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PubMed1992

The space life sciences strategy for the 21st century.

In the past, space life sciences has focused on gaining an understanding of physiological tolerance to spaceflight, but, for the last 10 years, the focus has evolved to include issues relevant to extended duration missions. In the 21st century, NASA's long-term strategy for the exploration of the solar system will combine the assurance of human health and performance for long periods in space with investigations aimed at searching for traces of life on other planets and acquiring fundamental scientific knowledge of life processes. Implementation of this strategy will involve a variety of disciplines including radiation health, life support, human factors, space physiology and countermeasures, medical care, environmental health, and exobiology. It will use both ground-based and flight research opportunities such as those found in current on-going programs, on Spacelab and unmanned biosatellite flights, and during Space Station Freedom missions.

Aerospace Medicine↗
PubMed1997

Angiogenesis and osteogenesis in an orthopedically expanded suture.

The purpose of this study was to examine the angiogenic and the subsequent osteogenic responses during a 96-hour time-course after sutural expansion. Fifty rats were divided into: (1) a control group that received only angiogenic induction through injection of 5 ng/gm recombinant human endothelial cell growth factor (rhECGF); (2) an experimental group that received orthopedic expansion and rhECGF; (3) a sham group that received expansion and sodium chloride (NaCl) injection; and (4) a baseline group that received no expansion or injection. All rats were injected with 3H-thymidine (1.0 microCi/gm) 1 hour before death to label the DNA of S-phase cells. Demineralized sections (4 microm thick) were stained with hematoxylin and eosin. Angiogenesis and cell migration were analyzed with a previously established cell kinetics model. Analysis of variance was used to test the hypothesis that enhancement of angiogenesis stimulates reestablishment of osteogenic capability. Blood vessel number, area, and endothelial cell-labeled index significantly increased in experimental groups, but no difference was found between control and baseline groups. Labeled-pericyte index and activated pericyte numbers in the experimental group were also higher than in the sham groups. These results show that supplemental rhECGF enhances angiogenesis in expanded sutures but not in nonexpanded sutures. Data also suggest that pericytes are the source of osteoblasts in an orthopedically expanded suture.

Analysis of Variance↗
PubMed1993

Risk from relativistic heavy ions on manned space missions.

The risk from exposure to radiation posed to space travelers outside the magnetic shielding provided by the geomagnetosphere will come from two sources: the slowly varying but low intensity high-energy galactic cosmic rays and the more intense predominantly low-energy protons from large solar particle events associated with magnetic disturbances originating sporadically on or within the solar surface during the active period of the 11-year solar cycle. The energy spectra of the protons in solar particle events are quite soft, with large numbers of low-energy protons and a rather steep decrease of the energy spectra with increasing energy. This allows for the possibility to provide, within the space vehicle or habitat, a well-shielded area sometimes called a "storm shelter" or "safe haven" where the travelers could gather during the largest particle events. Intensity risetimes on the order of half an hour or more and overall event durations of 1 to 2 days would make actively seeking a well-shielded shelter for the duration a distinct possibility. The high-energy and penetrating nature and relative constancy of the galactic cosmic rays, on the other hand, do not allow the use of highly shielded areas as a means of protection against them. The first question to answer becomes: what is the risk to human health from the galactic cosmic rays? We need to have a good idea of the answer to this question before we can address the problem of how to best protect human health or, indeed, whether any specific measures need to be taken.

Cosmic Radiation↗
PubMed1989

Studies of the horizontal vestibulo-ocular reflex in spaceflight.

Changes in the vestibulo-ocular reflex (VOR) during space flight have been suspected of contributing to space motion sickness. The horizontal VOR was studied in nine subjects on two space shuttle missions. Active unpaced head oscillation at 0.3 Hz was used as the stimulus to examine the gain and phase of the VOR with and without visual input, as well as the visual suppression of the reflex. No statistically significant changes were noted inflight in the gains or phase shifts of the VOR during any test condition, or between space motion sickness susceptible and nonsusceptible populations. Although VOR suppression was unaffected by spaceflight, the space motion sickness-susceptible group tended to exhibit greater error in the suppression than the nonsusceptible group. It is concluded that at this stimulus frequency, VOR gain is unaffected by spaceflight, and any minor individual changes do not seem to contribute to space motion sickness.

