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DOE OSTI2024

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1972

Olfactory bulb units - Activity correlated with inhalation cycles and odor quality.

Single olfactory bulb units were studied in two macrosmatic species of rodents under conditions intended to preserve the cyclical stimulation which normally accompanies nasal breathing. Patterns of unit activity related to the inhalation cycle were observed in all animals, often in the absence of specific stimuli, and could not be explained in simple mechanical terms. Distinctive changes in these patterns occurred in response to certain odors, and were generally independent of changes in the overall firing frequency. These findings indicate that a change in the overall firing frequency of unit discharges is neither a necessary nor sufficient measure of responsiveness to odors in the rodent olfactory bulb, and that stimulus-specific temporal distributions of unit firing may be involved in olfacto-endocrine activities.

Macrides, F.↗

NASA NTRS1975

Study of toxicological evaluation of fire suppressants and extinguishers

The application of fluorocarbons as possible candidates for fire extinguishers and/or suppressants in confined spaces (such as spacecraft, aircraft, or submarines) was investigated, with special emphasis on their safety to man since they would be inhaled on an almost continuous basis. Short-term exposure experiments, using various animal species, were devised to look at specific parameters in order to determine which of the candidate compounds were sufficiently non-toxic to warrant long-term investigations. The following physiologic criteria were examined; tissue distribution, fluoride concentration, effect on mitochondria, microsomes, liposomes, and liver cell nuclei, erythrocyte fragility, clinical chemistry values, hematology, pathology, cardiac sensitization, behavioral effects. Various rodent species were used for initial investigations, with non-human primate exposures for Freon 116 which was warranted for negative results on rodents. Various types of exposure chambers were used, including closed dynamic chambers allowing for a recirculating atmosphere.

Source record↗

NASA NTRS1985

Conceptual design and programmatics studies of space station accommodations for Life Sciences Research Facilities (LSRF)

Conceptual designs and programmatics of the space station accommodations for the Life Sciences Research Facilities (LSRF) are presented. The animal ECLSS system for the LSRF provides temperature-humidity control, air circulation, and life support functions for experimental subjects. Three ECLSS were studied. All configurations presented satisfy the science requirements for: animal holding facilities with bioisolation; facilities interchangeable to hold rodents, small primates, and plants; metabolic cages interchangeable with standard holding cages; holding facilities adaptable to restrained large primates and rodent breeding/nesting cages; volume for the specified instruments; enclosed ferm-free workbench for manipulation of animals and chemical procedures; freezers for specimen storage until return; and centrifuge to maintain animals and plants at fractional g to 1 g or more, with potential for accommodating humans for short time intervals.

Source record↗

NASA NTRS1988

Spacelab Life Sciences-2 ARC payload - An overview

The effects of microgravity on the anatomy and physiology of rodent and primate systems will be investigated on the Spacelab Life Sciences 2 (SLS-2) mission. Here, the payload being developed at NASA Ames Research Center (ARC) is described and illustrated with drawings. The ARC payload will build upon the success of previous missions. Experiments includes asssessment of rodent cardiovascular and vestibular system responses, primate thermoregulation and metabolic responses.

Savage, P. D., Jr.↗

NASA NTRS1991

Cosmos-1989 immunology studies

Sonnenfeld, Gerald↗

NASA NTRS1992

The effects of video compression on acceptability of images for monitoring life sciences experiments

