The effects of microgravity on ligase activity in the repair of DNA double-strand breaks

PURPOSE: In recent years, contradictory data have been reported about the effects of microgravity on radiation-induced biological responses in space experiments. The aim of the present study was to clarify whether enzymatic repair of DNA double-strand breaks is affected by microgravity using an in vitro enzymatic reaction system. MATERIALS AND METHODS: The DNA repair activity of T4 DNA ligase (EC 6.5.1.1) was measured in vitro for a DNA substrate damaged by restriction enzyme digestion during a US Space Shuttle mission (Discovery; STS-91). After the flight, the amount of ligated DNA molecules was measured using an electrophoresis method. RESULTS: Ligated products (closed circular DNA, open circular DNA and multimeric ligated products) were produced by T4 DNA ligase treatment of linear DNA containing double-strand breaks, and they increased with increasing T4 DNA ligase concentration (0-3 units per microg of plasmid DNA). Almost no difference in T4 DNA ligase activity was detected between the space experiments and the control ground experiments. CONCLUSIONS: No significant effect of microgravity on ligation of damaged DNA was found during space flight. Therefore, other mechanisms must account for the synergism between radiation and microgravity, if it exists.     

Medical qualification of a commercial spaceflight participant: not your average astronaut

BACKGROUND: Candidates for commercial spaceflight may be older than the typical astronaut and more likely to have medical problems that place them at risk during flight. Since the effects of microgravity on many medical conditions are unknown, physicians have little guidance when evaluating and certifying commercial spaceflight participants. This dynamic new era in space exploration may provide important data for evaluating medical conditions, creating appropriate medical standards, and optimizing treatment alternatives for long-duration spaceflight. CASE: A 57-yr-old spaceflight participant for an ISS mission presented with medical conditions that included moderately severe bullous emphysema, previous spontaneous pneumothorax with talc pleurodesis, a lung parenchymal mass, and ventricular and atrial ectopy. The medical evaluation required for certification was extensive and included medical studies and monitoring conducted in analogue spaceflight environments including altitude chambers, high altitude mixed-gas simulation, zero-G aircraft, and high-G centrifuge. To prevent recurrence of pneumothorax, we performed video-assisted thoracoscopic pleurodesis, and to assess lung masses, several percutaneous or direct biopsies. The candidate's 10-d mission was without incident. CONCLUSION: Non-career astronauts applying for commercial suborbital and orbital spaceflight will, at least in the near future, challenge aerospace physicians with unknowns regarding safety during training and flight, and highlight important ethical and risk-assessment problems. The information obtained from this new group of space travelers will provide important data for the evaluation and in-flight treatment of medical problems that space programs have not yet addressed systematically, and may improve the medical preparedness of exploration-class missions.     

Animal surgery during spaceflight on the Neurolab Shuttle mission

INTRODUCTION: A surgical procedure has never been required or performed on a human in space. Parabolic microgravity simulations have suggested that surgery would be technically feasible during spaceflight. PROCEDURES: Survival surgery was performed for the first time on rats during the STS-90 Neurolab Shuttle mission. Craniotomy, leg dissection, thoracotomy, laminectomy, and laparotomy were performed as a part of physiological investigations. RESULTS: Surgical techniques successfully demonstrated in rats during spaceflight included general anesthesia, wound closure, wound healing, hemostasis, control of surgical fluids, operator restraint, and control of surgical instruments. No decrement in manual dexterity was noted by the crew, although operative time was longer compared with ground experience due to the need to maintain restraint of surgical supplies and instruments. CONCLUSIONS: The demonstration that technically demanding dissections could be accomplished successfully in space on rats suggests that comparable complex surgical procedures should be feasible on humans, if necessary, on future long-duration missions.     

