MECHANISMS OF ANALEPTIC AND ANTIGIPOXIC EFFECTS OF HETEROSIDES – (DERIVATIVES FOR SULFUR AND NITROGEN CONTAINING HETEROCYCLES)

In order to expand the theoretical base of targeted search for analeptics, the awakening and antihypoxic properties of Heterosides-21, Heterosides-31 (derivatives of sulfur and nitrogen containing heterocycles) were studied and their mechanisms of action were established. Sodium thiopental (42 mg/kg) was used to simulate suppression of the respiratory and vasomotor centers of the brain. Comparative drugs were the combined analeptic sulfocamphocaine (SCC) (20 mg/kg) and antihypoxant Piracetam (300 mg/kg).The results were obtained on the models of thiopental anesthesia and normobaric hypoxia with hypercapnia, the analysis of which allowed: to qualitatively and quantitatively assess the awakening, antihypoxic activity of the studied substances and classical preparations; their effect on the respiratory center of the brain and the behavioral responses of animals; theoretically substantiate, experimentally confirm and establish aerobic, anaerobic and detoxification mechanisms for the realization of effects in various conditions; to formulate the theoretical foundations of a targeted search for universal analeptics and antihypoxic drugs, to offer an instrumental and methodological complex for their experimental reproduction.In order to expand the theoretical base of targeted search for analeptics, the awakening and antihypoxic properties of Heterosides-21, Heterosides-31 (derivatives of sulfur and nitrogen containing heterocycles) were studied and their mechanisms of action were established. Sodium thiopental (42 mg/kg) was used to simulate suppression of the respiratory and vasomotor centers of the brain. Comparative drugs were the combined analeptic sulfocamphocaine (SCC) (20 mg/kg) and antihypoxant Piracetam (300 mg/kg).The results were obtained on the models of thiopental anesthesia and normobaric hypoxia with hypercapnia, the analysis of which allowed: to qualitatively and quantitatively assess the awakening, antihypoxic activity of the studied substances and classical preparations; their effect on the respiratory center of the brain and the behavioral responses of animals; theoretically substantiate, experimentally confirm and establish aerobic, anaerobic and detoxification mechanisms for the realization of effects in various conditions; to formulate the theoretical foundations of a targeted search for universal analeptics and antihypoxic drugs, to offer an instrumental and methodological complex for their experimental reproduction

Linguo-pragmatic features of elliptic constructions in media discourse

The article is devoted to a linguistic research of the impact of social media texts on modern society. The article considers the linguistic and pragmatic features of ellipsis in mass media texts and their influence on readers. The argument of the article is illustrated through the discourse analysis of media texts. The object of the present paper is to analyze ellipsis as a particular characteristic of media text

Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma

The prevalence of bronchial asthma has shown its steady increase in the world in recent years. Despite all the achievements of Allergology, control of the disease can be achieved only in two-thirds of patients even if all social risk factors and the influence of concomitant diseases are excluded. Thus, it is necessary to study endogenous factors that modify the pathogenesis of the disease. Toll-like receptors are the main molecules for recognizing pathogenic patterns in the human immune system. Since any Allergy is a recognition error, mutation of the genes of the recognizing molecules can have a direct and multidirectional effect on the nature of the inflammation and its clinical manifestations in bronchial asthma (BA). To detect this effect, 65 patients with BA were examined, and mutations of Toll-like receptor genes were detected: TLR2-Arg753Glu, TLR4- Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G, lymphocyte subpopulations CD3, CD19, CD4, CD8, CD16, phagocytosis indicators, levels of IgA, IgM, IgG, IgE and IL-6, IL-7, IL-9. The assessment of the severity of asthma and its level of control were conducted according to clinical recommendations of the Ministry of health of the Russian Federation in 2019 criteria. We have shown characteristic clinical manifestations of the studied mutations. A lighter course of the disease, more complete control over it and a better response to therapy were found in single-nucleotide substitutions in the Toll-like receptor 4 and 9 (TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G). On the contrary, a heavier course and a worse response to therapy were detected in the TLR2 mutation with Arg753Glu replacement. In the studied groups, the features of immunity indicators characteristic of genotypes with a lighter and more controlled course of BA were determined: a higher absolute number of T-helpers, with multidirectional changes in the number of T-killers, but with invariably preserved higher ratio of CD4/CD8 in such genotypes. Higher levels of phagocytosis indicators (primarily characterizing chemotaxis) and IL-7, IL-9 were also detected. The exception is the TLR9-A2848G mutation, in which greater disease control and better response to therapy are combined with no changes in the studied laboratory characteristics. At the same time, a specific feature of the genotype of the studied patients with BA was revealed – a combination of Toll-like receptors 4 and 9 mutations. This suggests the presence of genetic patterns that characterize groups of patients with BA that differ in severity, response to therapy, and degree of control, which makes it possible to personalize approaches to diagnosis, prevention, and therapy of the disease

