Research Containing: Microgravity
Chemical Potency and Degradation Products of Medications Stored Over 550 Earth Days at the International Space Station
Medications degrade over time, and degradation is hastened by extreme storage conditions. Current procedures ensure that medications aboard the International Space Station (ISS) are restocked before their expiration dates, but resupply may not be possible on future long-duration exploration missions. For this reason, medications stored on the ISS were returned to Earth for analysis. This was an opportunistic, observational pilot-scale investigation to test the hypothesis that ISS-aging does not cause unusual degradation. Nine medications were analyzed for active pharmaceutical ingredient (API) content and degradant amounts; results were compared to 2012 United States Pharmacopeia (USP) requirements. The medications were two sleep aids, two antihistamines/decongestants, three pain relievers, an antidiarrheal, and an alertness medication. Because the samples were obtained opportunistically from unused medical supplies, each medication was available at only 1 time point and no control samples (samples aged for a similar period on Earth) were available. One medication met USP requirements 5 months after its expiration date. Four of the nine (44% of those tested) medications tested met USP requirements 8 months post expiration. Another three medications (33%) met USP guidelines 2-3 months before expiration. One compound, a dietary supplement used as a sleep aid, failed to meet USP requirements at 11 months post expiration. No unusual degradation products were identified. Limited, evidence-based extension of medication shelf-lives may be possible and would be useful in preparation for lengthy exploration missions. Only analysis of flight-aged samples compared to appropriately matched ground controls will permit determination of the spaceflight environment on medication stability.
Concurrent flame growth, spread and extinction over composite fabric samples in low speed purely forced flow in microgravity
As a part of the NASA BASS and BASS-II experimental projects aboard the International Space Station, flame growth, spread and extinction over a composite cotton-fiberglass fabric blend (referred to as the SIBAL fabric) were studied in low-speed concurrent forced flows. The tests were conducted in a small flow duct within the Microgravity Science Glovebox. The fuel samples measured 1.2 and 2.2 cm wide and 10 cm long. Ambient oxygen was varied from 21% down to 16% and flow speed from 40 cm/s down to 1 cm/s. A small flame resulted at low flow, enabling us to observe the entire history of flame development including ignition, flame growth, steady spread (in some cases) and decay at the end of the sample. In addition, by decreasing flow velocity during some of the tests, low-speed flame quenching extinction limits were found as a function of oxygen percentage. The quenching speeds were found to be between 1 and 5 cm/s with higher speed in lower oxygen atmosphere. The shape of the quenching boundary supports the prediction by earlier theoretical models. These long duration microgravity experiments provide a rare opportunity for solid fuel combustion since microgravity time in ground-based facilities is generally not sufficient. This is the first time that a low-speed quenching boundary in concurrent spread is determined in a clean and unambiguous manner.
INTRODUCTION: Countermeasures to prevent or partially offset the negative physiologic changes that are caused by the effects of microgravity play an important role in supporting the performance of crewmembers in flight and their safe return to Earth. Research conducted in Russia on the orbital stations Salyut and Mir, as well as simulation experiments on the ground, have demonstrated that changes that occur during extended spaceflight in various physiologic systems can be prevented or significantly decreased by using countermeasures. Hardware and techniques used on the ISS have been substantially improved to reflect the experience of previous extended missions on Russian orbital stations. Countermeasures used during early ISS missions consisted of the U.S. treadmill (TVIS), cycle ergometer (capital VE, Cyrilliccapital BE, Cyrillic-3), a set of resistance bands, a postural muscle loading suit (Penguin-3), electrical stimulator (Tonus-3), compression thigh cuffs (Braslet-capital EM, Cyrillic), a lower body negative pressure (LBNP) suit (Chibis), a lower body g-loading suit (Kentavr), and water/salt supplements. These countermeasures are described in this article.
Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight
Microgravity, or an altered gravity environment different from the 1 g of the Earth, has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies that have been conducted in space or by using simulated microgravity on the ground have focused on the growth or differentiation of these cells. It has not been specifically addressed whether nonproliferating cultured cells will sense the presence of microgravity in space. In an experiment conducted onboard the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 d, respectively, to investigate changes in gene and microRNA (miRNA) expression profiles in these cells. Results of the experiment showed that on d 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki-67(+) cells. Gene and miRNA expression data indicated activation of NF-kappaB and other growth-related pathways that involve hepatocyte growth factor and VEGF as well as the down-regulation of the Let-7 miRNA family. On d 14, when the cells were mostly nonproliferating, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample. Comparison of gene and miRNA expressions in the d 3 samples, with respect to d 14, revealed that most of the changes observed on d 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for alpha-tubulin and fibronectin showed no difference between the flown and ground samples. Taken together, our study suggests that in true nondividing human fibroblast cells in culture, microgravity experienced in space has little effect on gene and miRNA expression profiles.-Zhang, Y., Lu, T., Wong, M., Wang, X., Stodieck, L., Karouia, F., Story, M., Wu, H. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight.
