Structure functional status ofgastric mucous tunic and it microbiocenosis on chronical gastritis at children

The purpose of the research is to estimate morphofunctional condition mucus-producing apparatus of gaster according to its microbiocenosis at chronic gastritis. The objects of the research were gastric biopsy materials from 55 children at the age from 7 to 15 with diagnosis chronic gastritis (CG) which were divided into two groups: the 1st group — 35 patients with Helicobacter pylori (H.pylori)-fssociated CG; the 2nd — 20 patients with H.pylori-nonassociated CG. During the work there were used histologic, histochemical, lectinhistochemical, morphometric, bacteriologic and statistic methods.There was registered more evident recompartmentation of the lectin receptors on H.pylori-associated CG than on H.pylori-nonassociated CG, that was expressed by the elevation of the level of lectin connection by the cells having affinity to the Foucault mucins, and the reduction of the lectin receptors selectively reacting with the sialic acids (reduction of sialomucins's level) (p<0,05). It was found out that microbiocenosis disorders on H.pylori-associated CG and H.pylori-nonassociated CG have significant differences.Цель исследования — оценить морфофункциональное состояние компонентов слизьобразующего аппарата желудка в зависимости от его микробиоценоза при хроническом гастрите у детей. Объектами исследования стали гастробиоптаты от 55 детей в возрасте от 7 до 15 лет с диагнозом хронический гастрит (ХГ), которые сформировали две группы: 1-я — 35 пациентов с Helicobacter pylori (Н.ру1оп)-ассоциированным ХГ; 2-я группа — 20 больных с H.pylori-неассоциированным ХГ. В работе использованы гистологический, гистохимический, лектиногистохимический, морфометрический, бактериологический и статистический методы исследования. При H.pylori- ассоциированном ХГ зарегистрировано более выраженное перераспределение рецепторов к лектинам, чем при ХГ, не связанном с H.pylori, что выражалось в повышении уровня связывания клетками пектинов, имеющих сродство к фукомуцинам, и снижении содержания рецепторов к лектинам, селективно реагирующим с сиаловыми кислотами (падение уровня сиаломуцинов) (р<0,05). Показано, что нарушения микробиоценоза желудка при H.pylori-ассоциированном и при H.pylori-неассоциированном ХГ также имеют достоверные различия

Structure functional basis of remodeling of gastric mucous tunic on helicobacter pylori — associated gastritis at children

The purpose of the work is to estimate interaction between gelatinizes, tissular inhibitor of metalloproteinase-1 and growth factor in remodeling of gastric mucous tunic on Helicobacter pylori (H.pylori)-associated chronic gastritis (CG) at children. There were examined gastric biopsy materials from 35 children (25 boys and 10 girls) at the age from 7 to 15: 24 patients with H.pylori-associated CG (the 1st group) and 11 patients with functional dyspepsia (FD) (the 2nd group). There were used histologic, hietochemical, immunohistochemical. morphometric, bacteriologic and statistic methods. The results indicate reduction of production of the transforming growth factor-p receptors and elevation of production of the epidermal growth factor receptors, gelatinizes and tissular inhibitor of matrix metalloproteinase-1 on H.pylori-associated CG at children, that shows the formation of misbalance among growth factors, endoproteases and their inhibitors on this disease. There was proved the necessity of albation of the contagium at the earliest period of the disease beginning, and marked the ways for the target medical influence on some pathogenic points of the disease.Цель работы — оценить характер взаимодействий между желатиназами, тканевым ингибитором металлопротеиназ-1 и ростовыми факторами в ремоделировании слизистой оболочки желудка при Helicobacter pylori (H.pylori)-ассоциированном хроническом гастрите (ХГ) у детей. Изучены гастробиоптаты 35 детей (25 мальчиков и 10 девочек) в возрасте от 7 до 15 лет: 24 пациента с H.pylori-ассоциированным ХГ (1-я группа) и 11 больных с функциональной диспепсией (ФД) (2-я группа). Использовались гистологические, гистохимические, иммуногистохимические, морфометрические и статистические методы исследования. Полученные результаты свидетельствуют о снижении экспрессии рецепторов трансформирующего фактора роста-p и повышении уровня экспрессии рецепторов эпидермального фактора роста, желатиназ и тканевого ингибитора матриксных металлопротеиназ-1 при H.pylori-ассоциированном ХГ у детей, что свидетельствует о формировании при этом заболевании дисбаланса между факторами роста, эндопротеазами и их ингибиторами. Обоснована необходимость проведения эрадикации инфекта в наиболее ранние сроки от начала болезни, намечены подходы к таргетному медикаментозному воздействию на некоторые патогенетические звенья болезни

Non-hemagglutinating flaviviruses: molecular mechanisms for the emergence of new strains via adaptation to European ticks

Tick-borne encephalitis virus (TBEV) causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE

Structural characteristics of the processes of cell renewal in the gastric mucosa in chronic atrophic gastritis of various genesis

