[Specific features of the pathology of the respiratory system in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) infected Syrian hamsters (Mesocricetus auratus)].

INTRODUCTION: Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters. MATERIAL AND METHODS: Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory. RESULTS AND DISCUSSION: The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters. CONCLUSION: As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.

[Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated With Ischemic Heart Disease in Patients With Type 2 Diabetes].

OBJECTIVE: To examine associations between ischemic heart disease (IHD) and polymorphisms in cytokine genes (IL-1B, IL-4, IL-6, IL-10, TNFA, VEGF) and matrix metalloproteinase genes (MMP2, MMP3, MMP9) in patients with type 2 diabetes. MATERIAL AND METHODS: We studied 232 Caucasian diabetic subjects (33 men and 199 women aged 50-70 years). In 93 patients IHD was verified by treadmill test and/or coronary angiography (86 subjects with stable angina, 19 with previous myocardial infarction). Thirteen polymorphisms localized in the promoters of IL-1B (rs1143627), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800872, rs1800896), TNFA (rs361525, rs1800629, rs1800630), VEGF (rs699947, rs3025039), MMP2 (rs243865), MMP3 (rs3025058) and MMP9 (rs3918242) were investigated. RESULTS: Prevalence of G-allele and GG-genotype at -308 position of TNFA (rs1800629), as well as C-allele and CC-genotype at position +936 of VEGF (rs3025039) was higher in patients with IHD as compared to patients without IHD (OR=2.0, OR=2.2, OR=2.1, OR=2.4, respectively, all p=0.02). In logistic regression analysis, TNFA -308 A/G and VEGF +936 C/T polymorphisms showed associations with IHD (both p=0.009). These polymorphisms along with age, body mass index, duration of diabetes, low density and high density lipoprotein cholesterol were associated with IHD in multivariate models (p=0.0002 and p=0.00008, respectively). Nine combinations of TNFA -308 GG-genotype and variants of other genes demonstrated associations with IHD (p≤0.002). CONCLUSION: The polymorphisms in promoter regions of TNFA (rs1800629) and VEGF (rs3025039) are associated with IHD in patients with type 2 diabetes.

[Disturbance of monoaminooxidase activity and indices of endogenous intoxication in patients with the first episode of schizophrenia].

An aim of the paper was to study some biochemical parameters of drug-naïve patients with the first episode of schizophrenia. Activities of platelet monoaminooxidase (MAO) and semicarbazide, a sensitive blood serum aminooxidase (BSA), levels of middle-sized molecules (MSM) and malonic dialdehyde (MDA), parameters of functional state of serum albumin were assessed in 16 patients. Severity of symptoms in patients with the first episode of schizophrenia was assessed as moderate (PANSS scores 73.1+/-12.5) before the treatment. The increase of MAO by 107%, reduction of BSA by 29% and increase of MSM level by 140% was found in patients compared to controls (p<0.01). The study of other biochemical (MDA level) and biophysical (effective albumin concentration) parameters did not yield unequivocal results. It has been suggested that MAO and BSA are integral components of pathogenetic mechanisms in patients with the first episode of schizophrenia.

[Cytogenetic effects on blood lymphocytes of cosmonauts after low doses of space radiation].

Cytogenetic changes in cultures of blood lymphocytes from 37 cosmonauts returned from space flights of varying duration were analyzed. Prolonged stay in space was shown to increase numbers of stable and unstable chromosomal aberrations. Frequency of dicentric and centric rings depends on flight duration, as well as values of accumulated dose from and dose rate of space radiation. Egress into open space leads to an additional growth in the number of chromosomal aberrations. It was found that frequency of chromosomal aberrations in blood lymphocytes remains altered even after several years of cosmonaut's return from space flight. Based on the counts of symmetric translocations obtained with the FISH-technique, mean dose from space radiation following the maiden prolonged space flight amounted to 110 mGy which is in agreement with the biodosimetric data about frequency of dicentric and centric rings (140 mGy).

[The influence of chronic and of acute irradiation on the polymorphism of RAPD-markers in offspring for irradiated mice].

