия и респираторные вирусные инфекции: взгляд иммунолога

This aim of this review was an analysis of rational approaches to development and implementation of immunomodulating drugs for therapy of respiratory infections. One of the most explored immune substances is inosine pranobex (Groprinosin).Inability to control many infectious diseases effectively using chemotherapeutic drugs determined the need to search for alternative methods based particularly on modulation of the immune system. Rational approaches to immune therapy of respiratory infections have been analyzed in this review. Groprinosin could be used for prevention and therapy of respiratory infections. Reasonable algorithms involving this agent have been demonstrated.Актуальность поиска альтернативных методов, в частности основанных на модуляции иммунитета, определяется недостижимостью эффективного контроля над многими инфекционными заболеваниями с помощью этиотропных химиопрепаратов. В обзоре проанализированы рациональные подходы к иммунотерапии респираторных инфекций. Продемонстрирована возможность использования Гроприносина для профилактики и лечения респираторных инфекций и представлены рациональные схемы его применения

SERUM LEVEL AND GENE POLYMORPHISM OF INTERLEUKIN-1α, AND EFFICIENCY OF INFERTILITY TREATMENT BY IN VITRO FERTILIZATION

Search for novel prognostic criteria predicting successful in vitro fertilization remains a nonresolved problem at the present time. The aim of our study was to analyse a predictive role of IL-1α as an additional marker of pregnancy after in vitro fertilization (IVF). The study included 120 women with tubo-peritoneal infertility subjected to the IVF procedure. Retrospectively, two groups were formed of this cohort, dependent on efficiency of in vitro fertilization. Group I included 40 women with successful pregnancy whereas group II comprised 80 women with failed pregnancy. IL-1α concentrations in serum were detected by ELISA technique. A polymorphic rs1800587 marker at 5`UTR region has been amplified by PCR followed by Sanger sequencing. We have shown IL-1α hyperproduction in the women from group I. The women with effective IVF outcome exhibited positive correlation between IL-1α and luteinizing hormone, prolactin, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate levels. The women with ineffective in vitro fertilization have detected a negative correlation between IL-1α levels and anti-Muellerian hormone, a positive correlation of IL-1α with 17-hydroxyprogesterone. The women with T allele of the polymorphic rs1800587 marker at 5`UTR region have shown a 2.5-fold higher chance to become pregnant after IVF than the women carrying C allele (95% CI = [1.45-4.35], р = 0.0009). The women with T/T genotype exhibited a positive correlation between IL-1α and estradiol, testosterone; the subjects with heterozygous C/T genotype showed correlation with estradiol, and those harboring C/C genotype exhibited correlation with follicle-stimulating hormone. The revealed changes suggest a potential involvement of IL-1α into regulation of cyclic processes in the ovary including ovulation. Moreover, IL-1α may participate in formation of pro-inflammatory environment for successful blastocyst implantation

Improving the production technology of drilling and blasting operations by blasting of high ledges

In modern economic conditions, the issue of improving the efficiency of mining enterprises is very relevant. One of the key processes isdrilling and blasting operations (DBO), which determine the efficiency of the entire complex of mining operations. One of the main methods of controlling the explosion energy is the diameter of the blast wells. According to the recommendations of prof. B N Kutuzov the diameter of blast wells is correlated with the fracturing and strength of the exploding rocks. With increasing blockage and rock strength to achieve the required quality of explosive crushing preference is given to drilling equipment with a small diameter of wells. By blasting of high ledges, especially large-block rocks with a strength coefficient of more than 15 on the M M Protodyakonov scale; the use of high-performance drilling equipment for drilling small-diameter blast wells is difficult. This is due to the fact that the calculated value of the resistance line along sole (RLAS) does not pass the safety condition for drilling the first row of wells. In this regard, the paper proposes and justifies the use of extensions of the lower parts of wells using mechanical expanders. © Published under licence by IOP Publishing Ltd