The effect of magnetophoresis and Brownian diffusion on the levitation of bodies in a magnetic fluid

New aspects related to the redistribution of magnetic particles concentration in a magnetic fluid caused by magnetophoresis and Brownian diffusion in a nonuniform magnetic field are considered. These aspects deal with the influence of these processes on pressure redistribution and levitation of bodies in a magnetic fluid. It is shown that due to these processes the pressure force acting on bodies changes significantly with time and can be reduced dozens of percent if compared to a homogenous flui

Probleme der Initiierung und Katalyse der Flüssigphasenoxidation von Cyclohexan und der Aldehyde

Die Flüssigphasenoxidation organischer Verbindungen mit Sauerstoffmolekülen ist ein wertvoller, eingehend untersuchter Prozeß mit Nebenprodukten, bei dem die Geschwindigkeit der Keimbildung im Anfangsabschnitt wesentlich geringer ist als die Geschwindigkeit von dem einen Zwischenprodukt zu den verschiedenen Produkten führenden Folgereaktionen. Zur Beschleunigung der Oxidationsreaktionen muß man deshalb zu Beginn des Prozesses freie Radikale mit einer hohen Reaktionsgeschwindigkeit erzeugen. Die jüngsten Erfolge auf dem Gebiet der Erzeugung von leistungsstarken Ultraschall-Wellen (US) ergeben Energiedichten von 10 hoch 3 - 10 hoch 6 W/qu.cm bei einer Intensität von 10 hoch 5 W/qu.cm. Diese Werte liegen um ein Vielfaches über den Energiedichten, die beim Einsatz anderer physikalischer Methoden zur Einwirkung auf Substanzen erzielt werden, wie etwa Radiolyse und Photolyse. Somit ist die Ultraschallkavitation eine der neuesten und vielversprechenden Methoden zur Initiierung der Oxidationsvorgänge organischer Verbindungen. Die hohe Initiierungsgeschwindigkeit, die zu Beginn des Prozesses erzeugt wird, stellt sicher, daß der Prozess im Gesamten schnell abläuft; der Ultraschalleinfluß wirkt sich jedoch im Wesentlichen auf das Initiierungsstadium aus und für die gewünschte Regulierung der Produktzusammensetzung und zur Steigerung der Selektivität des Prozesses muß man Katalysatoren und katalytische Systeme einsetzen. Am Beispiel der katalytischen Flüssigphasenoxidation der alpha-Alkylacroleine und von Cyclohexan wurde gezeigt, daß man in Gegenwart von Co(II)- und Ce(III)-Verbindungen, die sich in ihrer Aktivitität und ihren Koordinationseigenschaften stark unterscheiden, die Produktzusammensetzung durch Veränderung der Reaktionsweisen regulieren kann, was auch eines der Prinzipien zur Steigerung der Selektivität der Oxidationsvorgänge ist

Features of mitochondrial membrane potential of immunocompetent blood cells in children with chronic nonspecific lung diseases accompanied by pneumofibrosis

Pneumofibrosis is a pathological outcome of pulmonary tissue inflammation. It can complicate any lung and bronchial disorder. The mitochondrial membrane potential reflects functional state of immunocompetent blood cells that influence progression of a chronic inflammatory process. The aim of this work was to study the features of mitochondrial membrane potential (MMP) of immunocompetent blood cells in children with chronic nonspecific lung diseases (CNPD), accompanied by pneumofibrosis. We have examined 79 children with CNPD manifesting with symptoms of focal pneumofibrosis. The group of patients included children with congenital lung malformations (43%), consequences of bronchopulmonary dysplasia (41%), chronic bronchitis (10%), post-pneumonic pulmonary fibrosis (6%). The average age of children was 6.5±1.2 years, including 43 boys (54%) and 36 girls (46%). The comparison group included 46 children with COPD without signs of pulmonary fibrosis, the control group consisted of 30 apparently healthy children. The contents of cells with reduced MMP among lymphocytes, monocytes, and granulocytes in peripheral blood was determined with JC-1 dye, using the BD FACSCalibur instrument and Cell Quest Pro software (Becton Dickinson, USA). The proportion of lymphocytes with reduced MMP in patients with COPD was similar in the children of the main and comparison group, exceeding the indexes of the control group by 1.7 times (p < 0.001). Decreased MMP of granulocytes in children with pneumofibrosis was detected 1.9 times more often than in children with fibrosis-free CNPD cases (p < 0.05), and 3.4 times more common than in children from the control group (p < 0.001). Monocytes with reduced MMM in children with pulmonary fibrosis were detected 2 times more often than in children with COPD without fibrosis (p < 0.05), and 7.3 times more frequent than in the control group (p < 0.001). The changes were more expressed in children during exacerbation of the disease. The revealed features suggest a decreased level of metabolic activity of blood cells, thus, probably, presenting an immunopathogenetic basis for development of pneumofibrosis