On mice lines BALB/c and CBA/lac was performed the study of molecular-genetics effects in mice progeny after the chronic (dose rate -0.0017 Gy/day, total dose -0.36 Gy) and acute (dose range 1-3 Gy) exposure of y-radiation on the parents. For variability analysis was used technique of amplification DNA with series of random primers (RAPD-assay). Random primers were used as single primer and in mixture of ones. In this work were held the comparative analysis of the genetic radiosensitivity for stem spermatogonia and spermatides. After the acute exposure the dose dependence for levels of polymorphism of RAPD-markers were obtained. After the chronic irradiation, significant differences from control group were obtained only by use primers mixture M1. Comparative analysis of the genetic radiosensitivity of different stages of mice spermatogenesis are display is similar sensitivity of stem spermatogonia and spermatides after doses of irradiation 1 Gy and 3 Gy. Indicated that after irradiation by dose 2 Gy, spermatogonia are more sensitivity than spermatides.

[The potential of 1,1'-hexamethylenebis [3-(3,5-dichloro-4-pyridyl)] urea to modify genotoxic actions of chemical mutagens in various test-systems].

The main tasks of this investigation were to investigate the potential genotoxic effect of 1,1'-hexamethylenebis [3-(3,5-dichloro-4-pyridyl)] urea and to analyze its capacity to induce adaptive response (AR) against chemical mutagens in various test-systems. Microbiological, cytogenetical and biochemical end-points were used. The sensitivity of test systems can be arranged as followed: human lymphocyte cultures > Chlamydomonas reinhardtii > Hordeum vulgare. It was obtained that HMPU can induce oxidative stress in Chlamydomonas reinhardtii cells (7.5 x 10(-4) mol/l) and at appropriate experimental conditions can trigger an AR against chemical mutagens in Hordeum vulgare (7.5 x 10(-3) mol/l) and human lymphocytes (10(-5), 10(-6) mol/l). The extent of the AR induction was closely connected with the increase of the inter-treatment time between the conditioning concentration of HMPU and the challenge concentration of chemical mutagens.

[Genetic polymorphism of glutathione-S-transferases and inhibition of DNA repair].

A complex investigation of different cell defence systems, such as: DNA repair, antioxidant system (SOD), xenobiotic detoxification system (glutathione-S-transferases M1 and T1), radioadaptive response (RAR) in lymphocytes of patients with hereditary disease of connective tissue (Elers-Danlose syndrome) was carried out. The frequency of genotype GSTM1 (0/0) in children with Elers-Danlose syndrome (23%) is lower as compared to the control group (44%). The lymphocytes of children with Elers-Danlose syndrome were characterized by reduced ability to repair gamma-induced damage of DNA. At given size of the samples of examined children no correlative relationships between GST-status of organism and the condition of other cell defence systems were revealed. The data obtained demonstrate the individual peculiarities of the defence systems in repair-deficient cells of the examined children.

[Genetic effects in plant populations in the zone of the Chernobyl accident].

During 6 years, starting from 1986, the monitoring of the dynamics of the frequency of embryo lethal and of chlorophyll mutations was carried out in arabidopsis populations in areas with different levels of radioactive contamination by the Muller embryo-test in the 30 km of ChNPP. The dose rate of chronic irradiation in the examined areas varied from 0.014 to 17 nA/Kg. Monitoring of the dynamics of the mutation process in natural arabidopsis populations showed the correlation between the level of the mutation process and the dose rate of chronic irradiation. The genetic effects of different levels of radioactive contamination were estimated by determining the frequency of mutations occurred in this generation and by calculating the dose of irradiation of one was found. That the dependence of the mutation frequency on the dose of irradiation presents a power function with a power index less 1, which suggests a higher efficiency of low radiation doses per unit dose. Possible explanations of this phenomenon are considered in the work. The studies of cytogenetic effects in chronically exposed Crepis tectorum populations in the zones of the Chernobyl accident showed that starting from the second year after the Chernobyl disaster there appeared plants with an altered karyotype and their frequency of chromosome aberrations correlates in root meristem cells.

[Genetic consequences of an increased radiation background at mouse-like rodents].

