Vol 20, No 3 (2020)

Оригинальные исследования
Structural and functional disorders of the respiratory system in laboratory animals when intoxicated by pyrolysis products of chlorine-containing polymer materials
Potapov P.K., Dimitriev Y.V., Tolkach P.G.

Relevance. The widespread use of chlorine-containing polymer materials in the modern world is due to their various advantages over natural analogues. Given the continuing large number of fires, there is still a high risk of exposure to pyrolysis products of chlorine-containing polymer materials, primarily hydrogen chloride and carbon monoxide on the victims. The complexity of determining the toxic effect of pyrolysis products of chlorine-containing polymers makes it necessary to conduct toxicological experimental studies.

Intention. The goal is to evaluate the structural and functional disorders of the respiratory system in laboratory animals when intoxicated by pyrolysis products of chlorine-containing polymer materials.

Methodology. In an experimental study, pyrolysis of chlorine-containing polymer materials was performed. The study was performed on 96 male rats, in which vital function indicators, pulmonary coefficient, parameters of oxygenation and acid-base state of arterial blood were determined, and histological examination of tracheal and lung tissues was performed.

Results and Discussion. It was found that the pyrolysis of chlorinated paraffin (CP-70) with a mass of 7 g and sawdust with a mass of 3 g produces thermal degradation products containing hydrogen chloride at a concentration of 7325 ppm and carbon monoxide at a concentration of 1000 ppm. Exposure to pyrolysis products in laboratory animals resulted in a pronounced irritant effect during intoxication and in the early post-intoxication period. Microscopic examination of lung tissue 48 hours after exposure showed histological signs of interstitial phase of toxic pulmonary edema. We found a decrease in vital functions (heart rate, respiratory rate, rectal temperature) 24, 48 and 72 hours after exposure. Exposure to pyrolysis products led to a violation of gas exchange through the alveolar-capillary membrane, which was confirmed by a decrease in the index of oxygenation and saturation. Violation of the integrity of the alveolar-capillary membrane contributed to the penetration of fluid into the interstitial and alveolar space and the development of toxic pulmonary edema. An increase in the pulmonary coefficient (p < 0.05) was observed, after 24 and 48 hours, respectively.

Conclusion. As a result of the study, toxic pulmonary edema was simulated in laboratory animals by inhalation of pyrolysis products of chlorine-containing polymer materials, and structural and functional disorders of the respiratory system were determined. It was found that intoxication with pyrolysis products of chlorine-containing materials led to the development of inflammatory changes in the trachea and the manifestation of interstitial pulmonary edema. These changes were accompanied by the development of bradycardia, bradypnea, a decrease in body temperature, as well as an increase (p < 0.05) in the pulmonary coefficient, and the development of decompensated respiratory acidosis. The obtained results indicate that the formation of a toxic effect when exposed to pyrolysis products is due to the combined action of hydrogen chloride and carbon monoxide.

Medical academic journal. 2020;20(3):13-22
Determination of the trace element composition of human hair
Savinov S.S., Riadchikova N.A., Pikalova T.M., Drobyshev A.I.

Hair is one of the promising non-invasive samples for monitoring the trace element composition of the human body. But it is necessary to take into account the individual and subpopulation characteristics of sample donors. In this work, we experimentally studied the features of the analysis of human hair samples for the determination of trace elements by arc atomic emission spectrometry using a dry residue after acid mineralization. Validation was carried out by comparative analysis by the method used, as well as by atomic emission spectrometry with inductively coupled plasma. It has been shown that the concentrations of Al, B, Ca, Cu, Fe, Mg, Mn, P, Pb, Zn in a set of 50 samples from different donors obey the lognormal law, and therefore, the geometric mean (or median) is preferable as mean value. The content of Ca and Mg is higher in the female hair, while the content of Pb is higher in the male hair. The concentrations of Fe, Mn, and Pb are slightly higher in the hair of smokers than in non-smokers, but this difference is not statistically significant (probably due to the small sample size). Although the concentrations of several elements (including Mg, Mn, and P) differ in the hair of donors living in different regions of Russia, we failed to establish a significant difference of this factor. Positive correlations were found between the contents of some elements, in particular, Mg/Ca, Al/Fe, Al/P, Cu/Fe, Cu/P, Fe/P, weaker relationships were found for Al/Cu, Ca/Mn, Cu/Pb, Mn/P.