Identification of apple genes <i>Md-Exp7</i> and <i>Md-PG1</i> alleles in advanced selections resistant to scab

The creation of apple varieties with a high level of flesh firmness and long shelf life is one of the important goals in breeding. Among the genes controlling these traits, the role of the endogenous ethylene biosynthesis control gene, Md-ACS1, the expansin gene, Md-Exp7, and the polygalacturonase gene, Md-PG1, has been established. The use of DNA marker analysis to solve problems in breeding for fruit quality traits allows one not only to track several target genes simultaneously, but also to cull plants with undesirable alleles at the early stages of development. In order to select complex donors of breeding traits, molecular genetic identification of the genes that determine the quality traits of apple fruits Md-Exp7 and Md-PG1 was performed in 256 breeding selections carrying the scab resistance gene Rvi6 and valuable allelic variants of the Md-ACS-1 gene, which determines the endogenous synthesis of ethylene in fruits: 90 samples with the Md-ACS1 allele (2/2) and 166 samples with Md-ACS1 (1/2). As a result of the study, an allelic combination for the Md-Exp7 and Md-PG1 genes was established. Analysis of the parental cultivars (Renet Simirenko, Modi, Smeralda, Renoir, Fulzhion and Granny Smith) used to obtain hybrid selections revealed three alleles 198, 202, 214 bp according to the DNA marker of the Md-Exp7 gene. The SSR marker for the Md-PG1 gene amplified three alleles (289, 292, 298 bp) on the abovementioned cultivars. Within the 256 breeding selections samples that have the most priority for breeding alleles of the desired genes in combination with the Rvi6 gene and/or with selection-priority allelic variants of the Md-ACS-1 gene were identified. Of the most valuable for breeding, 46 accessions carrying the combination Md-Exp7 (202:202) + Md-ACS1 (2/2) were distinguished. Hybrids with alleles Md-PG1 (292:292) + Md-ACS1 (2/2) are also most valuable for use in breeding and as donors of selection-valuable alleles; 21 samples were identified. Accessions with a complex of breeding-valuable target alleles are valuable complex donors, as well as valuable breeding material for creating varieties with improved fruit quality characteristics and scab resistance

Complex estimation of mitochondrial changes of immunocompetent blood cells in pregnant women with urgent and premature birth

Inflammation is among the factors promoting development of premature rupture of the membranes (PPROM). Upon the conditions of physiological immune imbalance in pregnancy, inflammation modifies its course and can even change the immune response. Appropriate indexes may be quantitative and functional. We used a marker of mitochondrial membrane potential (MPM, Ay) as an integral index of the functional state of immunocompetent blood cells (IBC) in 159 women who were examined at 8-14 weeks of gestation; they were observed up to 34-36 weeks. Of these cohort, 121 women were referred to a comparison group. The main group (n = 46) consisted of pregnant women with PPROM at the term of 28-33 weeks. The examination was carried out according to current medical standards, with informed consent, being approved by the Ethics committee at the Khabarovsk branch of Far Eastern Scientific Centre of Physiology and Pathology of Respiration — Research Institute of Maternity and Childhood Protection. Additionally, MPM and lymphocyte populations were determined by flow cytometry. The degree of disturbed energy supply in the IBC was based on the data of simultaneous determination of lymphocyte, granulocyte and monocyte numbers with reduced MPM values (application for invention No. 2020115963), thus revealing 3 degrees of energy deficiency: 1st degree, monovariant IBC composition with reduced MPM; 2nd degree, bivariant composition, 3rd degree, total changes. A relative and absolute decrease in CD3 (72% vs 78% and 1624 vs 1980), CD8 (28% vs 33% and 651 vs 851), an increase in CD19 (14% vs 9% and 304 vs 219) were revealed in pregnant women with PPROM. When assessing MPM values in the IBC populations, a decreased proportion of women without energy deficiency from the 1st to the 2nd trimester (from 41% to 30%), due to the 3rd degree of energy deficiency (from 17% to 26%) was detected. A shift of affected pools at the 2nd degree of energy deficiency in favor of lymphocytic-granulocytic association (from 7% to 25%) from lymphocytic-monocytic compartment (from 73% to 50%) was found. From the 2nd to 3rd trimester, we have detected redistribution of granulocyte pools at the 1st degree (0 to 8%) and from the lymphocytic-granulocytic association (25% and 5%) to monocytic-granulocytic (25% and 40%). In the group with PPROM, there was a decreased proportion of pregnant women without energy deficiency (13% and 27%), as well as with the 1st and 2nd degrees (17% vs 31% and 9% vs 17%), due to the 3rd degree of energy deficiency (61% and 26 %), relative to the comparison group. The IBC pools of in the main group were redistributed at the 1st degree in favor of granulocytes (25% and 8%), at the 2nd, in favor of the lymphocytic-monocytic association (100% and 55%) from the granulocytic-monocytic (0% and 40%). Such imbalance of bioenergetic processes in the IBC can be an important factor of pathologically ongoing inflammation. These changes could be caused by both higher incidence of infections in such patients and by alloimmune interactions between mother and fetus. However, they may also determine the pathological course of inflammation. Preterm birth, which is usually caused by PPROM, is a multifactorial pathological condition. However, independent on specific triggers, the changes in energy supply of IBC, at least, may serve as a significant biomarker of probability for this disorder