Modern T cell technologies for immunotherapy of solid tumors

According to the common concept of immune editing, the interaction of malignant tumor cells and immune system is a complex multifactorial process, which may result in both antitumor effector activity and development of suppressor mechanisms that promote tumor growth. Accumulation of scientific knowledge in the field of studying the antitumor immune response and tolerance has led to emergence of many research and therapeutic approaches that use different components of the immune system to combat neoplastic processes. Along with currently available approaches, there are strategies that use the potential of antigen-specific T lymphocytes, the main effectors of adaptive immunity, in order to fight malignant neoplasms which appeared more than a century ago and have built the scientific basis of cancer immunotherapy. One line of evidence of the significant antitumor potential of T cells in immunotherapeutic schemes for the cancer treatment was presented by successful therapy of hemato-oncological diseases, achieved at the end of the past decade. At the same time, however, the therapy of solid malignant neoplasms still faces significant difficulties that limit the efficiency of treatment. In this regard, the main objective of the review is to accumulate up-to-date information on the successes and limitations of T cell immunotherapy in the patients with solid tumors. To date, the phenotype and functionality of T cells is being investigated and modulated both towards enhancing antitumor cytotoxicity, increasing viability and proliferative activity of T cells, and in overcoming the immunosuppressive effect of the tumor and its tolerogenic microenvironment upon T cells, as well as ensuring targeted migration of the effector T cells to the malignant tissues. This review discusses immunotherapeutic approaches exploiting the potential of effector T lymphocytes, e.g., current clinical trials or applied therapeutic regimens for the treatment of solid malignant neoplasms. Antigen-independent approaches aimed at nonspecific enhancement of the T cell responses, i.e., therapy with recombinant cytokines and inhibition of immune checkpoint molecules. Antigendependent, or antigen-specific approaches such as adoptive T cell therapy with endogenous T lymphocytes are also discussed as well as trials on T cells with modified antigen-recognition receptor (CAR-Tcells, TCR-Tcells), like as usage of bispecific antibodies as T cell engagers. The review describes the benefits and disadvantages of these approaches in monotherapy, as well as current results and prospects for their mutual combinations

Synthesis of Fatty-Acid Ethanolamides from Linum catharticum Oils and Cololabis saira Fats

Ethanolamides of polyunsaturated fatty acids (9Z,12Z,15Z-octadecatrienoic; 5Z,8Z,11Z,14Z,17Z-eicosapentaenoic; and 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic) and mixtures of ethanolamides of fatty acids from natural fats (oils) were synthesized. It was found that the polyunsaturated fatty acids did not isomerize under the proposed conditions for aminolysis of the ester bond. Conditions for analyzing the complicated mixtures of ethanolamides of fatty acids by HPLC-MS were determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41528/1/10600_2004_Article_495514.pd

Применение азоксимера бромида в терапии инфекционно-воспалительных заболеваний органов дыхания у детей: мета-анализ контролируемых клинических исследований

Objective. The aim of this meta-analysis is to summarize clinical efficacy of azoximer bromide for treatment of inflammatory respiratory infections in children and adolescents based on data from controlled clinical trials.Materials and. methods. In total 5 clinical studies with data from 542 patients aged. 3—18 years were selected, where effectiveness of therapy with addition of azoximer bromide to combination, therapy was compared, to standard, symptomatic treatment.Results. The results of the meta-analysis demonstrate that the addition of azoximer bromide from the first day to respiratory infections treatment in patients aged. 3-18 years helps to reduce temperature normalization, time [mean difference -1,92 day in favour of treatment with investigational drug (95% confidence interval 1,65; 1,15) according to the random effects model or -1,4 days (95% confidence interval 3,16; 0,67) according to fixed effects model]. Moreover azoximer bromide use in inflammatory respiratory infections treatment reduces the duration of fever and intoxication symptoms by 1,4 days in comparison with the control group (95% confidence interval 1,65; 1,15), headache by 0,53 days (95% confidence interval -0,91; -0,15), muscle and. joint pain by 1,59 days (95% confidence interval -2,1854; -1,0028) and catarrhal symptoms by 1,23 days (95% confidence interval 1,32; 1,14).Conclusion. Addition of azoximer bromide as nosotropic therapeutic agent to combination, therapy of respiratory diseases make possible to control intoxication, symptoms in a better way, reduces the morbidity of infectious and inflammatory process, has positive effect on immune mechanisms and causes almost no side effects.Цель: обобщенная оценка клинической эффективности азоксимера бромида при лечении инфекционно-воспалительных заболеваний дыхательных путей у детей и подростков на основании данных контролируемых клинических исследований.Материалы, и методы: были отобраны. 5 клинических исследований, включающих данные 542 пациентов в возрасте 3—18 лет, в которых сравнивались эффективность терапии азоксимера бромидом в составе комплексной терапии и эффективность стандартной симптоматической терапии.Результаты: результаты, мета-анализа демонстрируют, что добавление азоксимера бромида к терапии респираторных инфекций у пациентов в возрасте 3—18 лет. с первого дня лечения позволяет, уменьшить срок нормализации температуры: обобщенная разница составила -1,92 дня в пользу терапии азоксимера бромидом (95% доверительный интервал -1,65; -1,15) согласно модели случайных эффектов и -1,4 дня (95% доверительный интервал -3,16; -0,67) согласно модели фиксированных эффектов. Кроме того, применение азоксимера бромида в терапии инфекционно-воспалительных заболеваний дыхательных путей сокращает, продолжительность симптомов лихорадки и интоксикации на 1,4 дня в сравнении с контрольной группой (95% доверительный интервал -1,65; -1,15), головной боли — на 0,53 дня (95% доверительный интервал -0,91; -0,15), боли в мышцах и суставах — на 1,59 дня (95% доверительный интервал -2,1854; -1,0028) и продолжительности клинических симптомов острого воспаления верхних дыхательных путей — на 1,23 дня (95% доверительный интервал -1,32; -1,14).Заключение: включение азоксимера бромида как препарата патогенетической терапии в состав комплексного лечения респираторных заболеваний дает возможность лучше контролировать симптомы, интоксикации, снижать тяжесть течения инфекционно-воспалительного процесса, оказывая положительное влияние на иммунные механизмы, и практически не вызывая при этом, побочных эффектов

