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At least 271 records · Page 15

Space travel directly induces skeletal muscle atrophy

Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

NASA Discipline Musculoskeletal↗

Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

Non-NASA Center↗

Recovery of postural equilibrium control following spaceflight

Decreased postural stability is observed in most astronauts immediately following spaceflight. Because ataxia may present postflight operational hazards, it is important to determine the incidence of postural instability immediately following landing and the dynamics of recovery of normal postural equilibrium control. It is postulated that postflight postural instability results from in-flight adaptive changes in central nervous system (CNS) processing of sensory information from the visual, vestibular, and proprioceptive systems. The purpose of the present investigation was to determine the magnitude and time course of postflight recovery of postural equilibrium control and, hence, readaptation of CNS processing of sensory information. Thirteen crew members from six spaceflight missions were studied pre- and postflight using a modified commercial posturography system. Postural equilibrium control was found to be seriously disrupted immediately following spaceflight in all subjects. Readaptation to the terrestrial environment began immediately upon landing, proceeded rapidly for the first 10-12 hours, and then proceeded much more slowly for the subsequent 2-4 days until preflight stability levels were reachieved. It is concluded that the overall postflight recovery of postural stability follows a predictable time course.

NASA Discipline Neuroscience↗

Compiling a Comprehensive EVA Training Dataset for NASA Astronauts

Training for a spacewalk or extravehicular activity (EVA) is considered a hazardous duty for NASA astronauts. This places astronauts at risk for decompression sickness as well as various musculoskeletal disorders from working in the spacesuit. As a result, the operational and research communities over the years have requested access to EVA training data to supplement their studies. The purpose of this paper is to document the comprehensive EVA training data set that was compiled from multiple sources by the Lifetime Surveillance of Astronaut Health (LSAH) epidemiologists to investigate musculoskeletal injuries. The EVA training dataset does not contain any medical data, rather it only documents when EVA training was performed, by whom and other details about the session. The first activities practicing EVA maneuvers in water were performed at the Neutral Buoyancy Simulator (NBS) at the Marshall Spaceflight Center in Huntsville, Alabama. This facility opened in 1967 and was used for EVA training until the early Space Shuttle program days. Although several photographs show astronauts performing EVA training in the NBS, records detailing who performed the training and the frequency of training are unavailable. Paper training records were stored within the NBS after it was designated as a National Historic Landmark in 1985 and closed in 1997, but significant resources would be needed to identify and secure these records, and at this time LSAH has not pursued acquisition of these early training records. Training in the NBS decreased when the Johnson Space Center in Houston, Texas, opened the Weightless Environment Training Facility (WETF) in 1980. Early training records from the WETF consist of 11 hand-written dive logbooks compiled by individual workers that were digitized at the request of LSAH. The WETF was integral in the training for Space Shuttle EVAs until its closure in 1998. The Neutral Buoyancy Laboratory (NBL) at the Sonny Carter Training Facility near JSC opened in March 1997 and is the current site for US EVA training. Other space agencies also have used water to simulate weightlessness and train for EVAs. Russia has a training facility similar to the NBL named the Hydro Lab. The Hydro Lab began operations at the Gagarin Cosmonaut Training Center (GCTC) in 1980 and has been used extensively to the present. Although a majority of training in the Hydro Lab uses the Russian Orlan suit, a small number of sessions have been conducted using a NASA suit. The Japanese Weightlessness Environment Test System (WETS) went into service at the Tsukuba Space Center in 1997 but was closed in 2011 due to extensive earthquake damage. Several sessions were performed using a NASA suit, but these sessions were short and considered "development" runs. LSAH has assembled records from the WETF, NBL and Hydro Lab. Recording of the EVA training data has changed considerably from 1967 to present. The goal of early record keeping was to track use of hardware components, and the person involved was treated as a suited operator, not as a focus of interest. Records from the past two decades are fairly precise with the person, date, suit type and size noted. On occasion the length of the session was listed, but this data is not included on all records. Records were merged from data sources and extensive cleaning of the records was required since the multiple sources frequently overlapped and duplicated records. To date the LSAH EVA training dataset includes over 12,500 EVA training sessions performed by NASA astronauts since 1981. The following variables are included for most records: Name, Sex, Event date, Event name, HUT type, HUT size, Facility, and Estimated run time. For a smaller subset of records, the following variables are available: Actual run time, Time inverted, and the suit components Waist bearing type, Shoulder harness, Shoulder pads, and Teflon inserts. The LSAH dataset is currently the most complete resource for data regarding EVA training sessions performed by NASA astronauts. However, it is not 100 percent complete since the WETS (Japan) and NBS (Marshall) training facility data were not included. This dataset has been compiled by LSAH to study the relationship of EVA training to musculoskeletal injuries but has many other non-medical applications. This dataset can be provided to other groups in order to respond to program and research questions with appropriate board approvals.

