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Protein kinetics during and after long-duration spaceflight on MIR

Human spaceflight is associated with a loss of body protein. Bed rest studies suggest that the reduction in the whole body protein synthesis (PS) rate should be approximately 15%. The objectives of this experiment were to test two hypotheses on astronauts and cosmonauts during long-duration (>3 mo) flights on MIR: that 1) the whole body PS rate will be reduced and 2) dietary intake and the PS rate should be increased postflight because protein accretion is occurring. The 15N glycine method was used for measuring whole body PS rate before, during, and after long-duration spaceflight on the Russian space station MIR. Dietary intake was measured together with the protein kinetics. Results show that subjects lost weight during flight (4.64 +/- 1.0 kg, P < 0.05). Energy intake was decreased inflight (2,854 +/- 268 vs. 2,145 +/- 190 kcal/day, n = 6, P < 0.05), as was the PS rate (226 +/- 24 vs. 97 +/- 11 g protein/day, n = 6, P < 0.01). The reduction in PS correlated with the reduction in energy intake (r2 = 0.86, P < 0.01, n = 6). Postflight energy intake and PS returned to, but were not increased over, the preflight levels. We conclude that the reduction in PS found was greater than predicted from ground-based bed rest experiments because of the shortfall in dietary intake. The expected postflight anabolic state with increases in dietary intake and PS did not occur during the first 2 wk after landing.

STS-40 Shuttle Project

Evidence of root zone hypoxia in Brassica rapa L. grown in microgravity

A series of experiments was conducted aboard the U.S. space shuttle and the Mir space station to evaluate microgravity-induced root zone hypoxia in rapid-cycling Brassica (Brassica rapa L.), using both root and foliar indicators of low-oxygen stress to the root zone. Root systems from two groups of plants 15 and 30 d after planting, grown in a phenolic foam nutrient delivery system on the shuttle (STS-87), were harvested and fixed for microscopy or frozen for enzyme assays immediately postflight or following a ground-based control. Activities of fermentative enzymes were measured as indicators of root zone hypoxia and metabolism. Following 16 d of microgravity, ADH (alcohol dehydrogenase) activity was increased in the spaceflight roots 47% and 475% in the 15-d-old and 30-d-old plants, respectively, relative to the ground control. Cytochemical localization showed ADH activity in only the root tips of the space-grown plants. Shoots from plants that were grown from seed in flight in a particulate medium on the Mir station were harvested at 13 d after planting and quick-frozen and stored in flight in a gaseous nitrogen freezer or chemically fixed in flight for subsequent microscopy. When compared to material from a high-fidelity ground control, concentrations of shoot sucrose and total soluble carbohydrate were significantly greater in the spaceflight treatment according to enzymatic carbohydrate analysis. Stereological analysis of micrographs of sections from leaf and cotyledon tissue fixed in flight and compared with ground controls indicated no changes in the volume of protoplast, cell wall, and intercellular space in parenchyma cells. Within the protoplasm, the volume occupied by starch was threefold higher in the spaceflight than in the ground control, with a concomitant decrease in vacuolar volume in the spaceflight treatment. Both induction of fermentative enzyme activity in roots and accumulation of carbohydrates in foliage have been repeatedly shown to occur in response to root zone oxygen deprivation. These results indicate that root zone hypoxia is a persistent challenge in spaceflight plant growth experiments and may be caused by microgravity-induced changes in fluid and gas distribution.

long duration

Neutron dosimetry in low-earth orbit using passive detectors

This paper summarizes neutron dosimetry measurements made by the USF Physics Research Laboratory aboard US and Russian LEO spacecraft over the past 20 years using two types of passive detector. Thermal/resonance neutron detectors exploiting the 6Li(n,T) alpha reaction were used to measure neutrons of energies <1 MeV. Fission foil neutron detectors were used to measure neutrons of energies above 1 MeV. While originally analysed in terms of dose equivalent using the NCRP-38 definition of quality factor, for the purposes of this paper the measured neutron data have been reanalyzed and are presented in terms of ambient dose equivalent. Dose equivalent rate for neutrons <1 MeV ranged from 0.80 microSv/d on the low altitude, low inclination STS-41B mission to 22.0 microSv/d measured in the Shuttle's cargo bay on the highly inclined STS-51F Spacelab-2 mission. In one particular instance a detector embedded within a large hydrogenous mass on STS-61 (in the ECT experiment) measured 34.6 microSv/d. Dose equivalent rate measurements of neutrons >1 MeV ranged from 4.5 microSv/d on the low altitude STS-3 mission to 172 microSv/d on the ~6 year LDEF mission. Thermal neutrons (<0.3 eV) were observed to make a negligible contribution to neutron dose equivalent in all cases. The major fraction of neutron dose equivalent was found to be from neutrons >1 MeV and, on LDEF, neutrons >1 MeV are responsible for over 98% of the total neutron dose equivalent. Estimates of the neutron contribution to the total dose equivalent are somewhat lower than model estimates, ranging from 5.7% at a location under low shielding on LDEF to 18.4% on the highly inclined (82.3 degrees) Biocosmos-2044 mission. c2001 Elsevier Science Ltd. All rights reserved.