Adult↗
PubMed1988

The endocrine system in space flight.

Hormones are important effectors of the body's response to microgravity in the areas of fluid and electrolyte metabolism, erythropoiesis, and calcium metabolism. For many years antidiuretic hormone, cortisol and aldosterone have been considered the hormones most important for regulation of body fluid volume and blood levels of electrolytes, but they cannot account totally for losses of fluid and electrolytes during space flight. We have now measured atrial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF had decreased by 59%, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell production, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1 alpha, 25-dihydroxyvitamin D3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.

Aerospace Medicine↗
PubMed1992

Further analyses of human kidney cell populations separated on the Space Shuttle.

Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 degrees C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another.

Cell Line↗
PubMed1995

Human fiber size and enzymatic properties after 5 and 11 days of spaceflight.

Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Medical approaches to technogenic risks mitigation: instructive experience of space medicine].

Medical approaches to mitigation of technogenic extreme risks are analyzed by the example of space medicine experience in handling of the risks caused to humans by specific and non-specific extreme factors in space flight. Discussion is centered on the amalgamation of closely interconnected fundamental and applied risk researches with the ultimate aim of determining the strategy of risk minimization through optimization of environment, professional activity, and development of effective medical care and prevention instruments. One of the major achievements of the Russian space program was giving evidence of the possibility to control risks in extended orbital missions. As far as the Moon and Mars exploration projects are concerned, views of the U.S. NASA have been formulated in "Bioastronautics Critical Path Roadmap". Excerpts from the document illustrate possible approaches to the current and prospective technogenic extreme risks.

Aerospace Medicine↗
PubMed2002

Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells.

Individual protein kinase C (PKC) isoforms fulfill distinct roles in the regulation of the commitment to differentiation, cell cycle arrest, and apoptosis in both monocytes and T-cells. The human monocyte like cell line U937 and T-cells were exposed to microgravity, during spaceflight and the translocation (a critical step in PKC signaling) of individual isoforms to cell particulate fraction examined. PKC activating phorbol esters induced a rapid translocation of several PKC isoforms to the particulate fraction of U937 monocytes under terrestrial gravity (1 g) conditions in the laboratory. In microgravity, the translocation of PKC beta II, delta, and epsilon in response to phorbol esters was reduced in microgravity compared to 1 g, but was enhanced in weak hypergravity (1.4 g). All isoforms showed a net increase in particulate PKC following phorbol ester stimulation, except PKC delta which showed a net decrease in microgravity. In T-cells, phorbol ester induced translocation of PKC delta was reduced in microgravity, compared to 1 g, while PKC beta II translocation was not significantly different at the two g-levels. These data show that microgravity differentially alters the translocation of individual PKC isoforms in monocytes and T-cells, thus providing a partial explanation for the modifications previously observed in the activation of these cell types under microgravity.

Blotting, Western↗
PubMed1992

Human exposure to large solar particle events in space.

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/cm2) and storm shelter (20 g/cm2) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high dose rate values prevalent in radiation therapy.

Bone Marrow↗
PubMed1997

Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells.

Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclooxygenases: COX-1 (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E2 (dmPGE2) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE2 concentration. DmPGE2 also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE2 regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE2 concentration, with maximum stimulation seen at 5 microg ml(-1). The non-steroidal anti-inflammatory drug flurbiprofen (5 microM), in the presence of exogenous dmPGE2, inhibited the up-regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE2 has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE2, perhaps resulting from changes in local cellular PGE2 concentrations.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Sustained microgravity reduces the human ventilatory response to hypoxia but not to hypercapnia.

We measured the isocapnic hypoxic ventilatory response and the hypercapnic ventilatory response by using rebreathing techniques in five normal subjects (ages 37-47 yr) before, during, and after 16 days of exposure to microgravity (microG). Control measurements were performed with the subjects in the standing and supine postures. In both microG and in the supine position, the hypoxic ventilatory response, as measured from the slope of ventilation against arterial O(2) saturation, was greatly reduced, being only 46 +/- 10% (microG) and 52 +/- 11% (supine) of that measured standing (P < 0.01). During the hypercapnic ventilatory response test, the ventilation at a PCO(2) of 60 Torr was not significantly different in microG (101 +/- 5%) and the supine position (89 +/- 3%) from that measured standing. Inspiratory occlusion pressures agreed with these results. The findings can be explained by inhibition of the hypoxic but not hypercapnic drive, possibly as a result of an increase in blood pressure in carotid baroreceptors in microG and the supine position.

