Catecholamines and their enzymes in discrete brain areas of rats after space flight on biosatellites Cosmos

The activity of the catecholaminergic system was measured in the hypothalamus of rats which had experienced an 18.5-19.5-day-long stay in the state of weightlessness during space flights on board Soviet biosatellites of the type Cosmos. In the first two experiments, Cosmos 782 and 936, the concentration of norepinephrine and the activities of synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase and of the degrading enzyme monoamine oxidase were measured in the total hypothalamus. None of the given parameters was changed after space flight. In the light of the changes of these parameters recorded after exposure to acute stress on Earth, this finding indicates that long-term state of weightlessness does not represent an intensive stressogenic stimulus for the system studied. In the space experiment Cosmos 1129, the concentration of norepinephrine, epinephrine, and dopamine was studied in isolated nuclei of the hypothalamus of rats within 6-10 hr following return from space. Norepinephrine was found to be significantly reduced in the arcuate nucleus, median eminence and periventricular nucleus, epinephrine in the median eminence, periventricular and suprachiasmatic nuclei, whereas dopamine was not significantly changed after space flight. The decreased catecholamine levels found in some hypothalamic nuclei of rats which had undergone space flight indicate that no chronic intensive stressor could have acted during the flight, otherwise the catecholamine concentration would have been increased in the nuclei. The decreased levels must have been induced by the effect of a stressogenic factor acting for a short time only, and that either during the landing maneuver or immediately after landing. Thus long-term exposure of the organism to the state of weightlessness does not represent a stressogenic stimulus for the catecholaminergic system in the hypothalamus, which is one of the regulators of the activation of neuroendocrine reactions under stress.     

Russian system of countermeasures on board of the International Space Station (ISS): the first results

The system of countermeasures used by Russian cosmonauts in space flights on board of International Space Station (ISS) was based on the developed and tested in flights on board of Russian space stations. It included as primary components: physical methods aimed to maintain the distribution of fluids at levels close to those experienced on Earth; physical exercises and loading suits aimed to load the musculoskeletal and the cardiovascular systems; measures that prevent the loss of fluids, mainly, water-salt additives which aid to maintain orthostatic tolerance and endurance to gravitational overloads during the return to Earth; well-balanced diet and medications directed to correct possible negative reactions of the body to weightlessness. Fulfillment of countermeasure's protocols inflight was thoroughly controlled. Efficacy of countermeasures used were assessed both in- and postflight. The results of studies showed that degrees of alterations recorded in different physiological systems after ISS space flights in Russian cosmonauts were significantly higher than those recorded after flights on the Russian space stations. This phenomenon was caused by the failure of the ISS crews to execute fully the prescribed countermeasures' protocols which was as a rule excused by technical imperfectness of exercise facilities, treadmill TVIS particularly.     

Bone effects of space flight: analysis by quantum concept of bone remodelling.

During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.     

Effects of space flights on human allergic status (IgE-mediated sensitivity)

Suppression of the immune system after space flights of different duration has been reported earlier by Konstantinova [Immune system in extreme conditions, Space immunology. B. 59. M. Science 1988. 289p. (in Russian) [4]; Immunoresistance of man in space flight, Acta Astronautica 23 (1991) 123–127 [5]]. Changes in T- and B-mediated activities of the immune system were demonstrated during and after space flight. However, the influence of the space flight conditions on the allergic status of cosmonauts and astronauts is still unclear. The goal of this investigation was to analyze total blood IgE levels, specific IgE-antibodies and interleukin-4 in blood of Russian crew members before and after space flights to the International Space Station (ISS) and during a long-term isolation study. For this purpose, we used the ELISA assays as well as other special kits. It was noticed that four out of nine cosmonauts had high total serum IgE (more than normal clinical values of 120 IU/ml). At the same time, there were no statistically significant changes in serum IgE levels before and after long-term space flights (128–195 days). A similar situation was observed regarding preflight IgE levels of cosmonauts who performed short-term flights (7–11 days). However, seven out of 11 cosmonauts had increased IgE level in blood post short flights as compared with pre-flight values. We also measured specific IgE-antibodies, because their high concentration may cause the increased production of total IgE indicating sensitization of cosmonauts. This becomes more important when humans spend a longer time in the closed environment of a space vehicle. Also our ground-based investigations showed that a stay in such conditions does not enhance sensitization to allergens (total number of tested allergens 27) including food, inhalants and cross-reactive proteins. Serum interleukin-4 level measured after short- and long-term space flights was identical. A linear correlation between levels of immunoglobulin E and interleukin-4 also was not significant. Despite the fact that our investigations did not establish any influence of space flight on sensitization and development of immediate-type allergic reactions, they demonstrated the necessity to control the allergic status of cosmonauts very carefully both before and after space flights. At the same time, it is necessary to pay special attention to outcomes of atopic individuals with high pre-flight level of total blood IgE.     

