Reference Values of the Hemostasis System Indices in Cosmonauts.

The values of 11 diagnostically significant hemostasis system indices in venous blood were determined during the preflight (30-45 days before start) clinical and physiological examination of 39 cosmonauts aged 35 to 54 who were the members of the main and backup crews of missions to the International Space Station in the period from 2007 to 2014. Since most of the cosmonauts performed several flights during this period, and they were repeatedly included in backup crews, each of the cosmonauts underwent preflight examinations one to five times. The reference values were calculated for each of the studied indices. It was'found that the reference ranges for parameters indicative of integral pro-, anticoagulant and fibrinolytic potential were narrowed and close to the boundaries of ranges for the general population,- which indicates that the cosmonauts had relatively decreased procoagulant potential and increased hemostasis regulative.potential. This was probably due to the criteria of selection, physical training status, and emotional status of crew members during the preflight professional activity, when the adaptive changes against the stress-inducing effects occur in the organism. The cosmonauts who underwent strict medical examination may also have some genetic features which provide higher body resistance and more rapid adaptation processes.

[Oxidation Stress Markers Dynamics in the Experiment of Long-Term Antiorthostatic Hypokinesia (Retrospective Study)].

In blood serum of 9 volunteers aged 27 to 42, participated in the experiment with 370-day antiorthostatic hypokinesia (-5 degrees), the lipid peroxidation derivates concentration--diene conjugates (DC), malonic dialdehyde (MDA), Schiff bases (SB) as well as antioxidant defense system indices--tocopherol (TP) concentration and total antioxidative activity level (AOA) were measured. The volunteers were divided into two groups subjected to physical training regimes and used prophylactic measures. In both groups the lipoperoxidation processes initial stages depression (by 54-73%) was observed starting from 50th day, thus the lipid peroxidation final product--SB level was decreased (by 50-61%) only to the 230 day and remains approximately at the same level till the end of the experiment. The restorative period was characterized by decreasing (in 1.6-2.3 times) of MDA and SB concentrations. The decrease in lotal AOA during the aftereffect period was detected in all volunteers, and its level was significantly lower physiological norm range. Probably, long-term adaptation to the simulated weightlessness conditions is accompanied by expressed decrease in biological oxidation processes intensity and significant stress effect, as indicates by essential depression of lipid free radical oxidation in the course of the experiment. At the same time the restorative period after 370-day antiorthostatic hypokinesia was characterized by significantly expressed and prolonged readaptation stress progress. It is evidenced by practically twofold decrease in lipoperoxidation processes intensity against significant increase in TP concentration and water-soluble antioxidants functional reserves exhaustion. Lipid peroxidation activation absence in all terms of examination reflects appropriate compensation of studying impact by volunteers.

[The Status of Hemostasis System in Hypoxic Nitrogen-Oxygen and Argon-Oxygen Diving Gases].

In this study the effect of factors of hermetic chamber with modified gas medium on the hemostasis system is analyzed in order to estimate and to compare different diving breathing gases. The parameters characterizing pro-, anticoagulant as well as fibrinolytic components of hemostasis were determined using clotting, chromogenic and immunological methods. The applied exposure did not affect the activity and regulatory potential of hemostasis significantly; however, the nitrogen-oxygen and argon-oxygen diving gases have a different effect on the hemostasis functioning, especially in the recovery period.

[COMPREHENSIVE ASSESSMENT OF THE HEMOSTASIS SYSTEM IN TEST-SUBJECTS IN EXPERIMENT "MARS-500"].

