DNA methylation-associated colonic mucosal immune and defense responses in treatment-na?ve pediatric ulcerative colitis

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P < 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.     

Inductive role of mossy fibers of hippocampus in the development of dendritic spines in aberrant synaptogenesis at neurotransplantation

The dentate fascia of the hippocampal formation isolated from 20-day-old Wistar rat fetuses was subjected to heterotopic transplantation into the somatosensory area of the neocortex of adult rats of the same strain. Five months after surgery, neurotransplantates, together with neighboring area of the neocortex, were studied using light and electron microscopy. We carried out a detailed study of the ultrastructure of the ectopic synaptic endings formed by the axons of granular neurons of the dentate fascia (mossy fibers) with neurons of the neocortex unusual for them in a normal state. Ultrastructural analysis revealed that most ectopic synaptic endings produce its determinant morphological features: giant sizes of presynaptic knobs, active zones with branched dendritic spines, and adherens junctions with the surface of dendrites. The data indicate that the mossy fibers growing from neurotransplantates induce structural and chemical reorganization of dendrites of the neocortex using transmembrane adherens junctions, such as puncta adherentia junctions. This results in the differentiation of active zones and development of dendritic spines typical for giant synaptic endings that are invaginated into presynaptic endings. Thus, the ability of neurons of the dentate fascia to form aberrant synaptic connections at transplantation results from the inductive synaptogenic properties of mossy fibers.     

Effect of Short-term Cooling at –70°C in an Air Cryogenic Sauna on Body Temperature and Lipid Profile of Healthy People

The investigation was aimed at evaluation of level and rate of cutaneous and tympanic temperature drop due to a single short-timed (3 min) cooling in a cryosauna (–70°С), and adaptation-indicative physiological parameters, including blood catecholamines, ACTH, lipoproteins and free fatty acids. The subjects were seven healthy men. Exposure to cold invariably reduced the internal (tympanic) and cutaneous temperature by 1°С and 7°С on average, respectively. Tympanic temperature remained 0.4°С low on the average for more than 20 min after exposure. Cutaneous temperature was 1°С below the norm for an hour after cooling. For one hour after the short-term cold exposure, blood norepinephrine remained increased, and so did the blood concentrations of high-density lipoprotein cholesterol and free fatty acids. These results demonstrate brief adaptive changes following a single exposure at–70°C.     

Antibiotic therapy of intestinal infections complicated by toxicosis and exicosis in children with immunodeficiency syndromes]

Clinical processes of acute intestinal infections complicated by toxicosis and exicosis and some host immunological parameters were studied in infants with secondary immunodeficiency. A special treatment scheme was developed including combined use of antibiotics, human immune globulin administered intravenously and cytochrome C. The scheme provided a decrease in the treatment duration by 8.6 +/- 1.1 days. Advanced and chronic diseases and fatal outcomes were absent. It was concluded that the developed scheme increased host immunological reactivity and efficacy of antibiotic therapy. It was recommended for wide clinical use in pediatric clinical care.     

Anton Chekhov and Robert Koch Cheek to Cheek: A Proteomic Study

Five different letters and post cards as well as the shirt worn by Anton Chekhov on his death bed, stored in the State Literary‐Memorial Museum‐Reserve A. P. Chekhov Melikhovo (nearby Moscow), have been analyzed by applying EVA (an ethyl vinyl acetate foil studded with crushed strong anion and cation exchangers and with C₈ resins) diskettes to these surfaces. Three different eluates (under acidic and basic conditions and with acetonitrile) were analyzed by high resolution mass spectrometry. The environmental microbiota present on samples and the Mycobacterium tuberculosis strain were described by a meta‐proteomics approach. Eight identified M. tuberculosis proteins confirmed the presence of the bacterium and the cause of Chekhov's death, in addition to several sequenced peptides belonging to other bacterial species. The human plasma proteins and human keratins, detected on a tiny blood spot on the shirt, demonstrated the power of the combined approach.