Laughlin, M. S.↗

Smart Ultrasound Remote Guidance Experiment (SURGE) Preliminary Findings

To date, diagnostic quality ultrasound images were obtained aboard the International Space Station (ISS) using the ultrasound of the Human Research Facility (HRF) rack in the Laboratory module. Through the Advanced Diagnostic Ultrasound in Microgravity (ADUM) and the Braslet-M Occlusion Cuffs (BRASLET SDTO) studies, non-expert ultrasound operators aboard the ISS have performed cardiac, thoracic, abdominal, vascular, ocular, and musculoskeletal ultrasound assessments using remote guidance from ground-based ultrasound experts. With exploration class missions to the lunar and Martian surfaces on the horizon, crew medical officers will necessarily need to operate with greater autonomy given communication delays (round trip times of up to 5 seconds for the Moon and 90 minutes for Mars) and longer periods of communication blackouts (due to orbital constraints of communication assets). The SURGE project explored the feasibility and training requirements of having non-expert ultrasound operators perform autonomous ultrasound assessments in a simulated exploration mission outpost. The project aimed to identify experience, training, and human factors requirements for crew medical officers to perform autonomous ultrasonography. All of these aims pertained to the following risks from the NASA Bioastronautics Road Map: 1) Risk 18: Major Illness and Trauna; 2) Risk 20) Ambulatory Care; 3) Risk 22: Medical Informatics, Technologies, and Support Systems; and 4) Risk 23: Medical Skill Training and Maintenance.

Hurst, Victor↗

A link-segment model of upright human posture for analysis of head-trunk coordination

Sensory-motor control of upright human posture may be organized in a top-down fashion such that certain head-trunk coordination strategies are employed to optimize visual and/or vestibular sensory inputs. Previous quantitative models of the biomechanics of human posture control have examined the simple case of ankle sway strategy, in which an inverted pendulum model is used, and the somewhat more complicated case of hip sway strategy, in which multisegment, articulated models are used. While these models can be used to quantify the gross dynamics of posture control, they are not sufficiently detailed to analyze head-trunk coordination strategies that may be crucial to understanding its underlying mechanisms. In this paper, we present a biomechanical model of upright human posture that extends an existing four mass, sagittal plane, link-segment model to a five mass model including an independent head link. The new model was developed to analyze segmental body movements during dynamic posturography experiments in order to study head-trunk coordination strategies and their influence on sensory inputs to balance control. It was designed specifically to analyze data collected on the EquiTest (NeuroCom International, Clackamas, OR) computerized dynamic posturography system, where the task of maintaining postural equilibrium may be challenged under conditions in which the visual surround, support surface, or both are in motion. The performance of the model was tested by comparing its estimated ground reaction forces to those measured directly by support surface force transducers. We conclude that this model will be a valuable analytical tool in the search for mechanisms of balance control.

NASA Discipline Neuroscience↗

Description of a prototype emission-transmission computed tomography imaging system

We have developed a prototype imaging system that can perform simultaneous x-ray transmission CT and SPECT phantom studies. This system employs a 23-element high-purity-germanium detector array. The detector array is coupled to a collimator with septa angled toward the focal spot of an x-ray tube. During image acquisition, the x-ray fan beam and the detector array move synchronously along an arc pivoted at the x-ray source. Multiple projections are obtained by rotating the object, which is mounted at the center of rotation of the system. The detector array and electronics can count up to 10(6) cps/element with sufficient energy-resolution to discriminate between x-rays at 100-120 kVp and gamma rays from 99mTc. We have used this device to acquire x-ray CT and SPECT images of a three-dimensional Hoffman brain phantom. The emission and transmission images may be superimposed in order to localize the emission image on the transmission map.

NASA Discipline Musculoskeletal↗

Paralysis recovery in humans and model systems

Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

Review↗

The timing of galvanic vestibular stimulation affects responses to platform translation

We compared the effects of galvanic vestibular stimulation applied at 0, 0.5, 1.5 and 2.5 s prior to a backward platform translation on postural responses. The effect of the galvanic stimulation was largest on the final equilibrium position of the center of pressure (CoP). The largest effects occurred for the 0.5 and 0-s pre-period, when the dynamic CoP pressure changes in response to both the galvanic stimulus and the platform translation coincided. The shift in the final equilibrium position was also larger than the sum of the shifts for the galvanic stimulus and the platform translation alone for the 0.5 and 0-s pre-periods. The initial rate of change of the CoP response to the platform translation was not significantly affected in any condition. Changes in the peak CoP position could be accounted for by local interaction of CoP velocity changes induced by the galvanic and translation responses alone, but the changes in final equilibrium position could only be accounted for by a change in global body orientation. These findings suggest that the contribution of vestibulospinal information is greatest during the dynamic phase of the postural response, and that the vestibular system contributes most to the later components of the postural response, particularly to the final equilibrium position. These findings suggest that a nonlinear interaction between the vestibular signal induced by the galvanic current and the sensory stimuli produced by the platform translation occurs when the two stimuli are presented within 1 s, during the dynamic phase of the postural response to the galvanic stimulus. When presented at greater separations in time, the stimuli appear to be treated as independent events, such that no interaction occurs. Copyright 1999 Elsevier Science B.V.

