Phadiatop as a screening method for prescribing immunobiological therapy

Over the past two decades, new opportunities have emerged in the treatment of severe bronchial asthma due to the development of immunobiological therapy. The effectiveness of biologics depends on correct phenotyping of asthma in patients.1 The Phadiatop test has been known since the 1980s and has established itself as a screening test for the detection of atopy, allergic rhinitis, and allergic asthma.2-9 When selecting patients with severe bronchial asthma for targeted therapy in the Sverdlovsk region, Russia, the Phadiatop™ (Phadia AB, Uppsala, Sweden) screening test was used for phenotyping asthma in this group of patient

Maternal smoking and DNA methylation abnormalities in children at early developmental stages

The paper analyzes the results of current studies of the role of DNA methylation during human embryonic development and the effects of tobacco smoke from maternal smoking on the epigenetic status of a developing child. The molecular mechanisms mediating the association between maternal smoking and its effects on the development and health of the offspring, especially its long-term effects that manifest throughout his/her life are the object of active research in medicine and biology. Human genomics studies in recent years have shown that one of these mechanisms may be the epigenetic regulation of gene activity, namely, stable tobacco smoke-induced alterations in this system can cause concomitant smoking-related developmental and health problems. Active smoking is an important risk factor for morbidity and premature mortality, while maternal smoking during pregnancy has a double effect: firstly, it adversely affects women’s health and secondly, it leads to irreparable fetal developmental disorders and affects the health and development of the newborn and the quality of his/her subsequent life

The Importance of Water for Purification of Longer Carbon Nanotubes for Nanocomposite Applications

Ultralong carbon nanotubes (UCNTs) are in high demand for nanocomposites applications due to their magnificent physical and chemical properties. UCNTs are synthesized by the catalytic chemical vapor deposition (CCVD) method and, before use as fillers in nanocomposites, should be purified of residual catalyst and non-CNT particles without significant destruction or scissoring of the UCNT. This study investigates the role of water vapor for purification of UCNTs from iron catalyst particles and the importance of water assistance in this process is confirmed. It was shown that wet air treatment of products of UCNTs CCVD synthesis under mild conditions can be used to sufficiently decrease residual iron catalyst content without significant carbon losses in comparison to the results obtained with dry air, while the residual iron content was shown to significantly influence the subsequent oxidation of different forms of carbons, including UCNTs. The increasing of D/G ratio of Raman spectra after wet air treatment of products of UCNTs CCVD synthesis makes it possible to conclude that iron catalyst particles transform into iron oxides and hydroxides that caused inner structural strains and destruction of carbon shells, improving removal of the catalyst particles by subsequent acid treatment. UCNTs purification with water assistance can be used to develop economically and ecologically friendly methods for obtaining fillers for nanocomposites of different applications

Ultrastructural liver changes in the experimental thyrotoxicosis

Aim of the study is to evaluate ultrastructural changes of rat liver in experimental thyrotoxicosis. For the study, 36 male rats have been utilized, weighing approximately 150-190 g, which were divided into three groups: the first, control group (12 animals) was composed of healthy rats that received intragastric sodium chloride 0.9% solution, the second group (12 animals) – animals with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 2 weeks, and the third group (12 animals) – rats with experimental thyrotoxicosis, which received intragastric solution of L-thyroxine at the rate of 200 μg/kg for 4 weeks. For electron-microscopic studies small pieces of liver tissue were taken at the end of the 2nd and 4th weeks of the experiment. The material was studied and documented in electron micrographs by using a TEM-125K electron microscope. In experiment in white male rats the electron-microscopic state of the liver in thyrotoxicosis has been studied. It has been established that thyrotoxicosis is accompanied by the significant changes of the hepatocytes ultrastructure, blood and bile capillaries. Experimental thyrotoxicosis causes significant damage of the liver plasma membranes and intracellular structural components of hepatocytes and endothelial cells. In experimental thyrotoxicosis, on the background of microcirculatory disorders, significant damage of plasmatic and intracellular organoid membranes of hepatocytes in the liver develops, which has an adverse effect on the functionality of the organ. The found ultrastructural changes are aggravated depending on the duration of thyrotoxicosis

