Characteristics of blood plasma proteome changes associated with the hemorrhagic purpura of cosmonauts on the first day after long-term space missions.

The interest in the role of the gravitational factor during landing after long-term space flights (SF) leads to the search for various innovative approaches to assessing the compliance of external changes observed by clinicians. The results of special research methods such as Omics technologies that may reflect physiological responses to the conditions created during landing are of great interest. Our purpose is to compare the blood plasma proteome changes associated with the trauma and endothelial dysfunction processes prior to launch and on the day of landing, as well as the groups of cosmonauts with and without the secondary hemorrhagic purpura. In our study, the concentrations of 125 plasma proteins in 18 Russian cosmonauts, measured using targeted proteomic analysis based on liquid chromatography and tandem mass spectrometry were analyzed. The results reveal the trends of 12 proteins participating in the processes that trigger hemorrhagic purpura under the effect of re-entry g-forces. Exposure to intense g-forces and return to the gravity are the key factors for external manifestations of changes in the body systems induced by a long-term stay in space microgravity. Our results may be useful for further research to experts in gravitational physiology, aviation and space medicine.

Relationship of collagen as the component of the extracellular matrix with the mechanisms of autonomic regulation of the cardiovascular system under simulated conditions of long-term isolation.

The study of proteins - potential markers, associated signal transduction pathways, and their targets - provides a new understanding of the fundamental mechanisms occurring at the level of regulatory processes in the cardiovascular system (CVS), especially in space flight, as well as in model experiments that reproduce its individual effects on the human body. The article presents the results of studies in an experiment with 120-day isolation within the framework of the SIRIUS project in which 6 volunteers aged 28 to 44 years (three men and three women) participated. SIRIUS (Scientific International Research in Unique Terrestrial Station) is the international research project, which studies the issues of biomedical and psychological support of long-term manned space flights. The possible involvement of collagen different types, an extracellular matrix protein, in the mechanisms of autonomic regulation of the CVS was studied. Using chromatic mass spectrometry in urine samples and analysis of heart rate variability, we have established that the extracellular matrix collagen, which is present, in particular, in the structure of the blood vessel wall, are markers associated with the modulating effect of the autonomic nervous system on the regulatory mechanisms of blood circulation. We hypothesized that these proteins may be a biomarker of the autonomic balance in the regulatory mechanisms of the circulatory system. In addition, these proteins can also be markers of the aging process, which increases the risks of developing autonomic dysfunction of the cardiovascular system (dominance of sympathicotonia) and changes in the quality of the tissue of the heart muscle and blood vessels, provoking the development of prenosological conditions and diseases of the cardiovascular system.

[Age features of heart rate variability in cosmonauts according to urine proteomics data.]

As the life of the International Space Station (ISS) is lengthening, Russian crews are dominated by cosmonauts over 40 years of age who have repeatedly made a space flight (SF) and have a long stay on the ISS. In order to study the age-related features of the regulation of heart rate variability (HRV) in cosmonauts, based on proteomics data, we analyzed simultaneously the obtained data on the proteomic composition of urine samples and electrocardiogram (ECG) parameters, followed by an analysis of heart rate variability (HRV) in cosmonauts in the age group of 46,5±3,4 (n=12). The survey was carried out in the period of preparation for the next flight. The urine proteome was studied by mass spectrometry and analyzed by bioinformatic methods. Heart rate variability was assessed by software methods for analyzing ECG fragments. For the first time, data based on proteomics on the age-related features of the regulation of heart rate variability in cosmonauts are presented. According to age periodization, cosmonauts are in the middle age of the second period. The concentrations of mucin 1, type VI collagen, and cadherin 13 were shown to change with age. A decrease in HRV was also observed with increasing age. There was an increase in sympathetic influence and a progressive decrease in parasympathetic influence.

[Characteristics of age-dependent changes in the urine´s proteom composition of the of the healthy persons (experimental and theoretical study).]

For the first time proteins are described, reliably increasing and decreasing in urine with age in the range of 20 to 60 years. The combinations of proteins associated with changes in immune processes, violation of blood reology, including the risk of coagulopathy, anticancer defense mechanisms, insulin signaling pathway, changes in cell characteristics are characterized division and quality of the newly formed fabric. Thus, the age dynamics of the main processes triggers a cascade of reactions manifested in the closure of «pathological biochemical circles¼ that form the prerequisites for the development of diseases and, over time, clinical manifestations.