Non-NASA Center↗

Improving science literacy and education through space life sciences

The National Space Biomedical Research Institute (NSBRI) encourages open involvement by scientists and the public at large in the Institute's activities. Through its Education and Public Outreach Program, the Institute is supporting national efforts to improve Kindergarten through grade twelve (K-12) and undergraduate education and to communicate knowledge generated by space life science research to lay audiences. Three academic institution Baylor College of Medicine, Morehouse School of Medicine and Texas A&M University are designing, producing, field-testing, and disseminating a comprehensive array of programs and products to achieve this goal. The objectives of the NSBRI Education and Public Outreach program are to: promote systemic change in elementary and secondary science education; attract undergraduate students--especially those from underrepresented groups--to careers in space life sciences, engineering and technology-based fields; increase scientific literacy; and to develop public and private sector partnerships that enhance and expand NSBRI efforts to reach students and families. c 2001. Elsevier Science Ltd. All rights reserved.

NASA Discipline General Space Life Sciences↗

Studies of matrix vesicle-induced mineralization in a gelatin gel

Matrix vesicles isolated from fourth-passage cultures of chondrocytes were tested for their ability to induce hydroxyapatite formation in a gelatin gel in order to gain insight into the function of matrix vesicles in in situ mineralization. These matrix vesicles did not appear to be hydroxyapatite nucleators per se since the extent of mineral accumulation in the gel diffusion system was not altered by the presence of matrix vesicles alone, and in the vesicle containing gels, mineral crystals were formed whether associated with vesicles or not. In gels with these matrix vesicles and beta-glycerophosphate, despite the presence of alkaline phosphatase activity, there was no increase in mineral deposition. This suggested that in the gel system these culture-derived vesicles did not increase local phosphate concentrations. However, when known inhibitors of mineral crystal formation and growth (proteoglycan aggregates [4 mg/ml], or ATP [1 mM], or both proteoglycan and ATP) were included in the gel, more mineral was deposited in gels with the vesicles than in comparable gels without vesicles, indicating that enzymes within these vesicles were functioning to remove the inhibition. These data support the suggestion that one function of the extracellular matrix vesicles is to transport enzymes for matrix modification.

Non-NASA Center↗

Plantar soft tissue thickness during ground contact in walking

A technique is introduced for the measurement of plantar soft tissue thickness during barefoot walking. Subjects stepped into an adjustable Plexiglas frame which ensured that the required bony landmarks were appropriately positioned relative to a linear ultrasound probe connected to a conventional 7.5 MHz ultrasound scanner. Clear images of the metatarsal condyles or other foot bones were obtained throughout ground contact. Subsequent analysis of the video taped images using a motion analysis system allowed the tissue displacement to be calculated as a function of time. The tissue underneath the second metatarsal head was shown to undergo an average maximum compression of 45.7% during the late stages of ground contact during first step gait in a group of five normal subjects with a mean unloaded tissue thickness of 15.2 mm. The technique has a number of applications, including use in the validation of deformation predicted by finite element models of the soft tissue of the foot, and the study of alterations in the cushioning properties of the heel by devices which constrain the displacement of the heel pad.

Non-NASA Center↗

Transcriptional profile of a myotube starvation model of atrophy

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

NASA Discipline Musculoskeletal↗

The response of bone to unloading

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

NASA Program Fundamental Space Biology↗

Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma

Rats implanted with Yoshida ascites hepatoma (YAH) show a rapid and selective loss of muscle protein due mainly to a marked increase (63-95%) in the rate of protein degradation (compared with rates in muscles of pair-fed controls). To define which proteolytic pathways contribute to this increase, epitrochlearis muscles from YAH-bearing and control rats were incubated under conditions that modify different proteolytic systems. Overall proteolysis in either group of rats was not affected by removal of Ca2+ or by blocking the Ca(2+)-dependent proteolytic system. Inhibition of lysosomal function with methylamine reduced proteolysis (-12%) in muscles from YAH-bearing rats, but not in muscles of pair-fed rats. When ATP production was also inhibited, the remaining accelerated proteolysis in muscles of tumor-bearing rats fell to control levels. Muscles of YAH-bearing rats showed increased levels of ubiquitin-conjugated proteins and a 27-kDa proteasome subunit in Western blot analysis. Levels of mRNA encoding components of proteolytic systems were quantitated using Northern hybridization analysis. Although their total RNA content decreased 20-38%, pale muscles of YAH-bearing rats showed increased levels of ubiquitin mRNA (590-880%) and mRNA for multiple subunits of the proteasome (100-215%). Liver, kidney, heart, and brain showed no weight loss and no change in these mRNA species. Muscles of YAH-bearing rats also showed small increases (30-40%) in mRNA for cathepsins B and D, but not for calpain I or heat shock protein 70. Our findings suggest that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome.