Bone and body mass changes during space flight

Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.     

Main medical results of extended flights on space station Mir in 1986-1990

During 1986-1990 seven prime spacecrews (16 cosmonauts) have flown on-board the Mir orbital complex. The longest space mission duration was 366 days The principal objectives of the medical tasks were the maintenance of good health and performance of the spacecrews and conducting medical research programs which included study of the cardiovascular, motor, endocrine, blood, immune, and metabolic systems. Results obtained point to the ability of humans to readily adapt to a year-long stay in space and maintain good health and performance. Readaptation had a similar course as after other previous long-term space flights of up to 8 months in duration. Primary body system changes were not qualitatively different from findings after flights aboard the Salyut 6 and 7 space stations. In this case, during and after an 11-12 month flight, body system alterations were even less severe which was a result of adequate countermeasure use, their systematic and creative employment and maintenance of required environments to support life and work in space.     

Radiation: risk and protection in manned space flight.

Space radiation is the primary source of hazard for orbital and interplanetary space flight. Radiation levels for different space mission durations, have been established in order to determine the level of hazard. The risk of exceeding the established levels should not be more than 1%. Radiation environment models have been developed to estimate these values. It is possible to build spacecraft shielding based on the calculation of doses and the risk of exceeding these. By reviewing various calculated estimates of the risk, the radiation hazard and the efficiency of protective measures can be established for specific flights.     

Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats

The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.     

Countermeasure of the negative effects of weightlessness on physical systems in long-term space flights

The system of countermcasure of microgravity effects has been developed in Russia that allowed to perform safely long-term space flights. This system that includes different means and methods such as special regimens of physical exercises, axial loading (“Pingiun”) and antigravity suits, low body negative pressure device (LBNP, “Chibis”) and “cuffs” and others has been used with certain variations at certain stages of flight in 27 successfully accomplished space flights that lasted from 60 to 439 days. The pre-, in- and postflight studies performed in 57 crew members of these flights have shown that the system of countermeasure is effective in preventing or diminishing to a great extent almost all the negative effects of weightlessness in flights of a year and more duration and that the intensity and duration of changes recorded in different body systems after flights do not correlate significantly to flight durations, correlating strongly to the volume and intensity of physical exercises used during flight and especially during concluding stage of it.     

Sleep in space

Manned space flights have shown it is possible to sleep in microgravity. However, some sleep disturbances have been reported which influence performance of the crew and safety of space flight. This paper reviews the main studies of in-flight sleep in animal and man. Most disturbances are related to phase lags due to operational requirements. Factors which can disturb in-flight sleep are analysed: environmental factors. Some of them are secondary to space flight ergonomics. Conversely, effects of microgravity on light-dark alternance are less known and lead to interesting problems of fundamental research, psychological factors, especially during long duration flights.     

The dynamics of blood biochemical parameters in cosmonauts during long-term space flights

Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carried out 30-60 days before launch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL - cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.     

Metabolic changes in the animals subjected to space flight

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.     

Mineral and nitrogen balance study: results of metabolic observations on Skylab II 28-day orbital mission

Prediction that the various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various observations of long-term immobilized or inactive bed rest. The only attempt at controlled measurement of metabolic changes in space prior to Skylab, a study during the 14-day Gemini VII flight, revealed rather modest losses of important elements. The three astronauts of Skylab II consumed a planned day-by-day, quite constant, dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, during the 28 days inflight, and for 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies: the mean plateau peak of urinary calcium excretion in the latter part of flight was double preflight levels. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative balance of nitrogen and phosphorus indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations and those in bed rest of the losses in calcium, phosphorus, and nitrogen, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur, indicative of continuing losses of these elements, in the planned Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration, and greater research attention will need to be given to development of protective counter-measures.     

