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Effect of space flight on cytokine production.

Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines. Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

Animals↗

Reproducible analyses of microbial food for advanced life support systems.

The use of yeasts in Controlled Ecological Life Support Systems (CELSS) for microbial food regeneration in space required the accurate and reproducible analysis of intracellular carbohydrate and protein levels. The reproducible analysis of glycogen was a key element in estimating overall content of edibles in candidate yeast strains. Typical analytical methods for estimating glycogen in Saccharomyces were not found to be entirely applicable to other candidate strains. Rigorous cell lysis coupled with acid/base fractionation followed by specific enzymatic glycogen analyses were required to obtain accurate results in two strains of Candida. A profile of edible fractions of these strains was then determined. The suitability of yeasts as food sources in CELSS food production processes is discussed.

Candida↗

Radiation hazards on space missions outside the magnetosphere.

Future space missions outside the magnetosphere will subject astronauts to a hostile and unfamiliar radiation environment. An annual dose equivalent to the blood-forming organs (BFOs) of approximately 0.5 Sv is expected, mostly from heavy ions in the galactic cosmic radiation. On long-duration missions, an anomalously-large solar energetic particle event may occur. Such an event can expose astronauts to up to approximately 25 Gy (skin dose) and up to approximately 2 Sv (BFO dose) with no shielding. The anticipated radiation exposure may necessitate spacecraft design concessions and some restriction of mission activities. In this paper we discuss our model calculations of radiation doses in several exo-magnetospheric environments. Specific radiation shielding strategies are discussed. A new calculation of aluminum equivalents of potential spacecraft shielding materials demonstrates the importance of low-atomic-mass species for protection from galactic cosmic radiation.

Aluminum↗

Galactic cosmic rays and cell-hit frequencies outside the magnetosphere.

An evaluation of the exposure of space travelers to galactic cosmic radiation outside the earth's magnetosphere is made by calculating fluences of high-energy primary and secondary particles with various charges traversing a sphere of area 100 microns2. Calculations relating to two shielding configurations are presented: the center of a spherical aluminum shell of thickness 1 g/cm2, and the center of a 4 g/cm2 thick aluminum spherical shell within which there is a 30 g/cm2 diameter spherical water phantom with the point of interest 5 g/cm2 from the surface. The area of 100 microns2 was chosen to simulate the nucleus of a cell in the body. The frequencies as a function of charge component in both shielding configurations reflects the odd-even disparity of the incident particle abundances. For a three-year mission, 33% of the cells in the more heavily shielded configuration would be hit by at least one particle with Z greater than 10. Six percent would be hit by at least two such particles. This emphasizes the importance of studying single high-Z particle effects both on cells which might be "at risk" for cancer induction and on critical neural cells or networks which might be vulnerable to inactivation by heavy charged particle tracks. Synergistic effects with the more numerous high-energy protons and helium ions cannot be ruled out. In terms of more conventional radiation risk assessment, the dose equivalent decreased by a factor of 2.85 from free space to that in the more heavily shielded configuration. Roughly half of this was due to the decrease in energy deposition (absorbed dose) and half to the decrease in biological effectiveness (quality factor).

Aluminum↗

Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Aging↗

Modification of plant growth and development by acceleration and vibration: concerns and opportunities for plant experimentation in orbiting spacecraft.

Growth, development, and orientation of higher plants is altered by physical disturbances such as shaking, touching, or vibration. Plant growth responses to thigmic (contact rubbing) forces are almost always negative, whereas growth responses to periodic seismic (shaking) or vibric (vibrational) disturbances may be positive or negative, depending on intensity and duration of force, and prevailing environmental conditions. Seedlings are most sensitive to mechanical stress when grown in darkness or under the low-light conditions typically available in plant flight hardware. Brief exposure to physical perturbation causes immediate growth inhibition of dark-grown seedlings followed by gradual recovery of growth rate beginning 10-12 minutes later. For mild vibration, growth rate may overshoot that of undisturbed control plants within an hour of a stress episode, whereas for thigmic stress recovery may remain incomplete for 24 hours or longer. Lack of physical stimulation by gravity should make plants even more responsive to random physical perturbation. Threshold growth response of seedlings to vibrational parameters needs to be determined under real spaceflight conditions.