Flight Experiment

The relationship between dietary intake, exercise, energy balance and the space craft environment

Space flight is associated with the loss of skeletal muscle, principally from muscles with anti-gravity functions. Examination of data across different missions can permit a distinction to be made between true microgravity responses and what are mission-specific responses. Protein metabolism has been investigated on six missions, four short-term [Shuttle missions Space Life Sciences 1 (1991, SLSI), Space Life Sciences 2 (1993, SLS2), Deutsche-2 (1993, D2) and the Life and Microgravity Sciences (1996, LMS)] and two long-term missions (Skylab 1993 and NASA/MIR, 1996-1998). Measurements made include dietary intake (six missions), nitrogen balance (four missions), whole-body protein kinetics with [15N]glycine as the tracer (four missions) and cortisol excretion (three missions). Also available for comparison are bed rest studies with and without exercise. The purpose of this paper is to see what can be learnt about the muscle loss problem by comparing metabolic results across the six missions for which data are available and against bed rest. The analysis suggests that there is a linkage between the inability to maintain energy balance and exercise, and the connection is the decreased efficiency of removal of the metabolic by-products of exercise (heat, CO2) during space flight.

long duration

Chest wall mechanics in sustained microgravity

We assessed the effects of sustained weightlessness on chest wall mechanics in five astronauts who were studied before, during, and after the 10-day Spacelab D-2 mission (n = 3) and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage and abdominal volumes during resting breathing and during a relaxation maneuver from midinspiratory capacity to functional residual capacity. Microgravity produced marked and consistent changes (Delta) in the contribution of the abdomen to tidal volume [DeltaVab/(DeltaVab + DeltaVrc), where Vab is abdominal volume and Vrc is rib cage volume], which increased from 30.7 +/- 3. 5 (SE)% at 1 G head-to-foot acceleration to 58.3 +/- 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values of DeltaVab/(DeltaVab + DeltaVrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects DeltaVab/(DeltaVab + DeltaVrc) was greater on postflight day 1 than on subsequent postflight days or preflight. In the two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations are similar to those previously reported during short periods of weightlessness inside aircrafts flying parabolic trajectories. They are also qualitatively similar to those observed on going from upright to supine posture; however, in contrast to microgravity, such postural change reduces rib cage compliance.

manned

Overview of spaceflight immunology studies

The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.

NASA Discipline Number 18-10

Water and Energy Dietary Requirements and Endocrinology of Human Space Flight

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

short duration

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.

Salyut Project

Space flight and oxidative stress

Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

long duration

Aging and space flight: findings from the University of Pittsburgh

For more than a decade, the Sleep and Chronobiology Center (SCC) at the University of Pittsburgh has received funding from the National Institute on Aging (NIA), the National Institute of Mental Health (NIMH) and the National Aeronautics and Space Administration (NASA) in order to study the sleep and circadian rhythms of healthy older people, as well as the sleep and circadian rhythms of astronauts and cosmonauts. We have always been struck by the strong synergism between the two endeavors. What happens to the sleep and circadian rhythms of people removed from the terrestrial time cues of Earth is in many ways similar to what happens to people who are advancing in years. Most obviously, sleep is shorter and sleep depth is reduced, but there are also more subtle similarities between the two situations, both in circadian rhythms and in sleep, and in the adaptive strategies needed to enhance 24h zeitgebers.

STS-78 Shuttle Project

Chromosome aberrations induced by high-LET radiations

Measurements of chromosome aberrations in peripheral blood lymphocytes are currently the most sensitive and reliable indicator of radiation exposure that can be used for biological dosimetry. This technique has been implemented recently to study radiation exposures incurred by astronauts during space flight, where a significant proportion of the dose is delivered by high-LET particle exposure. Traditional methods for the assessing of cytogenetic damage in mitotic cells collected at one time point after exposure may not be suitable for measuring high-LET radiation effects due to the drastic cell cycle perturbations and interphase cell death induced by this type of exposure. In this manuscript we review the recent advances in methodology used to study high-LET induced cytogenetic effects and evaluate the use of chemically-induced Premature Chromosome Condensation (PCC) as an alternative to metaphase analysis. Published data on the cytogenetic effects of in vitro exposures of high-LET radiation is reviewed, along with biodosimetry results from astronauts after short or long space missions.

