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Research Containing: Male

Immune system dysregulation following short- vs long-duration spaceflight

by on 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. If found to persist during lengthy flights, this phenomenon could be a serious health risk to crewmembers participating in lunar or Mars missions. METHODS: A comprehensive postflight immune assessment was performed on 17 short-duration Space Shuttle crewmembers and 8 long-duration International Space Station (ISS) crewmembers. Testing consisted of peripheral leukocyte subset analysis, early T cell activation potential, and intracellular/secreted cytokine profiles. RESULTS: For Shuttle crewmembers, the distribution of the peripheral leukocyte subsets was found to be altered postflight. Early T cell activation was elevated postflight; however, the percentage of T cell subsets capable of being stimulated to produce IL-2 and IFN gamma was decreased. The ratio of secreted IFN gamma:IL-10 following T cell stimulation declined after landing, indicating a Th2 shift. For the ISS crewmembers, some alterations in peripheral leukocyte distribution were also detected after landing. In contrast to Shuttle crewmembers, the ISS crewmembers demonstrated a statistically significant reduction in early T cell activation potential immediately postflight. The percentage of T cells capable of producing IL-2 was reduced, but IFN gamma percentages were unchanged. A reduction in the secreted IFN gamma:IL-10 ratio (Th2 shift) was also observed postflight in the ISS crewmembers. CONCLUSION: These data indicate that consistent peripheral phenotype changes and altered cytokine production profiles occur following spaceflight of both short and long duration; however, functional immune dysregulation may vary related to mission duration. In addition, a detectable Th2 cytokine shift appears to be associated with spaceflight.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/18785351

Posturography and locomotor tests of dynamic balance after long-duration spaceflight

by on 9 June 2015in Biology & Biotechnology No comment

The currently approved objective clinical measure of standing balance in astronauts after space flight is the Sensory Organization Test battery of computerized dynamic posturography. No tests of walking balance are currently approved for standard clinical testing of astronauts. This study determined the sensitivity and specificity of standing and walking balance tests for astronauts before and after long-duration space flight. Astronauts were tested on an obstacle avoidance test known as the Functional Mobility Test (FMT) and on the Sensory Organization Test using sway-referenced support surface motion with eyes closed (SOT 5) before and six months after (n=15) space flight on the International Space Station. They were tested two to seven days after landing. Scores on SOT tests decreased and scores on FMT increased significantly from pre- to post-flight. In other words, post-flight scores were worse than pre-flight scores. SOT and FMT scores were not significantly related. ROC analyses indicated supra-clinical cut-points for SOT 5 and for FMT. The standard clinical cut-point for SOT 5 had low sensitivity to post-flight astronauts. Higher cut-points increased sensitivity to post-flight astronauts but decreased specificity to pre-flight astronauts. Using an FMT cut-point that was moderately highly sensitive and highly specific plus SOT 5 at the standard clinical cut-point was no more sensitive than SOT 5, alone. FMT plus SOT 5 at higher cut-points was more specific and more sensitive. The total correctly classified was highest for FMT, alone, and for FMT plus SOT 5 at the highest cut-point. These findings indicate that standard clinical comparisons are not useful for identifying problems. Testing both standing and walking balance will be more likely to identify balance deficits.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/23142833

Hematopoietic stem cells in microgravity

by on 9 June 2015in Biology & Biotechnology No comment

Engraftment and progenitor expansion was compared after microgravity or conventional culture. Rotating Wall Vessels (RWV) were compared with Teflon flask cultures. Two systems were used: 1) Male BALB/c whole bone marrow was cultured with varying cytokines, time intervals ranging from 24 hours to 7 days at 10–40 RPM. The cultured marrow was competed with an equal amount of fresh female marrow into lethally ablated female BALB/c mice. 2) Male B6.SJL (CD45.1) marrow was cultured with varying time intervals ranging from 24 hours to 14 days at 10 RPM with FLT-3 ligand, steel factor, and thrombopoietin. Fresh C57BL/6J (CD 45.2) marrow (3 × 106 cells) was competed with 3 × 106 cultured B6SJL male cells in lethally ablated male C57BL recipients. Engraftment was analyzed at 3–10 weeks. Progenitor expansion increased over controls by 24 hours with significantly greater expansion in the RWV cultures by 48 hours. The dominant theme was a fluctuation in engraftment phenotype, which transcended cytokine combination and murine strain. A nadir of engraftable stem cells occurred between 36–44 hours in Teflon flask cultures and 30–48 hours in RWV cultures. There was a consistent phase shift of engraftment between culturing conditions of 4–6 hours. The engraftable stem cells in RWV showed superior support of short-term engraftment in multiple experiments up to 32 hours in culture. Slower rational speed improved RWV engraftment and in-vitro progenitor number. Longer culturing time gave similar engraftment results. Surrogate progenitors from both culture conditions did not reflect engraftment data, with an overall increase in progenitors over time compared with dramatic engraftment fluctuation. Enhanced plating efficiency and increased number of progenitors seen in the RWV cultures when compared with the Teflon flask cultures persisting after 24 hours in culture. The fluctuating engraftment phenotype persists with different strains and cytokine combinations, signifying that this is a crucial physiologic phenomenon.

