Research Containing: Male

Validation of centrifugation as a countermeasure for otolith deconditioning during spaceflight: preliminary data of the ESA SPIN study

by cfynanon 9 June 2015in Biology & Biotechnology No comment

In the framework of further space exploration, countermeasures to combat the drawbacks of human space flights are essential. The present study focuses on the influence of microgravity on the otolith-ocular reflex and aims to test the hypothesis of artificial gravity being an adequate countermeasure for the deconditioning of the aforementioned reflex. The so-called SPIN study, commissioned by the European Space Agency, can be considered as a control experiment in the broad sense for the Neurolab mission (STS-90) during which 4 crewmembers of the space shuttle were subjected to in-flight centrifugation on the visual and vestibular investigation system (VVIS). After their nearly 16-day mission, they did not suffer from orthostatic intolerance and spatial disorientation. In addition, the relevant parameters of the otolith-ocular interaction remained unaffected. For this study cosmonauts from a long duration stay in the International Space Station that were not centrifuged in-flight were tested on the VVIS (1 g centripetal interaural acceleration) on 6 different days. Three measurements were taken about 1.5-2 months prior to launch and 3 were taken at 1, 4 and 9 days after return from space. Ocular counter-rolling was measured before, during and after rotation on the VVIS using infrared video goggles and compared pair wise using Friedman tests. The perception of verticality was monitored using an ultrasound system for perceptual evaluation. The preliminary results of 4 cosmonauts showed a surprisingly large inter-individual variability of the measurements. Although OCR and perception of verticality appeared to be influenced overall by the exposure to microgravity, the wide variability among the cosmonauts obscured any statistical significance, in particular due to one cosmonauts being inconsistent with the other 3. Despite the specificity of the tests under normal conditions, the diverse response to spaceflight of our subjects exposes the complexity of the peripheral and central neural adaptive processes.

Formation and structure of transplantable tissue constructs generated in simulated microgravity from sertoli cells and neuron precursors

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Cell transplantation therapy for Parkinson's disease (PD) has received much attention as a potential treatment protocol for this neurodegenerative condition. Although there have been promising successes with this approach, it remains problematic, especially regarding the inability to provide immediate trophic support to the newly grafted cells and the inability to prevent acute and/or long-term graft rejection by the host. To address these issues of cell graftability, we have created a novel tissue construct from isolated rat Sertoli cells (SC) and the NTerra-2 immortalized human neuron precursor cell line (NT2) utilizing NASA-developed simulated microgravity technology. The two cell types were cocultured at a 1:4 (SC/NT2) ratio in the High Aspect Rotating Vessel (HARV) biochamber for 3 days, after which a disc-shaped aggregate (1-4 mm diameter) was formed. Sertoli neuron aggregated cells (SNAC) were collected by gravity sedimentation and processed either for light and electron microscopy or for fluorescent immunocytochemistry. Intra-SNAC clusters of SC and NT2 cells were identified by anti-human mitochondrial protein (huMT–specific for NT2 cells) and cholera toxin subunit B (CTb–specific for SC). There was little evidence of cell death throughout the aggregate and the absence of central necrosis, as might be expected in such a large aggregate in vitro. Ultrastructurally, SC did not express junctional modifications with NT2 cells nor with adjacent SC as is typical of SC in vivo and, in some protocols, in vitro. NT2 cells, however, showed distinct intercellular junction-like densities with adjacent NT2 cells, often defining canaliculi-like channels between the microvillus borders of the cells. The results show that the use of simulated microgravity coculture provides a culture environment suitable for the formation of a unique and viable Sertoli-NT2 (i.e., SNAC) tissue construct displaying intra-aggregate cellular organization. The structural integration of SC with NT2 cells provides a novel transplantable tissue source, which can be tested to determine if SC will suppress rejection of the grafted NT2 cells and provide for their short- and long-term trophic support in situ in the treatment of experimental PD.

The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

Nitric oxide affects preimplantation embryonic development in a rotating wall vessel bioreactor simulating microgravity

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Microgravity was simulated with a rotating wall vessel bioreactor (RWVB) in order to study its effect on pre-implantation embryonic development in mice. Three experimental groups were used: stationary control, rotational control and clinostat rotation. Three experiments were performed as follows. The first experiment showed that compared with the other two (control) groups, embryonic development was significantly retarded after 72 h in the clinostat rotation group. The second experiment showed that more nitric oxide (NO) was produced in the culture medium in the clinostat rotation group after 72 h (P < 0.05), and the nitric oxide synthase (NOS) activity in this group was significantly higher than in the controls (P < 0.01). In the third experiment, we studied apoptosis in the pre-implantation mouse embryos after 72 h in culture and found that Annexin-V staining was negative in the normal (stationary and rotational control) embryos, but the developmentally retarded (clinostat rotation) embryos showed a strong green fluorescence. These results indicate that microgravity induced developmental retardation and cell apoptosis in the mouse embryos. We presume that these effects are related to the higher concentration of NO in the embryos under microgravity, which have cause cytotoxic consequences. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