[Chromato-mass spectrometric analysis of urine proteins associated with the functions of Toll-receptors in a healthy person under conditions of 17-day isolation.] / Хромато-масс-спектрометрический анализ белков мочи, ÑÐ¾Ð¿Ñ€ÑÐ¶ÐµÐ½Ð½Ñ‹Ñ Ñ функциями Toll-рецепторов у здорового человека в ÑƒÑÐ»Ð¾Ð²Ð¸ÑÑ 17-суточной изоляции.

Under controlled conditions of 17-day isolation (Sirius-17 experiment), the protein composition of urine was studied in 6 healthy test volunteers-3 women and 3 men. Collection of samples in the form of a second freely separated morning urine fraction was carried out in the background (seven days before the experiment), as well as 1 day after the end of exposure. Chromatographic-mass-spectrometric semi-quantitative analysis of the protein composition of samples was performed on a system consisting of an Agilent 1100 chromatograph and an LTQ-FT Ultra hybrid mass spectrometer using bioinformatics resources UniProtKB, GeneOntology. An asymptomatic change in the immune defense system of kidney tissue after isolation in a closed hermetic object is associated with a change in the content of 7 proteins that provide functional activity of the TLR tubules of the kidneys - FcRIII, MUC1, Galectin-3, Ficolin-2, APOA1, FLNA, FCGR3A and Clusterin. These proteins are found to be useful biomarkers in the study of physiology and kidney diseases. They can be attributed to candidates for protein markers of the initial stages of impaired recognition by the epithelium of renal tubules of bacteria with known pathogenic potential.

[Scatological investigations during 105-day isolation].

Dynamics of the gastrointestinal functioning was reconstructed by analysis of the scatological data from volunteered subjects before, on days 16, 35, 45, 60, 90 and after completion of 105-day isolation experiment. The analysis showed that scatological investigations performed in the conditions imitating life in an exploration vehicle environment are instrumental in detecting deviations in the GI function indicative of pancreas excretory and hepar biliary excretion and synthetic hypofunction that can be responsible for intestinal dysfunction. Normalization of scatological parameters following the experiment witnesses to functional genesis of the changes observed during the exploration mission simulation.

[The quality of medical examination of persons who underwent the impact of especially harmful chemical factors].

The comprehensive analysis of the results of dynamic clinical functional examination of the contingent working or worked with especially harmful chemical substances and the corresponding medical documentation was made. The research approved the effectiveness of the system of medical examination of servicemen and mandatory medical check-ups of civilian personnel selected to service or work with toxic chemicals relevant to chemical weapon at the expense of optimization of the procedure of selection and dynamic observation. General morbidity among servicemen with maximal professional risk was on 20% lower than in the group with minimal risk and on 64% lower than in the control group. The algorithm was developed to apply the diagnostic techniques during medical examination of servicemen and mandatory medical check-ups of the civilian personnel of Military Forces of Russian Federation. The system differentiating approach was implemented to take into account the specifics of disease course and the succession in medical maintenance of this group of the examined. The optimization was applied to the system of quality management in medical examination of servicemen and mandatory medical check-ups of the civilian personnel, selected to service or work with toxic chemicals relevant to chemical weapon in accordance with requirements of the Federal Law On the social support of citizen employed to work with chemical weapon.

[To the question of the possibility of oral insulin administration]. / K voprosu o vozmozhnosti ispol'zovaniia peroral'noi formy insulina.

The influence of oral insulin upon carbohydrate exchange in healthy volunteers was evaluated. One of the two forms of insulin used in the study was insulin, immobilized in a volume of polyacrylamide gel, modified by ovomucoid (proteolytic enzyme inhibitor), isolated from duck eggs; the other form was enteric-coated tablets bases on hydrogel substance. The oral administration of the hydrogel substance or the tablets resulted in the fall of blood glucose concentration by 34.9 +/- 4.4% and 28.6 +/- 6.9%, respectively. The maximal effect of the hydrogel substance and the tablets was observed at the 90th and the 180th minutes.

[The influence of extended exposure in artificial hypercapnic environments on the function of external respiration and gas exchange]. / Vliianie dlitel'nogo nakhozhdenia v iskusstvennykh giperkapnicheskikh sredakh na funktsiiu vneshnego dykhaniia i gazoobmen.