Future manned space operations for Space Station Freedom will call for a variety of carefully planned multimedia digital communications, including full-frame-rate color video, to support remote operations of scientific experiments. This paper presents the results of an investigation to determine if video compression is a viable solution to transmission bandwidth constraints. It reports on the impact of different levels of compression and associated calculational parameters on image acceptability to investigators in life-sciences research at ARC. Three nonhuman life-sciences disciplines (plant, rodent, and primate biology) were selected for this study. A total of 33 subjects viewed experimental scenes in their own scientific disciplines. Ten plant scientists viewed still images of wheat stalks at various stages of growth. Each image was compressed to four different compression levels using the Joint Photographic Expert Group (JPEG) standard algorithm, and the images were presented in random order. Twelve and eleven staffmembers viewed 30-sec videotaped segments showing small rodents and a small primate, respectively. Each segment was repeated at four different compression levels in random order using an inverse cosine transform (ICT) algorithm. Each viewer made a series of subjective image-quality ratings. There was a significant difference in image ratings according to the type of scene viewed within disciplines; thus, ratings were scene dependent. Image (still and motion) acceptability does, in fact, vary according to compression level. The JPEG still-image-compression levels, even with the large range of 5:1 to 120:1 in this study, yielded equally high levels of acceptability. In contrast, the ICT algorithm for motion compression yielded a sharp decline in acceptability below 768 kb/sec. Therefore, if video compression is to be used as a solution for overcoming transmission bandwidth constraints, the effective management of the ratio and compression parameters according to scientific discipline and experiment type is critical to the success of remote experiments.

Haines, Richard F.↗

NASA NTRS1995

STS-66 Space Shuttle mission report

The primary objective of this flight was to accomplish complementary science objectives by operating the Atmospheric Laboratory for Applications and Science-3 (ATLAS-3) and the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere-Shuttle Pallet Satellite (CRISTA-SPAS). The secondary objectives of this flight were to perform the operations of the Shuttle Solar Backscatter Ultraviolet/A (SSBUV/A) payload, the Experiment of the Sun Complementing the Atlas Payload and Education-II (ESCAPE-II) payload, the Physiological and Anatomical Rodent Experiment/National Institutes of Health Rodents (PARE/NIH-R) payload, the Protein Crystal Growth-Thermal Enclosure System (PCG-TES) payload, the Protein Crystal Growth-Single Locker Thermal Enclosure System (PCG-STES), the Space Tissue/National Institutes of Health Cells STL/N -A payload, the Space Acceleration Measurement Systems (SAMS) Experiment, and Heat Pipe Performance Experiment (HPPE) payload. The 11-day plus 2 contingency day STS-66 mission was flown as planned, with no contingency days used for weather avoidance or Orbiter contingency operations. Appendix A lists the sources of data from which this report was prepared, and Appendix B defines all acronyms and abbreviations used in the report.

Fricke, Robert W., Jr.↗

NASA NTRS1995

STS-70 Mission Highlights

The highlights of the STS-70 mission are presented in this video. The flight crew consisted of Cmdr. Tom Henricks, Pilot Kevin Kregel, Flight Engineer Nancy Currie, and Mission Specialists Dr. Don Thomas and Dr. Mary Ellen Weber. The mission's primary objective was the deployment of the 7th Tracking Data and Relay Satellite (TDRS), which will provide a communication, tracking, telemetry, data acquisition, and command services space-based network system essential to low Earth orbital spacecraft. Secondary mission objectives included activating and studying the Physiological and Anatomical Rodent Experiment/National Institutes of Health-Rodents (PARE/NIH-R), The Bioreactor Demonstration System (BDS), the Commercial Protein Crystal Growth (CPCG) studies, the Space Tissue Loss/National Institutes of Health-Cells (STL/NIH-C) experiment, the Biological Research in Canisters (BRIC) experiment, Shuttle Amateur Radio Experiment-2 (SAREX-2), the Visual Function Tester-4 (VFT-4), the Hand-Held, Earth Oriented, Real-Time, Cooperative, User-Friendly, Location-Targeting and Environmental System (HERCULES), the Microcapsules in Space-B (MIS-B) experiment, the Windows Experiment (WINDEX), the Radiation Monitoring Equipment-3 (RME-3), and the Military Applications of Ship Tracks (MAST) experiment. There was an in-orbit dedication ceremony by the spacecrew and the newly Integrated Mission Control Center to commemorate the Center's integration. The STS-70 mission was the first mission monitored by this new control center. Earth views included the Earth's atmosphere, a sunrise over the Earth's horizon, several views of various land masses, some B/W lightning shots, some cloud cover, and a tropical storm.