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Foot forces during typical days on the international space station

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Decreased bone mineral density (BMD) in astronauts returning from long-duration spaceflight missions has been well documented, but the altered mechanical loading environment experienced by the musculoskeletal system, which may contribute to these changes, has not been well characterized. The current study describes the loading environment of the lower extremity (LE) during typical days on the International Space Station (ISS) compared to similar data for the same individuals living on Earth. Data from in-shoe force measurements are also used as input to the enhanced daily load stimulus (EDLS) model to determine the mechanical "dose" experienced by the musculoskeletal system and to associate this dose with changes in BMD. Four male astronauts on approximately 6-month missions to the ISS participated in this study. In-shoe forces were recorded using capacitance-based insoles during entire typical working days both on Earth and on-orbit. BMD estimates from the hip and spine regions were obtained from dual energy X-ray absorptiometry (DXA) pre- and post-flight. Measurable loading was recorded for only 30% of the time assigned for exercise. In-shoe forces during treadmill walking and running on the ISS were reduced by 25% and 46%, respectively, compared to similar activities on Earth. Mean on-orbit LE loads varied from 0.20 to 1.3 body weight (BW) during resistance exercise and were approximately 0.10 BW during bicycle ergometry. Application of the EDLS model showed a mean decrease of 25% in the daily load experienced by the LE. BMD decreased by 0.71% and 0.83% per month during their missions in the femoral neck and lumbar spine, respectively. Our findings support the conclusion that the measured ISS exercise durations and/or loading were insufficient to provide the loading stimulus required to prevent bone loss. Future trials with EDLS values closer to 100% of Earth values will offer a true test of exercise as a countermeasure to on-orbit bone loss.

Effect of gravity on human spontaneous 10-Hz electroencephalographic oscillations during the arrest reaction

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Electroencephalographic oscillations at 10 Hz (alpha and mu rhythms) are the most prominent rhythms observed in awake, relaxed (eye-closed) subjects. These oscillations may be considered as a marker of cortical inactivity or an index of the active inhibition of the sensory information. Different cortical sources may participate in the 10-Hz oscillation and appear to be modulated by the sensory context and functional demands. In microgravity, the marked reduction in multimodal graviceptive inputs to cortical networks participating in the representation of space could be expected to affect the 10-Hz activity. The effect of microgravity on this basic oscillation has heretofore not been studied quantitatively. Because the alpha rhythm has a functional role in the regulation of network properties of the visual areas, we hypothesised that the absence of gravity would affect its strength. Here, we report the results of an experiment conducted over the course of 3 space flights, in which we quantified the power of the 10-Hz activity in relation to the arrest reaction (i.e., in 2 distinct physiological states: eyes open and eyes closed). We observed that the power of the spontaneous 10-Hz oscillation recorded in the eyes-closed state in the parieto-occipital (alpha rhythm) and sensorimotor areas (mu rhythm) increased in the absence of gravity. The suppression coefficient during the arrest reaction and the related spectral perturbations produced by eye-opening/closure state transition also increased in on orbit. These results are discussed in terms of current theories on the source and the importance of the alpha rhythm for cognitive function.

Fate of the grafted ovaries from female salamander Pleurodeles waltl embarked on the Cosmos 2229 flight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The flight procedure of "Experience Triton" on Cosmos 2229 made necessary to sacrifice the embarked females just after landing. In order to detect genetic abnormalities in the progency of these adult females, we have performed a surgical procedure based on the transplantation of an ovarian piece on a recipient animal. One year later, as observed after laparotomy, the grafted ovaries exhibit oogonies and some growing oocytes. In present time, out of 10 castrated and grafted adult females only one is still alive bearing a large grafted ovary. Out of 5 castrated and grafted juvenile males, three are still alive, two of them exhibit a developing grafted ovary. The grafted animals will be ready for mating within a few months. Therefore, it will soon be possible to study the progeny of animals that have been submitted to space conditions.

Impairment of cerebral blood flow regulation in astronauts with orthostatic intolerance after flight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

BACKGROUND AND PURPOSE: We investigated cerebral blood flow regulation in astronauts before and after flights. We hypothesized that autoregulation would be different before flight and after flight between nonfinishers and the finishers of a stand test. METHODS: Twenty-seven astronauts from shuttle missions lasting 8 to 16 days underwent a 10-minute stand test: 10 days before flight, 1 to 2 hours and 3 days after landing. Mean blood flow velocity of the middle cerebral artery (MCA) was measured using transcranial Doppler; Mean arterial pressure was measured using a Finapres (Ohmeda, Englewood, CO) and was adjusted to the level of the MCA (BP(MCA)). Cross-spectral power, gain, phase, and coherence were determined for the relation between BP(MCA) and the cerebrovascular resistance index mean blood flow velocity/BP(MCA). RESULTS: BP(MCA) was reduced with stand (P<0.001). Differences between finishers and nonfinishers (P=0.011) and over test days (P=0.004) were observed. Cerebrovascular conductance was affected by stand (P<0.001), by group (P<0.001) with a group by stand, and test day interaction (P<0.01). Preflight data suggest that the nonfinishers were operating at a higher cerebral vasodilation than finishers for a given BP(MCA), and on landing day the nonfinishers had a greater decrease in mean blood flow velocity as a function of BP(MCA) with standing compared to finishers and preflight. There was a significant interaction effect of gender over the test days and from supine to stand (P=0.035). CONCLUSIONS: Our results indicate that the cause of presyncope in astronauts may be related to a mismatch of cerebral blood flow with blood pressure. Astronaut gender may also play a role in susceptibility to orthostatic intolerance after flight.