It was carried out histological analysis of gastric biopsies from 76 patients aged 19-74, which had chronic atrophic gastritis with immunopathological component, associated with H.pylori (CAG H.pylori-positive) and associated with absence of H.pylori (CAG H.pylori-negative). In the first group there were 30 patients with CAG H.pylori-positive, in the second group there were 46 patients with CAG H.pylori-negative. Proliferation index in gastric body in cases with HAG H.pylori-positive was authentically higher than in cases with CAG H.pylori-negative. Apoptosis index both in antrum and in gastric body in cases with CAG H.pylori-positive was also authentically higher than in cases with CAG H.pylori-negative. So CAG H.pylori-positive has morphological features, which can be characterized as "inflammatory type" of chronic gastritis with high levels of proliferation and apoptosis indexes. It can lead to intraepithelial neoplasia. CAG H.pylori-negative can be characterized as “atrophic type" of chronic gastritis with two variants of atrophy: absolute and metaplastic.Проведено гистологическое исследование гастробиоптатов от 76 пациентов с диагнозом хронический атрофический гастрит с иммунопатологическим компонентом. Среди обследованных было 30 пациентов в возрасте 19-74 лет с Н.pylori-ассоциированным атрофическим гастритом с иммунопатологическим компонентом, 46 больных с H.pylori-неассоциированным атрофическим гастритом с иммунопатологическим компонентом того же возраста. Изучение индекса пролиферации при Н.pylori-ассоциированном гастрите с иммунопатологическим компонентом показало, что в теле желудка этот показатель был выше, чем при Н.pylori-неассоциированном гастрите с иммунопатологическим компонентом. Индекс апоптоза при Н.pylori-ассоциированном гастрите с иммунопатологическим компонентом, зарегистрированный и в теле и в антруме, был также выше, чем при Н.pylori-неассоциированном гастрите с иммунопатологическим компонентом. Н.pylori-ассоциированный хронический атрофический гастрит с иммунопатологическим компонентом имеет морфологические признаки, характерные для «воспалительного типа» гастрита с наличием значительных показателей индексов апоптоза и пролиферации в теле желудка, что может способствовать развитию интразпителиальной неоплазии. Н.pylori-неассоциированный хронический атрофический гастрит с иммунопатологическим компонентом характеризуется гистологической картиной, свойственной «атрофическому типу» гастрита и вариантами атрофии, как абсолютной, так и метапластической

THE ROLE OF THE STRUCTURAL PROTEINS IN THE NON-VIRAEMIC TRANSMISSION OF TICK-BORNE ENCEPHALITIS VIRUS

There are 3 subtypes of tick-borne encephalitis virus (TBEV) distinguished, at present time: European (EU), Siberian (SIB) and Far Eastern (FE). The former one is associated with Ixodes ricinus tick, whereas the latter two - with I. persulcatus. The circulation of TBEV in nature is mediated by the non-viraemic transmission, between infected and. uninfected ticks co-feeding on the same hosts and. it was shown that transmission rate of «Hypr» strain (EU subtype) is much higher than rate of «Vasilchenko» strain (SIB subtype) - 60 and 5 % respectively. To reveal the viral determinants of transmission efficacy, we constructed the series of recombinant viruses with gradually exchanged genes coding structural (str) and. non-structural (ns) viral proteins. The recombinant virus Hypr[str]Vs[ns] achieved the rate of non-viraemic transmission of 70 %. The introduction of separate structural genes of Hypr into Vs infectious clone has enhanced the transmission efficacy as well, though not to such extent as entire structural region but up to 33 % only. Thus, it was shown that efficacy of non-viraemic transmission of TBEV depends from properties of viral structural proteins mainly

ПРОБЛЕМЫ ДИАГНОСТИКИ ТУБЕРКУЛЕЗА У ПАЦИЕНТОВ С РАЗНОЙ КОМОРБИДНОСТЬЮ

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Towards an alternative testing strategy for nanomaterials used in nanomedicine: lessons from NanoTEST.

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed

Allergenomics of the tick Ixodes ricinus reveal important α-Gal-carrying IgE-binding proteins in red meat allergy

Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3864]This is the peer-reviewed version of the following article: Apostolovic, D.; Mihailovic, J.; Commins, S. P.; Wijnveld, M.; Kazimirova, M.; Starkhammar, M.; Stockinger, H.; Platts-Mills, T. A. E.; Cirkovic Velickovic, T.; Hamsten, C.; et al. Allergenomics of the Tick Ixodes Ricinus Reveals Important α-Gal–Carrying IgE-Binding Proteins in Red Meat Allergy. Allergy: European Journal of Allergy and Clinical Immunology 2020, 75 (1), 217–220. [https://doi.org/10.1111/all.13978

Geographical Distribution and Genetic Diversity of Bank Vole Hepaciviruses in Europe

The development of new diagnostic methods resulted in the discovery of novel hepaciviruses in wild populations of the bank vole (Myodes glareolus, syn. Clethrionomys glareolus). The naturally infected voles demonstrate signs of hepatitis similar to those induced by hepatitis C virus (HCV) in humans. The aim of the present research was to investigate the geographical distribution of bank vole-associated hepaciviruses (BvHVs) and their genetic diversity in Europe. Real-time reverse transcription polymerase chain reaction (RT-qPCR) screening revealed BvHV RNA in 442 out of 1838 (24.0%) bank voles from nine European countries and in one of seven northern red-backed voles (Myodes rutilus, syn. Clethrionomys rutilus). BvHV RNA was not found in any other small mammal species (n = 23) tested here. Phylogenetic and isolation-by-distance analyses confirmed the occurrence of both BvHV species (Hepacivirus F and Hepacivirus J) and their sympatric occurrence at several trapping sites in two countries. The broad geographical distribution of BvHVs across Europe was associated with their presence in bank voles of different evolutionary lineages. The extensive geographical distribution and high levels of genetic diversity of BvHVs, as well as the high population fluctuations of bank voles and occasional commensalism in some parts of Europe warrant future studies on the zoonotic potential of BvHVs.Peer reviewe

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233