Comprehensive Study of the Influence of Altered Gravity on the Oxidative Burst of Mussel (Mytilus edulis) Hemocytes
Microgravity induces alterations in the function- ing of immune cell; however, the underlying mechanisms have not yet been identified. In this study, hemocytes (blood cells) of the blue mussel Mytilus edulis were investigated under altered gravity conditions. The study was conducted on the ground in preparation for the BIOLAB TripleLux- B experiment, which will be performed on the International Space Station (ISS). On-line kinetic measurements of reac- tive oxygen species (ROS) production during the oxidative burst and thus cellular activity of isolated hemocytes were performed in a photomultiplier (PMT)-clinostat (simulated microgravity) and in the 1g operation mode of the clino- stat in hypergravity on the Short-Arm Human Centrifuge (SAHC) as well as during parabolic flights. In addition to studies with isolated hemocytes, the effect of altered gravity conditions on whole animals was investigated. For this pur- pose, whole mussels were exposed to hypergravity (1.8 g) on a multi-sample incubator centrifuge (MuSIC) or to simu- lated microgravity in a submersed clinostat. After exposure for 48 h, hemocytes were taken from the mussels and ROS production was measured under 1 g conditions. The results from the parabolic flights and clinostat studies indicate that mussel hemocytes respond to altered gravity in a fast and reversible manner. Hemocytes (after cryo-conservation)exposed to simulated microgravity (μ g), as well as fresh hemocytes from clinorotated animals, showed a decrease in ROS production. Measurements during a permanent exposure of hemocytes to hypergravity (SAHC) show a decrease in ROS production. Hemocytes of mussels mea- sured after the centrifugation of whole mussels did not show an influence to the ROS response at all. Hypergravity dur- ing parabolic flights led to a decrease but also to an increase in ROS production in isolated hemocytes, whereas the cen- trifugation of whole mussels did not influence the ROS response at all. This study is a good example how ground- based facility experiments can be used to prepare for an upcoming ISS experiment, in this case the TRIPLE LUX B experiment.
This paper describes the activities for utilization and control of ELITE S2 on board the International Space Station (ISS). ELITE S2 is a payload of the Italian Space Agency (ASI) for quantitative human movement analysis in weightlessness. Within the frame of a bilateral agreement with NASA, ASI has funded a number of facilities, enabling different scientific experiments on board the ISS. ELITE S2 has been developed by the ASI contractor Kayser Italia, delivered to the Kennedy Space Center in 2006 for pre-flight processing, launched in 2007 by the Space Shuttle Endeavour (STS-118), integrated in the U.S. lab and used during the Increments 16 and 17 through 2008. The ELITE S2 flight segment comprises equipment mounted into an Express Rack and a number of stowed items to be deployed for experiment performance (video cameras and accessories). The ground segment consists in a User Support Operations Center (based at Kayser Italia) enabling real-time payload control and a number of User Home Bases (located at the ASI and PIs premises), for the scientific assessment of the experiment performance. Two scientific protocols on reaching and cognitive processing have been successfully performed in five sessions involving two ISS crewmembers: IMAGINE 2 and MOVE.
Space biology provides an opportunity to study plant physiology and development in a unique microgravity environment. Recent space studies with plants have provided interesting insights into plant biology, including discovering that plants can grow seed-to-seed in microgravity, as well as identifying novel responses to light. However, spaceflight experiments are not without their challenges, including limited space, limited access, and stressors such as lack of convection and cosmic radiation. Therefore, it is important to design experiments in a way to maximize the scientific return from research conducted on orbiting platforms such as the International Space Station. Here, we provide a critical review of recent spaceflight experiments and suggest ways in which future experiments can be designed to improve the value and applicability of the results generated. These potential improvements include: utilizing in-flight controls to delineate microgravity versus other spaceflight effects, increasing scientific return via next-generation sequencing technologies, and utilizing multiple genotypes to ensure results are not unique to one genetic background. Space experiments have given us new insights into plant biology. However, to move forward, special care should be given to maximize science return in understanding both microgravity itself as well as the combinatorial effects of living in space.
Due to spaceflight, astronauts experience serious, weightlessness-induced bone loss because of an unbalanced process of bone remodeling that involves bone marrow mes- enchymal stem cells (BMSCs), as well as osteoblasts, osteo- cytes, and osteoclasts. The effects of microgravity on osteo- cells have been extensively studied, but it is only recently that consideration has been given to the role of BMSCs. Pre- vious researches indicated that human BMSCs cultured in simulated microgravity (sim-μg) alter their proliferation and differentiation. The spaceflight opportunities for biomedical experiments are rare and suffer from a number of opera- tive constraints that could bias the validity of the experiment itself, but remain a unique opportunity to confirm and explain the effects due to microgravity, that are only par- tially activated/detectable in simulated conditions. For this reason, we carefully prepared the SCD – STEM CELLS DIFFERENTIATION experiment, selected by the European Space Agency (ESA) and now on the International Space Station (ISS). Here we present the preparatory studies per- formed on ground to adapt the project to the spaceflight constraints in terms of culture conditions, fixation and stor- age of human BMSCs in space aiming at satisfying the biological requirements mandatory to retrieve suitable sam- ples for post-flight analyses. We expect to understand better the molecular mechanisms governing human BMSC growth and differentiation hoping to outline new countermeasures against astronaut bone loss.
PROTEIN CRYSTALLIZATION FOR DRUG DEVELOPMENT: A Prospective Empirical Appraisal of Economic Effects of ISS Microgravity
The paper proceeds as follows. Section two below discusses the topic of protein crystallization in biomedical research as well as our current understanding regarding the contribution of microgravity in developing better quality crystals. Section three addresses possible policy intervention, also including the introduction of a government funded consortium to diffuse risk. Section four outlines a specific model that has recently been developed by RTI International, which provides an interesting quantitative framework for measuring private sector costs. The outcome of this section is essentially a list of needed data and data sources. Finally, Section five concludes.