载人航天飞行中的情绪研究进展

载人航天环境中的微重力、振动、辐射、限制和隔离等各种应激源会使航天员出现焦虑、抑郁等各种负性情绪,进而影响到航天员的操作效率和飞行计划执行,甚至航天飞行的安全;情绪应激长期作用还会对航天员的身心健康造成损害。情绪研究是航天心理学的重要研究方向,国内外学者对航天飞行以及类似环境中航天员的情绪变化进行了大量研究。本文总结了情绪的基本理论,情绪测评的方法以及载人航天领域情绪研究的现状,并对载人航天情绪研究的未来进行了展望。     

Changes in basal heart rate in spaceflights up to 438 days

BACKGROUND: The long-term acclimation of heart rate to microgravity was studied in a cosmonaut who stayed onboard the MIR space station for 438 d. This was the longest mission in the history of manned space exploration. The results are evaluated in the context of findings from three other cosmonauts who lived onboard MIR for a shorter time. HYPOTHESIS: The response of heart rate to the stimulus of microgravity was tested in the course of spaceflights during sleep across sleep stages and during supine waking. It was expected that heart rate would show adaptation effects beyond the first month in space. The size of the adaptation effect would depend on the stage of sleep. METHODS: For the record mission sleep polygraphies were obtained prior to mission on the ground, between the 3rd and the 30th d in space, after 6 mo in space, and toward the end of mission. From each of the sleep polygraphies beat-to-beat intervals of cardiac rhythms were determined and analyzed as the time series of the average beat-to-beat interval. RESULTS: A lengthening of the average beat-to-beat interval by 176 ms was found during the record flight compared with measurements on the ground. This increase in the average beat-to-beat interval corresponds to a reduction of heart rate by about 20%. The lengthening of the average beat-to-beat interval was more pronounced for non-REM sleep than for REM sleep. During the first month, a lengthening by 82 ms was observed. Measurements after 6 mo showed a further lengthening by 94 ms, and at the end of the mission no further change in average beat-to-beat interval was observed. CONCLUSIONS: Testing the response of heart rate to microgravity across distinct and stationary behavioral states appears to be appropriate to investigate the cardiovascular system. The long-term acclimation of heart rate is possibly due to an increased dominance of the parasympathetic control of cardiac rhythms in space.     

Spaceflight alters bone mechanics and modeling drifts in growing rats

BACKGROUND: Alterations in bone metabolism may be a particularly serious consequence of spaceflight and a major obstacle to long-term space exploration. The effects of spaceflight on bone mechanics are unclear. This study examined the effects of spaceflight on bone mechanics in a growing rat model during a 17-d mission aboard the space shuttle (STS-78). METHODS: There were 18 rats that were divided into 3 experimental groups: flight rats (n = 6), ground-based control rats housed in an animal enclosure module (AEM, n = 6), and ground-based control rats housed in standard vivarium caging (n = 6). At the conclusion of the mission, rat femurs were tested in three-point bending followed by static and dynamic bone histomorphometry. RESULTS: Maximum stress was unaffected by spaceflight, but flexural rigidity was significantly decreased in flight animals. Much of the decrease appeared to be the result of decreases in tissue properties (elastic modulus) rather than structural changes within the bone. No significant differences in cortical bone mass or geometry were observed. In contrast, endocortical resorption was significantly decreased in flight rats accompanied by a nonsignificant decrease in periosteal bone formation, suggesting alterations in bone modeling drifts during spaceflight. For nearly all measured indices, ground-based AEM rats displayed values intermediate to flight and ground-based vivarium rats. CONCLUSIONS: Spaceflight can impair tissue properties in femoral cortical bone during growth without significant decreases in bone mass or geometry.     

Incidence of Epstein-Barr virus in astronaut saliva during spaceflight

BACKGROUND: Astronauts experience psychological and physical stresses that may result in reactivation of latent viruses during space-flight, potentially increasing the risk of disease among crewmembers. HYPOTHESIS: The shedding of Epstein-Barr virus (EBV) in the saliva of astronauts will increase during spaceflight. METHODS: A total of 534 saliva specimens were collected from 11 EBV-seropositive astronauts before, during, and after four space shuttle missions. The presence of EBV DNA in saliva, assessed by polymerase chain reaction (PCR), was used to determine shedding patterns before, during, and after space-flight. RESULTS: EBV DNA was detected more frequently before flight than during (p < 0.001) or after (p < 0.01) flight. No significant difference between the inflight and postflight periods was detected in the frequency of occurrence of EBV DNA. CONCLUSIONS: The increased frequency of shedding of EBV before flight suggests that stress levels may be greater before launch than during or after spaceflight.     