Source record↗

NASA NTRS1995

STS-70 Space Shuttle Mission Report - September 1995

The STS-70 Space Shuttle Program Mission Report summarizes the Payload activities as well as the Orbiter, External Tank (ET), Solid Rocket Booster (SRB), Reusable Solid Rocket Motor (RSRM), and the Space Shuttle main engine (SSME) systems performance during the seventieth flight of the Space Shuttle Program, the forty-fifth flight since the return-to-flight, and the twenty-first flight of the Orbiter Discovery (OV-103). In addition to the Orbiter, the flight vehicle consisted of an ET that was designated ET-71; three SSMEs that were designated as serial numbers 2036, 2019, and 2017 in positions 1, 2, and 3, respectively; and two SRBs that were designated 81-073. The RSRMs, designated RSRM-44, were installed in each SRB and were designated as 36OL044A for the left SRB, and 36OL044B for the right SRB. The primary objective of this flight was to deploy the Tracking and Data Relay Satellite-G/Inertial Upper Stage (TDRS-G/IUS). The secondary objectives were to fulfill the requirements of the Physiological and Anatomical Rodent Experiment/National Institutes of Health-Rodents (PARE/NIH-R); Bioreactor Demonstration System (BDS); Commercial Protein Crystal Growth (CPCG) experiment; Space Tissue Loss/National Institutes of Health - Cells (STL/NIH-C) experiment; Biological Research in Canisters (BRIC) experiment; Shuttle Amateur Radio Experiment-2 (SAREX-2); Visual Function Tester-4 (VFT-4); Hand-Held, Earth-Oriented, Real-Time, Cooperative, User-Friendly Location-Targeting and Environmental System (HERCULES); Microencapsulation in Space-B (MIS-B) experiment; Window Experiment (WINDEX); Radiation Monitoring Equipment-3 (RME-3); and the Military Applications of Ship Tracks (MAST) payload.

Fricke, Robert W., Jr.↗

NASA NTRS1996

Spaceflight and Development of Immune Responses

Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The objective of the studies contained in this project was to determine the effects of space flight on immune responses of pregnant rats and their offspring. The hypothesis was that space flight and the attendant period of microgravity will result in alteration of immunological parameters of both the pregnant rats as well as their offspring carried in utero during the flight. The parameters tested included: production of cytokines, composition of leukocyte sub- populations, response of bone marrow/liver cells to granulocyte/monocyte colony stimulating factor, and leukocyte blastogenesis. Changes in immune responses that could yield alterations in resistance to infection were determined. This yielded useful information for planning studies that could contribute to crew health. Additional information that could eventually prove useful to determine the potential for establishment of a permanent colony in space was obtained.

Sonnenfeld, Gerald↗

NASA NTRS1993

Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

Zimmer, J. Paul↗

NASA NTRS1984

The Structure of the Mammalian Area Postrema

The area postrema in mammals other than rodents and lagomorphs is a bilateral mound of gelatinous-appearing tissue that protrudes into the caudal fourth ventricle on either side of the obex. In rodents and lagomorphs it is a single midline structure at the apex of the calamus scriptorius. The vasculature is derived mainly from the posterior inferior cerebellar arteries and consists mainly of sinusoidal capillaries. It appears to constitute a portal system, at least in the rat. Many of the capillaries are fenestrated, and many large perivascular spaces with both vascular and parenchymal basal laminae are present. The cell population is composed of flattened ependymal cells exhibiting microvilli, and of small neurons, normal astrocytes, glialoid cells, and a very few oligodendroglia. Mast cells are occasionally present. The glialoid cells appear to be the predominant cell type and exhibit great numbers of vascular podia. Axodendritic synapses are numerous and axosomatic synapses are occasionally seen in the parenchyma. Synaptic vesicles are mainly of the clear-cored type but large dense-cored vesicles are commonly observed in some axon terminals.

