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The effect of space flight on monoclonal antibody synthesis in a hybridoma mouse cell line.

The hybridoma cell line, 3G10G5, producing a monoclonal antibody to the major capsid protein VP1 from the avian polyomavirus budgerigar fledgling disease virus, was produced from a Balb/C mouse. This cell line was used to test the effects of microgravity on cellular processes, specifically protein synthesis. A time course study utilizing incorporation of [35S]methionine into newly synthesized monoclonal antibody was performed on STS-77. After 5.5 days, it was observed that cell counts for the samples exposed to microgravity were lower than those of ground-based samples. However, radiolabel incorporation of the synthesized monoclonal antibody was similar in both orbiter and ground control samples. Overall, microgravity does not seem to have an effect on this cell line's ability to synthesize IgG protein.

Animals↗

Haemodynamics of leg veins during a 30-days-6 degrees head-down bedrest with and without lower body negative pressure.

Venous distensibility of the lower limbs was assessed in six healthy men who were submitted twice successively to 1 month of -6 degrees head-down bedrest, with and without lower body negative pressure (LBNP) (LBNP subjects and control subjects, respectively). Venous capacity (delta Vv,max, in ml.100 ml-1) of the legs was determined by mercury strain gauge plethysmography with venous occlusion. Plethysmographic measurements were made on each subject before (Dc), during (D6 and D20) and after (5th day of recovery, D+5) bedrest. During bedrest, LBNP was applied daily, several times a day to the subjects submitted to this procedure. Results showed a gradual increase in Vv,max (ml.100 ml-1) throughout the bedrest, both in the control group [delta Vv,max = 2.11 SD 0.54 at Dc, 2.69 SD 0.29 at D6, 4.39 SD 2.08 at D20, 2.39 SD 0.69 at D+5, P less than 0.001 (ANOVA)] and in the LBNP group [delta Vv,max = 2.07 SD 0.71 at Dc, 2.85 SD 1.19 at D6, 3.75 SD 1.74 at D20, 2.43 SD 0.94 at D+5, P less than 0.001 (ANOVA)], without significant LBNP effect. These increases were of the same order as those encountered during spaceflight. It is concluded that -6 degrees head-down bedrest is a good model to simulate the haemodynamic changes induced by exposure to weightlessness and that LBNP did not seem to be a good technique to counteract the adverse effects of weightlessness on the capacitance vessels of the lower limbs. This latter conclusion raises the question of the role and magnitude of leg venous capacitance in venous return and cardiac regulation.

Adult↗

Establishment of a three-dimensional human prostate organoid coculture under microgravity-simulated conditions: evaluation of androgen-induced growth and PSA expression.

A novel in vitro human prostate cancer model was established by using a coculture technique in which isolated human prostate fibroblasts were observed to grow as a mixed culture with isolated human prostate cancer cells (LNCaP) on microcarrier beads under microgravity-simulated conditions. This model appears to be promising and deserves further exploration because: (a) cocultured human prostate fibroblasts and cancer epithelial cells appear to undergo patterns of histogenesis similar to those observed in human prostate tumors and (b) unlike the conventional cell culture on plastic dishes, cocultured human prostate fibroblasts and LNCaP cells in microgravity-simulated conditions responded to the inductive signals of growth and differentiation from dihydrotestosterone in a manner similar to that observed in the in vivo condition. These results offer an opportunity to examine molecular mechanisms of cellular signaling in response to androgen stimulation during normal and aberrant human prostate development. The microgravity-simulated three-dimensional prostate epithelial cell culture with prostate fibroblasts can be further explored as an ideal in vitro model for the study of normal and neoplastic prostate development. This model could also be adopted as a drug screening program for the discovery of novel therapeutic agents in the treatment of human prostate cancer and benign hyperplastic growth.

Bioreactors↗

EVA design: lessons learned.

Extravehicular Activities (EVAs) are very demanding and specialized space flight activities. There are many aspects to consider in the design of hardware, tools, and procedures to be used on an EVA mission. To help minimize costs and optimize the EVA productivity, experience shows that astronauts should become involved early in the design process.

Astronauts↗

[Russian intra vehicular space suit and cold protection].

During space flights, astronauts use equipment allowing protection against many environmental factors. During tests realised in Russia, space suit efficiency was evaluated particularly concerning cold protection capacity in cold water (3 degrees C) and in cold air (-30 degrees C). Obtained results prove that this equipment allows to prevent hypothermia in cold water and ensure thermal comfort in cold air.

Cold Temperature↗

Soviet space stress.

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Adaptation, Psychological↗

Consequences of contamination of the spacecraft environment: immunologic consequences.