Effects of early social deprivation on epigenetic statuses and adaptive behavior of young children: A study based on a cohort of institutionalized infants and toddlers

Early social deprivation (i.e., an insufficiency or lack of parental care) has been identified as a significant adverse early experience that may affect multiple facets of child development and cause long-term outcomes in physical and mental health, cognition and behavior. Current research provides growing evidence that epigenetic reprogramming may be a mechanism modulating these effects of early adversities. This work aimed to investigate the impact of early institutionalization—the immersion in an extreme socially depriving environment in humans—on the epigenome and adaptive behavior of young children up to 4 years of age. We conducted a cross-sectional study involving two comparison groups: 29 children raised in orphanages and 29 children raised in biological families. Genome-wide DNA methylation profiles of blood cells were obtained using the Illumina MethylationEPIC array; the level of child adaptive functioning was assessed using the Vineland Adaptive Behavior Scales-II. In comparison to children raised in families, children residing in orphanages had both statistically significant deficits in multiple adaptive behavior domains and statistically significant differences in DNA methylation states. Moreover, some of these methylation states may directly modulate the behavioral deficits; according to preliminary estimates, about 7–14% of the deviation of adaptive behavior between groups of children may be determined by their difference in DNA methylation profiles. The duration of institutionalization had a significant impact on both the adaptive level and DNA methylation status of institutionalized children

Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity

Background: Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow’s milk protein are increasingly considered for therapy and prevention of cow’s milk allergy. The aim of this study was to investigate the allergenic activity and ability to induce T cell and cytokine responses of an infant formula based on extensively hydrolyzed cow’s milk protein (whey) (eHF, extensively hydrolyzed formula) supplemented with Galactooligosaccharides (GOS) and Limosilactobacillus fermentum CECT5716 (LF) to determine its suitability for treatment and prevention of CMA. Methods: eHF and standard protein formula based on intact cow’s milk proteins (iPF) with or without Galactooligosaccharide (GOS) and Limosilactobacillus fermentum CECT5716 (LF) were investigated with allergen-specific antibodies and tested for IgE reactivity and allergenic activity in basophil degranulation assays with sera from cow’s milk (CM)-allergic infants/children. Their ability to stimulate T cell proliferation and cytokine secretion in cultured peripheral blood mononuclear cells (PBMC) from CM-allergic infants and children was studied with a FACS-based carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and xMAP Luminex fluorescent bead-based technology, respectively. Results: An eHF supplemented with GOS and LF exhibiting almost no IgE reactivity and allergenic activity was identified. This eHF induced significantly lower inflammatory cytokine secretion as compared to an intact protein-based infant formula but retained T cell reactivity. Conclusions: Due to strongly reduced allergenic activity and induction of inflammatory cytokine secretion but retained T cell reactivity, the identified eHF may be used for treatment and prevention of CMA by induction of specific T cell tolerance

Natural human Bet v 1‐specific IgG antibodies recognize non‐conformational epitopes whereas IgE reacts with conformational epitopes

AbstractBackgroundThe nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen‐exposed but non‐sensitized subjects has not been studied in detail.ObjectiveTo investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1‐specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1‐induced basophil activation.MethodsSera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non‐allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG1 and IgG4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N‐terminal (F1) and C‐terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro‐array analysis. The ability of Bet v 1‐specific serum antibodies from non‐allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1‐derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non‐allergic subjects to modulate Bet v 1‐induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients.ResultsIgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG1 and IgG4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen‐containing food. Natural Bet v 1‐specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1‐specific basophil activation.ConclusionIgE and IgG antibodies from BPA patients and birch pollen‐exposed non‐sensitized subjects recognize different epitopes. These findings explain why natural allergen‐specific IgG do not protect against allergic symptoms and suggest that allergen‐specific IgE and IgG have different clonal origin.</jats:sec