MULTIVARIATE ANALYSIS USE IN THE EFFICACY EVALUATION OF IMMUNOTHERAPY WITH VP-4 IN THE PATIENTS WITH BRONCHIAL ASTHMA COMPLICATED BY CHRONIC INFLAMMATION NIDI

65 patients with infection-dependent and mixed forms of bronchial asthma have been provided with immunotherapy with VP-4. With the help of multivariate analysis there have been defined the main efficacy criteria and the mathematical prediction model of the positive effect of this therapeutic method have been made

Валідація алкаліметричної методики кількісного визначення вільних органічних кислот у листі малини

 Organic acids are a large group of biologically active compounds that perform important functions in the plant organism. Moreover, all plants, regardless of the species and family, contain organic acids to a small or large extent as organic acids belong to intermediate metabolites arising from the oxidation of proteins and amino acids, fats and carbohydrates.Aim. To validate the method of alkalimetry proposed with potentiometric detection of the end-point for the quantitative determination of free organic acids in raspberry leaves.Results and discussion. The method proposed was validated according to the International Conference on Harmonization (ICH) guidelines. The linearity was in the concentration range of 40 – 200 % (r2 = 0.9991). The percentage of recovery was found to be in the range of 98.77 – 102.48 %. The repeatability and intermediate precision were 1.58 % and 1.74 %, respectively. The method is accurate and reliable, with the relative standard deviation of less than 2 %.Experimental part. Leaves of raspberry were collected in the Kharkiv region during the period of full ripening. A Hanna 2550 pH-meter with a HI 1131P potentiometric electrode was used for alkalimetric titration of free organic acids. The titration was carried out using a microburette with Class A accuracy.Conclusions. The alkalimetry method for the quantitative determination of free organic acids in raspberry leaves has been proposed and validated according to the following parameters: specifcity, linearity, accuracy, repeatability, intermediate precision, robustness. It has been confrmed that the method is simple, reliable, accurate and cost-effective.Key words: raspberry; leaves; free organic acids; alkalimetry; validationОрганічні кислоти – велика група біологічно активних сполук, які виконують важливі функції в обміні речовин рослин. Усі рослини, незалежно від виду та родини, містять органічні кислоти в невеликій або значній кількості, бо ці речовини належать до проміжних метаболітів, що утворюються в результаті окиснення білків, амінокислот, жирів та вуглеводів.Мета. Валідувати запропоновану алкаліметричну методику з потенціометричним виявленням кінцевої точки титрування для кількісного визначення вільних органічних кислот у листі малини.Результати та їх обговорення. Запропонований метод валідовано згідно з директивою International Conference on Harmonization. Лінійність зберігалася в діапазоні концентрацій 40 – 200 % (r2= 0,9991). Визначено, що відсоток відновлення становить 98,77 – 102,48 %, повторюваність та проміжна точність – 1,58 % та 1,74 % відповідно. Метод характеризується як точний і надійний, має відносне стандартне відхилення менше 2 %.Експериментальна частина. Листя малини в період повного дозрівання збирали в Харківській області. Для алкаліметричного титрування вільних органічних кислот використовували рН-метр Hanna 2550 з потенціометричним електродом HI 1131P. Титрування проводили мікробюреткою з класом точності А.Висновки. Розроблену титриметричну методику кількісного визначення вільних органічних кислоту листі малини валідовано за такими параметрами: специфічність, лінійність, точність, збіжність, внутрішня прецизійність, робасність. Підтверджено, що метод є простим, надійним, точним та економічно вигідним.Ключові слова: малина; листя; вільні органічні кислоти; алкаліметрія; валідаці