Effect of short-duration spaceflight on thigh and leg muscle volume

PURPOSE: Human skeletal muscle probably atrophies as a result of spaceflight, but few studies have examined this issue. Thus, little is known about the influence of microgravity upon human skeletal muscle, nor is it possible to assess the validity of ground based models of spaceflight. This study tested the hypothesis that the magnitude of spaceflight induced muscle atrophy would be a function of flight duration and greater than that of bed rest. METHODS: Three astronauts flew 9, 15, and 16 d in space. Volume of the knee extensor (quadriceps femoris), knee flexor (hamstrings, sartorius, and gracilis), and plantar flexor (triceps surae) muscle groups was measured using magnetic resonance imaging before and after spaceflight and during recovery. The volume of each muscle group in each image was determined by multiplying cross-sectional area by slice thickness. These values were subsequently summed to calculate muscle volume. RESULTS: Volume changes in the knee extensor, knee flexor, and plantar flexor muscle groups ranged from -15.4 to -5.5, -14.1 to -5.6, and -8.8 to -15.9%, respectively. Muscle volume decreases normalized by flight duration ranged from 0.62 to 1.04% x d(-1). These relative changes appeared to be greater than those that we have reported previously for bed rest (Akima et al., J. Gravitat. Physiol. 4:15-22, 1997). CONCLUSIONS: These results suggest that atrophy as a result of at least 2 wk of spaceflight varied among individuals and muscle groups and that the degree of atrophy appeared to be greater than that induced by 20 d of bed rest.     

载人航天飞行对认知能力影响的研究进展

目的 综述当前用于载人航天飞行认知能力研究的方法、工具、内容以及研究结果,并指出研究中存在的问题以及未来的研究方向.资料来源与选择国内外相关领域的学术论著和综述.资料引用引用文献31篇.资料综合载人航天飞行环境存在着失重、隔离、限制等许多应激源,这些应激源会对航天员的认知能力造成一定影响.航天飞行中航天员认知能力改变的研究对于确保航天任务成功和飞行乘组安全有重要意义.当前载人航天飞行认知能力研究主要采用计算机化的测验工具,对影响航天飞行安全和操作效率的能力进行研究.结论 载人航天飞行对航天员认知能力有损害,具体的机制需要通过生理心理学和神经科学的手段进行深入研究. Abstract： Objective To discuss the matters in space cognition study and foresee its development in future by reviewing the methods, tools and results of current space cognition study.Literature resource and selection Domestic and abroad published papers and reviews in the related field. Literature quotation Thirty-one related papers and reviews were citied. Literature synthesis There are many stressors, such as microgravity, isolation, confinement, etc. , in space flight and those would influence astronaut's cognition. The study of cognition in space has a significant meaning for ensuring the success of mission and crew's safety. The computerized testing tools have being used in current space cognition study for assessing the influence of space to flight safety and operation efficiency. Conclusion The stressors in spaceflight would harm astronaut's cognitive abilities. But the mechanism needs to be further explored by means of the studies on physiopsychology and neuroscience.     

Assessment of simulated surgical skills in parabolic microgravity

BACKGROUND: During spaceflight crew health is paramount in the success of flight missions. The delivery of healthcare during flight requires crew readiness for medical and surgical response. METHODS: There were 20 participants who were evaluated for accurate performance of 4 basic laparoscopic surgical skills (clip applying, cutting, grasping, and suturing) during parabolic weightlessness using an inanimate workstation aboard the NASA KC-135 aircraft. RESULTS: Data indicate that motor skill performance decreased within the parabolic microgravity flight environment. Performance in parabolic microgravity flight included futile effort with an increase in number of tasks attempted and a decrease in tasks completed successfully. CONCLUSIONS: There is a decreased frequency of accurate task completion in parabolic microgravity flight, but it is not an obstacle to implementation of effective training for providing in-flight medical care. The data reveal that individuals perform basic laparoscopic surgical simulation with greater effort in microgravity following simulation training.     

