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Purpose of the investigation was microscopic examination of changes in cyto architectonics of the spleen and jejunum lymph (immune) tissue in 19-20-week C57BL/6N male mice exposed to some conditions their counterparts had lived in during the 30-d Bion-M1 mission (ground experiment). Local deviations in reactions of the morphofunctional zones of these organs were found. In the spleen, reaction in the centers of lymph nodules generation or the B-lymphocytes maturation zone grows strong. Changes in the cell composition of periarterial lymph sheaths that constitute the morphological site of T-lymphocytes accumulation suggest inhibition of its functional activity. Cell composition of the jejunum wall structure implies a decline of the jejunal immune activity. Our investigation of the organs taken from the ground control mice maintained in the flight BIOS-MLZh module evidences that unceasing noise, hypokinesia, isolation, and paste-like feed weaken general immunity of laboratory animals.

The article reports the results of studying the lymph tissue of mesenteric and cervical lymphatic nodes in C57BL/6N mice after the 30-day orbital flight onboard biosatellite Bion-M1. Histological and morphometric investigations revealed changes in the ratio of the nodes structural-functional zones and microstructure. Reductions in reticular cells, plasmocytes, macrophages and blasts in the nodes point to degradation of both humoral and cellular immunity.

Purpose of the BION-M1 project was laying the evidence and technological basis for addressing the medical issues of future remote space exploration missions by humans. The program of researches with the use of mice was focused on elicitation of cellular and molecular mechanisms of the muscular, cardiovascular and immune reactions to extended exposure in microgravity. The comprehensive studies combined lifetime measurements with investigations of mice tissues and cells by dint of the cutting-edge morphological, biochemical and molecular biology techniques. Males of mice C57/BL6 aged 4 to 5 months were chosen as the object of studies. They were distributed into the flight, ground control and two vivarium (laboratory control) groups and investigated immediately on return and after 7 days of readaptation. Some of the physiological functions were recorded throughout the flight. To ensure wellbeing of the animals in the experiments and to enhance data quality, prior to launch the mice were specially trained so as to accommodate to the group living, eating space food, and in-flight stress factors. Those of the mice that were designated for lifetime investigations were tested and received training pre-launch.

Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

Missions of unmanned spacecraft Foton-M2 (2005) and Foton-M3 (2007) of 16 and 12 days in duration, respectively, provided an opportunity to conduct the Russian/US experiments with snails (Helix lucorum and Helix aspera), newts (Pleurodeles waltli), geckos (Pachydactilus turneri) and microorganisms (Streptomyces lividans 66, E. coli and others). Besides, Foton-M3 carried a Russian experiment with Mongolian gerbils (Meriones unguiculatus). Objectives of the space experiments were to study the micro-g effects on the living systems' behavior, structure and functioning, post-traumatic regeneration of bone and organs, stable inheritance of plasmid pIJ 702, and melanin pigment synthesis by streptomycets. The survey paper presents the major findings of a large team of investigators.

Experiments involving lower tetrapods demonstrate that the degree of skeletal demineralization in spaceflights is related to the type of environmental behaviour of the animal. Probably the sensing of support reaction decreases the negative effect of spaceflight upon the bone tissue.

Animal research has been critical to the initiation and progress of space exploration. Animals were the original explorers of "space" two centuries ago and have played a crucial role by demonstrating that the space environment, with precautions, is compatible with human survival. Studies of mammals have yielded much of our knowledge of space physiology. As spaceflights to other planets are anticipated, animal research will continue to be essential to further reveal space physiology and to enable the longer missions. Much of the physiology data collected from space was obtained from the Cosmos (Bion) spaceflights, a series of Russian (Soviet)-International collaborative flights, over a 22 year period, which employed unmanned, free flyer biosatellites. Begun as a Soviet-only program, after the second flight the Russians invited American and other foreign scientists to participate. This program filled the 10 year hiatus between the last US biosatellite and the first animal experiments on the shuttles. Of the 11 flights in the Cosmos program nine of them were international; the flights continued over the years regardless of political differences between the Soviet Union and the Western world. The science evolved from sharing tissues to joint international planning and development, and from rat postmortem tissue analysis to in vivo measurements of a host of monkey physiological parameters during flight. Many types of biological specimens were carried on the modified Vostok spacecraft, but only the mammalian studies are discussed herein. The types of studies done encompass the full range of physiology and have begun to answer "critical" questions of space physiology posed by various ad hoc committees. The studies have not only yielded a prodigious and significant body of data, they have also introduced some new perspectives in physiology. A number of the physiological insights gained are relevant to physiology on Earth. The Cosmos flights also added significantly to flight-related technology, some of which also has application on our planet. In summary, the Cosmos biosatellite flights were extremely productive and of low cost. The Bion vehicles are versatile in that they can be placed into a variety of orbits and altitudes, and can carry radiation sources or other hazardous material which cannot be carried on manned vehicles. With recent advances in sensor, robotic, and data processing technology, future free flyers will be even more productive, and will largely preclude the need to fly animal experiments on manned vehicles. Currently, mammalian researchers do not have access to space for an unknown time, seriously impeding the advancement and understanding of space physiology during long duration missions. Initiation of a new, international program of free flyer biosatellites is critical to our further understanding of space physiology, and essential to continued human exploration of space.

