Semiquantitative Proteomic Research of Protein Plasma Profile of Volunteers in 21-Day Head-Down Bed Rest.
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ABSTRACT:
SUBMITTER: Kashirina DN
PROVIDER: S-EPMC7396636 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Semiquantitative Proteomic Research of Protein Plasma Profile of Volunteers in 21-Day Head-Down Bed Rest.
Kashirina Daria N DN Brzhozovskiy Alexander G AG Pastushkova Ludmila Kh LK Kononikhin Alexey S AS Borchers Christoph H CH Nikolaev Evgeny N EN Larina Irina M IM
Frontiers in physiology 20200724
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Project description:Hemoconcentration is observed in bed rest studies, descent from altitude, and exposure to microgravity. Hemoconcentration triggers erythrocyte losses to subsequently normalize erythrocyte concentration. The mechanisms of erythrocyte loss may involve enhanced hemolysis, but has never been measured directly in bed rest studies. Steady-state hemolysis was evaluated by measuring two heme degradation products, endogenous carbon monoxide concentration [CO] and urobilinogen in feces, in 10 healthy men, before, during, and after two campaigns of 21 days of 6° head-down-tilt (HDT) bed rest. The subjects were hemoconcentrated at 10 and 21 days of bed rest: mean concentrations of hemoglobin (15.0 ± 0.2 g/L and 14.6 ± 0.1 g/L, respectively) and erythrocytes (5.18 ± 0.06E6/μL and 5.02 ± 0.06E6/μL, respectively) were increased compared to baseline (all Ps < 0.05). In contrast, mean hemoglobin mass (743 ± 19 g) and number of erythrocytes (2.56 ± 0.07E13) were decreased at 21 days of bed rest (both Ps < 0.05). Indicators of hemolysis mean [CO] (1660 ± 49 ppb and 1624 ± 48 ppb, respectively) and fecal urobilinogen concentration (180 ± 23 mg/day and 199 ± 22 mg/day, respectively) were unchanged at 10 and 21 days of bed rest compared to baseline (both Ps > 0.05). A significant decrease in [CO] (-505 ppb) was measured at day 28 after bed rest. HDT bed rest caused hemoconcentration in parallel with lower hemoglobin mass. Circulating indicators of hemolysis remained unchanged throughout bed rest supporting that enhanced hemolysis did not contribute significantly to erythrocyte loss during the hemoconcentration of bed rest. At day 28 after bed rest, decreased hemolysis accompanied the recovery of erythrocytes, a novel finding.
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Project description:Spaceflight is associated with deregulation in the immune system. Head-down bed rest (HDBR) at -6° is believed to be the most practical model for examining multi-system responses to microgravity in humans during spaceflight. In the present study, a 45-day HDBR was performed to investigate the alterations in human immune cell distributions and their functions in response to various stimuli. The effect of countermeasure, Rhodiola rosea (RR) treatment, was also examined. A significant decrease of interferon-γ (IFN-γ) and interleukin-17 (IL-17) productions by activated T cells, increase of IL-1β and IL-18 by activated B and myeloid cells were observed during HDBR. The upregulation of serum cortisol was correlated with the changes of IL-1 family cytokines. In addition, a significant increase of memory T and B cell and regulatory T cells (Treg) were also detected. The uptake of RR further decreased IFN-γ level and slowed down the upregulation of IL-1 family cytokines. These data suggest that for prolonged HDBR and spaceflight, the decreased protective T cell immunity and enhanced proinflammatory cytokines should be closely monitored. The treatment with RR may play an important role in suppressing proinflammatory cytokines but not in boosting protective T cell immunity.
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Project description:Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR.