Acceleration↗

Galactic cosmic ray abundances and spectra behind defined shielding.

LET spectra have been measured for lunar missions and for several near Earth orbits ranging from 28 degrees to 83 degrees inclination. In some of the experiments the flux of GCR was determined separately from contributions caused by interactions in the detector material. Results of these experiments are compared to model calculations. The general agreement justifies the use of the model to calculate GCR fluxes. The magnitude of variations caused by solar modulation, geomagnetic shielding, and shielding by matter determined from calculated LET spectra is generally in agreement with experimental data. However, more detailed investigations show that there are some weak points in modeling solar modulation and shielding by material. These points are discussed in more detail.

Cosmic Radiation↗

Solar modulation and nuclear fragmentation effects in galactic cosmic ray transport through shielding.

Crews of manned interplanetary missions may accumulate significant radiation exposures from the galactic cosmic ray (GCR) environment in space. Estimates of how these dose levels are affected by the assumed temporal and spatial variations in the composition of the GCR environment, and by the effects of the spacecraft and body self-shielding on the transported radiation fields are presented. In this work, the physical processes through which shielding alters the transported radiation fields are described. We then present estimates of the effects on model calculations of (1) nuclear fragmentation model uncertainties, (2) solar modulation, (3) variations between solar cycles, and (4) proposed changes to the quality factors which relate dose equivalent to absorbed dose.

Aluminum↗

Galactic cosmic ray radiation levels in spacecraft on interplanetary missions.

Using the Langley Research Center galactic cosmic ray (GCR) transport computer code (HZETRN) and the computerized anatomical man (CAM) model, crew radiation levels inside manned spacecraft on interplanetary missions are estimated. These radiation-level estimates include particle fluxes, LET (linear energy transfer) spectra, absorbed dose, and dose equivalent within various organs of interest in GCR protection studies. Changes in these radiation levels resulting from the use of various different types of shield materials are presented.

Bone Marrow↗

Recent space shuttle observations of the South Atlantic Anomaly and the radiation belt models.

Active instruments consisting of a tissue equivalent proportional counter (TEPC) and a proton and heavy ion detector (PHIDE) have been carried on a number of Space Shuttle flights. These instruments have allowed us to map out parts of the South Atlantic Particle Anomaly (SAA) and to compare some of its features with predictions of the AP-8 energetic proton flux models. We have observed that consistent with the generally observed westward drift of the surface features of the terrestrial magnetic field the SAA has moved west by about 6.9 degrees longitude between the epoch year 1970 of the AP-8 solar maximum model and the Space Shuttle observations made twenty years later. However, calculations indicate that except for relatively brief periods following very large magnetic storms the SAA seems to occupy the same position in L-space as in 1970. After the great storm of 24 March 1991 reconfiguration of the inner radiation belt and/or proton injection into the inner belt, a second energetic proton belt was observed to form at L approximately = 2. As confirmed by a subsequent flight observations, this belt was shown to persist at least for six months. Our measurements also indicate an upward shift in the L location of the primary belt from L = 1.4 to L = 1.5. In addition we confirm through direct real time observations the existence and the approximate magnitude of the East-West effect.

Atlantic Ocean↗

Results of time-resolved radiation exposure measurements made during U.S. Shuttle missions with a tissue equivalent proportional counter.

Time-resolved radiation exposure measurements inside the crew compartment have been made during recent Shuttle missions with the USAF Radiation Monitoring Equipment-III (RME-III), a portable four-channel tissue equivalent proportional counter. Results from the first six missions are presented and discussed. The missions had orbital inclinations ranging from 28.5 degrees to 57 degrees, and altitudes from 200-600 km. Dose equivalent rates ranged from 40-5300 micro Sv/dy. The RME-III measurements are in good agreement with other dosimetry measurements made aboard the vehicle. Measurements indicate that medium- and high-LET particles contribute less than 2% of the particle fluence for all missions, but up to 50% of the dose equivalent, depending on the spacecraft's altitude and orbital inclination. Iso-dose rate contours have been developed from measurements made during the STS-28 mission. The drift rate of the South Atlantic Anomaly (SAA) is estimated to be 0.49 degrees W/yr and 0.12 degrees N/yr. The calculated trapped proton and Galactic Cosmic Radiation (GCR) dose for the STS-28 mission were significantly lower than the measured values.