Brizzee, K. R.↗

NASA NTRS1994

Microscopy in Space Research: Learning More About Gravitational Effects on Living Systems

Investigators are using light, scanning and transmission electron microscopic (TEM) methods to investigate the effects of microgravity on the development, maintenance and aging of biological systems. The capabilities of the spacelab for life sciences research in space will be described. Among the many results to be discussed are the effects of microgravity on amphibian fertilization and early development, and on the rodent musculoskeletal and neural systems. Xenopus laevis eggs fertilized in space developed normally during and after an eight day spaceflight. Ultrastructural studies of rodent tissue demonstrated that spaceflight-induced atrophy of antigravity skeletal muscles renders muscle fibers susceptible to structural failure upon return to weight bearing postflight. Principle TEM changes in neuromuscular junctions are the decrease or absence of synaptic vesicles and degeneration of axon terminals. In bone, architectural rather than compositional changes may be the primary perturbation. Thus, many techniques used on Earth (such as density determinations) would not detect significant changes in bone strength. An increment in synaptic number and changes in synapse distribution occur in peripheral gravity sensors. There is a decrease in muscarinic cholinergic receptor density in the striatum. Striatal receptor changes suggest spaceflight-related alterations in motor activity. Opportunities for future life sciences research in space will be discussed.

Ross, Muriel D.↗

NASA NTRS1995

Space Station Biological Research Project

NASA Ames Research Center is responsible for the development of the Space Station Biological Research Project (SSBRP) which will support non-human life sciences research on the International Space Station Alpha (ISSA). The SSBRP is designed to support both basic research to understand the effect of altered gravity fields on biological systems and applied research to investigate the effects of space flight on biological systems. The SSBRP will provide the necessary habitats to support avian and reptile eggs, cells and tissues, plants and rodents. In addition a habitat to support aquatic specimens will be provided by our international partners. Habitats will be mounted in ISSA compatible racks at u-g and will also be mounted on a 2.5 m diameter centrifuge except for the egg incubator which has an internal centrifuge. The 2.5 m centrifuge will provide artificial gravity levels over the range of 0.01 G to 2 G. The current schedule is to launch the first rack in 1999, the Life Sciences glovebox and a second rack early in 2001, a 4 habitat 2.5 in centrifuge later the same year in its own module, and to upgrade the centrifuge to 8 habitats in 2004. The rodent habitats will be derived from the Advanced Animal Habitat currently under development for the Shuttle program and will be capable of housing either rats or mice individually or in groups (6 rats/group and at least 12 mice/group). The egg incubator will be an upgraded Avian Development Facility also developed for the Shuttle program through a Small Business and Innovative Research grant. The Space Tissue Loss cell culture apparatus, developed by Walter Reed Army Institute of Research, is being considered for the cell and tissue culture habitat. The Life Sciences Glovebox is crucial to all life sciences experiments for specimen manipulation and performance of science procedures. It will provide two levels of containment between the work volume and the crew through the use of seals and negative pressure. The glovebox will accommodate use by two crew persons simultaneously and the capability for real time video down-link and data acquisition. In house testbeds and Phase B studies of the centrifuge validated the concepts of vibration isolation and autobalancing systems to meet the ISSA microgravity requirements. The vibration isolation system is effective above the centrifuge rotation frequency while the autobalancing system on the rotor removes vibration at and below the rotation rate. Torque of the Station, induced by spin-up/spindown of the centrifuge, can be minimized by controlling spin-up/spin-down rates. The SSBRP and ISSA will provide the opportunity to perform long-term, repeatable and high quality science. The long duration increments available on the Station will permit multigeneration studies of both plants and animals which have not previously been possible. The u-g habitat racks and the eight habitat centrifuge will accommodate sufficient number of specimens to permit statistically significant sampling of specimens to investigate the time course of adaptation to altered gravity environments. The centrifuge will, for the first time, permit investigators to use gravity itself as a tool to investigate fundamental processes, to investigate the intensity and duration of gravity to maintain normal structure and function, to separate the effects of u-g from other environmental factors and to examine artificial gravity as a potential countermeasure for the physical deconditioning observed during space flight.