Effects of artificial hypercapnic atmosphere were studied in a series of ten 40-d experiments with participation of 42 volunteers aged from 20 to 61 years. Partial pressure of carbon dioxide was maintained at 27 +/- 2 mm Hg (3.4-3.8% CO2); partial pressure of oxygen was in the range of 122-136 mm Hg. Barometric pressure, air temperature and humidity had normal values. Results of the experiments were subjected to the variation analysis. Continuous breathing the gas mixture with specified PCO2 increased CO2 sensitivity of the breathing center in all age-groups both at rest and during exercise. The ventilatory reaction of subjects aged 41-61 grew to a less degree as compared to the subjects below 40. Medical selection of members for space crew to go to a distant voyage should take into consideration the parameters of oxygen demand and the volume of pulmonary ventilation per a time unit.

[Experience of selecting test-subjects for extended model studies]. / Opyt otbora ispytatelei dlia uchastiia v dlitel'nykh model'nykh issledovaniiakh.

Methodical approaches to selection and results of examination of test-subjects (aged 18 to 50 yr) volunteered to participate in extended model studies were reviewed. General and age-specific morbidity was analyzed. Various diseases (163 nosologic forms) were found in 94.3% of candidates. This fact raises concern since the age group of 18-50 represents the main employable cohort of population. Given rare visits of this age group to policlinic, the health service personnel should concentrate attention on prophylactic medical examination of "no-complaint" patients.

Male reproductive system in conditions of bed-rest in a head-down tilt.

Study of reproductive function in simulating experiments is important as for expansion of our theoretical knowledge in the field of gravitational physiology and space biology and for the decision of applied problems in space and clinical medicine. Long-term bed rest in a head-down tilt--6 degrees (BRHDT)--antiorthostatic hypokinesia is a wide spread method for ground-based simulation of space flight's conditions (mainly of hemodynamical effects of microgravity and restriction of locomotor activity). The aim of the present research was to study a reproductive function in males during 60-120 day BRHDT.

[Effect of 120-day antiorthostatic hypokinesia on the reproductive function in women]. / Vliianie 120-sutochoi antiortostaticheskoi gipokinezii na reproduktvnuiu sistemu zhenshchin.

Original data on the peculiarities of adaptation to and functional status of the reproductive system in long-term antiorthostatic hypokinesia (AOH) have been obtained. The studies involved eight healthy female volunteers aged 26-37 years who were exposed to the head-down tilt (-6 degrees) for 120 days. The test subjects were divided into 2 groups of 4 persons each. In Group A, the countermeasures, i.e. physical exercise and pharmacological means, were used. In Group B, at no time did the test subjects use the countermeasures throughout the 120-day AOH. With and without the countermeasures, hypokinesia was found to impact the female reproductive system developing clinical symptoms of deficiency of the menstrual lutein phase and giving rise to small inclusions of functional fluids in the ovaries. Within 6 months after AOH, the ovarial function of the test subjects was fully recovered which may be indicative of the functional character of changes. These changes can be explained by dissociation of the functional relations in the hypothalamo-hypophyseal-ovarial system manifested by increases in the plasmic concentrations of luteinizing hormone (LH) against normal levels of follicle-stimulating hormone (FSH) and prolactin, and moderately increased levels of testosterone, relative hyperestrogenemia and hypoprogesteronemia. These clinical and hormonal developments are contrary to the observations usually made in various models of stress. Similarity of the hormonal profiles under hypokinesia and long-term immersion of female swimmers may be ascribed to common mechanisms underlying the disturbance of the reproductive function.

[The effect of the 120-day antiorthostatic hypokinesia on the functional state of female thyroid]. / Vliianie 120-sutochnoi antiortostaticheskoi gipokinezii na funktsional'noe sostoianie shchitovidnoi zhelezy u zhenshchin.

Investigations of eight healthy female volunteers aged 26-37 in 120-days antiorthostatic hypokinesia (AOH, -5 degrees) gave original data about peculiarities of adaptation and functional state of female thyroid and the thyreotrophic activity of adenohypophysis. The test-subjects were divided into two equal groups. Group 1 administered a set of countermeasures including exercise and pharmacy. In the other group, no health control was used. By days 90-100 in AOH thyroid glands of the females were slightly more compact but remained diffuse. Thyroid sizes were not altered. Chemical/biochemical examination did not elicit any noteworthy shifts in the thyreotrophic activity of hypophysis or thyroid function in the bedrested females. The countermeasures did not enhance the thyroid function. Results of the investigation point to the completion of thyroid adaptation of females by days 90-100 in AOH.