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At least 19 records

VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major angiogenesis signaling pathway. It needs to be determined whether pro biotic yeast represents a promising approach to GI protection in space. GRC performed only the VESGEN post-testing analysis.

Parsons-Wingerter, P. A.↗

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

Non-NASA Center↗

Formation and inflammation of a turbulent jet

The formation and inflammation of a planar, turbulent jet in an incompressible medium is modeled numerically by the use of the random vortex method amended by a flame propagation algorithm. The results demonstrate the dominant influence of turbulent eddies and their interactions upon the development of the jet. Its growth is shown to consist of three stages: formation of small eddies, pairing of eddies with the same sign of circulation, and pairing of eddies of opposite signs. On this basis a number of features of the jet mechanism are revealed, namely penetration, engulfment, entrainment, and intermittency. Two cases of inflammation are considered. In one, the jet is ignited at the center of the orifice, the solution tracing its own inflammation. In the other, combustion is initiated across its full cross section, the results modeling the action of a turbulent torch as it spreads the flame into the combustible surroundings. In both cases the flow field is still dominated by the turbulent eddies and their interactions. However, the coherence among them is encumbered as a consequence of expansion due to the exothermicity of the combustion process.

Ghoniem, A. F.↗

Relation Between Inflammables and Ignition Sources in Aircraft Environments

A literature survey was conducted to determine the relation between aircraft ignition sources and inflammables. Available literature applicable to the problem of aircraft fire hazards is analyzed and, discussed herein. Data pertaining to the effect of many variables on ignition temperatures, minimum ignition pressures, and minimum spark-ignition energies of inflammables, quenching distances of electrode configurations, and size of openings incapable of flame propagation are presented and discussed. The ignition temperatures and the limits of inflammability of gasoline in air in different test environments, and the minimum ignition pressure and the minimum size of openings for flame propagation of gasoline - air mixtures are included. Inerting of gasoline - air mixtures is discussed.

Scull, Wilfred E↗

Relation between inflammables and ignition sources in aircraft environments

A literature survey was conducted to determine the relation between aircraft ignition sources and inflammables. Available literature applicable to the problem of aircraft fire hazards is analyzed and discussed. Data pertaining to the effect of many variables on ignition temperatures, minimum ignition pressures, minimum spark-ignition energies of inflammables, quenching distances of electrode configurations, and size of openings through which flame will not propagate are presented and discussed. Ignition temperatures and limits of inflammability of gasoline in air in different test environments, and the minimum ignition pressures and minimum size of opening for flame propagation in gasoline-air mixtures are included; inerting of gasoline-air mixtures is discussed.

Scull, Wilfred E↗

Survey of less-inflammable hydraulic fluids for aircraft

A survey of current information on civil and military development of less-inflammable hydraulic fluids for aircraft is presented. Types of less-inflammable fluid reported include: glycol derivative, water base, silicone, ester, and halogenated compound. Specification requirements, physical and chemical properties, hydraulic-system test results, and advantages and disadvantages of various hydraulic fluids are discussed. For completely satisfactory service, some modification of currently available fluids or of present hydraulic-system parts still appears necessary.

FRICTION AND LUBRICATION↗

Complement activation promotes muscle inflammation during modified muscle use

Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

NASA Discipline Musculoskeletal↗

Macrophage invasion does not contribute to muscle membrane injury during inflammation

Previous observations have shown that neutrophil invasion precedes macrophage invasion during muscle inflammation and that peak muscle injury is observed at the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages then contribute significantly to muscle membrane injury during modified muscle use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal ambulation to induce inflammation. Membrane injury was measured by assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly during the first 2 h of reloading but ED1+ macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasion by reloading rat hindlimbs for 2 h to cause neutrophil invasion, followed by resuspension for hours 2-24. This produced similar increases in neutrophil concentration as measured in muscles continuously reloaded for 24 h without causing an increase in macrophages. However, resuspension did not reduce the extent of muscle damage compared with that occurring in muscles that were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. In addition, muscle membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages.

NASA Discipline Musculoskeletal↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

A Preliminary Analysis of Calcifying Particles in the Serum and Prostates of Patients with Prostatic Inflammation

