Biochemical and histochemical observations of vastus medialis from rats flown in Cosmos 1887 (experiment K608).
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Future space missions of long duration may require that autologous leukocytes be stored in flight for infusion to restore normal immune competence in crewmembers. Peripheral blood mononuclear cells (PBMNCs), as leukocyte concentrates in autologous plasma and 2% dextrose, were stored in the microgravity conditions provided by the U.S. Space Shuttle Columbia (Mission 61-C). Activity of PBMNC after space flight was compared with that from a series of preflight ground control experiments, which demonstrated in culture a progressive daily loss in mitogen-stimulated protein synthesis at 24 h and thymidine uptake at 72 h after storage for 7 d at 4 degrees C. Post-storage viabilities were at least 90% as determined by trypan dye exclusion. A progressive reduction in the percentage of PBMNC expressing cell-surface phenotype markers, which was similar for monocytes, B cells, and T-cell subsets, also occurred after storage. The ability of PBMNC, stored for 8 d in Columbia's middeck, to become activated and proliferate in vitro was similar to that of cells that remained in identical flight lockers on the ground as 1-G controls, thus indicating that PBMNCs were not adversely affected by storage under microgravity conditions.
The nematode C. elegans was used to measure the effectiveness of high-energy ionized particles in the induction of 3 types of genetic lesions. Recessive lethal mutations in a 40-map unit autosomal region, sterility, and X-chromosome nondisjunction or damage were investigated. Induction rates were measured as a function of linear energy transfer, LET infinity, for 9 ions of atomic number 1-57 accelerated at the BEVALAC accelerator. Linear kinetics were observed for all 3 types of lesions within the dose/fluence ranges tested and varied strongly as a function of particle LET infinity. Relative Biological Effectiveness (RBE) values of up to 4.2 were measured and action cross sections were calculated and compared to mutagenic responses in other systems.
5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.
Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.
Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).
The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.
The reduction of muscle strength and size of the lower extremities has been observed following spaceflight. However, there are virtually no data from direct measurements of muscle tissue which provide a means of understanding the physiological alterations associated with the impaired function. We therefore conducted a study in which eight healthy men underwent 30 days of continuous exposure to 6 degrees headdown tilt as an analogue for space microgravity. We used percutaneous muscle biopsy, computed tomography, anthropometry, and in vivo muscle strength measures under controlled experimental conditions to provide new data about mechanical, structural, and metabolic characteristics of skeletal muscle in man following exposure to microgravity.
The question of the composition of exercise protocols for use by astronauts in microgravity is unresolved. Based on our knowledge of physical working requirements for astronauts during intra- and extravehicular activity and on the findings from bed-rest studies that utilized exercise training as a countermeasure for the reduction of aerobic power, deterioration of muscular strength and endurance, decrements in mood and cognitive performance, and possibly for bone loss, two exercise protocols are proposed. One assumes that, during microgravity, astronaut exercise physiological functions should be maintained at 100% of ground-based levels; the other assumes that maximal aerobic power in flight can be reduced by 10% of the ground-based level. A recommended prescription for in-flight prevention or partial suppression of calcium (bone) loss cannot be written until further research findings are obtained that elucidate the site, the magnitude, and the mechanism of the changes. Hopefully these proposed exercise prescriptions will stimulate further research and discussion resulting in even more efficient protocols that will help ensure the optimal health and well-being of our astronauts.
In planning for long-duration (1- to 2-yr) space missions (microgravity), the availability of oxygen, water, and food is critical for survival. If astronauts would consume approximately 3,100 kcal and 2.2 liters of fluid per day, the requirements for a 2-yr flight would be 2,263,000 kcal and 1,606 liters for each astronaut. These estimates, based on limited microgravity simulation and flight data, include 1 h/day of moderate isotonic exercise. Each 30-min/day reduction in exercise training time would save 110,869 kcal and 91 liters of water per year. One daily 5-h extravehicular sortie at an average work rate of 1.7 l/min would require an additional 529,250 kcal and 1,095 liters of water per year. Results from microgravity simulation (bed rest) experiments suggest that 1) there is uncertainty whether basal metabolism is unchanged, 2) submaximal ergometer exercise oxygen uptake appears to be unchanged or lower, and 3) without vigorous exercise training near peak levels, the peak oxygen uptake is definitely reduced. In addition, the equilibrium level of exercise core temperature is elevated excessively by approximately 0.5 degrees C after bed-rest acclimation. Changes in the efficiency of work or metabolism in any or all of these conditions could affect nutritional requirements for long spaceflights. Further research is necessary to elucidate the metabolic factors that would be changed and the energy cost of intra- and extravehicular activity during prolonged exposure to microgravity.
Increased leg venous compliance may contribute to postflight orthostatic intolerance in astronauts. We reported that leg compliance was inversely related to the size of the muscle compartment. The purpose of this study was to test the hypothesis that reduced muscle compartment after long-duration exposure to microgravity would cause increased leg compliance. Eight men, 31-45 yr old, were measured for vascular compliance of the calf and serial circumferences of the calf before and after 30 days of continuous 6 degrees head-down bed rest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the calf were determined before and after bed rest by computed tomography. From before to after bed rest, calculated calf volume (cm3) decreased (P less than 0.05) from 1,682 +/- 83 to 1,516 +/- 76. Calf muscle compartment CSA (cm2) also decreased (P less than 0.05) from 74.2 +/- 3.6 to 70.6 +/- 3.4; calf compliance (ml.100 ml-1.mmHg-1.100) increased (P less than 0.05) from 3.9 +/- .7 to 4.9 +/- .5. The percent change in calf compliance after bed rest was significantly correlated with changes in calf muscle compartment CSA (r = 0.72, P less than 0.05). The increased leg compliance observed after exposure to simulated microgravity can be partially explained by reduced muscle compartment. Countermeasures designed to minimize muscle atrophy in the lower extremities may be effective in ameliorating increased venous compliance and orthostatic intolerance after spaceflight.
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.
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The Biomedical Operations and Research Office at the NASA John F. Kennedy Space Center has been supporting environmental monitoring and research since the mid-1970s. Program elements include monitoring of baseline conditions to document natural variability in the ecosystem, assessments of operations and construction of new facilities, and ecological research focusing on wildlife habitat associations. Information management is centered around development of a computerized geographic information system that incorporates remote sensing and digital image processing technologies along with traditional relational data base management capabilities. The proactive program is one in which the initiative is to anticipate potential environmental concerns before they occur and, by utilizing in-house expertise, develop impact minimization or mitigation strategies to reduce environmental risk.
An easy to use, interactive FORTRAN program for analyzing the results of parallel line assays is described. The program is menu driven and consists of five major components: data entry, data editing, manual analysis, manual plotting, and automatic analysis and plotting. Data can be entered from the terminal or from previously created data files. The data editing portion of the program is used to inspect and modify data and to statistically identify outliers. The manual analysis component is used to test the assumptions necessary for parallel line assays using analysis of covariance techniques and to determine potency ratios with confidence limits. The manual plotting component provides a graphic display of the data on the terminal screen or on a standard line printer. The automatic portion runs through multiple analyses without operator input. Data may be saved in a special file to expedite input at a future time.