The paper is devoted to the hemostasis studies in the course of long-term (520 d) isolation in an airtight chamber. Measured parameters included activated partial thromboplastin time (APTT), international normalized ratio (INR), thrombin time (TT); concentrations of fibrinogen (FBG), plasminogen (PG), Willebrand factor (WF), tissue factor pathway inhibitor (TFPI), and tissue plasminogen activator (TPA), thrombomodulin (TM); activities of the coagulation cascade factors (II, V, VII, X, VIII, IX, XI, XII), antithrombin III (ATIII), protein C (PC), C1-inhibitor (C1), α2-antiplasmin (AP), TPA and TFPI. The investigation revealed a diversity of changes in the plasma fibrinogen concentration, slower blood coagulation in the intrinsic pathway and the final stage, and a relative rise in the activities of ATIII and PC-inhibited factors. The rest parameters showed different trends.

[Effect of physical countermeasures against support load deficiency on the hemostasis system in an experiment with 7-day immersion].

In an experiment with 7-d dry immersion for testing the mechanic foot and electrical muscle stimulation procedures of compensating the support load deficiency the following biochemical parameters were studied: activated partial thromboplastin time, prothrombin time, prothrombin index, international normalized ratio, thrombin time (TT), fibrinogen, soluble fibrin-monomer complexes, D-dimer (DD), plasminogen (PG); antithrombin III activity (ATIII), protein C (PC) and alpha2-antiplasmin (AP). Control subjects (immersed w/o stimulation) did not exhibit significant shifts in the hemostasis system: however, they decreased ATIII, PC and PG in the post-experimental period. Mechanic foot stimulation did not have a noteworthy effect on the hemostasis system functioning during immersion, whereas electromyostimulation increased procoagulant and fibrinolytic activity in blood plasma.

[Reference values of Russian cosmonauts blood biochemical indices].

Within the period of 2000 to 2012 the values of 40 diagnostically significant biochemical indices in venous blood were being determined during the pre-flight clinical and physiological examination of 28 Russian cosmonauts aged 35 to 54, members of main and back-up crews of expeditions to the International Space Station. The above examination was conducted 45-30 days prior to the launch. Taking account of the fact that each of the most of the cosmonauts performed several flights over the mentioned period and they were repeatedly included in back-up crews over and over again, each of cosmonauts participated in pre-flight examinations 1 to 5 times. Reference values were calculated for each of the studied indices. It was found that reference interval boundaries for 15 indices were narrower as compared to the generally accepted ranges. The upper boundaries of activity reference ranges of a number of enzymes, as well as of concentration of some metabolites of energy and plasticity metabolism were raised relative to mean population values. Thus, it was found that Russian cosmonauts being a specific professional team featured inherent reference values which differed from mean population values in a number of blood biochemical indices. It is conditioned by peculiarities of selection, physical training and psychic and emotional status of crew members during a pre-flight period.

[Intensity of lipid peroxidation and antioxidant protection system indices in the course of a 3-day "dry" immersion experiment].

In the course of a 3-day "dry" immersion experiment involving participation of five male test volunteers aged 25 to 40, in the blood serum of participants were determined the content of LPO (lipid peroxidation) products, namely diene conjugates, malon dialdehyde, shiffbases, as well as the values of the antioxidant protection system (AOP) indices - the concentration of tocopherol as the main lipid antioxidant and the level of general antioxidant activity. During the immersion action no deviations of indices under study from the background values were revealed, with the exception of a certain increase in tocopherol concentration within two hours after experiment beginning. At the restoring period after two hours upon immersion completion a reliable increase of lipid peroxidation products, particularly diene conjugates in participants' blood serum was made evident. At this, the tocopherol content was significantly below the background values. It is therefore concluded that the test participants' adaptation to the simulated weightlessness conditions shows no pronounced stress component, whereas bringing back to normal vital functions after exposure to immersion occurs with significantly pronounced stress reaction development, as demonstrated by considerable growth of LPO processes against the background of AOP system functional activity reducing.

[Metabolic effects of physical countermeasures against deficient weight-bearing in an experiment with 7-day immersion].

