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

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

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

Bi-enzyme sensor based on thick-film carbon electrode modified with electropolymerized tyramine

Bi-enzyme sensor based on thick-film epoxy-carbon electrode modified with polytyramine has been developed and examined for the determination of peroxidase substrates and cholinesterase inhibitors. Polytyramine was obtained on the electrode surface by repeated scanning of the potential from +600 to +1800 mV vs. Ag/AgCl in tyramine solution. The enzymes were immobilized in the polytyramine matrix by cross-linking with glutaraldehyde. The biosensor developed provides a reliable and inexpensive way for preliminary testing of common environmental pollutants with a single sensor in accordance with assumed toxic effect by the choice of appropriate substrate and measurement conditions. The bi-enzyme sensor makes it possible to determine substituted phenols and aromatic amines in the micromolar range of their concentrations and anticholinesterase pesticides with detection limits of 0.1 (Coumaphos) and 0.03 μmol l-1 (Chloropyrifos-methyl). © 2004 Published by Elsevier B.V

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

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