Homeostasis of metals plays an important role in functioning of the body. Not only the concentrations of toxic and essential metals in bodily fluids, but also their ability of interaction with proteins and enzymes defining the enzyme activity, are important. The study was aimed to compare the possibilities of binding interactions between various metal ions and human serum proteins. Chemical reactions between the immobilized metal ions (Cu2+, Zn2+, Mn2+, Ca2+, Fe3+, Mg2+, Hg+, Cd2+, Pb2+, Cr3+, Co2+, Ag+, Bi2+, Ba2+, Sr2+) and the serum proteins or highly purified blood metalloprotein (alpha-2-macroglobulin, α2M) were assessed by the crossed immunoelectrophoresis with in situ adsorption in the second dimension. It has been shown that Hg+, Cu2+, Zn2+, Cd2+ ions more actively interact with metalloproteins (particularly, with α2M) and many other human blood proteins in in vitro reactions than other ions. We have demonstrated that α2M interacts not only with Zn2+ and Cd2+ ions, as earlier reported, but also with Ca2+, Mg2+, Fe3+, Mn2+, Pb2+, Sr2, Ag+. Interaction of a number of metal ions, including highly toxic ones, with blood proteins that are not metalloproteins has been revealed. The findings confirm the fundamental possibility of the metal ion imbalance active involvement in metabolic disorders via effects on the body's regulatory and transport proteins, which requires further investigation
VIEWS 809
Inadequate ultraviolet insolation is one of the the key prerequisites for the pathogenesis of body's vitamin D insufficiency in the North. The study was aimed to assess the body's vitamin D, calcium and phosphorus sufficiency in the contract servicemen deployed in Arctic. The contract servicemen deployed on the Cape Chelyuskin and Dixon Island were surveyed (n = 51). The serum levels of 25(OH)D, the intermediate of the vitamin D conversion, along with the ionized calcium, total calcium, and inorganic phosphorus levels, were determined in June. Three degrees of the vitamin D sufficiency were revealed in the military, who had been deployed in Arctic for 5.9 ± 0.4 years: deficiency (in 29.4%), insufficiency (in 52.9%), and optimal levels (in 17.7%). However, the optimal levels revealed were close to the lower limit of normal range. Low ionized calcium levels were found in 29.4% of blood samples (15.5 ± 0.6 ng/mL). A total of 70.6% of samples that were within normal range were close to the lower limit of normal range based on Q25 (1.16 mmol/L) and were within the lower half of normal range (1.15–1.35 ng/mL) based on Q75 (1.22 mmol/L). The measured total calcium and inorganic phosphorus levels were close to the lower limits of reference ranges (2.29 ± 0.009 and 0.83 ± 0.006 mmol/L, respectively). In general, the reduced ionized calcium levels associated with vitamin D insufficiency were revealed, which were indicative of impaired calcium metabolism. The vitamin D deficiency results from the total calcium and inorganic phosphorus concentrations that are close to lower limits of reference ranges. Further negative changes in the body's vitamin D, phosphorus and calcium sufficiency should be expected during polar night. The study actualizes the year-round replenishement of the vitamin D and mineral deficiency in the military.
VIEWS 780
Curiosity about the activity of neural networks in the human brain results from the search for definition of human self-consciousness as an identifier of human personality. Today, the RS-fMRI technology occupies a leading position among methods used to study this problem. The widespread use of the technology is limited by certain drawbacks. Starting from 2010, there is a growing interest in the possibility of using neurophysiological methods for the diagnosis of the brain's default mode network (DMN) state based on the analysis of EEG microstates. The study was aimed to demonstrate the possibility of recording the activity of brain networks both at rest and under exposure to the stimulus evoking a known response. A total of 42 people underwent assessment in the relaxed wakefulness state with the eyes closed that involved extraction of certain EEG microstate sequences and the EEG inverse problem solution. The data obtained were tested for adequacy via comparison with the results obtained by the preset stimulation of auditory and language function. The conclusion was made about the possibility of assesing the brain's DMN’s activity by combining the analysis of EEG microstates with the EEG inverse problem solution. The proposed technology can be used in both scientific research and clinical practice in the form of new techniques and systems allowing one to determine alterations in neuropsychological processes.
VIEWS 1201
Assessment of individual responses of cells, tissues and the whole body to radiation exposure is an important challenge for radiobiology and radiation safety. The study was aimed to develop the method for estimation of the human hematopietic stem cell (HSC) individual response in the humanized mouse model. The cord blood or peripheral blood HSCs were administered to the NOD SCID immunodeficient mice. The number of maturing HSCs (CD34+ cells) and mature CD45+ leukocytes was assesed after the acute gamma exposure to the doses of 0.5 Gy, 1 Gy, and 1.5 Gy, along with the HSC share among all CD45low/+ cells within three days (period of maximum mortality) and 14 days (period of active restoration) after exposure. The relationship between the indicato values and the exposure dose was calculated by regression analysis. There was exponential relationship between the human HSC survival rate in humanized mice and the dose on day three after exposure (R2 = 0.93; F = 211; p < 0.01), while the relationship between the number of HSCs and the dose on day 14 after exposure was linear (R2 = 0.65; F = 12.9; p = 0.01). The C14/3 coefficient calculated as a ratio of the HSC share among all human CD45low/+ cells on day 14 after exposure to the same parameter on day three after exposure was proposed as an indicator of HSC mortality and HSC number restoration. C14/3 negatively correlated with the exposure dose (R2 = 0.57; F = 13.3; p = 0.004), it was higher in radioresistant mice and the model of  cysteamine-induced radioresistance in humanized mice. The model mice humanized using the peripheral blood HSCs can be used to assess individual HSC response to acute external gamma exposure based on C14/3 and the data on the HSC survival and restoration.
VIEWS 943
Mathematical modeling is a promising method enabling in silico calculations with subsequent suggestion of cell membrane protective agents used to reduce the consequences of exposure to hydrogen sulfide-containing gas in emergency situations. This study aimed to investigate the nature of interaction of hydrogen sulfide (H2S) and N-Acetyl-L-Cycteine (NAC) with the components of cell membranes. We built a mathematical model of interatomic interactions of cell membrane components with H2S and NAC (two separate models), then made the quantum-chemical calculations using our proprietary technique and set up GAMESS Z-matrices reflecting type and position of atoms in the molecules. The structure of the molecules was optimized with the help of MOPAC package built into ChemOffice. Lecithin-based liposomes in a sulfide solution (with Na2S being the donor of H and HS ions) were used as an experimental model of the biological membrane. Redox potential in mV was the comparison parameter in assessment of interaction of the H2S system components and NAC with phospholipid. The results include patterns showing the phospholipid reactive centers blocked by NAC under toxic exposure to H2S. Liposomal models of cell membranes were formed and redox parameters measured. Biological experiment confirmed the acceptable accuracy of the designed method of calculation of intermolecular interactions when used as a basis for further selection of agents capable of adjusting toxic doses of hydrogen sulfide. Membrane models of H2S interaction with protein and lecithin were visualized in silico and in vitro. The possibility of using NAC as an H2S inhibitor has been confirmed.
VIEWS 1294