Metabolic effects of physical countermeasures against deficient weight-loading were studied in three groups of 21-30 y.o. volunteers for 7-d dry immersion. Blood serum was investigated for 38 biochemical parameters that characterize myocardium, skeletal musculature, hepatobiliary system, kidney, pancreas, GI tract, prostate, and protein-nucleic, carbohydrate, electrolyte and mineral metabolism. Seven-day DI w/o countermeasures (n = 5) increased concentration of conjugated bilirubin, suppressed activities of muscular (creatine phosphokinase MM) and myocardial enzymes (CPK MB, OBDH), and caused an upward trend in cholesterol, its atherogenic LDP fraction and triglycerides. Mechanic sole stimulation (n = 6) intensified, within the physiological norm, erythrocyte hematolysis raising total bilirubin and potassium. Despite the stimulation, activity of muscle and myocardial enzymes made a decrease. Blood creatinine decreased to a less extent than in the immersed group w/o stimulation, however, lipid parameters did not rise. High-frequency stimulation of the lower leg and hip muscles in the course of immersion (n = 5) was noted to heighten the activity of muscle enzymes and potassium level in blood beyond the physiological norm. Change in creatinine did not reach a statistical significance and lipid metabolism parameters were not different from baseline values. Application of these physical methods of counteracting deficiency of weight bearing did not interfere with redistribution of body liquids due to immersion. Values of the parameters under study were mostly within the normal limits throughout the experimental exposure suggesting absence of pathological developments during DI or in consequence of physical stimulation. Therefore, the reactions were obviously of normal adaptive character.

[Intensity of lipid peroxidation and antioxidant protection system indices during re-adaptation period after long-term space flights at the international space station].

In the blood serum of seventeen members of crews which participated in 14 orbital expeditions to the International Space Station with the duration of 125 to 217 days, during the pre-flight period and on the day of landing on the 1st, 7th and 14th days of the rehabilitation period (RP) the content of LPO products was determined, namely diene conjugates (DC), malon dialdehyde (MDA), shiffbases (SB) and the main lipid oxidant - tocopherol (TP). The group of astronauts who made landing in the Space Shuttle spacecraft (8 persons) and the group of astronauts who accomplished space mission in the Soyus TM spacecraft (9 persons) demonstrated a decrease in DC and MDA levels with a rise in TF concentration in the course of the rehabilitation period. Changes in the group of the American spacecraft astronauts were more pronounced. LPO inhibition during the rehabilitation period is recognized [treated] as an adequate reaction to the stress caused by re-adaptation to the ground conditions. Also are discussed probable mechanisms of intergroup differencies in LPO intensity degree: biomembrane phase state changing under the influence of overloads during de-orbiting and stress response intensity during landing in different types of spacecraft.

[Dynamics of the protein content of human urine during 5-day immersion].

Variations in the protein spectrum (12 groups) of native daily urine were studied during 5-day dry immersion (DI) of 14 subjects at the age of 19 to 26 years using gradient electrophoresis in polyacrylamide gel. Protein excretion with urine did not alter in the course of the experiment. However, the urine proteins spectrum trended to some shifts. Excretion of low-molecular proteins decreased and of albumin increased pointing to remodulation of tubular reabsorption initiated by the experimental conditions. Steady growth of the Tamm-Horsfall protein concentration seems to be a defense reaction. There was an incremental decrease in immunoglobulins that could be associated with a reduction of glomerular filter permeability for high-molecular proteins.

[Hemostasis system indices after short-term space flights and during 7-day "dry" immersion experiment].

The present paper deals with studying ofhemostasis system indices after short-term (10-11 days) space flights as well as in the course of the experiment with a 7-day "dry" immersion. The following values were determined: activated partial thromboplastin time, prothrombin time, prothrombin index, international normalized ratio (INR), thrombin time (TT); fibrinogen, soluble fibrin-monomer complexes, D-dimer, plasminogen (PG) concentration; activity of antithrombin III (ATIII), protein C (PC), alpha2-antiplasmin (AP). In the 1st day after space flights a fibrinogen concentration was increased significantly as well as TT shortening tendency and fibrinolysis activation tendency were observed. There were no significant changes in ATI I11 and PC activities. During the immersion period there were no significant changes in investigated indices, with the exception of AP activity increase in 3rd day of experiment. In readaptation period, however, a decrease in ATIII and PC activities as well as PG concentration was observed. Hemostasis system response features after space flights and during immersion are probably due to different intensity and duration of external factors effects.

