[The role of systemic immune activation in the development of thyroid dysfunction in COVID-19].

BACKGROUND: The research of cytokine-induced thyropathies in the midst of continuing coronavirus infection (COVID-19) pandemic is a very important and urgent problem. On the one hand, COVID-19 is often accompanied by a massive overproduction of cytokines, so we can expect an enhanced cytokines effects impact on the thyroid gland. On the other hand, it is possible that biological therapy with tocilizumab, which has a powerful immunosuppressive effect, plays a protective role to the development of cytokines-induced thyropathies amidst COVID-19. The results of the study should be the starting point for understanding the mechanisms of possible compromise of thyroid function during COVID-19. AIM: The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, FT3 and FT4 values, and patient survival. MATERIALS AND METHODS: This retrospective, single-center study included 122 patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, FT3, FT4, antibodies to thyroid peroxidase, antibodies to the TSH receptor (AT-recTSH). The markers of the inflammatory process were assessed: interleukin-6, C-reactive protein, the degree of lung tissue damage according to multispiral computed tomography of the lungs, the percentage of blood oxygen saturation (SpO2), the treatment outcomes. RESULTS: Five (4%) patients were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with interleukin-6 (r=-0.221; p=0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p=0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. CONCLUSION: Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. This study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate.

ADAPTATION OF HUMAN ROTAVIRUS STRAINS OF GROUP A TO THE REPRODUCTION IN PASSAGED CELL CULTURES.

The incidence of rotavirus gastroenteritis in the world still has no tendency to reduction. The development of an effective vaccine would reduce or, in the future, even defeat this highly contagious dangerous disease. However, both in Russia and abroad there is still no developed technique for adapting and cultivating strains of the human rotavirus A that would stably produce a high "yield" of virus progeny in transplanted culture cells. The phenomenon of gene exchange for the segmented genome of rotavirus was used by foreign researchers to create the rotavirus vaccine using reassortant strains which are the result of joint cultivation of low-titer (1-2·106 virions per ml) human rotavirus strains and rotavirus strains of animals, such as monkey rotavirus SA-11 or Nebraska calf rotavirus diarrhea providing a relatively high "yield" of virus progeny (1·107-1·108). It is clear that such vaccine compositions will not be able to replace a full-fledged vaccine of human rotavirus strains of different serotypes, but they can be used for the time being as a solution to the problem. Ideally, a rotavirus vaccine is needed that includes the full set of G and P serotypes of rotaviruses circulating in the territory of their application. The paper describes an original technique for adaptation and cultivation of human rotaviruses of group A on the culture of transplantable cells developed by the authors. This technique allows 5·108 virions to be obtained per 1 ml of culture fluid. High-titer cultivated strains of human rotavirus that can be used as vaccine strains were obtained, as well as highly-active antigens for the construction of diagnostic test-systems.

Photosensitization with protoporphyrin IX inhibits attachment of cancer cells to a substratum.

Effects of photodynamic therapy (PDT) on adhesion of human adenocarcinoma cells of the line WiDr to a plastic substratum were investigated. Protoporphyrin IX induced by 5-aminolevulinic acid (ALA) was used as a photosensitizer. Light exposure inhibited attachment of suspended cells to a substratum. The adhesion was most strongly pronounced for light exposures around 200 mJ/cm(2) causing cell death. However, sub-lethal exposures (42 mJ/cm(2), 97% survival) inhibited cell adhesion as well. Sub-lethal ALA-PDT increased the intracellular space in dense colonies of WiDr cells. This was attributed to formation of lamellipodia between the cells and to increased numbers of focal contacts containing alpha(V)beta(3) integrin in some of the cells. The E-cadherin distribution was not changed by the treatment. Complex processes, including changes in cellular shape and reorganization of the cytoskeleton, are suggested to participate in the observed ALA-PDT effect on the cell adhesion.

[Electrochemical methods of control of iodine contents in drinks]. / Elektrokhimicheskie metody dlia kontrolia soderzhaniia ioda v napitkakh.

The simple and express methods of determination of iodide ions (0.01-0.20 mg/decimeter3) in iodine-enriched drinks by potentiometry and inversion voltamperometry were developed. The studies on influencing a storage time hermetically packaged carbonated beverages, a storage time of the depressurized drinks, stuff of ware on the contents of iodine in drinks are held.

Organization, chromosomal localization and promoter analysis of the gene encoding human acidic fibroblast growth factor intracellular binding protein.

Acidic fibroblast growth factor (aFGF) intracellular binding protein (FIBP) is a protein found mainly in the nucleus that might be involved in the intracellular function of aFGF. Here we present a comparative analysis of the deduced amino acid sequences of human, murine and Drosophila FIBP analogues and demonstrate that FIBP is an evolutionarily conserved protein. The human gene spans more than 5 kb, comprising ten exons and nine introns, and maps to chromosome 11q13.1. Two slightly different splice variants found in different tissues were isolated and characterized. Sequence analysis of the region surrounding the translation start revealed a CpG island, a classical feature of widely expressed genes. Functional studies of the promoter region with a luciferase reporter system suggested a strong transcriptional activity residing within 600 bp of the 5' flanking region.

Uptake and intracellular transport of acidic fibroblast growth factor: evidence for free and cytoskeleton-anchored fibroblast growth factor receptors.

Endocytic uptake and intracellular transport of acidic FGF was studied in cells transfected with FGF receptor 4 (FGFR4). Acidification of the cytosol to block endocytic uptake from coated pits did not inhibit endocytosis of the growth factor in COS cells transfected with FGFR4, indicating that it is to a large extent taken up by an alternative endocytic pathway. Fractionation of the cells demonstrated that part of the growth factor receptor was present in a low-density, caveolin-containing fraction, but we were unable to demonstrate binding to caveolin in immunoprecipitation studies. Upon treatment of the cells with acidic FGF, the activated receptor, together with the growth factor, moved to a juxtanuclear compartment, which was identified as the recycling endosome compartment. When the cells were lysed with Triton X-100, 3-([3-chloramidopropyl]dimethylammonio)-2-hydroxy-1-propanesulfona te, or 2-octyl glucoside, almost all surface-exposed and endocytosed FGFR4 was solubilized, but only a minor fraction of the total FGFR4 in the cells was found in the soluble fraction. The data indicate that the major part of FGFR4 is anchored to detergent-insoluble structures, presumably cytoskeletal elements associated with the recycling endosome compartment.

Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor.

In addition to its extracellular action, there is evidence that acidic fibroblast growth factor (aFGF) acts inside cells. To identify intracellular proteins interacting with aFGF, we screened a HeLa cell library in the yeast two-hybrid system using pLex-aFGF as a bait. A clone binding to aFGF, but not to the non-mitogenic mutant aFGF-K132E, was isolated and characterized. The insert contained an open reading frame corresponding to a novel protein of 42 kDa. The protein, termed aFGF intracellular binding protein (FIBP), is mainly hydrophilic and does not contain an N-terminal signal sequence. In vitro-translated FIBP bound specifically to a fusion protein of maltose-binding protein and aFGF. FIBP became post-translationally associated with microsomes added to the cell-free protein synthesizing system, and the membrane-associated protein bound aFGF with high efficiency. Immunoblots and fluorescence microscopy demonstrated that the protein is present in nuclei and, to a lesser extent, associated with mitochondria and other cytoplasmic membranes. The possibility is discussed that FIBP may be involved in the mitogenic action of aFGF.