Advances in space biology and medicine最新文献

Space life sciences is not really a new life sciences discipline such as immunology was some decades ago and it may never be so. Rather it is a field that will provide each existing life sciences discipline with new and more information gathered from space research. In fact, the danger is that space research will be confined in a separate discipline, and thus it will be cut off from classical ground research. Conversely, scientists should increasingly consider spaceflight as a tool and should integrate the findings of space research into their traditional disciplines. A brief survey of topics and main findings in the various subdisciplines of space life sciences is provided. This is followed by a discussion of typical problems encountered such as access to space, controls, ground-based simulations, medical care in space, extravehicular activity, and environmental control and life support. As many space life sciences courses are initiated around the world either by space agencies or universities or jointly, there is a need to consider the international, intercultural, and interdisciplinary aspects of such programs. It is argued that the growing knowledge derived from space research should be integrated into the regular teaching of life sciences rather than leaving it confined to a separate field. Teaching of space life sciences is a prime candidate for the application of the new techniques of "cyberspace education", where interactive learning and globalization of the learning process will take a leading place. The experts and student body are dispersed over many nations, research is of necessity conducted on a basis of international cooperation. The conduct of tele-education is discussed and existing information sources and courses are listed.

The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.

The results of immunological analyses before, during and after spaceflight, have established the fact that spaceflight can result in a blunting of the immune mechanisms of human crew members and animal test species. There is some evidence that the immune function changes in short-term flights resemble those occurring after acute stress, while the changes during long-term flights resemble those caused by chronic stress. In addition, this blunting of the immune function occurs concomitant with a relative increase in potentially infectious microorganisms in the space cabin environment. This combination of events results in an increased probability of inflight infectious events. The realization of this probability has been shown to be partially negated by the judicious use of a preflight health stabilization program and other operational countermeasures. The continuation of these countermeasures, as well as microbial and immunological monitoring, are recommended for continued spaceflight safety.

The effects of weightlessness on vestibular function have been studied since the beginning of manned spaceflight. The results of these studies have been highly variable and to some extent even contradictory, which makes it difficult to draw unambiguous conclusions. This variability is probably due to at least three factors: (1) individual differences in the adaptive process, (2) non-standardized experimental methods and conditions, (3) a lack of integrated experiments. For this reason, we have used a single integrated approach with a specially developed battery of tests. The results thus obtained for 21 cosmonauts on short- and long-term flights are reviewed here, and discussed in the light of the results obtained by others. Changes in the operation of the vestibular system and in all functions based on vestibular afferent input are commonly observed in spaceflight. These changes are characteristic for the process of adaptation and re-adaptation to altered gravity. They occur in a high proportion of persons exposed to such conditions, although there are individual differences with regard to severity, nature, time and duration of occurrence, and the dynamics of the process. Analysis of the observations in a large number of cosmonauts has permitted to distinguish three types of adaptation of the system to altered gravity. The first type of adaptation is characterized by a strong response to any stimulus during the initial adaptation period. The second type of adaptation is characterized by responses that are drastically decreased or even absent. The third type of adaptation is distinguished by the selective response of the sensory system to certain types of stimulation only. After long-term missions the process of re-adaptation usually takes a more severe course than the earlier process of adaptation to microgravity. Both adaptation and re-adaptation follow an undulating course, in which adaptation and re-adaptation are alternating. This is most conspicuous during long-term flights, and it suggests that in the initial stage of adaptation to weightlessness the vestibular input plays a dominant role, while at the end of the adaptation process the visual input prevails.

The gravitropic response of plants to a change in the gravity vector may be divided. in the phase of induction and expression. During the induction phase the amyloplasts, due to their greater density than the cytoplasmic density, shift their position in less than a minute. During this shift there is an interaction with the endoplasmic reticulum, although a role of actin-like proteins of the cytoskeleton may also be involved in this process. The endoplasmatic reticulum maintains a store of sequestered calcium through the action of an ATP-dependent calcium uptake mediated by the Ca2+, Mg(2+)-ATPase system present in the membrane of this organelle. The interaction of the amyloplast with the endoplasmic reticulum leads to the release of free calcium ions from the endoplasmic store. The increased free Ca2+ level in the cytoplasm may modify the activities of certain enzymes and receptor proteins. The gravitropic induction phase is completed when the lateral polarization of the tissues has taken place. These tissues contain information about changes in direction of the IAA transport system and in competition of the IAA-receptor system for the phytohormone. This information is fixed in "memory" and its expression is achieved when the lateral gradient of IAA concentration and of the activity of the IAA-receptor protein complexes is formed in the horizontally oriented plant organ. Flows of IAA and calcium ions in opposite directions may lead to the expression of laterally differentiated growth.