[Evaluation of the 7-day immersion effect on the renal excretory function].

In an experiment with 7-d immersion of 8 male test-subjects (21-26 y.o.) we investigated excretion with urine of total protein, creatinine, urea, uric acid, glucose, K, Na, Ca, P, Mg, 12 groups of proteins and 5 enzymes. Results of the investigation bring to the conclusion that 7-d immersion does not impact the kidney functioning. Analysis of uroproteinogram failed to detect shifts in glomerular filtration or tubular reabsorption which correlates with the absence of significant changes in uroenzymogram. Even profuse diuresis was unable to provoke abnormally high protein and glucose excretion, whereas electrolyte excretion normalized fairly soon. Increased excretion of creatinine, urea, Ca, Mg and P appears to reflect activation of catabolism in skeletal muscles.

[Dynamics of blood biochemical parameters in an experiment with 7-day immersion].

Blood samples were taken from 8 volunteers (21 to 26 years of age) for 7-day immersion 7 days prior to, on days 3 and 7 of the experiment and on days 1 and 8 of recovery. Serum was analyzed for 38 biochemical markers of the functional state of the myocardium, skeletal muscles, hepatobiliary system, kidney, pancreas, GI tract, prostate, and protein-nucleic, carbohydrate, electrolyte and mineral metabolism. Seven-day immersion was found to alter the biochemical parameters within the physiological norm boundaries. The observed changes included lower activities of enzymes associated with muscular and myocardial constellation, shifts in electrolytes (K, Na, Mg), and increases in the biliary function parameters. Increased concentrations of the lipid metabolism parameters suggest a higher risk of atherogenesis. Biochemical parameters of bone tissues and erythrocyte activity were essentially unchanged. Most of the parameters returned to pre-experimental values by day 8 of recovery.

[Characteristics of cosmonauts' metabolism after extended missions on the international space station].

In eight Russian members of the ISS crews 1 to 5 enzymes and some other metabolites were analyzed in blood in the pre- launch period, on the landing day, and on days 6-8 and 14-19 of recovery. Deviations in the biochemical parameters were typically within the physiological norm without clinical implications. Biochemical deviations on the landing day seemed to relate to metabolic shifts due to long-term microgravity and, on the other hand, were a reaction to acute gravitational stress on return to 1 g. Dynamics of a number of parameters was markedly different as compared with the data from cosmonauts who had made long missions to the Mir space station, but this can be attributed to different g-profiles during descent and blood sampling schedule. In two to three wks the parameters regained normal values suggesting that negative effects of readaptation to the Earth's gravity were fully remedied.

[Metabolism, intensity of lipid peroxidation and the antioxidant defense system in humans during chamber experiments with long-term isolation]. / Obmen veshchestv, intensivnost' perekisnogo okisleniia lipidov i sistema antioksidantnoi zashchity u cheloveka v éksperimente c dlitel'noi izoliatsiei v germoob"ekte.

Blood biochemical parameters of lipid, protein, carbohydrate and energy metabolism were measured in a 135-day chamber experiment. Also, dynamics of the intensity of lipid peroxidation and status of the antioxidant defence system were evaluated. Results of the investigation showed that extended chamber isolation led to modifications of several biochemical parameters including hemoglobin, bilirubin, cholesterol and its fractions, elevated transaminase activity which are typical for long-term space mission. However, these were not accompanied by substantive changes in protein, energy and carbohydrate metabolisms, or intensity of free radical processes. Effects of prolonged stay in chamber was successfully counterbalanced by organism.