ROLE OF IL-4, IL-6, IL-8, IL-10 CYTOKINES IN THE IMMUNOPATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is socially significant disease. COPD is based on chronic inflammatory process of respiratory tract, which determines steady progression of the bronchial obstruction. Studies of the role of cytokines in immune pathogenesis of COPD are of crucial importance. The biological mediators determine local, systemic inflammation, and pathophysiological effects of extra-systemic pathological manifestations. In this work, we studied spontaneous and induced production of IL-4, IL-6, IL-8, IL-10 cytokines by blood leukocytes from the patients with moderate and severe chronic obstructive pulmonary disease, beyond the exacerbation phase. It is shown that the evident role in formation of the inflammatory process in COPD belongs to the IL-6, IL-8. We have found a significant increase in both spontaneous and induced production of IL-6 and IL-8 (p < 0.05) in the patients. Induced production of cytokines strongly suggests the reserve capabilities of immunocompetent cells in response to the pathogenic factor. Neutrophilic type of inflammation, manifesting as activation of granulocytes, mostly, neutrophils, in response to toxic agents (in particular, smoking) and bacterial pathogens, is primarily associated with IL-6 and IL-8. These results reflect the type and intensity of respiratory tract inflammation in patients with chronic obstructive pulmonary disease and its persistent course.High levels of the studied cytokines confirm their role in bronchial remodeling and contribute to irreversibility of bronchial obstruction in this disorder. The relationship between spontaneous and induced production of the studied cytokines and the clinical indices of the disease course has been shown. Statistically significant increase between frequency of COPD recurrences (more than 2 times pro year, p < 0.05), and low FEV1 values (p < 0.05) were observed in patients with high values of spontaneous and induced production of IL-6 and IL-8. It may be associated with persistent course of neutrophilic inflammation of respiratory tract and progressive bronchial obstruction. IL-6 and IL-8 significantly contribute to pathogenetic mechanisms, determining the clinical course of COPD and may serve as markers of severity in this disorder. Certainly, the immune mechanisms of pathological inflammation in COPD are complex and multifaceted. Studies of clinical significance of induced cytokine production will help the physician when determining type and duration of treatment. Personalized approach to the therapy of patients with COPD depends on the phenotype of pathology, pattern, severity and intensity of inflammation

Immunological features of allergic rhinitis in combination with chronic rhinosinusitis of bacterial etiology

Rhinitis is a socially significant and widespread disease. Often, various forms of rhinitis are combined, and thus cause severe clinical manifestations, insufficient effectiveness of drug treatment, as well as difficulties in differential diagnosis. It is known that a significant number of patients have a combination of allergic rhinitis (AR) with chronic rhinosinusitis of bacterial etiology. This condition is based on a chronic multifactorial inflammatory process of the nasal mucosa, which determines the steady progression of the disease. Of interest is the study of a number of allergo-immunological parameters in nasal secretions in order to assess local inflammation and changes in mucosal immunity in allergic rhinitis in combination with chronic rhinosinusitis of bacterial etiology (AR with HRSBE). Mucosal immunity and biological mediators determine local inflammation and pathophysiological response to etiological factors in the immunopathogenesis of AR with CRSBE. The work carried out the determination of the level of cytokines: IL-4, IL-10, TGF-â1, IFNã spontaneous and induced; immunoglobulins: IgA, IgM, IgG, sIgA in nasal secretions; leukotrienes: LT C4/ D4/E4 and LTB4 in plasma and total IgE in serum in patients with AR with moderate-severity HRSBE without exacerbation. It has been shown that the leading role in the formation of the inflammatory process in AR with CRSBE belongs to cytokines: IL-4, IL-10, TGF-â; immunoglobulins: IgM, sIgA; leukotrienes: LT C4/D4/E4 and LTB4 and total IgE. Induced cytokine production largely reflects the reserve capabilities of immunocompetent cells in response to the action of a pathogenic factor. The results obtained are associated with the persistent course of allergic and infectious inflammation and the progression of the disease. Thus, cytokines: IL-4, IL-10, TGF-â1; immunoglobulins: IgM, sIgA, IgE total and LT C4/D4/E4 and LTB4 make a significant contribution to pathogenetic mechanisms, determining the clinical course of AR with CRSBE, and can serve as biological markers of the activity of the pathological process. Undoubtedly, the immune mechanisms in the combined pathological inflammatory reaction from the mucosa in AR with HRSBE are complex and multifaceted. A personalized approach to the treatment of patients with AR with CRSBE is determined by the severity and intensity of the inflammatory reaction, as well as mucosal mucosal immunity disorders. The study of the role and significance of the production of leading cytokines, immunoglobulins in nasal secretions, as well as leukotrienes and total IgE in the blood will help the doctor in determining the tactics and duration of pharmacotherapy