Cognitive demand of human sensorimotor performance during an extended space mission: a dual-task study

by cfynanon 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: Two previous single-case studies found that the dual-task costs of manual tracking plus memory search increased during a space mission, and concluded that sensorimotor deficits during spaceflight may be related to cognitive overload. Since dual-task costs were insensitive to the difficulty of memory search, the authors argued that the overload may reflect stress-related problems of multitasking, rather than a scarcity of specific cognitive resources. Here we expand the available database and compare different types of concurrent task. METHODS: Three subjects were repeatedly tested before, during, and after an extended mission on the International Space Station (ISS). They performed an unstable tracking task and four reaction-time tasks, both separately and concurrently. Inflight data could only be obtained during later parts of the mission. RESULTS: The tracking error increased from pre- to in flight by a factor of about 2, both under single- and dual-task conditions. The dual-task costs with a reaction-time task requiring rhythm production was 2.4 times higher than with a reaction-time task requiring visuo-spatial transformations, and 8 times higher than with a regular choice reaction-time task. CONCLUSIONS: Long-term sensorimotor deficits during spaceflight may reflect not only stress, but also a scarcity of resources related to complex motor programming; possibly those resources are tied up by sensorimotor adaptation to the space environment.

Carotid distensibility following a long-duration stay on the International Space Station

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Two recent reports have indicated increased arterial stiffness in predominantly male astronauts returning from short- and long-duration missions. These results suggesting reduced arterial distensibility have widespread health implications. In addition to cushioning against the high pulsatile pressures from reaching the microcirculation and minimizing left ventricular work, the elastic nature of the aorta and carotid arteries is important for ensuring adequate coronary perfusion and for baroreflex-mediated regulation of sympathetic activity. The altered fluid distribution associated with microgravity affects arterial distending pressures, and can acutely decrease functional distensibility and potentially stimulate processes involved with vascular remodelling. PURPOSE: We are currently testing the hypothesis that long-duration exposure to microgravity is associated with reduced common carotid artery (CCA) distensibility on return to earth. METHODOLOGY: The first three participants included one man and two women. Each astronaut underwent a comprehensive vascular assessment before launch and one day after return to earth following six months aboard the International Space Station. Distensibility was assessed by ultrasonic imaging (M-mode) of the right CCA to examine rhythmic changes in vessel diameter, while simultaneously holding a pressure transducer on the left CCA. RESULTS: Contrary to our hypothesis, long duration exposure to microgravity was not associated with a reduction in distensibility (post-flight vs. pre-flight; 0.006 mmHg-1 vs. 0.004 mmHg-1). In addition, changes in secondary indicators of arterial stiffness, including carotid-ankle pulse wave transit time (PWTT) and carotid pulse pressure (cPP), were not indicative of arterial stiffening following spaceflight (PWTT: 151 ms vs. 138 ms; cPP: 48 mmHg vs. 60 mmHg). The likelihood of structural adaptation within these central arteries is not ruled out as noted by a small, but consistent increase in the diastolic cross-sectional area of the CCA lumen (0.27 cm2 vs. 0.25 cm2). CONCLUSIONS: The inability to detect signs of arterial stiffening following exposure to microgravity contrasts with earlier reports. These disparate findings, albeit by different methods, might be a consequence of the small sample number to date or the inclusion of women, who may be relatively protected from vascular change. Alternatively, it might be that current countermeasures, including daily exercise regimens, are sufficient to maintain central arterial distensibility during a six-month exposure to microgravity. Supported by Canadian Space Agency.

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Research Containing: Male

Validation of centrifugation as a countermeasure for otolith deconditioning during spaceflight: preliminary data of the ESA SPIN study

Formation and structure of transplantable tissue constructs generated in simulated microgravity from sertoli cells and neuron precursors

The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice

Nitric oxide affects preimplantation embryonic development in a rotating wall vessel bioreactor simulating microgravity

Foot forces during typical days on the international space station

Effect of gravity on human spontaneous 10-Hz electroencephalographic oscillations during the arrest reaction

Fate of the grafted ovaries from female salamander Pleurodeles waltl embarked on the Cosmos 2229 flight

Impairment of cerebral blood flow regulation in astronauts with orthostatic intolerance after flight

Cognitive demand of human sensorimotor performance during an extended space mission: a dual-task study

Carotid distensibility following a long-duration stay on the International Space Station