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PubMed1991

Effects of saline loading during head down tilt on ANP and cyclic GMP levels and on urinary fluid excretion.

In the present study the renal and humoral effects of acute saline infusions were investigated in six healthy male volunteers before, during and after a ten day period of -6 degrees head-down-tilt (HDT). During the whole 23-day study period the subjects received a standardized diet including 40 ml water and 125 mg NaCl per kg body weight per day. After the infusion of 0.9% saline (22 ml/kg within 20 minutes) plasma atrial natriuretic peptide (ANP) levels were only slightly increased (not significant) at the end of the infusion, while plasma cyclic GMP levels were significantly increased by about 40% (p<0.05) one hour later. No difference was observed in the plasma ANP and cyclic GMP changes between the pre-HDT, the HDT and the post-HDT infusion experiment. Urine flow, sodium excretion and urinary cyclic GMP excretion were significantly increased (p<0.05 and below) by 100 to 300% during the second and third hour after each saline infusion. However, during these short-term periods only 20% of the infused water and less than 20% of the infused sodium were excreted. Furthermore, a significantly increased volume, sodium and cyclic GMP excretion was observed for over 48 hours after each fluid load experiment. These data suggest that HDT does not induce major alterations in the regulation of an acute saline infusion and plasma ANP does not play a major role in the diuretic/natriuretic effects of volume loading.

Adult↗
PubMed1994

Metabolic adaptation of skeletal muscles to gravitational unloading.

Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, beta-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes.

Animals↗
PubMed1996

Effects of altered loading states on muscle plasticity: what have we learned from rodents?

This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

Adaptation, Physiological↗
PubMed1993

Activity-induced regulation of myosin isoform distribution: comparison of two contractile activity programs.

This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that: 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.

Animals↗
PubMed1996

Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers.

The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.

Animals↗
PubMed1993

Hormonal and electrolyte responses to acute isohemic volume expansion in unanesthetized rats.

This study was undertaken to explore the time course of the metabolic response to isohemic blood volume expansion (30%) in normotensive, unanesthetized Sprague-Dawley rats. Whole blood, drawn from a femoral artery catheter of conscious donor rats, was infused into the jugular vein of recipient rats. Blood samples were drawn from a carotid artery of recipient rats at time points beginning immediately post-volume expansion (IPVE) up through 5 days post-volume expansion (PVE). To characterize the attendant compensatory mechanisms, the plasma concentrations of electrolytes and fluid regulatory hormones were determined. Hematocrit began to raise IPVE and was significantly elevated above control IPVE 20, 30, 40, 60, and 90 min, and 2, 4, 6, 8, 12, and 24 hr PVE. Consistent with our current understanding of the hormonal response to excess volume, atrial natriuretic factor was significantly increased above the prevolume expansion (control) values 0-30 min PVE. Surprisingly, plasma aldosterone levels were significantly increased above control at 20 and 30 min and 6 hr PVE, whereas plasma renin activity was significantly decreased 30-40 min PVE. Plasma sodium was not changed from control values except for a significant increase at 6 hr post-volume expansion. Plasma potassium, osmolality, and arginine vasopressin levels were not altered by the volume expansion. These studies delineate the physiologic time scheme operative in the regulation of fluid volume during acute ischemic volume expansion.

Aldosterone↗
PubMed1994

The Pittsburgh Sleep Diary.

Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).

Activities of Daily Living↗
PubMed1988

Gravitational effects on mammalian cells.

In this paper we present first the results of our most recent investigations on gravitational effects on the activation of human lymphocytes: by immunoenzymatic staining and by using concanavalin A (Con A) coated to red blood cells (RBC) we demonstrate that the increase of activation measured at 10xg is due to a simultaneous activation of T- and B-lymphocytes whereas at 1xg only T-cells are stimulated. Conversely, activation of T-cells by chemical modification of the membrane with sodium periodate is depressed at 10xg. Secondly, experiments performed in the centrifuge as well as in the clinostat with Friend, K-562, and hybridoma cells show that each cell line develops its own adaptation reaction to gravitational stress.

B-Lymphocytes↗
PubMed1988

Adaptation to restraint in the rat.

Use of telemetry in physiological research is still in early stages. Cardiovascular studies planned for gravitational work during the next few years on primates or squirrel monkeys depend on restraint devices. Two rat cardiovascular experiments (US Space Lab SLS I and SLS II) use unrestrained rats for resting cardiovascular measurements (chronic intravascular cannulas and implanted blood flow probes), but employ semi-restrained animals for microcirculatory investigations. Prior to weightlessness, these instrumented rats will be exposed a number of times to semi-restraint. In order to ascertain if there is adaptation to restraint (decreased toward normal of plasma stress hormones), the rats were exposed 18 times to restraint chambers, but the level of stress hormones stayed elevated.

Adaptation, Physiological↗
PubMed1993

[Determination of six main components in compound theophylline tablet by convolution curve method after prior separation by column partition chromatography].

On a partition chromatographic column in which the support is Kieselguhr and the stationary phase is sulfuric acid solution (2 mol/L), three components of compound theophylline tablet were simultaneously eluted by chloroform and three other components were simultaneously eluted by ammonia-saturated chloroform. The two mixtures were determined by computer-aided convolution curve method separately. The corresponding average recovery and relative standard deviation of the six components were as follows: 101.6, 1.46% for caffeine; 99.7, 0.10% for phenacetin; 100.9, 1.31% for phenobarbitone; 100.2, 0.81% for theophylline; 99.9, 0.81% for theobromine and 100.8, 0.48% for aminopyrine.