Effect of the secretome of multipotent mesenchymal stromal cells induced by dexamethasone in vitro on the expression of phospho-NF-κB p65 and Ki-67 in mononuclear cells

To investigate the influence of secretomes from native and dexamethasone-treated adipose-derived multipotent mesenchymal stromal cells (MMSC) on the proliferation of mononuclear cells (MNCs) and on their expression of phospho-NF-κB p65 in vitr

Management of in-tube projectiles using acoustic channel

The article describes the method of measuring the distance from the operator's console installed outside the pipe to the in-tube projectile. A method for measuring distance in the absence of an echo signal is proposed. To do this, two identical ultrasonic locators operating at different frequencies were installed inside and outside the pipeline. The change in the duration of an acoustic pulse propagating in a circular waveguide with rigid walls is shown, which leads to a decrease in the data transfer rate

Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers

Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine “click”-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar “raft-like” nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity. © 2020 National Academy of Sciences. All rights reserved

Studyng the effects of Cantharellus cibarius fungi on Opisthorchis felineus trematode and on parasite host - C57BL/6 inbred mice

Opisthorchiasis is a dangerous parasitic disease caused by trematodes in the family Opisthorchiidae. One of the causes of this infection is the species Opisthorchis felineus, which is common in the Russian Federation and Western Europe. The disease has a large number of complications and relatively few effective treatments, so nowadays it is relevant to look for new drugs for the treatment of opisthorchiasis, with the maximum antiparasitic and minimal side effect. In this work, a potentially anthelmintic effect of the methanol extract of the golden chanterelle mushroom (Cantharellus cibarius) was investigated. In in vitro experiments, the significantly reduced mobility and survival rates of juvenile O. felineus specimens with increasing concentrations (10-1000 pg/ml) of the C. cibarius extract were shown. In in vivo studies, administration of the C. cibarius extract on the first day after parasitic infection of inbred C57BL/6 mice resulted in a decrease of the number of helminths in the bile ducts of the liver, evaluated 6 weeks after infection. In another series of experiments, administration of the C. cibarius extract for 7 days to mice infected with O. felineus for five weeks had no anthelmintic effect. In both cases, the state of the infected hosts, evaluated by a number of physiological and biochemical parameters (relative weight of organs, blood indices), did not deteriorate, indicating that there was no adverse effect of the C. cibarius extract. The results obtained suggest that the C. cibarius extract might have anthelmintic properties if applied as parasite larvae excyst

Development of DNA-Biochip for Identification of Influenza A Virus Subtypes

Developed was the DNA-biochip to identify subtypes of influenza A virus, pathogenic for humans. Microchip was capable of detecting H1, H3, H5-subtypes of hemagglutinin (including H1-subtype of pandemic A/H1N1(2009) influenza virus ) and neuraminidase subtypes N1,N2 of influenza virus. This microchip was successfully tested on the strains of A/H5N1 highly pathogenic avian influenza virus, A/H1N1(2009) pandemic influenza virus, A/H1N1 and A/H3N2 seasonal influenza viruses

First experience of using Brentuximab vedotin and modified program NHL-BFM-90 in the front-line treatment of patient with anaplastic large-cell lymphoma: a case report and a review of literature

Nodal anaplastic ALK-negative large cell lymphoma (nALCL, ALK-) is a Т-cell lymphoma that is characterized by aggressive clinical course and low sensitivity to СНОР (cyclophosphamide, doxorubicin, vincristine, prednisolone) and other chemotherapy regimen. In the article we present a literature review and describe our clinical case of nALCL, ALK-. For the first time a combination of Brentuximab vedotin with modified program NHL-BFM-90 was used as a first-line therapy. As a result of immunochemotherapy a complete antineoplastic effect was obtained. For consolidation of this effect high-dose chemotherapy with following autologous blood stem cell transplantation was performed. The chosen treatment tactics allowed to achieve a complete remission in a medium risk group patient