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

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

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

Bipolaron Binding in Quantum Wires

A theory of bipolaron states in quantum wires with a parabolic potential well is developed applying the Feynman variational principle. The basic parameters of the bipolaron ground state (the binding energy, the number of phonons in the bipolaron cloud, the effective mass, and the bipolaron radius) are studied as a function of sizes of the potential well. Two cases are considered in detail: a cylindrical quantum wire and a planar quantum wire. Analytical expressions for the bipolaron parameters are obtained at large and small sizes of the quantum well. It is shown that at $R\gg 1$ [where $R$ means the radius (halfwidth) of a cylindrical (planar) quantum wire, expressed in Feynman units], the influence of confinement on the bipolaron binding energy is described by the function $\sim 1/R^{2}$ for both cases, while at small sizes this influence is different in each case. In quantum wires, the bipolaron binding energy $W(R)$ increases logarithmically with decreasing radius. The shapes and the sizes of a nanostructure, which are favorable for observation of stable bipolaron states, are determined.Comment: 17 pages, 6 figures, E-mail addresses: [email protected]; [email protected]

P and CP violation in B physics

While the Kobayashi--Maskawa single phase origin of CP violation passed its first crucial precision test in $B\to J/\psi K_S$, the chirality of weak $b$-quark couplings has not yet been carefully tested. We discuss recent proposals for studying the chiral and CP-violating structure of these couplings in radiative and in hadronic B decays.Comment: 15 pages, talk at PASCOS'03, Tata Inst., Mumbai, Jan. 200

Glycerol valorization: dehydration to acrolein over silica-supported niobia catalysts

The catalytic dehydration of glycerol to acrolein is investigated over silica-supported niobia catalysts in a continuous fixed-bed gas-phase reactor. Various supported niobia catalysts are prepared and characterized using surface analysis and spectroscopic methods (XRD, UV–Vis, XPS, N2 adsorption), as well as with ammonia adsorption microcalorimetry. Good results are obtained with initial glycerol conversions of over 70% and with 50–70% selectivity to acrolein. We investigate the influence of changing the catalyst acid strength by varying the niobia content and catalyst calcination temperature. Glycerol conversion and acrolein selectivity depend on the surface acid strength. Catalyst deactivation by coking is also observed, but simple oxidative treatment in air restores the activity of the catalysts completely

Vilnius Declaration on chronic respiratory diseases : multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases

Correction: Volume: 10 Issue: 1 Article Number: 49 DOI: 10.1186/s13601-020-00357-4 Published: DEC 17 2020Background: Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patients are still uncontrolled and the cost of inaction is unacceptable. A meeting was held in Vilnius, Lithuania (March 23, 2018) under the patronage of the Ministry of Health and several scientific societies to propose multisectoral care pathways embedding guided self-management, mHealth and air pollution in selected chronic respiratory diseases (rhinitis, chronic rhinosinusitis, asthma and COPD). The meeting resulted in the Vilnius Declaration that was developed by the participants of the EU Summit on chronic respiratory diseases under the leadership of Euforea. Conclusion: The Vilnius Declaration represents an important step for the fight against air pollution in chronic respiratory diseases globally and has a clear strategic relevance with regard to the EU Health Strategy as it will bring added value to the existing public health knowledge.Peer reviewe