Medical academic journal. 2020;20(3):23-32
Immunogenicity and protective activity of recombinant influenza viruses expressing fragments of ScaAB lipoprotein of group B streptococci in a mouse model
Stepanova E.A., Isakova-Sivak I.N., Matyushenko V.A., Matushkina A.S., Smolonogina T.A., Donina S.A., Leontieva G.F., Suvorov A.N., Rudenko L.G.

Group B streptococci (GBS) cause a number of serious diseases in humans. The development of an effective vaccine against GBS requires special approaches. In the present study, three recombinant influenza viruses were constructed on the backbone of H7N9 live attenuated influenza vaccine (LAIV) strain expressing fragments of the ScaAB lipoprotein of Streptococcus agalactiae, fused to the surface protein of the virus, hemagglutinin, using a flexible linker. Recombinant viruses with ScaAB inserts of 85, 141, and 200 amino acids were successfully rescued by the means of reverse genetics. The recombinant strains were able to grow in developing chicken embryos and MDCK cells and retained the temperature-sensitive phenotype attributable to the LAIV viruses. Studies of immunogenicity and protective activity of the vaccine candidates in BALB/c mice revealed that the most promising strain was a strain with an insert of 141 amino acids: this variant had optimal immunogenicity against influenza and GBS and had a protective effect against both pathogens. These data indicate that further studies of the recombinant vectored vaccine H7-ScaAB-141 as a combined viral-bacterial vaccine capable of protection against both influenza virus and bacterial infections caused by group B streptococci are warranted.

Medical academic journal. 2020;20(3):33-42
The effect of various phases of the menstrual cycle on the tolerance of a statoergonometric test
Lapshina T.A., Shmidt A.A., Emelianov Y.A., Blaginin A.A., Barannik I.A.

Relevance. Nowadays, there is a worldwide practice of training women for piloting combat aircraft. An important problem arises of studying the tolerability of aerobatic overload by the female body, including during various periods of the ovarian-menstrual cycle.

The main aim of the study is to assess the tolerance of prolonged static tension of the muscles of the lower extremities and the abdominal press, as an equivalent to the tolerance of overload, by women in various phases of ovarian-menstrual cycle.

Methods. The static tension of the muscles of the legs and abdominal muscles is modeled using a five-step statergometric test. Tolerance is evaluated by the dynamics of indicators of computer stabilization before and after the test. The study involves 15 healthy women aged 21-23 years. Registration of estimated indicators is carried out in different phases of the ovarian-menstrual cycle.

Results. It is established that the postmenstrual phase of ovarian-menstrual cycle is characterized by good tolerance to long-term static tension of the muscles of the legs and abdominal muscles. Load tolerance decreases in the premenstrual phase.

Conclusion. The obtained data suggest that the tolerance of aerobatic overload in women may decrease in the premenstrual phase compared with the postmenstrual phase.

Medical academic journal. 2020;20(3):43-48
Аналитический обзор
Genetic engineering approaches to the development of modern therapeutics
Bogomolova E.G., Kopeykin P.M., Tagaev A.A.

The classic approach to production of protein-based therapeutics is their isolation from natural sources. This approach was associated with a number of difficulties, such as collecting the primary material from natural sources, isolating and purifying the protein, and its standardizing. With the development of recombinant DNA technology, it became possible to obtain large quantities of protein preparations lacking any contaminations. Human insulin produced using recombinant DNA technology is the first commercial therapeutic obtained by this way. Due to the rapid development of genetic engineering technologies, a large number of proteins have been obtained in Escherichia coli cells. In recent years, the approach for the development of drugs based on DNA molecules containing genes encoding therapeutic proteins has been developing more actively. Today, many scientists believe in the prospects of application of DNA vaccines. The ease of production, stability, the ability to mimic natural infections and elicit appropriate immune responses make this vaccine platform extremely attractive. Delivery and targeting of immunologically relevant cells are major tasks for maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently being used to achieve this goal are discussed in this review. Pharmaceuticals based on nucleic acids have a number of undeniable advantages. The main options for prophylactic RNA vaccines, the methods used to deliver RNA to the cell, and methods for increasing the effectiveness of RNA vaccines are discussed. Usage of therapeutic drugs based on protein molecules and low molecular weight compounds is complicated by the fact that they cannot be targeted at a specific gene or its protein product, responsible for the occurrence of the disease. Action of nucleic acids can be directly directed to a particular DNA region in order to edit its nucleotide sequence. This method allows to correct a genetic defect, eliminating the cause of the disease. The principles of gene therapy and the successes achieved in this area are discussed. This review summarizes current achievements in the development of drugs based on recombinant proteins and nucleic acids.

