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Space flight and humoral and cellular immunity of animals.

The use of animal surrogates for the study of the effects of space flight on immune responses is desirable for several reasons. First, animal models are very useful in conditions where the use of human subjects would be difficult. This is certainly true in the space flight environment, where the number of human subjects is small, the human subjects are often too occupied with space flight duties to serve as subjects, and where sampling could be difficult under adverse conditions. Second, because of the intense interest in the immune system, many animal models and reagents already exist that are readily adaptable to space flight studies. Therefore, animal models have been used for many years for space flight studies on immunity. The predominant model used has been the rat, although recently, development of a rhesus monkey model has begun. The focus of this paper will be a description of the results of ground-based and space flight animal models to determine the effects of space flight on immune responses.

Animals↗

[Organ and tissue regeneration in lower vertebrate animals during space flight and after its completion].

The most important data obtained in studies of the influence of space flight factors on the limb and lens regeneration in the newt Pleurodeles waltlii have been summarized. Regeneration of these organs under the conditions of space flight and after its termination proceeded just as on the ground. However after the 7th, 13th and 16th days of space flight, a trend was shown toward acceleration of the limb and lens regenerates development according to the regeneration stages and synchronization of the achieved stages, which was accompanied in some cases by an increased proliferative activity of the regenerate cells. It was shown that in two groups of animals operated before the 16-day space flight (I) and just after its termination (II) accelerated development of the limb and lens regenerates was observed. In group II, at the large bud stage, the index of 3H-thymidine labeled blastema cells was more than twice that in the control. The size of regenerates in groups I and II exceeded reliably those in the control. These results suggest a prolonged effect of space flight factors on the limb and lens regeneration. It was also shown that the capacity of the muscle minced 14 days before the flight for regeneration was not suppressed, although somewhat decreased. An electron microscopic study showed degenerative-atrophic changes in the intact hind limb muscle after the 16-day space flight. We believe that the phenomenon of synchronization and accelerated regeneration of the limb and lens observed in the most experiments are due to the effect of microgravity on the animals.

Animals↗

Alteration in human mononuclear leucocytes following space flight.

Reduced in vitro mitogen-stimulated proliferative responses have routinely been observed from astronauts' mononuclear leucocytes following space flight. This study investigated the effect of space flight on subpopulations of peripheral blood mononuclear cells from 30 shuttle astronauts prior to launch, upon landing and 3 days after flight. The total number of peripheral blood leucocytes, granulocytes and monocytes were increased after space flight (5.7 +/- 0.2 versus 7.0 +/- 0.2; 3.1 +/- 0.1 versus 5.0 +/- 0.1; and 0.16 +/- 0.02 versus 0.25 +/- 0.28 x 10(3) cells/mm3, respectively) whereas lymphocytes were decreased (2.2 +/- 0.1 versus 1.7 +/- 0.1 x 10(3) cells/mm3). Flow cytometry analysis on Ficoll-Hypaque isolated mononuclear cells upon landing revealed significant decreases in T-inducer (CD4+, Leu-8+; 32 +/- 2 versus 23 +/- 2%) and T-cytotoxic lymphocytes (CD8+, CD11b-; 17 +/- 1 versus 12 +/- 1%), and increases in monocytes (CD14+; 13 +/- 1 versus 21 +/- 1%) compared to pre-flight and post-flight samples whereas B cells (CD19+), T-helper (CD4+, Leu-8-) and T-suppressor (CD8+, CD11b+) populations did not change. Additional phenotypic analysis of these mononuclear leucocytes from 10 crew members upon landing revealed a reduction in natural killer (NK) cells (CD16+ or CD56+; 9 +/- 1 versus 3 +/- 1%) and an increase in monocytes that were negative for insulin and insulin-like growth factor-1 (IGF-1) receptor expression. Flow cytometric analysis indicated these hormone receptor negative monocytes were smaller and less granular than receptor positive monocytes. Therefore, a novel population of monocytes may be released into the peripheral blood during the stress of space flight or upon landing. These findings may explain some of the diverse in vitro immunological and endocrine changes observed in crew members following space flight.