Related URLs:
<Go to ISI>://WOS:000088004200267

Immune system changes during simulated planetary exploration on Devon Island, high arctic

by on 9 June 2015in Biology & Biotechnology No comment

BACKGROUND: Dysregulation of the immune system has been shown to occur during spaceflight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions have yet to be established. Also, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive immune assessment on field team members participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate the effect of mission-associated stressors on the human immune system. To perform the study, the development of techniques for processing immune samples in remote field locations was required. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, whole-blood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles, plasma cortisol and EBV viral antibody levels. Study timepoints were 30 days prior to mission start, mid-mission and 60 days after mission completion. RESULTS: The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed on Devon Island, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in astronauts following spaceflight. CONCLUSION: The immune system changes described during the HMP field deployment validate the use of the HMP as a ground-based spaceflight/planetary exploration analog for some aspects of human physiology. The sample processing protocol developed for this study may have applications for immune studies in remote terrestrial field locations. Elements of this protocol could possibly be adapted for future in-flight immunology studies conducted during space missions.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/17521440

Immune system dysregulation occurs during short duration spaceflight on board the space shuttle

by on 9 June 2015in Biology & Biotechnology No comment

BACKGROUND: Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight. METHODS: Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles. RESULTS: Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNalpha, IFNgamma, IL-1beta, IL-4, IL-10, IL-12, and TNFalpha were significantly elevated in-flight, while IL-6 was significantly elevated at R + 0. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNgamma, IL-17 and IL-10 were reduced, but production of TNFalpha and IL-8 were elevated during spaceflight. CONCLUSIONS: This study indicates that specific parameters among leukocyte distribution, T cell function and cytokine production profiles are altered during flight. These findings distinguish in-flight dysregulation from stress-related alterations observed immediately following landing.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/23100144

Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight

by on 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. As the initial bias and magnitude for an immune response is heavily influenced by monocyte/macrophage secreted cytokines, this study investigated monocyte phenotype and cytokine production patterns following short-duration spaceflight. METHODS: Secreted cytokine profiles were examined by cytometric bead array analysis of culture supernatants following whole blood culture activation with LPS or PMA+ionomycin. Nine short-duration Space Shuttle crewmembers participated in this study. RESULTS: Peripheral monocyte percentages were unaltered postflight. Constitutive monocyte expression of both CD62L and HLA-DR was reduced following spaceflight in a mission-specific fashion. Loss of either molecule indicates a functional disability of monocytes, either by inhibition of adhesion and tissue migration (CD62L) or by impaired antigen presentation (HLA-DR). Following LPS stimulation of monocytes, postflight expression of IL-6, TNFalpha, and IL-10 were significantly reduced (by 43%, 44%, and 41%, respectively) and expression of IL-1b was elevated (65%). IL-8 production was either elevated or reduced in a mission-specific fashion. Following PMA+ionomycin stimulation of all leukocyte populations, only expression of IL-6 was significantly reduced postflight. DISCUSSION: These data indicate that changes in monocyte constitutive phenotype and inflammatory cytokine production occur following short-duration spaceflight, which may impact overall crewmember immunocompetence. Also, monocyte/macrophage function may be highly sensitive to mission specific parameters.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/21888268

Immune status, latent viral reactivation, and stress during long-duration head-down bed rest

by on 9 June 2015in Biology & Biotechnology No comment

INTRODUCTION: As logistical access for space research becomes more limited and NASA prepares for exploration-class missions, ground-based spaceflight analogs will increase in importance for biomedical countermeasures development. A monitoring of immune parameters was performed during the NASA Flight Analogs Project bed rest study (without countermeasure); to establish 'control' data against which future studies (with countermeasure) will be evaluated. Some of the countermeasures planned to be evaluated in future studies may impact immune function. METHODS: The immune assessment consisted of: leukocyte subset distribution, early T cell activation, intracellular cytokine profiles, latent viral reactivation, virus specific T cell levels and function, stress hormone levels, and a behavioral assessment using stress questionnaires. RESULTS: In general, subjects did not display altered peripheral leukocyte subsets, constitutive immune activation, altered T cell function, or significant latent viral reactivation (EBV, VZV). Levels of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) decreased during the study. Cortisol levels (plasma and saliva) did not vary significantly during 90-d bed rest. CONCLUSIONS: These data demonstrate the absence of significant immune system alteration and physiological stress during 90-d bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/19476168