The frequency of genetic disturbances in germ-line and in somatic cells was studied in animals caught in radionuclide-cotaminated areas within the 30-km Chernobyl NPP zone as well as in model experiments in laboratory mice exposed to chronic external gamma-radiation or to the internal action of incorporated radionuclides (131I, 137Cs, 238Pu). The results of genetic and of cytologic analysis of germ-line and somatic cells in the caught or exposed house mice and in laboratory mice after incorporation of radionuclides are presented. An estimation of relative genetic efficiency of the most harmful radionuclides was made.

[The significance of cytogenetic investigation for the estimation of Chernobyl accident consequences].

The results of the cytogenetic investigation of people, which were exposed to radiation in the result of the Chernobyl NPP accident, were presented. Also the possibilities of the application of cytogenetic findings for dose estimations and for the prediction of the radiation influence consequences were examined. During the period of time since 1986 till 2004 the cytogenetic investigations of 1724 liquidators participating in the liquidation works after the Chernobyl accident were carried out. The radiation dose estimated by the frequency of dicentrics in 1986 was about 0.16 Gy. The doses for liquidators were determined by the frequency of translocations (FISH method) during the period from 1992 till 1995. For liquidators who worked in Chernobyl only in 1986 the average dose of radiation was about 0.19 Gy and for liquidators who worked repeatedly during the period from 1986 till 1995 - 0.39 Gy. There was shown that during the whole period of investigation (1986-2004) the frequency of dicentrics in peripheral blood lymphocytes was significantly higher than the control level. The cytogenetic investigation of Bryansk region inhabitants which was carried out in 1992-1994 discovered heightened value in 5 times than the control one. Findings are of great importance for the prediction of ill effects of radiation and for the development of sensitive criterions for early exposure disturbances in state of health.

[Genetic effects of low-dose chronic irradiation of developing seeds of Arabidopsis thaliana Heynh].

A six-year study, starting in 1987, focused on the frequency of embryonic lethals and chlorophyll mutations that arose in developing seeds of Arabidopsis thaliana growing at sites varying in the level of radioactive contamination in the 30-km control region of the Chernobyl Atomic Power Plant. The dose rate of chronic irradiation varied from 200 microR/h to 2.4 R/h. To study the genetic effects of various levels of radioactive contamination, the frequency of mutations arising in a particular generation was determined and the irradiation dose was estimated for the given generation. The dose dependence of the mutation frequency proved to follow a power function with a power less than unity, suggesting a relatively high effect for low-dose irradiation. Possible explanations of this phenomenon are discussed.

[Multiyear monitoring of the ecological status of industrial zones of Moscow using a test line of Drosophila melanogaster]. / Mnogoletnii monitoring za ékologicheskim sostoianiem promzony g. Moskvy s primeneniem test-linii Drosophila melanogaster.

For 12 years, recombination rate was assessed in Drosophila melanogaster males exposed on a thermoelectric power station (TPS) of Moscow. In 1994, experiments were also carried out on another Moscow TPS for comparison. The recombination frequency in exposed males was two- or threefold higher than in the control sample. Recombination frequencies observed in different years did not significantly differ from each other. Likewise, no significant difference was observed for the results obtained on two TPSs. A dramatic increase in recombination frequency in flies exposed on TPS was considered as an adequate response to high concentrations of effective mutagens discharged by TPS.

[Synthesis of some thiourea derivatives and their influence on biological and genetic effects of gamma rays]. / Sintez nekotorykh proizvodnykh tiomocheviny i ikh vliianie na biologicheskoe i geneticheskoe vozdeistvie gamma-luchei.

The synthesis of the new radioprotective compounds ATB (I, 2-allylthioureidobenzoic acid), PTB (II, 2-phenylthioureidobenzoic acid), A-2-PTU (III, N-allyl-N'-2-pyridylthiourea), and P-2-PTU (IV, N-phenyl-N'-2-pyridylthiourea) and their influence on biological and genetic effects of gamma rays was studied. In result of investigations it must be noted that PTB displayed radioprotective effect as a result of which more plants in M1 germination and survive in M2 of the induced mutations is increased. The cytological analysis reveals that the studied substance (PTB) decreases chromosome aberration in meristem cells of pea roots almost twice as a result of postirradiation treatment. The effect of A-2-PTU in the experiments with peas greatly depends on the dose of irradiation, i.e., on the degree of damaging of the processes of cell restoration and the possibility of their partial restoration after the treatment with the protector. The results obtained suggest that chemical compounds of N,N'-disubstituted thiourea group (A-2-PTU and P-2-PTU) exert strong radioprotective effect in the experiments with peas. This is of great importance to modern radiobiology and radiation mutagenesis and also to protect hereditary structures against radiation.