Aminopyrine↗
PubMed1991

From gravity and the organism to gravity and the cell.

This workshop on Gravity and the Cell was modeled on a 1968 conference on Gravity and the Organism. Each conference tried to identify the most salient scientific questions about how gravity is important to living systems. In the roughly two decades between the conferences there have been impressive advances in experimental methods, but the major scientific questions that have driven their applications to problems of gravitational biology, i.e., our broad research goals, remain much the same. In the case of plant research, improvements and extensions of biochemical techniques for investigating the ways organisms use environmental (g-force) information in salubrious ways has kept pace with progress in plant biochemistry. We now know much more about the roles of organic and inorganic substances that plants employ for information transfer and growth regulation and about the avenues and mechanisms for transport of those key substances within organisms. We have seen the acceptance of a "local control" concept that regulation of g-responses depends critically on plasmodesmata and gap junctions which allow plants and animals to throttle the transport of growth regulators across tissue boundaries often, especially in the case of plants, far removed from the morphological regions of concentration of statocytes that were once thought to be the exclusive bioaccelerometers used by plants. NASA's sponsorship of ground-based research in gravitational biology has served as important underpinning for orbital flight programs in space biology. The currently most noteworthy research area of ignorance is the mechanism by which the physical event of g-force susception becomes the biological process of g-force perception. Only rarely has it been possible to perform a definitive test of a theory of mechanism of gravity perception. Therefore, experimental research efforts in gravitational physiology still are essentially dependent on exploratory studies for which stimulus/response experiments require experimental manipulation of test subjects' g-force environment. Many research efforts have focused narrowly on contrasting the responses of test subjects to only two gravitational environments, 1 g versus real or simulated zero g. Much less effort has been devoted to studies at other g levels. For experiments in gravitational physiology three rotating machines have made, and no doubt will continue to make, important contributions: the centrifuge, the clinostat, and, most of all, the orbiting space vehicle. Some research trends, viewpoints, and shifts of emphasis are discussed.

Animals↗
PubMed1992

Microgravity effects on sea urchin fertilization and development.

Gravity has been a pervasive influence on all living systems and there is convincing evidence to suggest that it alters fertilization and embryogenesis in several developmental systems. Notwithstanding the global importance of gravity on development, it has only been recently possible to begin to design experiments which might directly investigate the specific effects of this vector. The goal of this research program is to explore and understand the effects of gravity on fertilization and early development using sea urchins as a model system. Sea urchin development has several advantages for this project including the feasibility of maintaining and manipulating these cells during spaceflight, the high percentage of normal fertilization and early development, and the abundant knowledge about molecular, biochemical, and cellular events during embryogenesis which permits detailed insights into the mechanism by which gravity might interfere with development. Furthermore, skeletal calcium is deposited into the embryonic spicules within a day of fertilization permitting studies of the effects of gravity on bone calcium deposition.

Animals↗
PubMed1997

Changes in the immune system during and after spaceflight.

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.

Acute Disease↗
PubMed1993

Treatment efficacy of intramuscular promethazine for space motion sickness.

Intramuscular promethazine and its efficacy in the treatment of Space Motion Sickness (SMS) were evaluated using standardized questions administered during postflight debriefings to crewmembers immediately after their first Shuttle flight. Space Motion Sickness was graded as none, mild, moderate, or severe, based on published criteria. Immediate symptom relief (within 1-2 h) was evaluated by subjective reports; medication efficacy was based on scores derived from the four most frequently reported symptoms of SMS: nausea, vomiting, loss of appetite, and stomach awareness. Scores were given for each symptom, mild = 1, moderate = 2, and severe = 3, and added for a total score for each flight day. Following intramuscular (IM) promethazine on flight day 1, the scores were used to determine if the crewmembers were "sick" or "not sick" on flight day 2. On the basis of the scoring criteria, any subject with a score adding to greater than three, with any severe symptom, or with vomiting was defined as "sick." The comparison showed that 25% of crewmembers treated with IM promethazine were "sick" on flight day 2, compared to 50% of crewmembers who did not receive promethazine (p = 0.046). Of crewmembers treated with IM promethazine, 90% reported immediate symptom relief as well. Untreated crewmembers typically have slow symptom resolution over 72-96 h, and those treated with oral scopolamine/dextroamphetamine show delayed symptom development. This study suggests that intramuscular promethazine is an effective treatment for SMS and merits continued use and further controlled investigations.

Female↗
PubMed1997

Activation and proliferation of lymphocytes and other mammalian cells in microgravity.

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.

Animals↗
PubMed1989

Studies of the horizontal vestibulo-ocular reflex in spaceflight.

Changes in the vestibulo-ocular reflex (VOR) during space flight have been suspected of contributing to space motion sickness. The horizontal VOR was studied in nine subjects on two space shuttle missions. Active unpaced head oscillation at 0.3 Hz was used as the stimulus to examine the gain and phase of the VOR with and without visual input, as well as the visual suppression of the reflex. No statistically significant changes were noted inflight in the gains or phase shifts of the VOR during any test condition, or between space motion sickness susceptible and nonsusceptible populations. Although VOR suppression was unaffected by spaceflight, the space motion sickness-susceptible group tended to exhibit greater error in the suppression than the nonsusceptible group. It is concluded that at this stimulus frequency, VOR gain is unaffected by spaceflight, and any minor individual changes do not seem to contribute to space motion sickness.

Adult↗