Johnson, Catherine C.↗

NASA NTRS2002

Is Animal Age a Factor In the Response of Bone to Spaceflight?

The rodent bone response to spaceflight may be influenced by a multitude of actors including flight duration, strain, and housing. Review of bone formation rates during spaceflight suggests that age may also play a role in the response. Weanling rats show fewer bone changes than older rats. To determine if the long bones of weanling rats were insensitive to weight-bearing, a hindlimb unloading experiment was conducted simultaneously with a 9d shuttle flight in 34d old group-housed male rats. All animals were injected with bone markers 7d and 1d before flight and euthanized at landing, 24hr, and 72hr following recovery. If no differences in body weight, bone length, or bone formation at the tibiofibular junction were noted at the different time points, data were combined for each group. No significant differences in body weight were found at any time period among the groups. The humerus, tibia, and femur elongated significantly during the flight period with no difference in lengths between groups at the end of the flight period. The group-housed flight rats showed no change in cortical bone formation rate compared to preflight values, flight controls, or vivarium controls. However, the hindlimb unloading group showed a significant 30% decrease in bone formation rate compared to all other groups. Individually-housed 38d old animals flown for 14d showed approx. 10% suppression of cortical growth. We speculate that the mechanical threshold required for cross-sectional bone growth is reached in group-house weanling rats during spaceflight, perhaps, through physical interactions, and that the weanling animals are sensitive to loading. However, the threshold is not fully reached in either singly-housed flight or hindlimb unloaded weanling rats. Older singly-housed flight animals appear to show equal or greater bone changes compared to hindlimb unloaded rats. We conclude that age, flight duration, strain, and housing have important roles in rodent skeletal responses to spaceflight.

Morey-Holton, E. R.↗

NASA NTRS2010

Neurolab: Final Report for the Ames Research Center Payload

Neurolab, the final Spacelab mission, launched on STS-90 on April 17, 1998, was dedicated to studying the nervous system. NASA cooperated with domestic and international partners to conduct the mission. ARC's (Ames Research Center's) Payload included 15 experiments designed to study the adaptation and development of the nervous system in microgravity. The payload had the largest number of Principal and Co-Investigators, largest complement of habitats and experiment unique equipment flown to date, and most diverse distribution of live specimens ever undertaken by ARC, including rodents, toadfish, swordtail fish, water snails, hornweed and crickets To facilitate tissue sharing and optimization of science objectives, investigators were grouped into four science discipline teams: Neuronal Plasticity, Mammalian Development, Aquatic, and Neurobiology. Several payload development challenges were experienced and required an extraordinary effort, by all involved, to meet the launch schedule. With respect to hardware and the total amount of recovered science, Neurolab was regarded as an overall success. However, a high mortality rate in one rodent group and several hardware anomalies occurred inflight that warranted postflight investigations. Hardware, science, and operations lessons were learned that should be taken into consideration by payload teams developing payloads for future Shuttle missions and the International Space Station.

Maese, A. Christopher↗

NASA NTRS1998

Gravity-Loading During Pregnancy and Birth: Effects on Neonatal Outcome

In this presentation, I will describe the effects of increased gravity on mammalian development in rodents, from gestation throughout weaning. The work is based on studies of centrifugation-induced hypergravity-rearing, the fundamentals of which will be described. The key variables include: 1) comparison of first-time (primparous) and experienced (multiparous) rodent mothers; 2) prenatal adaptation to the centrifuge; and 3) application of a modest g-load (1.5-g). The reported findings emphasize pregnancy, labor and birth, maternal care and lactation in the dams, and suckling, growth, development, and weaning in the offspring. Pregnancy success and offspring growth and survival will be discussed.

Ronca, April E.↗