[The estimation of molecular and cytogenetic effects in mice exposed to chronic low dose gamma-radiation]. / Otsenka molekuliarnykh i tsitogeneticheskukh éffektov khronicheskogo vozdeistviia nizkointensivnogo gamma-izlucheniia u myshei.

Molecular and cytogenetic parameters were estimated in male CBA/lac mice exposed to chronic low dose-rate gamma-radiation (62 cGy/year) for 40, 80, 120, 210, and 365 days. After 40 days of exposure (6.7 cGy), spleen lymphocyte susceptibility to hydrogen peroxide was shown to increase. However, beginning from the day 120 of the treatment (20.4 cGy), the opposite effect was observed. An increase in number of the DNA-protein crosslinks was recorded in spleen lymphocytes only on day 40 of the experiment. The number of DNA breaks increased significantly beginning from day 120 of the experiment, as shown by the DNA-comet method. On the day 210 of irradiation, the frequency of abnormal sperm heads in the mice significantly increased. The number of normochromatic micronucleated erythrocytes of the peripheral blood remained unchanged.

[Assessment of single-stranded DNA breaks in spleen lymphocytes using the DNA comet assay in the long term after acute irradiation of mice at sublethal and moderately-lethal doses]. / Otsenka metodom DNK-komet odnonitevykh razryvov DNK limfotsitov selezenki v otdalennye sroki posle ostrogo oblucheniia myshei v subletal'nykh i sredneletal'nykh dozakh.

The single-strand DNA level in spleen lymphocytes of BALB/c male-mice after 11 month acute exposure to gamma-radiation at doses 1, 3 and 6 Gy has been investigated by comet assay. The results of our study showed that at 11 month after irradiation at different doses a significant increase in the level of DNA breaks in spleen lymphocytes and decrease in the total number of these cells in mice was registered. It is possible that the increase in the DNA breaks is due to the effort of the compensatory proliferation process in lymphoid system that can give the increase in the number of different genetic disturbances in lymphocytes.

[Cytogenetic effects in plant populations from the East Urals Radioactive Track]. / Tsitogeneticheskie éffekty v populiatsiiakh rastenii, proizrastaiushchikh na Vostochno-Ural'skom radioaktivnom slede.

Mutation dynamics in generations was studied in natural populations of plants from the East Ural Radioactive Track (EURT, Kyshtym accident). The experiments were aimed at the investigation of the formation of genetic load in natural plant populations under conditions of prolonged radiation exposure. The main approach used in the study was the analysis of cytogenetic alteration, chlorophyll and gene mutations in plants exposed for more than 40 years to chronic beta-irradiation and in their progeny.

[Restoration of pine plantations after effect of ionizing radiation in the region of the accident at the Chernobyl Atomic Energy Station]. / Vosstanovlenie posle vozdeistviia ioniziruiushchikh izluchenii sosnovykh lesonasazhdenii v zone avarii na Chernobyl'skoi AES.

The main results of the 12-year radiation-genetic monitoring of radiobiological, cytogenetic, and genetic parameters in the Pinus sylvestris L. forest plantations from the zone of the accident at the Chernobyl nuclear power plant presented. Acute ionizing irradiation at doses > 1 Gy was shown to induce the formation of morphoses and depressed growth; at doses > 2 Gy, the reproductive ability of the trees declined. The radiobiological parameters showed a linear (or close to linear) dose-effect relationship. Acute irradiation at a dose of 0.5 Gy induced cytogenetic and genetic effects that were significantly higher than the corresponding control values. The relationship between the cytogenetic effects and the absorbed dose was exponential. The dependence of the mutation frequency at specific loci on the absorbed dose was described by a nonlinear curve. The results of cytogenetic analysis of sprouts obtained from seeds annually (1986-1998) collected in zones of slight, moderate, and strong damage of Pinus sylvestris L. are presented.