ISS Project

Human interactions in space: results from Shuttle/Mir

Background: Anecdotal reports from space and results from simulation studies on Earth have suggested that space crewmembers may experience decrements in their interpersonal environment over time and may displace tension and dysphoria to mission control personnel. Methods: To evaluate these issues, we studied 5 American astronauts, 8 Russian cosmonauts, and 42 American and 16 Russian mission control personnel who participated in the Shuttle/Mir space program. Subjects completed questions from subscales of the Profile of Mood States, the Group Environment Scale, and the Work Environment Scale on a weekly basis before, during, and after the missions. Results: Among the crewmembers, there was little evidence for significant time effects based on triphasic (U-shaped) or linear models for the 21 subscales tested, although the presence of an initial novelty effect that declined over time was found in three subscales for the astronauts. Compared with work groups on Earth, the crewmembers reported less dysphoria and perceived their crew environment as more constraining, cohesive, and guided by leadership. There was no change in ratings of mood and interpersonal environment before, during, and after the missions. Conclusions: There was little support for the presence of a moderate to strong time effect that influenced the space crews. Crewmembers perceived their work environment differently from people on Earth, and they demonstrated equanimity in mood and group perceptions, both in space and on the ground. Grant numbers: NAS9-19411. c 2001. Elsevier Science Ltd. All rights reserved.

Soyuz Project

Physiology of a microgravity environment invited review: microgravity and skeletal muscle

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

short duration

Control of red blood cell mass during spaceflight

Data are reviewed from twenty-two astronauts from seven space missions in a study of red blood cell mass. The data show that decreased red cell mass in all astronauts exposed to space for more than nine days, although the actual dynamics of mass changes varies with flight duration. Possible mechanisms for these changes, including alterations in erythropoietin levels, are discussed.

STS Shuttle Project

Gravity and space flight: effects on nutritional status

The final decade of the millennium has seen an enormous amount of on-orbit life sciences research, including both short- and long-duration flight research. Life sciences dedicated Space Shuttle flights have made intensive research opportunities available to study on the acute adaptation to weightlessness. The NASA/Mir Science Program combined resources of the USA and Russia to provide the first long-duration flight opportunities for the United States since the Skylab program of the early 1970s. Many of the results of these studies are still being evaluated, and in some cases data are still being collected to assess long-term readaptation to gravity after several months in weightlessness. The surge in life sciences research during this decade serves as a preamble to the opportunities to be provided by the latest addition to the Earth-orbiting structures--the International Space Station.

short duration

[Characteristics of morphogenesis of the Japanese quail embryos during microgravity]

Experiments performed in the period of 1995-1996 cooperatively with US investigators within the MIR/SHUTTLE and MIR/NASA space science projects continued exploration of avian embryogenesis in microgravity. Evaluation of Japanese quail embryos incubated in spaceflight microgravity showed that for the most part they were normally developed and compliant with duration of incubation. One of the major morphometric characteristics of embryo are its mass and size. Comparative analysis of body mass values in the space and laboratory and synchronous control groups pointed to a slight retardation. Body length of space embryos mimicked their mass curve. Data on the dynamics of mass and length of Japanese quail embryos support the well-known theory according to which growth and formation are distinguished by equifinality. No differences were revealed by the investigations of individual parts of embryonic bodies in the space and control groups. However, this finding was true only with regard to the embryos that had no developmental abnormalities. A part of embryos had defective eyes (microphtalmia), limbs (twisted fingers), and beaks.

manned

Analysis of complex-type chromosome exchanges in astronauts' lymphocytes after space flight as a biomarker of high-LET exposure

High-LET radiation is more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. To investigate if complex chromosome exchanges are induced by the high-LET component of space radiation exposure, damage was assessed in astronauts' blood lymphocytes before and after long duration missions of 3-4 months. The frequency of simple translocations increased significantly for most of the crewmembers studied. However, there were few complex exchanges detected and only one crewmember had a significant increase after flight. It has been suggested that the yield of complex chromosome damage could be underestimated when analyzing metaphase cells collected at one time point after irradiation, and analysis of chemically-induced PCC may be more accurate since problems with complicated cell-cycle delays are avoided. However, in this case the yields of chromosome damage were similar for metaphase and PCC analysis of astronauts' lymphocytes. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.

manned