航天飞行和模拟微重力下微生物次级代谢研究与太空微生物制药

随着人类对宇宙的不断探索,大量研究观察到微生物次级代谢在航天飞行中的变化,为人类利用太空环境进行高产和高质量微生物制药带来了希望。研究者认为,太空环境下微生物生长停滞期缩短,更早进入生长期,更早产生次级代谢产物。由于空间飞行的稀缺性和高昂成本,研究者利用微重力模拟设备进行微生物次级代谢研究。目前,不同的航天飞行和模拟微重力下微生物次级代谢研究并未观察到趋势相对一致的结果,其表型变化背后的分子生物学机制也有待进一步研究。太空微生物制药利用太空诱变筛选具有商业和医学价值的制药微生物菌株,这种航天飞行后地面筛选的模式具有无法控制诱变方向、被动筛选的缺陷,有待相关诱变通路进一步研究后予以改进。     

Changes of posture during transient perturbations in microgravity

The control of goal-directed arm movement and of body stability before, during, and 3 d after a 7-d spaceflight has been investigated. The findings show that the anticipatory and compensatory activities of the postural muscles were highly reproducible during the first days of the space mission. The sequence of these activities, studied in two situations--in which the platform either was fixed or could rotate about near the rotation axis of the ankle--was similar to a ground-based situation. The trajectory of various body segments demonstrates that a 7-d exposure to microgravity did not result in major changes in posture. Furthermore, vision seemed to play an important role in the control of standing posture at the beginning of the flight. Postural perturbations, elicited by unexpected displacements of the foot support, involved leg muscle reflexes whose amplitudes were greatly reduced compared to those on earth.     

Microgravity effects on fine motor skills: tying surgical knots during parabolic flight

INTRODUCTION: The health provider on a space exploration mission cannot evacuate a patient to Earth. Contingency plans for medical intervention must be designed for autonomy. This study measured the effect of microgravity on performance of fine motor skills such as basic surgical tasks. METHODS: Eight subjects, six with medical and two with non-medical backgrounds, were evaluated during parabolic microgravity flights aboard NASA's KC-135. We evaluated their skill in tying surgical knots on simulated skin made of silicone using standard techniques for minimally invasive surgery. LabView software was developed to archive forces applied to the laparoscopic tool handles during knot-tying. Studies were controlled for medication (ScopeDex) and the aircraft environment. RESULTS: All participants completed the tests successfully. The data indicated that increased force was applied to the instruments and knot quality decreased during flight compared with ground control sessions. CONCLUSION: Specific metrics of surgical task performance are essential in developing education modules for providers of medical care during exploration-class missions.     

Histologic changes in the adrenal cortex from young rats following spaceflight

BACKGROUND: Potential stresses associated with spaceflight include microgravity, acceleration and deceleration forces, a crowded environment and re-adaptation to normal gravity after landing. HYPOTHESIS: We hypothesized that spaceflight would result in histological changes in the adrenal glands of young rats. METHODS: Six week old male rats were group-housed in an Animal Enclosure Module (AEM) for a 17 d shuttle flight (STS-78). Ground-based controls included a baseline group, an AEM-housed group and a vivarium group. Adrenal glands were collected from 4-6 hours after flight, fixed, embedded in plastic and sections prepared for light microscopy. RESULTS: The adrenals from the baseline and vivarium groups had normal histological features. Some changes in the adrenal cortices from the ground-based AEM group included greater parenchymal cord-like formation. The adrenal weights and width of the zona fasciculata were greater in the flight group than the controls. There were also increased parenchymal cord-like formation with better demarcation of the vascular sinusoids in the zona reticularis and zona fasciculata, greater depletion of cytoplasmic lipid vacuoles, and an increased nuclear volume of the cells in the zona fasciculata when compared with the controls. CONCLUSIONS: The adrenal changes in the ground-based AEM animals may be attributed to the confined space in the AEM. The adrenal enlargement and the histological changes observed in the flight animals may be attributed to spaceflight and possibly re-entry in addition to possible confinement stress in the AEM.     