NASA Discipline Musculoskeletal↗

Vestibulospinal adaptation to microgravity

Human balance control is known to be transiently disrupted after spaceflight; however, the mechanisms responsible for postflight postural ataxia are still under investigation. In this report, we propose a conceptual model of vestibulospinal adaptation based on theoretical adaptive control concepts and supported by the results from a comprehensive study of balance control recovery after spaceflight. The conceptual model predicts that immediately after spaceflight the balance control system of a returning astronaut does not expect to receive gravity-induced afferent inputs and that descending vestibulospinal control of balance is disrupted until the central nervous system is able to cope with the newly available vestibular otolith information. Predictions of the model are tested using data from a study of the neurosensory control of balance in astronauts immediately after landing. In that study, the mechanisms of sensorimotor balance control were assessed under normal, reduced, and/or altered (sway-referenced) visual and somatosensory input conditions. We conclude that the adaptive control model accurately describes the neurobehavioral responses to spaceflight and that similar models of altered sensory, motor, or environmental constraints are needed clinically to predict responses that patients with sensorimotor pathologies may have to various visual-vestibular or changing stimulus environments.

manned↗

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Exposure to musculoskeletal disuse and radiation result in bone loss; we hypothesized that these catabolic treatments cause excess reactive oxygen species (ROS), and thereby alter the tight balance between bone resorption by osteoclasts and bone formation by osteoblasts, culminating in bone loss. To test this, we used transgenic mice which over-express the human gene for catalase, targeted to mitochondria (MCAT). Catalase is an anti-oxidant that converts the ROS hydrogen peroxide into water and oxygen. MCAT mice were shown previously to display reduced mitochondrial oxidative stress and radiosensitivity of the CNS compared to wild type controls (WT). As expected, MCAT mice expressed the transgene in skeletal tissue, and in marrow-derived osteoblasts and osteoclast precursors cultured ex vivo, and also showed greater catalase activity compared to wildtype (WT) mice (3-6 fold). Colony expansion in marrow cells cultured under osteoblastogenic conditions was 2-fold greater in the MCAT mice compared to WT mice, while the extent of mineralization was unaffected. MCAT mice had slightly longer tibiae than WT mice (2%, P less than 0.01), although cortical bone area was slightly lower in MCAT mice than WT mice (10%, p=0.09). To challenge the skeletal system, mice were treated by exposure to combined disuse (2 wk Hindlimb Unloading) and total body irradiation Cs(137) (2 Gy, 0.8 Gy/min), then bone parameters were analyzed by 2-factor ANOVA to detect possible interaction effects. Treatment caused a 2-fold increase (p=0.015) in malondialdehyde levels of bone tissue (ELISA) in WT mice, but had no effect in MCAT mice. These findings indicate that the transgene conferred protection from oxidative damage caused by treatment. Unexpected differences between WT and MCAT mice emerged in skeletal responses to treatment.. In WT mice, treatment did not alter osteoblastogenesis, cortical bone area, moment of inertia, or bone perimeter, whereas in MCAT mice, treatment increased these parameters. Taken together, this typically catabolic treatment (disuse and irradiation) appeared to stimulate cortical expansion in MCAT mice but not WT mice. In conclusion, these results reveal the importance of mitochondrial ROS generation in skeletal remodeling and show that MCAT mice provide a useful animal model for bone studies.

trandgenic↗

Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons

Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of neurons in the dorsolateral region of the ventral horn at the L5 segmental level of the spinal cord in the rat were determined after 14 days of spaceflight and after 9 days of recovery on earth. The results were compared to those in age-matched ground-based control rats. Spinal cords were quick-frozen, and the SDH activity and CSA of a sample of neurons with a visible nucleus were determined using a digitizer and a computer-assisted image analysis system. An inverse relationship between CSA and SDH activity of neurons was observed in all groups of rats. No change in mean CSA or mean SDH activity or in the size distribution of neurons was observed following spaceflight or recovery. However, there was a selective decrease in the SDH activity of neurons with soma CSA between 500 and 800 microns2 in the flight rats, and this effect persisted for at least 9 days following return to 1 g. It remains to be determined whether the selected population of motoneurons or the specific motor pools affected by spaceflight may be restricted to specific muscles.

short duration↗