Cosmic Radiation↗

A consensus approach to planetary protection requirements: recommendations for Mars lander missions.

Over the last several years, the nature of the surface conditions on the planet Mars, our knowledge of the growth capabilities of Earth organisms under extreme conditions, and future opportunities for Mars exploration have been under extensive review in the United States and elsewhere. As part of these examinations, in 1992 the US Space Studies Board made a series of recommendations to NASA on the requirements that should be implemented on future missions that will explore Mars. In particular, significant changes were recommended in the requirements for Mars landers, changes that significantly alleviated the burden of planetary protection implementation for these missions. In this paper we propose a resolution implementing this new set of recommendations, for adoption by COSPAR at its 30th meeting in Hamburg. We also discuss future directions and study areas for planetary protection, in light of changing plans for Mars exploration.

Consensus Statements as Topic↗

Bursting into space: alterations of sympathetic control by space travel.

AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

Adult↗

Effects of spaceflight on the musculoskeletal system: NIH and NASA future directions.

Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors. Studies are in progress to develop interventions that preserve or improve musculoskeletal integrity in 1g. The NIAMS and NASA are interested in basic and clinical studies of the influence of microgravity on the musculoskeletal system. The interagency workshop results form the basis for new collaborative and cooperative research emphases for the biomedical community under a broad agreement between the National Institutes of Health and NASA.

Bone and Bones↗

Folic acid content in thermostabilized and freeze-dried space shuttle foods.

This study was designed to determine whether freeze-dried and thermostabilized foods on a space shuttle contain adequate folate and to investigate any effects of freeze-drying on folacin. Frozen vegetables were analyzed after three states of processing: thawed; cooked; and rehydrated. Thermostabilized items were analyzed as supplied with no further processing. Measurable folate decreased in some freeze-dried vegetables and increased in others. Folacin content of thermostabilized food items was comparable with published values. We concluded that although the folacin content of some freeze-dried foods was low, adequate folate is available from the shuttle menu to meet RDA guidelines.

Folic Acid↗

Plants in space.

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Calcium↗

Large solar flare radiation shielding requirements for manned interplanetary missions.

As the 21st century approaches, there is an ever-increasing interest in launching manned missions to Mars. A major concern to mission planners is exposure of the flight crews to highly penetrating and damaging space radiations. Beyond the protective covering of the Earth's magnetosphere, the two main sources of these radiations are galactic cosmic rays and solar particle events. Preliminary analyses of potential exposures from galactic cosmic rays (GCR's) were presented elsewhere. In this Note, estimates of shielding thicknesses required to protect astronauts on interplanetary missions from the effects of large solar flare events are presented. The calculations use integral proton fluences for the February 1956, November 1960, and August 1972 solar particle events as inputs into the NASA Langley Research Center nucleon transport code BRYNTRN. This deterministic computer code transports primary protons and secondary protons and neutrons through any number of layers of target material of arbitrary thickness and composition. Contributions from target nucleus breakup (fragmentation) and recoil are also included. The results for each flare are presented as estimates of dose equivalent [in units of roentgen equivalent man (rem)] to the skin, eye, and bloodforming organs (BFO) behind various thicknesses of aluminum shielding. These results indicate that the February 1956 event was the most penetrating; however, the August 1972 event, the largest ever recorded, could have been mission- or life-threatening for thinly shielded (< or = 5 g/cm2) spacecraft. Also presented are estimates of the thicknesses of water shielding required to reduce the BFO dose equivalent to currently recommended astronaut exposure limits. These latter results suggest that organic polymers, similar to water, appear to be a much more desirable shielding material than aluminum.

Aluminum↗