Optokinetic stimulation in microgravity: torsional eye movements and subjective visual vertical

INTRODUCTION: Microgravity provides unique sensory inputs to the vestibular and oculomotor systems. We sought to determine the effects of long-term spaceflight on sensing of spatial orientation. METHODS: Two cosmonauts participated in experiments on human vestibulo-visual interactions during a long-term mission (178 d) in the MIR station in 1995. During circular optokinetic stimulation (OKS) the tonic torsional eye position (torsional beating field, TBF) and the subjective visual vertical (SVV) were recorded on several days of the space mission as well as pre- and post-flight. A reference data set was obtained from healthy subjects on Earth, in whom the TBF was measured in upright and in prone positions. RESULTS: Neither cosmonaut showed changes in the SVV or the TBF values during the first days in microgravity. On flight day 149, cosmonaut A showed an increase of both values, which continued to rise by 4- and 10-fold until the end of the flight (TBF: 8.1 degrees; SVV: 216.8 degrees). This cosmonaut reported that the increase was accompanied by a loss of spatial orientation. In contrast, cosmonaut B's values remained at pre-flight levels (TBF: 1.6 degrees; SVV: 4.4 degrees). Post-flight values of the TBF did not significantly differ from pre-flight values for either cosmonaut. Subjects showed an increase of the TBF by more than a factor of 2 in prone position (range -7.7 degrees to +10.2 degrees) compared with upright position (range -3.7 degrees to +3.4 degrees). CONCLUSIONS: Pre-flight, post-flight and during the first part of the flight, both cosmonauts exhibited values similar to those of normal subjects in an upright position. The increased TBF values of cosmonaut A from flight day 110 on were within the range of the normal subjects in prone (face-down) position, when the gravity vector cannot be used to stabilize the TBF against the rotating stimulus (the axis of rotation is parallel to the gravity vector). The increasing deviations of cosmonaut A's SVV values in-flight suggest the presence of an internal body reference system, which weakened throughout the flight and thus lost its stabilizing effect.     

Responses of plasma proenkephalin peptide F in rats following 14 days of spaceflight

INTRODUCTION:. Proenkephalin peptide F [107-140] is related to the enhancement of immune function, while microgravity has been shown to cause immuno-suppression. We investigated the physiological response of proenkephalin peptide F to microgravity. METHODS: There were 12 Fischer 344 female rats, ovariectomized at 10.5 wk of age, used to determine plasma concentrations of peptide F in response to a 14-d flight aboard the Columbia Space Shuttle mission STS-62. There were 36 other such rats that served as ground-based controls to separate the effects of microgravity from those of thermal stress, flight stress, and crowded habitats. Control groups of 12 rats each were kept under the following conditions: 1) 22 degrees C vivarium, 2) 28 degrees C vivarium, and 3) variable (Var) to mimic flight. The flight and control groups were housed in animal enclosure modules 21 d prior to flight and for the duration of the study. The rats were sacrificed within 4-5 h after landing, at which time blood samples were obtained. RESULTS: Body weights were obtained prior to sacrifice; mean values were flight, 199 g; 22 degrees C, 193 g; 28 degrees C, 192 g; and Var, 194 g. The flight group produced a significantly greater (p < or = 0.05) level of plasma peptide F (0.056 pmol x ml(-1)) compared with the controls (0.016, 0.022, and 0.016 pmol x ml(-1) for 22 degrees C, 28 degrees C, and Var, respectively). Flight animals demonstrated higher corticosterone concentrations and reduced T and B cell splenocyte counts than controls. CONCLUSIONS: These data indicate that the increases in proenkephalin peptide F observed with exposure to microgravity may present an adrenal-medullary response to cope with the decreased immune function and increased stress experienced during spaceflight and landing.     

Review of main medical results of a one-year manned space mission on "Mir"

The objective of medical investigations during and after the 366-day manned mission was to accumulate information about human responses to long-term effects of microgravity. To do this, cardiovascular and other systems were examined in detail during and after exposure. The results gave evidence that the crewmembers well adapted to the long-term flight effects. Their good health condition and high work capacity were supported by adequate medical procedures. Postflight readaptation developed similarly to what was seen after previous flights of shorter duration (6-11 months). No qualitatively new changes in the physiological systems were detected during or after this mission.     