基于多层PCB的基板射频信号传输性能研究

随着射频产品的小型化,特别是射频SIP（systems in package）产品的逐渐应用,基于多层PCB的基板射频组件等射频集成产品的应用越来越多,基板内射频信号传输性能的研究也越来越重要。通过对基于多层PCB的基板射频传输性能进行仿真测试,验证了DC-40GHz范围内射频基板传输性能,针对射频传输中极为关注的传输损耗问题,通过改进介质厚度或者铜箔材料实现基板射频传输损耗的优化,单位长度传输线射频传输损耗减小20%以上。同时针对星载等应用环境,通过深层充放电、总剂量试验,表明多层PCB的基板满足星载等航天应用。     

Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.     

Long-term biological investigations in space

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.     

Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments)

Fluid and electrolyte shifts occuring during human spaceflight have been reported and investigated at the level of blood, cardio-vascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70–90 % of cerebrospinal fluid (CSF) and which are involved in brain homeostasis. Rats flown aboard space shuttles were sacrificed either in space (SLS-2 experiment, on flight day 13) or 4–8 hours after landing (SLS-1 and SLS-2 experiments). Quantitative autoradiography performed by microdensitometry and image analysis, showed that lateral and third ventricle choroid plexuses from rats flown for SLS-1 experiment demonstrated an increased number (about x 2) of binding sites to natriuretic peptides (which are known to be involved in mechanisms regulating CSF production). Using electron microscopy and immunocytochemistry, we studied the cellular response of choroid plexuses, which produce cerebrospinal fluid (CSF) in brain lateral, third and fourth ventricles. We demonstrated that spaceflight (SLS-2 experiment, inflight samples) induces changes in the choroidal cell structure (apical microvilli, kinocilia organization, vesicle accumulation) and protein distribution or expression (carbonic anhydrase II, water channels,…). These observations suggested a loss of choroidal cell polarity and a decrease in CSF secretion. Hindlimb-suspended rats displayed similar choroidal changes. All together, these results support the hypothesis of a modified CSF production in rats during long-term (9, 13 or 14 days) adaptations to microgravity.     

基于气动辅助变轨的变气动外形飞行器概念研究--最优控制律问题

从一个天地往返飞行器的上升轨道和再入返回轨道的优化，以及适用不同飞行任务的变轨要求的气动外形问题，提出一项基于气动力辅助变轨的变气动外形飞行器的新概念研究。对于一个固定气动外形飞行器要同时满足上升轨道有效载荷最大和再入轨道热流峰值、过载峰值及机动性能约束下的成本最低往往是困难的。若同时满足不同飞行任务：飞往太空站的运输任务，空间拦截和交会机动巡航任务及星际探测任务，则更为困难，实际上是不可能的。文章研究基于气动力辅助变轨，在热流约束下，气动外形参数变化对最优控制的影响。其结论为：热流约束下的最优控制解，包括考虑推力协同变轨，除了在非约束弧的滚转角不直接受气动外形影响外，其余的控制律，升力系数和滚转角都是气动外形参数和攻角的函数。因而变气动外形可作为一项新技术，即通过气动外形参数变化和相应的变轨策略而获得性能和成本都最佳的用途很广的一种新型飞行器。     

Degraded EEG response of the human brain in function of gravity levels by the method of chaotic attractor

The measurement of the influence of different gravity levels on the brain allows to explain how humans react to microgravity in space and to predict the adaptation capability of astronauts. Human electroencephalographic (EEG) signals were recorded during low and high gravity phases of three consecutive days of parabolic flights on the Caravelle aircraft in 1991. EEG signals were processed, using the method of correlation dimensions d of chaotic strange attractors. Results show clear differences between the three flights, with a general decrease over time in the attractor dimensions, a measure of the brain response to changing g levels. However, the dimension is not a one-to-one relation with g levels, as additional variations are observed. Two hypotheses are introduced, the "fatigue/stress" and the "g stress" hypotheses corresponding, respectively, to long-term fatigue accumulated over the three flights, and to short-term fatigue in response to change in g levels. The former explains the overall decrease of dimensions, the latter yields additional variations on shorter time scales. As the brain response degrades with time, at least six degraded modes were observed, explained by both short- and long-term fatigue.     

Effects of microgravity and hypergravity on the cell: investigations on Paramecium tetraurelia.

Previous space CYTOS experiments have shown that space flights resulted in an increase in growth of Paramecia cultures. Microgravity is the major factor responsible of this response: indeed the stimulatory effect disappeared in inflight cultures placed on a 1 g centrifuge aboard the Spacelab. On the other hand, exposure to different levels of hypergravity on Earth resulted in an opposite response, i.e. to a reduced cell growth rate. A possible mechanism of microgravity on paramecia is discussed.