Adult↗

A review and comparative analysis of the biological damage induced during space flight by HZE particles and space hadrons.

We have studied the somatic and genetic effects of heavy ions (HZE particles) and the very high energy hadrons of space radiation on various organisms ranging in complexity from bacteriophage to man. Experimental data were obtained in space, on high mountains and in a proton accelerator at energies of 76 GeV. In all these experiments local micro- and macroradiational damage was observed. This damage was characterized by severity over large local regions and for the most part was due to cascades of secondary particle bundles resulting from the collision of very high energy space hadrons with atomic nuclei rather than from cellular hits from relatively low energy single HZE particles. At present there does not appear to be any effective way to provide shielding against these cosmic hadrons.

Animals↗

Space flight experiment on Chinese silkworm on board the Russian 10th Biosatellite.

Space flight experiments on Chinese silkworm (Bombyx mori L.) were conducted on board the Russian 10th Biosatellite for 12 days. The samples included silkworm eggs, larvae, cocoons, pupae and moths. The processes of spinning, cocooning, mating, oviposition, larval hatching, pupation and moth emergence all completed well in space. The following effects of space flight on silkworm development were observed: The times of hatching and oviposition in the flight group were 2 to 3 days earlier than in the control group; the hatching rate of diapause eggs during space flight seemed higher than that of the control group; the life span of 2 of the 7 varieties flown was shortened; genetical variations appeared in 3 varieties. The results showed that the embryonic stage was probably the period most sensitive to the space flight environment.

Animals↗

Changes in the central nervous system during long-duration space flight: implications for neuro-imaging.

The purpose of this paper is to review the potential functional and morphological effects of long duration space flight on the human central nervous system (CNS) and how current neuroimaging techniques may be utilized to study these effects. It must be determined if there will be any detrimental changes to the CNS from long term exposure to the space environment if human beings are to plan interplanetary missions or establish permanent space habitats. Research to date has focused primarily on the short term changes in the CNS as the result of space flight. The space environment has many factors such as weightlessness, electromagnetic fields, and radiation, that may impact upon the function and structure of the CNS. CNS changes known to occur during and after long term space flight include neurovestibular disturbances, cephalic fluid shifts, alterations in sensory perception, changes in proprioception, psychological disturbances, and cognitive changes. Animal studies have shown altered plasticity of the neural cytoarchitecture, decreased neuronal metabolism in the hypothalamus, and changes in neurotransmitter concentrations. Recent progress in the ability to study brain morphology, cerebral metabolism, and neurochemistry in vivo in the human brain would provide ample opportunity to investigate many of the changes that occur in the CNS as a result of space flight. These methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).

Adaptation, Physiological↗

Soviet space flight: the human element.

Building on past experience and knowledge, the Soviet manned space flight effort has become broad, comprehensive, and forward-looking. Their long-running space station program has provided the capabilities to investigate long-term effects of microgravity on human physiology and behavior and test various countermeasures against microgravity-induced physiological deconditioning. Since the beginning of Soviet manned space flight, the biomedical training and preparation of cosmonauts has evolved from a process that increased human tolerance to space flight factors, to a system of interrelated measures to prepare cosmonauts physically and psychologically to live and work in space. Currently, the Soviet Union is constructing a multimodular space station, the Mir. With the emergence of dedicated laboratory modules, the Soviets have begun the transition from small-scale experimental research to large-scale production activities and specialized scientific work in space. In the future, additional laboratory modules will be added, including one dedicated to biomedical research, called the "Medilab." The longest manned space flight to date (326 days) has been completed by the Soviets. The biomedical effects of previous long-duration flights, and perhaps those of still greater length, may contribute important insight ito the possibility of extended missions beyond Earth, such as a voyage to Mars.