Percutaneous aspiration of fluid for management of peritonitis in space

BACKGROUND: As a medical emergency that can affect even well-screened, healthy individuals, peritonitis developing during a long-duration space exploration mission may dictate deviation from traditional clinical practice due to the absence of otherwise indicated surgical capabilities. Medical management can treat many intra-abdominal processes, but treatment failures are inevitable. In these circumstances, percutaneous aspiration under sonographic guidance could provide a "rescue" strategy. Hypothesis: Sonographically guided percutaneous aspiration of intra-peritoneal fluid can be performed in microgravity. METHODS: Investigations were conducted in the microgravity environment of NASA's KC-135 research aircraft (0 G). The subjects were anesthetized female Yorkshire pigs weighing 50 kg. The procedures were rehearsed in a terrestrial animal lab (1 G). Colored saline (500 mL) was introduced through an intra-peritoneal catheter during flight. A high-definition ultrasound system (HDI-5000, ATL, Bothell, WA) was used to guide a 16-gauge needle into the peritoneal cavity to aspirate fluid. RESULTS: Intra-peritoneal fluid collections were easily identified, distinct from surrounding viscera, and on occasion became more obvious during weightless conditions. Subjectively, with adequate restraint of the subject and operators, the procedure was no more demanding than during the 1-G rehearsals. CONCLUSIONS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid collections is feasible in weightlessness. Treatment of intra-abdominal inflammatory conditions in spaceflight might rely on pharmacological options, backed by sonographically guided percutaneous aspiration for the "rescue" of treatment failures. While this risk mitigation strategy cannot guarantee success, it may be the most practical option given severe resource limitations.     

Anesthesia during and after exposure to microgravity

Human spaceflight has evolved over the past 40 yr in pursuit of larger, more complex, and more distant missions. As this evolution continues, inevitably a spaceflight crewmember will require medical treatment involving anesthesia, either during flight or immediately upon return. If the need occurs during a deep space mission, onboard medical staff will need to be capable of surgery and anesthesia because evacuation and telemedicine will be impractical. In addition, current anesthesia techniques and procedures will have to be adapted to meet the special problems and risks that arise in administering anesthesia in space or to microgravity-exposed patients. However, very little is known about what those adaptations will entail. While there has been some presentient research regarding airway management in microgravity suggesting the laryngeal mask airway (LMA) be used, only four articles have directly treated the topic of anesthesia care in microgravity. Many others, though, have extrapolated applications and considerations for microgravity-exposed patients from patients and conditions that offer useful adaptation parallels. Researchers have explored parallels to orthostatic intolerance adaptations and related neurological, cardiovascular, and multifactorial causes. Investigators have also focused on skeletal muscle adaptations, especially acetylcholine receptor functional changes and redistribution with disuse. These changes may influence the use of depolarizing and non-depolarizing neuromuscular blockers in microgravity-exposed patients, suggesting they be used with caution. This review surveys, assesses, and compiles the existing literature to provide a foundation of consolidated reference for future investigations.     

Dose-response relationship for radiation-induced mutations at micro- and minisatellite loci in human somatic cells in culture

Purpose : The study was designed to determine the dose-response relationship for radiation induction of mutations at mini- and microsatellite loci in human somatic cells. Mutations induced by graded doses of gamma-irradiation were quantified by screening clones derived from single irradiated cells for micro- and minisatellite alterations following irradiation with 1, 2 or 3 Gy. Materials and methods : After irradiation, the moderately radioresistant glioma cell line UVW was seeded at low density into Petri dishes to allow formation of discrete colonies, 100 of which were examined at each dose. All the cells within a colony were presumed to have arisen from a single irradiated cell. Radiation-induced microsatellite alterations were determined at 16 different loci, by PCR amplification and visualization on polyacrylamide gels. Minisatellite alterations were identified at four different minisatellite loci by restriction enzyme digestion and Southern blotting. Results : A dose-response curve for mutation frequency was obtained by analysis of 100 clones, yielding a minisatellite mutation rate of 5.5 X 10 -3 mutations/locus/Gy/cell and a microsatellite mutation rate of 8.75 X 10 -4 mutations/locus/Gy/cell. At microsatellite loci, alterations were predominantly simple loss or gain of repeat units and loss of heterozygosity (LOH). The mutations in minisatellite loci resulted predominantly in LOH and variation in repeat number. The background instability at each locus was determined by analysis of non-irradiated clones. Only 2% and 1% of the micro- and minisatellite loci respectively showed altered bands. Conclusions : This is the first report of a dose-response relationship for radiation-induced micro- and minisatellite mutations in human somatic cells. Described is a sensitive method for analysis of low-dose radiation mutagenesis in somatic cells that may prove to be a useful tool for radiation protection and dosimetry.