Adult↗
PubMed1989

Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity.

The purpose of these experiments was to test the hypothesis that reduced size of the leg muscle compartment following exposure to long-duration microgravity would be associated with increased leg compliance. Eight men, 31-45 years of age, were measured for vascular compliance of the calf and serial circumferences of the thigh and calf before, during and after 30 d of continuous 6 degrees head-down bedrest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the thigh and calf were determined pre- and post-bedrest by computed tomography. Calculated leg volumes decreased (p less than 0.05) in the calf by 9.9% and in the thigh by 4.5% from pre- to post-bedrest. Muscle compartment CSA also decreased (p less than 0.05) in both calf (-4.8%) and thigh (-8.1%); leg compliance (vol%/mm Hg x 100) increased (p less than 0.05) from 3.9 +/- 0.7 to 4.9 +/- 0.5. Calf compliance measured before and after bedrest was inversely related to calf muscle compartment CSA (r = -0.61, p less than 0.05) and the percent decrease in calf muscle compartment CSA from pre- to post-bedrest was inversely correlated with an increase in calf compliance (r = -0.72, p less than 0.05). Increased leg compliance following long-duration spaceflight is associated with reduced size of the leg muscle compartment.

Adipose Tissue↗
PubMedDate not supplied

Space analogue studies in Antarctica.

Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

Adaptation, Psychological↗
PubMed1989

A parametric study of space radiation exposures to critical body organs for low earth orbit missions.

The geomagnetically-trapped and galactic cosmic radiation environments are two of the major sources of naturally-occurring space radiation exposure to astronauts in low earth orbit. The exposure is dependent primarily on altitude, spacecraft shielding, crew stay-times, and solar cycle effects for a 28.5 deg orbital inclination. Based on Space Shuttle experience, the calculated results of a parametric study are presented for several mission scenarios using a computerized anatomical man model and are compared with the NASA crew exposure limits for several critical body organs.

Altitude↗
PubMed1994

Single-track effects and new directions in GCR risk assessment.

Light flashes in the eye as recorded by astronauts on missions outside the geomagnetosphere are presumably caused by single particle traversals of galactic cosmic rays traversing the retina. Although these flashes are not considered to have deleterious short- or long-term effects on vision, they are testimony that the body can detect single particle traversals. The frequencies of the flashes implicate ions in the charge range of 6 to 8 (i.e., carbon and/or oxygen ions). Other particles with higher charge and causing more ionization are present at lower frequencies. The possibility of the importance of such single-track effects in radiation carcinogenesis and other late effects suggest that a risk assessment system based on particle fluence rather than absorbed dose might be useful for assessing risk on long-term space missions. Such a system based on the concept of a risk cross section is described. Human cancer risk cross sections obtained from recently compiled A-bomb survival data are presented, and problems involving the determination of the LET-dependence of such cross sections are discussed.

Breast Neoplasms↗
PubMed1993

Evaluation of muscle injury using magnetic resonance imaging.

The objective of this study was to investigate spin echo T2 relaxation time changes in thigh muscles after intense eccentric exercise in healthy men. Spin echo and calculated T2 relaxation time images of the thighs were obtained on several occasions after exercise of one limb; the contralateral limb served as control. Muscle damage was verified by elevated levels of serum creatine kinase (CK). Thirty percent of the time no exercise effect was discernible on the magnetic resonance (MR) images. In all positive MR images (70%) the semitendinosus muscle was positive, while the biceps femoris, short head, and gracilis muscles were also positive in 50% and 25% of the total cases, respectively. The peak T2 relaxation time and serum CK were correlated (r = 0.94, p<0.01); temporal changes in muscle T2 relaxation time and serum CK were similar, although T2 relaxation time remained positive after serum CK returned to background levels. We conclude that magnetic resonance imaging can serve as a useful tool in the evaluation of eccentric exercise muscle damage by providing a quantitative indicator of damage and its resolution as well as the specific areas and muscles.

Adult↗