Adaptation, Physiological↗

The risk of renal stone formation during and after long duration space flight.

BACKGROUND: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. METHODS: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. RESULTS: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. CONCLUSIONS: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk.

Adult↗

Investigation of erythrocyte shape, plasma membrane fluidity and conformation of haemoglobin haemoporphyrin under the influence of long-term space flight.

The investigation of long-term space flight (SF) effect on the blood cells function is of great importance for modern space biology and medicine. We established that the number of discocytes decreased in the period of early rehabilitation after long-term SF. After SF plasma membrane fluidity and phospholipid content decreased and cholesterol content increased. After SF the amount of haemoglobin decreased and the parameters characterizing haemoglobin haemoporyphyrin (HH) conformation changed. We suppose that erythrocyte shape, membrane fluidity and HH conformation are among factors affecting oxygen transfer during and after space flight.

Cholesterol↗

[Effect of space flight factors on hemopoiesis].

Published data concerning space flight effects upon hemopoiesis are discussed. Possible pathogenetic mechanisms of hemopoietic changes in response to space flight effects are described.

Bone Marrow Cells↗

Soviet space flight: the human element.

Building on past experience and knowledge, the Soviet manned space flight effort has become broad, comprehensive, and forward-looking. Their long-running space station program has provided the capabilities to investigate long-term effects of microgravity on human physiology and behavior, and test various countermeasures against microgravity-induced physiological deconditioning. Since the beginning of Soviet manned space flight, the biomedical training and preparation of cosmonauts has evolved from a process that increased human tolerance to space flight factors, to a system of interrelated measures to prepare cosmonauts physically and psychologically to live and work in space. Currently, the Soviet Union is constructing a multimodular space station, the Mir. With the emergence of dedicated laboratory modules, the Soviets have begun the transition from small-scale experimental research to large-scale production activities and specialized scientific work in space. In the future, additional laboratory modules will be added, including one dedicated to biomedical research, called the "Medilab." The longest manned space flight to date (326 d) has been completed by the Soviets. The biomedical effects of previous long-duration flights, and perhaps those of still greater length, may contribute important insight into the possibility of extended missions beyond Earth, such as a voyage to Mars.

Adaptation, Physiological↗

The effect of a 10-day space flight on the function, phenotype, and adhesion molecule expression of splenocytes and lymph node lymphocytes.

Previous studies have indicated that space flight affects the activation of lymphocytes from humans, monkeys, and rodents. In rats, where lymphocytes from blood, spleen, and lymph nodes have been tested, the accumulated data suggest that the effects of flight on various cells are lymphoid organ-specific. Thus, cells may be affected by variations in trafficking brought about by fluid shifts in microgravity (< 10(-3) g). In this study we examined lymphocyte activation (IL-2 production) as well as the expression of surface differentiation antigens and of adhesion molecules by splenocytes and lymph node lymphocytes (LNL) after a 10-day flight (Space Shuttle Mission STS-57). For splenocytes and LNL from flight (FLT) animals, IL-2 production decreased in response to the T cell receptor-independent mitogen 12-O-tetradecanoylphorbol-13-acetate plus ionomycin, but was not affected by stimulation with the T cell receptor-dependent mitogens Concanavalin A or phytohemagglutinin. In addition, the percentage, as well as fluorescent intensity, of splenocytes which expressed CD8, CD4, or kappa increased after flight. The percentage of LNL expressing CD2 also increased but those expressing CD5 decreased. The percentage of cells expressing the integrins LFA-1 alpha and beta increased with splenocytes from FLT animals but decreased for LNL. In contrast, FLT animals showed a decrease in the percentage of selectin-positive splenocytes. ICAM-1 expression did not change. In summary, these data are consistent with a model in which microgravity affects lymphocyte redistribution among organs, which in turn influences the activation potential of the cells.

Analysis of Variance↗

Nutritional biochemistry of space flight.