Contemporary issues in ensuring biological safety during disposal of biological wastes of animal origin by incineration in the Russian Federation

Animal management and breeding as well production, transportation, preparation, and processing of animal products and raw material result in generation of a considerable amount of biological wastes being a source of biological contamination of the environment and a clear threat to human and animal health. The animal biowaste incineration units are high threat facilities and require constant surveillance and control. Collection and analysis of data provided by the RF veterinary executive authorities were performed to objectively reflect the actual situation of the biological waste incineration facilities in the RF Subjects and to create a holistic view on the problem of interest in the country. The following parameters were analyzed: their number, type (stationary and mobile), type of ownership, location, availability of the certificate and highly-qualified specialists serving the biological waste incineration equipment as well as the availability of such facilities in the RF Subjects as for January 1, 2021. The analysis demonstrated that 4,459 biowaste incinerators were registered in the country. Most of these units are stationary and they belong to establishments involved in farm animal keeping, animal product processing, production and storing. Such equipment is mostly serviced by non-qualified staff ignorant of the technical characteristics and operating principles of this equipment. Almost one third of these units in the country are home made that is why their use does not guarantee complete destruction of biological wastes and pathogen inactivation. It was also revealed that the procedure for the incineration of biological waste of animal origin using home made incinerators is not legally fixed in the country. The results obtained show that the situation of the animal biowaste incineration in the Russian Federation is quite complicated

Organization of live animal transportation process in the Russian Federation

The paper covers the issues of organization of live animal transportation process in the Russian Federation as one of the factors of epidemiological risk associated with the spread of infectious animal disease pathogens. The legal framework, regulating the organization of live animal transportation using different vehicles, as well as quantitative data on live animal movements, taken from state veterinary information system “VetIS” (“Mercury” and “Cerberus” components) were analyzed. The analysis showed that live farmed animals are moved using all transportation means available, motor vehicles, planes, trains, ships as well as by driving. It was established that the major means of transport used to move live animals in the territory of the Russian Federation are motor vehicles. According to the analysis results 4.49 billion animals, including 4.41 billion poultry, 79.8 million large and small ruminants, pigs, horses, fur animals and bees were moved within the country in 2021. At the same time the number of issued veterinary accompanying documents for movements of cattle, poultry and pigs (i.e. in fact the transportations themselves) is much higher than the number of movements of other species. It was revealed that today only the movement of animals by railway is regulated in one way or another. The paper presents the suggestions to introduce the procedures aimed at improvement of biological safety and animal welfare during transportation. The results of the analysis performed can be used to optimize the control of animal transportation in the territory of the Russian Federation by competent authorities

Изменение гуморальных и секреторных факторов защиты при иммунотерапии часто и длительно болеющих детей

Clinical and immunological efficiency of immunotherapy with thymus and bone marrow peptides, Ribomunyl, IRS 19 and their combination was assessed in 370 children being frequently ill in the near (12 months) and remote periods. In contradistinction to the thymus and bone marrow peptides a long-term positive influence of Ribomunyl alone and in combination with IRS 19 on the synthesis of lgA, SlgA and saliva lyzosime was shown, especially in the children with recurrent respiratory infections. A necessity of the immunologic monitoring in children frequently being ill was marked not only for systemic immunity but also for local (mucous) one.У 370 часто болеющих детей проведена оценка клинико-иммунологической эффективности иммунотерапии тимогеном, миелопидом и их комбинацией, а также рибомунилом, ИРС19 и их комбинацией в ближайшей (12 мес) и отдаленной (36 мес) перспективе. В отличие от тимусного и костномозгового пептидов показано долгосрочное позитивное влияние рибомунила и его комбинации с ИРС19 на синтез lgA, SlgA и лизоцима слюны, особенно у детей дошкольного возраста, имеющих очаги хронических инфекций носоглотки. Отмечена необходимость иммунологического мониторинга не только системных, но и секреторных факторов иммунитета у часто болеющих детей