Assessment of breeding lines of rice (Oryza sativa L.) carrying the Pi-40 gene for resistance to rice blast strains from Krasnodar region

Blast caused by fungal pathogen Magnaporthe oryzae B.C. Couch, 2002, is one of the most harmful diseases of rice (Oryza sativa L.), and so the development of resistant varieties is important in rice breeding. Evaluation of the efficiency of blast resistance genes against local populations of the blast pathogen is an important preliminary stage in the formation of the breeding program. In the course of the study, the level of resistance to blast pathogen was estimated for hybrid lines BC1F3 derived from local rice variety Khazar and containing the Pi-40 gene. Plants carrying the dominant allele of the Pi-40 gene in the homozygous state were used in the study. A synthetic population of Magnaporthe oryzae consists of six strains selected at different rice-growing regions in the Krasnodar territory and Rostov region in the season with epiphytotic development of blast disease was used for phytopathological evaluation. Resistance to neck and panicle blast was estimated. Phytopathological testing revealed that the disease had high prevalence in domestic rice varieties Diamant, Courage and Khazar (74.4 %, 57.9 % and 83.3 %, respectively). Khazar/IR 83260-2-10-5-2-1-B hybrid plants from population BC1F3 carrying the target gene showed a high level of resistance (7.6 % prevalence). They are valuable for breeding blast resistant varieties. These findings confirmed a wide spectrum of blast resistance of the Pi-40 gene and promise for use for development of rice cultivars resistant to the population of Magnaporthe oryzae common in the Krasnodar territory

Nomenclatural standards and genetic certificates for apple-tree cultivars developed at the North Caucasian Federal Scientific Center of Horticulture, Viticulture, wine-making

Background. The development of genetic certificates and nomenclatural standards for newly released cultivars of Malus domestica Borkh. (apple tree) ensures an opportunity to preserve the original and authentic genetic and morphological information on domestic cultivars promising for the south of Russia. The purpose of this study was to develop genetic certificates and nomenclatural standards for 7 apple-tree cultivars developed at the North Caucasian Federal Scientific Center of Horticulture, Viticulture, Wine-making (NCFSCHVW), five of which were released jointly with the All-Russian Research Institute of Fruit Crop Breeding (VNIISPK).Materials and methods. The materials included apple-tree cultivars resistant or immune to scab (Venturia inaequalis (Cooke) G. Winter) from the NCFSCHVW collection stock. Conventional herbarization and DNA fingerprinting methods were used. For cultivar certification, an improved technique of DNA sampling and 12 microsatellite markers were applied.Results. Unique DNA profile certificates and nomenclatural standards were produced for 7 apple-tree cultivars: ‘Vasilisa’, ‘Karmen’, ‘Krasny Yantar’, ‘Soyuz’ and ‘Rassvet’ (with the Rvi6 gene) released jointly by the NCFSCHVW and VNIISPK, plus ‘Zolotoye Letneye’ and ‘Feya’ developed at the NCFSCHVW. The apple-tree herbarium specimens were placed for perpetual storage in the WIR Herbarium of the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR).Conclusion. The results obtained are promising for identification and authenticity verification of new domestic apple-tree cultivars during their reproduction and cultivation