Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population

INTRODUCTION: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. MATERIAL AND METHODS: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. RESULTS: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. CONCLUSIONS: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.INTRODUCTION: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. MATERIAL AND METHODS: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. RESULTS: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. CONCLUSIONS: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB

Towards sustainable development through bridging digital penetration gaps

The aim of the article is to study the impact of the digital environment on the economic conditions of economic entities, as well as to assess the gaps between economic development, changes in social relations and environmental well-being. It is proved that gaps in digital penetration can cause the deepening of existing inequalities and risks: digital inequality, social inequality, inequality in the appropriation of benefits, environmental risks. Approaches to assessing the impact of digital artifacts on the environment (in the context of the concept of "circular economy") and sustainable development of the economic system are investigate

Związek wariantów polimorficznych genów kodujących interleukiny z występowaniem wielolekoopornej gruźlicy w populacji Ukrainy

WSTĘP: Gruźlica wielolekooporna (MDR-TB) stanowi poważny problem zdrowotny w pewnych regionach świata. Interleukiny 2 (IL-2), 4 (IL-4) i 10 (IL-10) odgrywają istotną rolę w immunopatogenezie gruźlicy. Podatność na gruźlicę wielolekooporną może być genetycznie uwarunkowana. Celem badania była ocena związku pomiędzy polimorfizmem genów IL-2, IL-4, IL-10 a występowaniem gruźlicy wielolekoopornej w populacji ukraińskiej. MATERIAŁ I METODY: Do badania włączono 140 chorych na gruźlicę naciekową i 30 osób zdrowych (grupa kontrolna). Wyodrębniono grupę chorych na gruźlicę wielolekooporną (MDR TB) i gruźlicę z zachowaną opornością na leki przeciwgruźlicze (non-MDR TB). Zbadano polimorfizm T330G genu IL-2, C589T genu IL-4 i G1082A genu IL-10 przy zastosowaniu łańcuchowej reakcji polimerazy. Stężenia IL-2, IL-4 and IL-10 w surowicy oznaczono za pomocą testu ELISA. WYNIKI: Przed leczeniem u chorych na gruźlicę stężenia w surowicy IL-2 były wyższe, a IL-4 i IL-10 niższe w porównaniu z grupą kontrolną. Stężenia IL-4 i IL-10 były istotnie niższe, podczas gdy stężenie IL-2 było istotnie wyższe w grupie MDR TB w porównaniu z pozostałymi chorymi (non- MDR TB). Opisane zmiany związane były z homozygotycznymi lub heterozygotycznymi mutacjami polimorficznymi C589T genu IL-4, G1082A genu IL-10 i T330G genu IL-2. WNIOSKI: Mutacje genów badanych cytokin mogą stanowić czynnik ryzyka gruźlicy i prowadzić do progresji i przewlekania się choroby. W grupie MDR TB genotypy heterozygotyczne badanych cytokin występowały najczęściej.WSTĘP: Gruźlica wielolekooporna (MDR-TB) stanowi poważny problem zdrowotny w pewnych regionach świata. Interleukiny 2 (IL-2), 4 (IL-4) i 10 (IL-10) odgrywają istotną rolę w immunopatogenezie gruźlicy. Podatność na gruźlicę wielolekooporną może być genetycznie uwarunkowana. Celem badania była ocena związku pomiędzy polimorfizmem genów IL-2, IL-4, IL-10 a występowaniem gruźlicy wielolekoopornej w populacji ukraińskiej. MATERIAŁ I METODY: Do badania włączono 140 chorych na gruźlicę naciekową i 30 osób zdrowych (grupa kontrolna). Wyodrębniono grupę chorych na gruźlicę wielolekooporną (MDR TB) i gruźlicę z zachowaną opornością na leki przeciwgruźlicze (non-MDR TB). Zbadano polimorfizm T330G genu IL-2, C589T genu IL-4 i G1082A genu IL-10 przy zastosowaniu łańcuchowej reakcji polimerazy. Stężenia IL-2, IL-4 and IL-10 w surowicy oznaczono za pomocą testu ELISA. WYNIKI: Przed leczeniem u chorych na gruźlicę stężenia w surowicy IL-2 były wyższe, a IL-4 i IL-10 niższe w porównaniu z grupą kontrolną. Stężenia IL-4 i IL-10 były istotnie niższe, podczas gdy stężenie IL-2 było istotnie wyższe w grupie MDR TB w porównaniu z pozostałymi chorymi (non- MDR TB). Opisane zmiany związane były z homozygotycznymi lub heterozygotycznymi mutacjami polimorficznymi C589T genu IL-4, G1082A genu IL-10 i T330G genu IL-2. WNIOSKI: Mutacje genów badanych cytokin mogą stanowić czynnik ryzyka gruźlicy i prowadzić do progresji i przewlekania się choroby. W grupie MDR TB genotypy heterozygotyczne badanych cytokin występowały najczęściej

Cardioinotropic effects in subchronic intoxication of rats with lead and/or cadmium oxide nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO– NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The work was carried out partly within the framework of the IIF UrB RAS themes No AAA?A18?118020590031?8 and AAAA?A18?118020590135?3. This work was performed using the equipment of the Shared Research Center of Scientific Equipment SRC IIP UrB RAS

Morphological changes in experimental tuberculosis resulting from treatment with quercetin and polyvinylpyrrolidone

Research objective: Morphological study of tissue necrosis stages in experimental organ-preserving tuberculosis pharmacotherapy using Quercetin and Polyvinylpyrrolidone (QP). Background and methods: 32 laboratory mice of C57BL/6JLacSto strain were used in the experiment. The animals were divided into five groups, six to seven mice in each: group 1- Mycobacterium tuberculosis (MBT) uninfected mice; group 2- MBT infected mice; group 3- MBT infected and treated with antituberculosis preparation (ATP); group 4- MBT infected and QP treated; group 5- MBT infected and treated with ATP and QP. The mice were infected through caudal vein injection with MTB H37Rv strain. The preparation QP, which belongs to the capillary-stabilizing-remedy group, was used for the research. The ATP were izoniazid and streptomycin. Results: QP produced a strict delineation of caseous necrosis from the unaffected parts of the connective tissue with fibrosis in the center and a large number of Langerhans cells, which was not observed in the control groups without QP. The combination of QP and ATP had more pronounced effects. In MBT-infected mice, where QP was not used, unlike the group where QP was used, adipose dystrophy of hepatocytes was observed. Thus, the hepatoprotective effect of QP against TB can be suggested. Conclusion: QP produces a clear delineation of caseous necrosis from an uninfected tissue by connective-tissue formation, and by forming fibrotic tissue in the center of epithelioid cells that prevents further TB dissemination by enhancing TB pharmacotherapy