In recent years, investigators began studying the effect of hypergravity on pathological developments in the animal and human body. It was shown that a regular exposure of tail suspended rats to normal gravity diminished osteopenia and muscle atrophy. Moderate gravitational loading produced by a G-suit dramatically increased the therapeutic success rate in children with cerebral palsy. Rotation of patients with obliterating endarteritis and limb bone fractures in a short-radius centrifuge in hospitals of the city of Samara (Russia) yielded promising results. The purpose of our investigations was to investigate the effects of hypergravity on chemically induced carcinogenesis in mice. We hypothesized that gravitational loading may produce a generalized effect on the animal body and thus to enhance its nonspecific anti-tumor resistance.

The Bion project was initiated in 1970 and became the longest space research project in existence. Its primary goal was to perform theoretical and applied research on animals and other specimens flown onboard dedicated unmanned space vehicles, termed biosatellites. The Bion project included flights of 11 biosatellites carrying Wistar rats, rhesus monkeys, and other representatives of the animal and plant worlds. Scientists and engineers from many different countries have taken part in these Bion experiments.

A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

Space flight experiments on Chinese silkworm (Bombyx mori L.) were conducted on board the Russian 10th Biosatellite for 12 days. The samples included silkworm eggs, larvae, cocoons, pupae and moths. The processes of spinning, cocooning, mating, oviposition, larval hatching, pupation and moth emergence all completed well in space. The following effects of space flight on silkworm development were observed: The times of hatching and oviposition in the flight group were 2 to 3 days earlier than in the control group; the hatching rate of diapause eggs during space flight seemed higher than that of the control group; the life span of 2 of the 7 varieties flown was shortened; genetical variations appeared in 3 varieties. The results showed that the embryonic stage was probably the period most sensitive to the space flight environment.

This paper presents the set of specific problems in manned Mars mission, connected with human factor, and scientific approaches for their resolution. The concept of multifunctional medical Complex for Martian spacecraft is discussed.

This paper discusses goals and objectives of the Soviet project to build an orbital bio-medical laboratory "Medilab". Special attention is given to the programme of scientific and practical use, design, structure and information support of the dedicated space laboratory.

The program of the 7-day flight of the biosatellite Cosmos-1667 launched in July 1985 included experiments on two rhesus monkeys, ten Wistar SPF rats, ten newts, Drosophila flies, maize seedlings, lettuce sprouts, and unicellular organisms--Tetrahymena. The primate study demonstrated that transition to orbital flight was accompanied by a greater excitability of the vestibular apparatus and an increased linear blood flow velocity in the common carotid artery. The rat studies showed that atrophy of antigravity muscles and osteoporosis of limb bones developed even during short-term exposure to microgravity. The experiments on other living systems revealed no microgravity effects on the cell division rate, proliferative activity of cells of regenerating tissues and organs, energy metabolism of developing insects, structure or chemical composition of higher plant seedlings.

This review surveys data in the literature and our own findings concerning the effects of weightlessness on bones and muscles of white rats flown on Cosmos biosatellites and Spacelab-3. It has been shown that the magnitude and sign of functional changes in muscles depend on their biomechanical profile. Structural and metabolic foundations of functional adaptation and its dynamics have been identified: in 5-7 day flights muscle contractility changes are mainly associated with a diminished activity of excitation-contraction coupling, in longer-term flights they are produced by changes in myosin populations specific for myofibers of different functional profile. At early flight stages (up to 1 week) osteoporosis and bone demineralization are very mild; therefore decrease in bone mechanical strength may be caused by changes in physico-chemical parameters of the collagen-crystal system. In flights of up to 3 weeks noticeable osteoporosis develops which is primarily produced by osteogenesis inhibition and which is responsible for a marked decrease of bone strength. These changes may result from uncoupling of bone resorption and remodelling processes. This uncoupling is characterized as incomplete osteogenesis and may be caused by changes in the collagen composition of the organic bone matrix. The above-mentioned adaptive changes in muscle functions of specific skeletal compartments may play a role in different responses of various bones to weightlessness.