Ocular examination for trauma; clinical ultrasound aboard the International Space Station

by on 9 June 2015in Biology & Biotechnology No comment

BACKGROUND: Ultrasound imaging is a successful modality in a broad variety of diagnostic applications including trauma. Ultrasound has been shown to be accurate when performed by non-radiologist physicians; recent reports have suggested that non-physicians can perform limited ultrasound examinations. A multipurpose ultrasound system is installed on the International Space Station (ISS) as a component of the Human Research Facility (HRF). This report documents the first ocular ultrasound examination conducted in space, which demonstrated the capability to assess physiologic alterations or pathology including trauma during long-duration space flight. METHODS: An ISS crewmember with minimal sonography training was remotely guided by an imaging expert from Mission Control Center (MCC) through a comprehensive ultrasound examination of the eye. A multipurpose ultrasound imager was used in conjunction with a space-to-ground video downlink and two-way audio. Reference cards with topological reference points, hardware controls, and target images were used to facilitate the examination. Multiple views of the eye structures were obtained through a closed eyelid. Pupillary response to light was demonstrated by modifying the light exposure of the contralateral eye. RESULTS: A crewmember on the ISS was able to complete a comprehensive ocular examination using B- and M-mode ultrasonography with remote guidance from an expert in the MCC. Multiple anteroposterior, oblique, and coronal views of the eye clearly demonstrated the anatomic structures of both segments of the globe. The iris and pupil were readily visualized with probe manipulation. Pupillary diameter was assessed in real time in B- and M-mode displays. The anatomic detail and fidelity of ultrasound video were excellent and could be used to answer a variety of clinical and space physiologic questions. CONCLUSIONS: A comprehensive, high-quality ultrasound examination of the eye was performed with a multipurpose imager aboard the ISS by a non-expert operator using remote guidance. Ocular ultrasound images were of diagnostic quality despite the 2-second communication latency and the unconventional setting of a weightless spacecraft environment. The remote guidance techniques developed to facilitate this successful NASA research experiment will support wider applications of ultrasound for remote medicine on Earth including the assessment of pupillary reactions in patients with severe craniofacial trauma and swelling.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/15920397

Geometric illusions in astronauts during long-duration spaceflight

by on 9 June 2015in Biology & Biotechnology No comment

In our previous studies, we have shown that the occurrence of geometric illusions was reduced in vestibular patients who presented signs of otolith disorders and when healthy observers were tilted relative to gravity. We hypothesized that the alteration in the gravitational (otolith) input was responsible for this change, presumably because of a connection between vestibular and visual-spatial cognitive functions. In this study, we repeated similar experiments in astronauts during long-duration spaceflight. In agreement with the data of otolithic patients, the inverted-T geometric illusion was less present in the astronauts in 0 g than in 1g. In addition, the vertical length of drawings made by astronauts in orbit was shorter than that on the ground. This result is also comparable with the otolithic patients who perceived the vertical length of line drawings to be smaller than healthy individuals. We conclude that the impairment in the processing of gravitational input in long-duration astronauts affects their mental representation of the vertical dimension similar to the otolithic patients. The astronauts, however, recover to baseline levels within 1 week after returning to Earth.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/22955144

Eye movements and motion perception during off-vertical axis rotation after spaceflight

by on 9 June 2015in Biology & Biotechnology No comment

Constant velocity off-vertical axis rotation (OVAR) provides dynamic linear acceleration stimuli that can be used to assess otolith function. Eight astronauts were rotated in darkness about their longitudinal axis 20 degrees off vertical at low (0.125 Hz) and high (0.5 Hz) frequencies and their responses were compared before and after spaceflight. Eye movements were recorded using infrared videography and perceived motion was evaluated using a joystick with four degrees of freedom – pitch and roll tilt, front-back and lateral translation. Low-frequency OVAR generates tilt otolith-induced responses – modulation of ocular counter-roll and counter-pitch with perceived conical motion path – whereas high-frequency OVAR generates translational otolith-induced responses – modulation of horizontal and vergence slow phase velocity with perceived cylindrical motion path. While there were transient changes in the amplitude of the translational ocular responses on landing day, there were no major changes in the tilt ocular reflexes after adaptation to weightlessness. However, there was an increase in sensitivity to motion perception after spaceflight. Direct comparisons of pre- and postflight stimuli suggested that OVAR on landing day was less provocative of motion sickness than before spaceflight. These results confirm that some otolith reflexes elicited during passive motion may not be altered by short-duration spaceflight – or may readapt very quickly – and that the resolution of sensory conflict associated with postflight recovery involves higher-order neural processes.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/23549051