Japanese tree frogs (Hyla japonica) showed unique postures and behavior during an 8-day flight to the Russian space station Mir. When floating in the air, the animals arched their back and extended their four limbs. This posture resembles that observed during jumping or parachuting of the animals on the ground. Frog sitting on a surface bent their neck backward sharply, did not fold their hind limbs completely, and pressed their abdomen against the substrate. They walked backwards in this posture. The typical posture resembles that adopted during the emetic behavior process on the ground, although the posture in space lasts much longer. The possible mechanism of induction of this unique posture in orbit is discussed. Frogs in this posture might be in an emetic state, possibly due to motion sickness. Response behavior to some stimuli was observed in orbit. Body color change in response to the background color appeared to be delayed or slowed down. Response behavior to other stimuli showed little change as long as the animal maintained contact with a substrate. Once it left the surface, the floating frog could not control its movements so as to provide coordinated motility for locomotion and orientation. Adaptation to microgravity was observed in the landing behavior after jumping. Readaptation of the frogs to the Earth environment took place within a few hours after return. Postflight histological and biochemical analysis of organs and tissues showed some changes after the 8-day spaceflight. Weakening and density loss in vertebrae was noted. The beta-adrenoreceptor activity of the gastrocnemius was natriuretic decreased. Skin collagen and liver protein synthesis were lowered. The distribution of the atrial factor-like peptides in the brain was changed.

The experimental findings reviewed in this chapter support the following conclusions: Proliferation. Human T-lymphocytes, associated with monocytes as accessory cells, show dramatic changes in the centrifuge, in the clinostat and in space. In free-floating cells the mitogenic response is depressed by 90% in microgravity, whereas in cells attached to a substratum activation is enhanced by 100% compared to 1-G ground and inflight controls. The duration of phase G1 of the mitotic cycle of HeLa cells is reduced in hypergravity, resulting in an increased proliferation rate. Other systems like Friend cells and WI38 human embryonic lung cells do not show significant changes. Genetic expression and signal transduction. T-lymphocytes and monocytes show important changes in the expression of cytokines like interleukin-1, interleukin-2, interferon-gamma and tumor necrosis factor. The data from space experiments in Spacelab, Space Shuttle mid-deck, and Biokosmos have helped to clarify certain aspects of the mechanism of T-cell activation. Epidermoid A431 cells show changes in the genetic expression of the proto-oncogenes c-fos and c-jun in the clinostat and in sounding rockets. Membrane function, in particular the binding of ligates as first messengers of a signal, is not changed in most of the cell systems in microgravity. Morphology and Mortility. Free cells, lymphocytes in particular, are able to move and form aggregates in microgravity, indicating that cell-cell contacts and cell communications do take place in microgravity. Dramatic morphological and ultrastructural changes are not detected in cells cultured in microgravity. Important experiments with single mammalian cells, including immune cells, were carried out recently in three Spacelab flights, (SL-J, D-2, and IML-2 in 1992, 1993, and 1994, respectively). The results of the D-2 mission have been published in ref. 75; those of the IML-2 mission in ref. 76. Finally, many cell biology experiments in space have suffered in the past from a lack of adequate controls (like 1-G centrifuges) and of proper experimental conditions (like well-controlled temperature). In this respect the availability of Biorack, outfitted with proper incubators with 1-G control centrifuge as well as a glovebox with a microscope, is a great advantage. It is also desirable that cell biology experiments in space are accompanied or even preceded by a program of ground-based investigations in the fast rotating clinostat and in the centrifuge, and that preparatory experiments be done in parabolic flights and sounding rockets, whenever possible. Proper publication of the results of space experiments is another important need. A great number of data have been published in proceedings and reports that are not available to the broad scientific community. To guarantee the credibility and the international recognition of space biology it is important that the results be published in international, peer reviewed journals.