Many rat experiments onboard Cosmos biosatellites have furnished information concerning the effects of weightlessness, artificial gravity, and ionizing radiation combined with weightlessness on structural and biochemical parameters of the animal body. The necessity to expand the scope of physiological investigations has led to the project of flight primate studies. It is planned to carry out the first primate experiments onboard the Cosmos biosatellite in 1982. At present investigations of weightlessness effects on the cardiovascular and vestibular systems, higher nervous activity, skeletal muscles and biorhythms of two rhesus monkeys are being developed and tested. It is also planned to conduct a study of weightlessness effects on embryogenesis of rats and bioenergetics of living systems onboard the same biosatellite. Further experiments onboard Cosmos biosatellites are planned.

The effect was investigated of continued growth of animals on bone formation and resorption under conditions when their musculoskeletal systems were unloaded. Studied were rats aged 1, 2.5, and 6 months. To provide the unloading, the rats were suspended at an angle so that their hindlimbs did not touch the floor. After 22 days, the animals were sacrificed, and the length and width of the diaphysis of the femoral bone and its calcium content were measured. Bone reactions to the suspension were found to be age-dependent. The rats of 2.5 months showed the highest and the rats of 6 months the lowest increase in bone reabsorption at the side of the bone-marrow canal and in reduction of the cortical layer. With age, calcium decrease in the femur of suspended rats became less pronounced compared to controls. The age-related bone reactions to the musculoskeletal unloading must be taken into consideration when planning and conducting rat studies.

Preliminary results of the radiobiological experiments carried out on the biosatellite Cosmos 690 with a radiation exposure unit on board are presented. The duration of the satellite flight was 20.5 days. On the tenth day of the flight 35 rats were exposed on board the satellite to 220 or 800 rads of gamma radiation. Comparison of data obtained in test and control groups of animals has shown that under the influence of space flight factors a somewhat more severe radiation injury develops than in on-ground conditions.

Physiological, morphological and biochemical studies of mammals flown onboard biosatellites of the series Cosmos revealed changes in their cardiovascular, musculoskeletal, endocrine and vestibular systems. Space flight resulted in moderate stress reactions, intralabyrinthine conflict information during movements and changes in fluid-electrolyte metabolism. Exposure to artificial gravity (1 g) decreased the level of myocardial, musculoskeletal and excretory changes, but disturbed the function of equilibrium. Studies with combined weightlessness and ionizing radiation demonstrated that weightlessness did not produce a significant modifying effect on radiation damage and postradiation recovery. Consistent changes in certain systems of animals and humans in weightlessness confirm the practical importance of biosatellite studies, which also contribute to the solution of general biology, problems associated with gravity effects on life processes.

Over the past decade, the USSR has launched six biosatellites of the Cosmos series. The first biosatellite flew 6 d; the remaining five flew 18-21 d. The principal purpose of this investigation was to continue studies on the adaptation of living systems to weightlessness; to investigate the modifying effect of weightlessness on the organism's radiosensitivity; and, to examine the biological effects of artificial gravity. The investigations involved 37 kinds of biological models; rats were the principal test models. It was established that weightlessness induces in the organism symptoms of moderately pronounced stress together with a number of other specific changes. First and foremost are changes in the locomotor system (atrophy of the muscles and lowered mechanical strength of the bones, as examples). An artificial gravity of 1 G employed during space flight helps preserve the "terrestrial" rate of functioning of most physiological systems in the organism. The irradiation of rats during space flight from the Cesium-137 isotope revealed no tangible modifying effect of weightlessness on the course of radiation injuries. No distinct effect of weightlessness on the intracellular processes of vital activity has yet been observed. Contradictory results have been obtained in the growth and development of organisms during weightlessness.

The results of biomedical investigations carried out in flights of the Salyut and Skylab orbital stations give evidence that during prolonged weightlessness cosmonauts and astronauts remain in a good physical and mental condition. They fill specialists with optimism in regards to a further increase of the duration of manned space flights. In order to make reliable plans for such missions, it is necessary to accumulate detailed knowledge about the mechanism of the effect of weightlessness on different functions of the human body. In addition to manned experiments, of great interest are animal experiments. They may yield data that cannot be obtained in human studies, which is obviously very important from the point of view of space medicine. This was the purpose of the experiment carried out in November 1973 on the biosatellite Cosmos-605; 45 rats aboard the biosatellite flew for 22 d. Preliminary results of examinations of rats after a 22-d space flight in the Cosmos-605 satellite demonstrated not only physiological and biochemical but also morphological changes in the animal body due to prolonged weightlessness. These changes were reversible.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.

In 1974, the USSR launched the biosatellite Cosmos-690 equipped with a gamma-irradiation unit that carried 35 rats. On the 10th flight day, the rats were exposed to radiation at doses of 220 or 800 rads. During the subsequent 10 d, radiation injury developed in a space environment. Similar ground-based experiments were carried out to simulate space flight environment effects. The results obtained were studied on a comparative basis. The conclusion is made that effects of a short-term space flight, as long as 20 d, do not essentially modify the radiobiological effect.