Long-term space voyages pose numerous known and unknown health hazards, to the human immune system. Well-studied clinical examples of secondary immunodeficiencies created on Earth, lead one to predict that the conditions of prolonged space flight would weaken the human immune responses that normally hold infection and cancer in check. From evidence gathered from humans flown for prolonged periods in space and from human models of space flight studied on Earth it is reasonable to suspect that space travelers to the planet Mars would experience a weakening of immunity. Subtle defects of immune cell structure and function have been observed in astronauts, such as weakening of specific T-lymphocyte recall of specific antigens. Ground-based models also have demonstrated alterations of immune function, such as the elevation of neuroendocrine immune system messengers, interleukin-6, and soluble tumor necrosis factor-alpha receptor in sleep deprivation. Since severe immune compromise the clinical consequences of reactivation of latent virus infections and the development of cancer, has yet to be seen in space flight or in the Earth models, it is extremely important to begin to quantify early changes in immunity to predict the development of immune system collapse with poor clinical outcomes. This approach is designed to validate a number of surrogate markers that will predict trouble ahead. Inherent in this research is the development of countermeasures to reduce the risks of infection and cancer in the first humans going to Mars.

Aerospace Medicine↗

European isolation and confinement study. Blood pressure, volume-regulating hormones, and electrolytes.

In the ISEMSI confinement experiment we observed three main reactions concerning blood volume regulation: first, a stress activation produced by the high workload that the subjects had to accomplish, both before the isolation period and during the two first weeks of isolation; second, a typical defense reaction to the environment occurred, at least during the two initial days of isolation and later perhaps between crew members themselves; and third, a change in blood volume regulating hormone levels may have been the result of the increase of sympathetic system activity and of dehydration. Confinement is certainly a good and valid method to simulate space station life (with the absence of weightlessness). So, it is interesting to use these confinement studies to perform biological and physiological experiments to obtain greater knowledge, but also to prepare and validate new scientific protocols or new scientific equipment suitable for spaceflights. Even more so, confinement is a good way to prepare and train crew members for long-term space missions. It would seem desirable to confirm the scientific results obtained during the ISEMSI campaign, and especially those for the regulation of the blood volume. This will be done during the next confinement experiment, called EXEMSI, in which four subjects will be subjected to 60 days of confinement.

Adult↗

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗

Are energy metabolism alterations involved in cardiovascular deconditioning after weightlessness? An hypothesis.

The physiopathogenesis of the cardiovascular deconditioning syndrome observed after actual and simulated microgravity is still under debate, despite numerous studies conducted on the role of blood volume, hormones involved in its regulation, sympathetic nervous system, baroreflexes and venous compliance. Orthostatic intolerance, a reduced exercise capacity and an increased heart rate at rest characterize this syndrome. Recent data suggest, first, the presence of a complex loop between the sympathetic nervous system, carbohydrate metabolism (insulin) and leptin hormone and, second, that this loop, an overall reflection of energy metabolism, participates in cardiovascular regulation. After a resume of studies conducted on fuel homeostasis during actual and simulated microgravity, the possible implications of energy metabolism in the development of the cardiovascular deconditioning syndrome will be discussed.

Adaptation, Physiological↗

[Effect of stable regional vascular hypotension on malignant tumor growth].

Weightlessness effects on the cardiovascular system of laboratory rats were simulated by prolonged arterial hypotension. In this situation antitumor stability of the animal body increased. The effect resulted from the compensatory reactions in vessels of blastomas and adjacent tissues. It is recommended to carry out such experiments in real space flights.

Animals↗

Bone mineral loss and recovery after 17 weeks of bed rest.

The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88.

Adult↗

Biochemical changes in rats flown on board the Cosmos 690 biosatellite.

Male rats of the Wistar strain were examined one day and 26 days after the 20-day space flight on board the Cosmos 690 biosatellite. On the 10th flight day the animals were exposed to 24-hour gamma irradiation: some animals were irradiated at a dose of 220 rad and the others at a dose of 800 rad. The data were compared with the results obtained from two control groups one day and 26 days after the experiment: (i) rats kept in the vivarium and fed with a special diet, and (ii) rats from a synchronous experiment (which simulated the flight profile with the exception only of weightlessness). The studies showed the following changes one day after flight: an increase in the concentration of total cholesterol, glucose, urea and corticosterone in the blood plasma, an increase in the concentration of triglycerides in the plasma, liver and bone marrow, a decrease in the concentration of total cholesterol in the adrenals, a reduction in the DNA and RNA content in the spleen and bone marrow, a decline in the potassium concentration together with an increase in the sodium concentration in soleus muscle. The degree and pattern of the changes depended largely on the dose of irradiation. The parameters returned to normal 26 days post-flight.

Adaptation, Physiological↗

Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids.

Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360-410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.

Amino Acids↗

[Analysis of human posture control under weightlessness].