Chronic diseases of the prostate such as benign prostatic hyperplasia (BPH) & chronic pelvic pain syndrome (CPPS) have associated findings of chronic inflammation, despite a lack of causal relationship. Numerous attempts to define an infectious agent responsible for the clinical findings have been inconsistent. The possibility of an infectious agent, that has not been uncovered with routine culturing methods, forms the basis for this study. Serum from 940 healthy Finnish men were compared with serum from 40 Crohn's, 40 path dx prostatitis, & 40 with path dx carcinoma, using an enzyme-linked immunosorbant assay (ELISA), to detect antigens specific to Nanobacteria(NB) utilizing monoclonal antibodies (Ab) 5/3 and 8D10. This ELISA has not been validated for detecting NB-associated with clinical prostatic disease, yet cross-reactivity with other bacterial species is low. Immunohistochemistry was performed on de-paraffinized prostatic tissue slides, de-calcified with EDTA and stained with the DAKO Catalyzed Signal Amplification kit, employing 8D10 as the primary (target/antigen-detecting) Ab. The mean (plus or minus SD) & median concentrations of NB antigen (U/50 L) were 379.59 (plus or minus 219.28) & 640.00 for patients with prostatitis (BPH) vs 3.31 (plus or minus 3.55) & 2.94 for prostate adenocarcinoma, 1.88 (plus or minus 2.94) & 0.80 for Crohn's disease, & 7.43 (plus or minus 25.57) & 0.00 for patients with no clinical prostatic disease. Unpaired t-tests revealed statistically significant differences between the prostatitis (BPH) sera & each of the other groups with p less than 0.005, but no differences between the other groups themselves. Preliminary studies with immunohistochemistry & 3-D confocal microscopy reveal 16/24 tissue sections + for NB Ag in BPH vs. only 2/22 tissue sections with prostate cancer. The preliminary findings of this serum screening study suggest that NB antigen may be commonly found in the serum of patients with the pathological diagnosis of prostatitis. Preliminary immunohistologic studies, suggest that NB may be found within the gland itself at a higher rate in patients with BPH relative to patients with adenocarcinoma, however confirmatory studies with a more specific ELISA technique, primary cultures, & with larger numbers of patients in a prospective design are required to determine if 1) NB are a causative organism for clinical hyperplastic and inflammatory disease, & if 2) serological testing can be used to discriminate patients with nanobacterial-associated prostatic disease.

Jones, Jeffrey A.↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

Solid Inflammability Boundary at Low Speed (SIBAL)

This research program is concerned with the effect of low speed flow on the spreading and extinction processes of flames over solid fuels. We are particularly interested in the flammability boundary and the near-limit flame behavior in a microgravity environment. Primary attention is given to flame propagation in concurrent flow - the more hazardous situation from the point of view of fire safety. Both theoretical modeling and experimental research are in progress. This project passed the Science Concept Review (SCR) in 1996. As a result, the experiment continues on the flight definition path, and is currently scheduled to be performed in the Space Station Fluids and Combustion Facility (FCF).

Tien, James S.↗

Solid Inflammability Boundary at Low Speed (SIBAL)

This research program is concerned with the effect of low-speed, concurrent flow on the spreading and extinction processes of flames over solid fuels. The primary objective is to verify the theoretically predicted extinction boundary, using oxygen percentage and flow velocity as coordinates. In particular, we are interested in the low-speed quenching limits and the existence of the critical oxygen flammability limit. Detailed flame spread characteristics, including flame spread rate, flame size, and flame structure are sought. Since the predicted flame behavior depends on the inclusion of flame and surface radiation, the measured results will also be used to assess the importance of radiative heat transfer by direct comparison to a comprehensive numerical model. This project passed the Science Concept Review (SCR) in 1996. As a result, the experiment continues on the flight definition path, and is currently scheduled to be performed in the Space Station Combustion Integrated Rack (CIR). We present an overview of recent and ongoing work, including selected experimental and theoretical topics.

T'ien, James S.↗

Solid Inflammability Boundary at Low-Speed (SIBAL)

This research program is concerned with the effect of low-speed, concurrent flow on the spreading and extinction processes of flames over solid fuels. The primary objective is to verify the theoretically predicted extinction boundary, using oxygen percentage and flow velocity as coordinates. Of particular interest are the low-speed quenching limits and the existence of the critical oxygen flammability limit. Detailed flame spread characteristics, including flame spread rate, flame size, and flame structure are sought. Since the predicted flame behavior depends on the inclusion of flame and surface radiation, the measured results will also be used to assess the importance of radiative heat transfer by direct comparison to a comprehensive numerical model. The solid fuel used in this experiment is a custom-made fabric consisting of a 1:1 blend of cotton and fiberglass. This choice was made following an extensive search to yield a material with favorable properties, namely, rollability, non-cracking behavior during combustion, strength after combustion, and flammability in a range of oxygen limits permissible within the Combustion Integrated Rack (CIR) on the International Space Station. At the present time, an effort is being made to characterize both the radiative properties of the fuel and the flame spreading behavior in normal gravity at reduced pressure. These will provide a basis for comparison with the microgravity results as well as aid in bracketing the anticipated flammability boundary for the flight experiment. An overview of recent work, with emphasis on theoretical results, is presented.

T'ien, James↗

Solid Inflammability Boundary At Low-Speed (SIBAL)

This research program is concerned with the effect of low-speed flow on the spreading and extinction processes over solid fuels. The project has passed the Science Concept Review and the experiment is currently scheduled to be performed in the ISS Combustion Integrated Rack. We present an overview of recent and ongoing experimental and theoretical efforts.

T'ien, J.↗