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The effects of spaceflight on human physiology is an increasingly studied field, yet the molecular mechanisms driving physiological changes remain unknown. With that in mind, this study was performed to obtain a deeper understanding of changes to the human proteome during space travel, by quantitating a panel of 125 proteins in the blood plasma of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station. The panel of labeled prototypic tryptic peptides from these proteins covered a concentration range of more than 5 orders of magnitude in human plasma. Quantitation was achieved by a well-established and highly-regarded targeted mass spectrometry approach involving multiple reaction monitoring in conjunction with stable isotope-labeled standards. Linear discriminant function analysis of the quantitative results revealed three distinct groups of proteins: 1) proteins with post-flight protein concentrations remaining stable, 2) proteins whose concentrations recovered slowly, or 3) proteins whose concentrations recovered rapidly to their pre-flight levels. Using a systems biology approach, nearly all of the reacting proteins could be linked to pathways that regulate the activities of proteases, natural immunity, lipid metabolism, coagulation cascades, or extracellular matrix metabolism.

This work was aimed at estimating the concentrations of proteins encoded by human chromosome 18 (Chr 18) in plasma samples of 54 healthy male volunteers (aged 20-47). These young persons have been certified by the medical evaluation board as healthy subjects ready for space flight training. Over 260 stable isotope-labeled peptide standards (SIS) were synthesized to perform the measurements of proteins encoded by Chr 18. Selected reaction monitoring (SRM) with SIS allowed an estimate of the levels of 84 of 276 proteins encoded by Chr 18. These proteins were quantified in whole and depleted plasma samples. Concentration of the proteins detected varied from 10 -6 M (transthyretin, P02766) to 10 -11 M (P4-ATPase, O43861). A minor part of the proteins (mostly representing intracellular proteins) was characterized by extremely high inter individual variations. The results provide a background for studies of a potential biomarker in plasma among proteins encoded by Chr 18. The SRM raw data are available in ProteomeXchange repository (PXD004374).

The system of countermeasures used by Russian cosmonauts in space flights on board of International Space Station (ISS) was based on the developed and tested in flights on board of Russian space stations. It included as primary components: physical methods aimed to maintain the distribution of fluids at levels close to those experienced on Earth; physical exercises and loading suits aimed to load the musculoskeletal and the cardiovascular systems; measures that prevent the loss of fluids, mainly, water-salt additives which aid to maintain orthostatic tolerance and endurance to gravitational overloads during the return to Earth; well-balanced diet and medications directed to correct possible negative reactions of the body to weightlessness. Fulfillment of countermeasure's protocols inflight was thoroughly controlled. Efficacy of countermeasures used were assessed both in- and postflight. The results of studies showed that degrees of alterations recorded in different physiological systems after ISS space flights in Russian cosmonauts were significantly higher than those recorded after flights on the Russian space stations. This phenomenon was caused by the failure of the ISS crews to execute fully the prescribed countermeasures' protocols which was as a rule excused by technical imperfectness of exercise facilities, treadmill TVIS particularly., (c2004 Published by Elsevier Ltd.)

The present review aimed to suggest approaches to prospective medical problems related to the health maintenance of space crews during future manned interplanetary, particularly Martian, missions up to 2-3 years with a possible stay on a planet with gravity different from that on Earth. The approaches are based on knowledge so far obtained from our analysis of the medical support of long-term orbital flights up to one year, as well as on the consideration of specific conditions of interplanetary missions. These specific conditions include not only long-term exposure to microgravity, but also a prolonged stay of unpredictable duration (2-3 years) on board a spacecraft or on a planet without direct contact with Earth, and living in a team with a risk of psychological incompatibility and the impossibility of an urgent return to Earth. These conditions necessitate a highly trained medical person in the crew, diagnostic tools and equipment, psychophysiological support, countermeasures, as well as the means for urgent, including surgical, treatment on board a spacecraft or on a planet. In this review, the discussion was focused on the following predictable medical problems during an interplanetary mission; 1) unfavorable effects of prolonged exposure to microgravity, 2) specific problems related to Martian missions, 3) medical monitoring, 4) countermeasures, 5) psychophysiological support and 6) the medical care system.

Results of the joint Russian/US studies of the effect of microgravity on bone tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in the whole body, the scalp including cervical vertebra, arms, ribs, sternal and lumbar regions of the spinal column, pelvis and legs. A clearly defined dependence of topography of changes upon the position of a skeletal segment in the gravity vector was established. The greatest BMD losses have been observed in the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged (insignificant) or showed a positive trend. Overall changes in bone mass of the whole skeleton of male cosmonauts during the period of about 6 months on mission made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of cosmonauts' bone tissues as local osteopenia. On the literature and results of authors' clinical evidence, discussed is availability of the densitometric data for predicting risk of trauma. A biological nature of the changes under observation is hypothesized.

The health condition and work capacity of space travellers during many flights remained adequate. Medical examinations performed during and after space flights consistently revealed the following symptom-complexes: space motion sickness, changes in the muscles system, hemodynamics, fluid-electrolyte balance and its regulation, calcium metabolism and bone density, transient erythrocytopenia and immunity decline. This paper presents a detailed discussion of the changes observed in space flight.

Manned missions onboard orbital stations Salyut-6 and Salyut-7 have led us to the conclusion that a long-term space mission can be viewed as a complex socio-man-machine system whose effectiveness largely depends on the quality of interaction between its subsystems. When analyzing and assessing the reliability of this system, it is important to consider ethical aspects, because they concern human relations, permeating its very component and in the long run determining its efficiency. Psychological and medical examinations before, during and after manned missions have helped us to identify the major points of interaction of the subsystems which require adequate monitoring and optimization using socio-psychological and organization-technical approaches: arrangement and evaluation of the quality of work, arrangement of proper leisure, psychological comfort in the interpersonality and intergroup relations during prolonged space missions. This paper also discusses adaptive changes in the mental and physical state due to prolonged exposure to space flight factors such as microgravity and confinement.