Humans have flown in space for more than 35 years. Since that time, Americans have walked on the moon, launched two space stations (Skylab and the International Space Station), docked during orbit with a Soviet Soyuz space capsule and the Russian Mir space station, flown the only reusable space vehicle, and visited a Russian space station for more then 6 months at a time. Nutritional intake has not been considered a high priority during relatively brief flights of the Space Shuttle and other programs (i.e., less than 21 days). However, as we embark on extended-duration (i.e., > 30 days up to several years) missions, nutrition becomes a critical issue. The impact of weightlessness on human physiology is profound. We are in the very early stages of understanding how space flight affects nutrient requirements and related issues such as absorption, metabolism, and excretion. Apart from the obvious role of providing energy and required nutrients, nutrition is also important in terms of enhancing psychosocial interactions among crews, and ameliorating some of the effects of microgravity on the body (i.e., acting as a "countermeasure"). The interrelationships among space flight, nutrition, and physiology suggest that a program of specified nutritional intake may be required to enhance mission safety and crew productivity. Defining which nutrients are essential for the space flight environment depends on a more complete understanding of how weightlessness affects physiology. Providing the required nutrients is also limited by the types of foods that can be provided by the food system on board the space craft, and the dietary habits of space crews.

Adaptation, Physiological↗

[Development of fixed-base full task space flight training simulator].

Fixed-base full task flight training simulator is a very critical and important integrated training facility. It is mostly used in training of integrated skills and tasks, such as running the flight program of manned space flight, dealing with faults, operating and controlling spacecraft flight, communicating information between spacecraft and ground. This simulator was made up of several subentries including spacecraft simulation, simulating cabin, sight image, acoustics, main controlling computer, instructor and assistant support. It has implemented many simulation functions, such as spacecraft environment, spacecraft movement, communicating information between spacecraft and ground, typical faults, manual control and operating training, training control, training monitor, training database management, training data recording, system detecting and so on.

Astronauts↗

Physiology, medicine, long-duration space flight and the NSBRI.

The hazards of long-duration space flight are real and unacceptable. In order for humans to participate effectively in long-duration orbital missions or continue the exploration of space, we must first secure the health of the astronaut and the success of such missions by assessing in detail the biomedical risks of space flight and developing countermeasures to these hazards. Acquiring the understanding necessary for building a sound foundation for countermeasure development requires an integrated approach to research in physiology and medicine and a level of cooperative action uncommon in the biomedical sciences. The research program of the National Space Biomedical Research Institute (NSBRI) was designed to accomplish just such an integrated research goal, ameliorating or eliminating the biomedical risks of long-duration space flight and enabling safe and productive exploration of space. The fruits of these labors are not limited to the space program. We can also use the gained understanding of the effects and mechanisms of the physiological changes engendered in space and the applied preventive and rehabilitative methods developed to combat these changes to the benefit of those on Earth who are facing similar physiological and psychological difficulties. This paper will discuss the innovative approach the NSBRI has taken to integrated research management and will present some of the successes of this approach.

Academies and Institutes↗

Blood and clonogenic hemopoietic cells of newts after the space flight.

Ribbed newts were used for studying the effect of space flight on board of the biosatellite (Cosmos-2229) on blood and clonogenic hemopoietic cells. In blood of newts of the flight group, the relative proportion of neutrophils increased, whereas that of lymphocytes and eosinophils decreased. Space flight did not result in loss of the ability of newt blood cells to incorporate H3-thymidine. Analysis of clonogenic hemopoietic cells was performed using the method of hemopoietic colony formation on cellulose acetate membranes implanted into the peritoneal cavity of irradiated newts. To analyze reconstitution of hemopoiesis after irradiation donor hemopoietic cells from flight or control newts were transplanted into irradiated newts whose hemopoietic organs were investigated. The newt can be considered an adequate model for studying hemopoiesis under the conditions of the space flight.

Animals↗