ESA has been studying a small-scale bioregenerative system to support long-term biological experiments on-board spacecraft with oxygen, water and food. Core component of this system is a special photo-bioreactor in which a maltose-producing strain of the green micro alga Chlorella is cultivated. A number of auxiliary system components have been developed and are functioning on the ground according to the design specifications, among them a gas/liquid phase separator operating at the same time as a low shear-stress pneumatic pump, a dehumidifier, a maltose separator, and a liquid transfer system. All components have been designed so that--in principle--they will operate in weightlessness, though this has so far only been verified for the gas/liquid separator. The bioreactor and some of the auxiliary components have been integrated in a prototype system, which has been subjected to preliminary testing. The prototype has been sterilized successfully by autoclaving, except for the liquid transfer unit which is disinfected with isopropyl alcohol. Chlorella 241.80 has been cultured several times under controlled conditions for up to 8 weeks. Algal growth to a biomass concentration of 9 g.l-1 dry weight and maltose production to a concentration of 17 g.l-1 have been achieved. The low shear-stress pneumatic pump works reliably without the mechanical cell damage produced by other types of pumps. Contamination of the algal cultures by other micro-organisms has been avoided in most of the experiment runs. The maximum oxygen production rate observed was 2 ml.min-1, when the culture was aerated with air +0.5% CO2. This production rate is well below the CO2 gas transfer rate of 5 ml.min-1 under these conditions. It can probably be doubled by increasing the maximum light intensity of the illumination unit (currently 300 micro E.m-2S-1). In a preliminary closed gas loop experiment with Periplaneta as consumer, the possibility of controlling the Chlorella culture so as to match the needs of the consumer colony has been established. A maltose excreting Chlorella strain has been selected as the photosynthetic producer, because the technique for automatic culturing of this organism and harvesting its products was expected to be much less complex than that required for culturing higher plants. Although the prototype system developed in our laboratory has reached a high level of sophistication, there remain still a number of technical and biological problems to be solved before the feasibility of this concept is definitely demonstrated. The major problem is maintaining sterility, and eventually automatic cleaning and resterilization when contamination occurs during operation. The culture medium, which contains minerals, cell fragments and considerable amounts of sugars, is an ideal substrate for many other microorganisms. Another problem is long term operation. The prototype system contains many tubes and ducts which are perfused with culture medium. These may c

The following principles, derived from the experience of medical support during past spaceflights, can provide a basis for a system of health monitoring and diagnosis during long-term and interplanetary missions: a system of preflight medical screening; medical screening on a systemic basis, which may include purposeful diagnosis in subsystems following the method of hierarchic structure; use of an individual approach; correction of the medical program with respect to the space crew status; assessment of the interrelations of the entire complex of parameters; utilization of the methods of correlation, classification and identification to elicit interrelations between different functions; evaluation of shifts in body functions and their adequacy to ambient conditions; continuity of medical examinations during all pre-flight stages, during flight and after completion of flight; analysis of information and anamnestic data by means of data bases; confidentiality of medical conclusions. Discussed are a classification of unfavorable microgravity-related syndromes, possible impairments due to abnormal situations, and some approaches to the prediction of the risk of various diseases, in relation to the construction of a conceptual diagnostic model for interplanetary missions. In the interest of medical monitoring special significance is attributed to the knowledge of individual norms for each crew member and of his unique peculiarities. Such data can be compiled by means of statistical analysis (single and multidimensional analysis) of the results of medical examinations and of observations during selection, training and tests. Selection of necessary physiological parameters, functional loads and data processing techniques which can be used in combination with other data sources for inflight diagnosis should be based on the following principles: the use of informative, non-invasively registered parameters and functional tests to reveal adverse states or most probable diseases; the possibility to assess the dynamics of physiological parameters and the status of the regulatory systems, and to predict possible developments in the body; the possibility to check the efficiency of countermeasures; the possibility to differentiate a physiological state adapted to the current environment from a pathological state; the possibility to differentiate between specific and non-specific reactions; the possibility to differentiate defensive, adaptive or compensatory phenomena from pathological manifestations. This paper describes the application of single- and multidimensional, statistical methods to process diagnostic information, to reduce the vector dimension of the chosen parameters, and to classify and identify individual and crew physiological standards providing the ability to assign an individual to a suitable team. Thus it will be possible to acquire comprehensive and statistically reliable information in compact format, and thus to perform a more incisiv