Dynamic equations of human trunk and limbs in weightlessness were established, and the motions in 6 dimensions were resolved into 3 motions in 3 dimensions. The feasibility and operability of human posture control in weightlessness by using simple actions were described directly with analysis, calculation and dynamic simulation, and the training methods on the Earth were proposed.

Aerospace Medicine↗

Mass discrimination under Gz acceleration.

The purpose of this study was to assess how the perception of mass discrimination is affected by elevated Gz acceleration. Previous experiments studied mass discrimination under weightless conditions. Ten subjects were tested with the Dynamic Environment Simulator (DES) at Wright-Patterson Air Force Base. Masses of 105, 110, 115, 120, and 125 g were compared to a 100-g standard for delta Ms of 5, 10, 15, 20, and 25 g. The subject had to choose which mass felt heavier. This was done at 1, 2, and 4 Gz. Significant differences were found between each of the G levels, and the subjects made more errors at higher Gz. Significant differences were also found between each of the delta Ms, except between delta Ms of 20 and 25 g. Using regression lines, the difference limen was calculated at the 75% correct response level for each Gz. The Weber fraction was found by dividing the difference limen by the 100-g standard. Weber fraction of 0.085, 0.116, and 0.145 were found at 1, 2, and 4 Gz, respectively. Impairment to discrimination was shown by calculating the ratio of the Weber fraction of the elevated Gz to 1 Gz. This demonstrated an impairment to mass discrimination at 1.36 at 2 Gz and 1.71 at 4 Gz. Impairment of mass discrimination under elevated G indicates that loss of adaptation is more important than weight or mass constancy or any other factors which would increase gravitational sensory cues. This study attempted to show adaptation by comparing runs done on different days. To show aftereffect, intervals of 1 G were compared to each other. The study did not find any adaptation or aftereffect. When compared to previous studies done in weightlessness, microgravity was found to be more detrimental to mass discrimination than macrogravity, at least up to 4 Gz.

Acceleration↗

Energy requirements of man living in a weightless environment.

The ability to maintain energy balance is a vital factor in maintaining body composition. A negative energy balance requires that body tissue be consumed to sustain biochemical and physiological activity. Such a caloric imbalance coupled with reduced physical activity results in (among other things): a negative balance which can not be reversed by increased protein intake; negative balances for electrolytes; and a suspension of erythrocyte production. Body weight losses were experienced by all astronauts during Gemini and Apollo missions. Data on the magnitude of the changes, together with data on energy consumption, were used to calculate energy imbalances. These data, when compared with results obtained from precise energy balance measurements made on 64 men living in low pressure chambers, show close correlation. When energy requirements are expressed in kilocalories per kilogram of body weight, the difference in energy requirements among the astronauts and chamber subjects was small and not statistically significant. These data indicated that reliable prediction of energy needs for astronauts, during long-term space missions, can be made by studying either the astronauts or healthy subjects in a ground-based environment similar to that of the spacecraft. These data also indicate that changes in body weight and certain other body measurements detected during Gemini and Apollo missions were probably caused, at least in part, by a calorie deficit.

Adipose Tissue↗

Modeling locomotor dysfunction following spaceflight with Galvanic vestibular stimulation.

In this study locomotor and gaze dysfunction commonly observed in astronauts following spaceflight were modeled using two Galvanic vestibular stimulation (GVS) paradigms: (1) pseudorandom, and (2) head-coupled (proportional to the summed vertical linear acceleration and yaw angular velocity obtained from a head-mounted Inertial Measurement Unit). Locomotor and gaze function during GVS were assessed by tests previously used to evaluate post-flight astronaut performance; dynamic visual acuity (DVA) during treadmill locomotion at 80 m/min, and navigation of an obstacle course. During treadmill locomotion with pseudorandom GVS there was a 12% decrease in coherence between head pitch and vertical translation at the step frequency relative to the no GVS condition, which was not significantly different to the 15% decrease in coherence observed in astronauts following shuttle missions. This disruption in head stabilization likely resulted in a decrease in DVA equivalent to the reduction in acuity observed in astronauts 6 days after return from extended missions aboard the International Space Station (ISS). There were significant increases in time-to-completion of the obstacle course during both pseudorandom (21%) and head-coupled (14%) GVS, equivalent to an ISS astronaut 5 days post-landing. An attempt to suppress head movement was evident during both pseudorandom and head-coupled GVS while negotiating the obstacle course, with a 20 and 16%, decrease in head pitch and yaw velocity, respectively. The results of this study demonstrate that pseudorandom GVS generates many of the salient features of post-flight locomotor dysfunction observed in astronauts following short and long duration missions. An ambulatory GVS system may prove a useful adjunct to the current pre-flight astronaut training regimen.

Adult↗