Medical academic journal. 2020;20(3):49-60
Personalized toxicology: phenomenology, relevance, development prospects
Rembovskiy V.R., Mogilenkova L.A.

Personalized toxicology is a research area that studies the individual toxicity of hazardous chemical compounds by experimental and clinical toxicology based on new molecular medicine approaches, including genetics and epigenomics, for prevention, diagnosis, and treatment of chemically induced diseases.

Goal of Research. To study individual genetically and epigenetically induced mechanisms of body’s response to exposure to chemical substances, and their effect on preclinical and reversible changes, development of intoxications, and long-term effects, as well as assessment of the individual health risk of exposure to a chemical factor.

Medical academic journal. 2020;20(3):61-73
Covid-19: features of the pathogenesis of the disease and targets for immunotherapeutic effects
Klimov N.A., Simbirtsev A.S.

An analysis of current scientific literature on the pathogenesis of the coronavirus infection that caused the 2019 pandemic, COVID-19, was carried out. The structure, genome, introduction into the cell and the life cycle of the SARS-CoV-2 virus that caused the pandemic, the mechanisms of protection of the virus from the host’s immune system, features of the clinical picture of coronavirus infection, the pathogenesis of viral pneumonia, in particular, disruption of the renin-angiotensin system, cytokine storm, participation of the complement system in the pathogenesis of COVID-19 are reviewed. The models of infections caused by SARS-CoV and SARS-CoV-2 in laboratory mice are also considered.

Medical academic journal. 2020;20(3):75-88
Sas enterprise guide 6.1: independent groups comparison for nominal data
Bunenkov N.S., Bunenkova G.F., Komok V.V., Grinenko O.A., Nemkov A.S.

Objective: to develop algorithm of independent groups comparison for nominal data of prospective non-randomized clinical trial AMIRI – CABG (ClinicalTrials.gov Identifier: NCT03050489) using SAS Enterprise Guide 6.1.

Materials and methods. Data collection was performed according to prospective non-randomized clinical trial AMIRI – CABG in Pavlov First St. Petersburg State Medical University, Saint Petersburg, Russia between 2016-2019 years with 336 patients. Patients were allocated into three groups of treatment. There is database which include following information: gender, myocardial infarction, stroke and postoperative bleeding. Comparison for nominal data (gender and incidence of myocardial infarction, stroke and bleeding) were calculated with SAS Enterprise Guide 6.1 software with Chi-squared test and exact Fisher test.

Results. There was developed algorithm of two independent groups comparison for nominal data.

Conclusion. Presented algorithm of data analysis allows to compare independent groups for nominal data.

Medical academic journal. 2020;20(3):89-98
Клинические исследования и практика
Laboratory and instrumental study of knee joints in patients with early gonarthrosis: search for relationship
Klementeva V.I., Chernisheva T.V., Korochina K.V., Korochina I.E.

Aim was to identify features of subchondral bone remodeling and synovitis severity in patients with early knee osteoarthritis using laboratory and instrumental methods.

Materials and methods. The study covered 60 patients with I-II radiological stages (by J. Kellgren and J. Lawrence, 1952) of gonarthrosis (according to R.D. Altman, 1991). Complex of clinical (history, complaints, palpation of joints, pain assessment by Visual Analogue Scale [VAS]), laboratory (interleukin-6, osteocalcin, Beta-Cross Laps, C-reactive protein [CRP] and others) and instrumental (X-ray, ultrasonography of knee joints) examinations of patients was carried out with subsequent statistical data processing.

Results. In patients with stage II gonarthrosis, Beta-Cross Laps, CRP levels, osteophyte size were significantly higher, and articular cartilage thickness was lower in comparison with stage I group. Correlations were found between: pain intensity according to VAS and volume of upper torsion of knee joint; interleukin-6 and osteophyte size, volume of upper torsion, Beta-Cross Laps; level of Beta-Cross Laps and osteocalcin, osteophyte size; and some other relationships.

Conclusion. In patients with I-II radiological stages of gonarthrosis, remodeling of subchondral bone is observed and accompanied by tissue turnover changes that it is could be used in targeted therapy. Serum Beta-Cross Laps is important marker for early progression of gonarthrosis.

Medical academic journal. 2020;20(3):99-106

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