2024-08-10 | PXD053149 | Pride
Project description:Current inflight countermeasures do not completely prevent bone and cardiovascular changes induced by microgravity. High load Resistance Exercise combined with whole body Vibration (RVE) demonstrated benefits on bone and cardiovascular system during previous Head-Down Bed Rest (HDBR) studies. We examined the effectiveness of RVE alone or combined with a nutritional supplementation of Whey protein (NeX) on cardiovascular deconditioning. Eight male subjects (age 34 ± 8 years) in a crossover design completed three 21-day HDBR campaigns (Control-CON, RVE, and NeX). Pre and post HDBR Orthostatic Tolerance (OT) was evaluated by a 15-min head-up tilt test followed by increasing levels of Lower Body Negative Pressure (LBNP). Heart rate (HR), blood pressure (BP), and Sympathetic Index (ΣI) through spectral analysis were measured during OT test. Plasma Volume (PV), and Maximal Oxygen Uptake (VO2max) were measured before and after each campaign. Left ventricular mass, left ventricular end diastolic (LVEDV), end systolic (LVESV), stroke (SV) volumes, and circumferential deformation at rest and during an orthostatic stress simulated by a 30 mmHg LBNP were measured by cardiac MRI. RVE failed to prevent any change in these variables and NeX did not have any additional effect over exercise alone. In the 3 groups, (1) OT time dropped similarly (bed rest p < 0.001), (2) HR and ΣI were increased at rest at the end of HDBR and HR increased markedly during LBNP-tilt test, with inability to increase further the ΣI, (3) PV dropped (bed rest p < 0.001), along with LVEDV, LVESV and SV (p = 0.08, p < 0.001, and p = 0.045, respectively), (4) Left ventricle mass did not change significantly, (5) Deformation of the heart assessed by global circumferential strain was preserved and early diastolic circumferential strain rate was increased during orthostatic stress at the end of HDBR, illustrating preserved systolic and diastolic function respectively, without any difference between groups. Despite the drop in PV and LV volumes, RVE and NeX tended to alleviate the decrease in VO2max. In conclusion, RVE and NeX failed to prevent the cardiovascular deconditioning induced by a 21 day-HDBR.
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Project description:The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P < 0.001), respectively, and recovered immediately after HDT on R + 2. Such small changes in the ONSSA were below the lateral resolution limit of ultrasound (0.4 mm) and may not be clinically relevant, possibly due to ONS hysteresis causing persistent ONS distension. Future research can explore advanced quantitative portable ultrasound-based techniques and establish comparisons containing the pre-HDT measurements to deepen our understanding of SANS.
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Project description:Artificial gravity through short-arm centrifugation has potential as a multi-system countermeasure for deconditioning and cranial fluid shifts that may underlie ocular issues in microgravity. However, the optimal short-arm centrifugation protocol that is effective whilst remaining tolerable has yet to be determined. Given that exposure to centrifugation is associated with presyncope and syncope and in addition motion sickness an intermittent protocol has been suggested to be more tolerable. Therefore, we assessed cardiovascular loading and subjective tolerability of daily short arm centrifugation with either an intermittent or a continuous protocol during long-term head-down bed rest as model for microgravity exposure in a mixed sex cohort. During the Artificial Gravity Bed Rest with European Space Agency (AGBRESA) 60 day 6° head down tilt bed rest study we compared the tolerability of daily +1 Gz exposure at the center of mass centrifugation, either performed continuously for 30 minutes, or intermittedly (6 x 5 minutes). Heart rate and blood pressure were assessed daily during centrifugation along with post motion sickness scoring and rate of perceived exertion. During bed rest, 16 subjects (6 women, 10 men), underwent 960 centrifuge runs in total. Ten centrifuge runs had to be terminated prematurely, 8 continuous runs and 2 intermittent runs, mostly due to pre-syncopal symptoms and not motion sickness. All subjects were, however, able to resume centrifuge training on subsequent days. We conclude that both continuous and intermittent short-arm centrifugation protocols providing artificial gravity equivalent to +1 Gz at the center of mass is tolerable in terms of cardiovascular loading and motion sickness during long-term head down tilt bed rest. However, intermittent centrifugation appears marginally better tolerated, albeit differences appear minor.
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Project description:BackgroundThe most applicable human models of weightlessness are -6° head-down bed rest (HDBR) and head-out dry immersion (DI). A detailed experimental comparison of cardiovascular responses in both models has not yet been carried out, in spite of numerous studies having been performed in each of the models separately.ObjectivesWe compared changes in central hemodynamics, autonomic regulation, plasma volume, and water balance induced by -6° HDBR and DI.MethodsEleven subjects participated in a 21-day HDBR and 12 subjects in a 3-day DI. During exposure, measurements of the water balance, blood pressure, and heart rate were performed daily. Plasma volume evolution was assessed by the Dill-Costill method. In order to assess orthostatic tolerance time (OTT), central hemodynamic responses to orthostatic stimuli, and autonomous regulation, the 80° lower body negative pressure-tilt test was conducted before and right after both exposures.ResultsFor most of the studied parameters, the changes were co-directional, although they differed in their extent. The changes in systolic blood pressure and total peripheral resistance after HDBR were more pronounced than those after DI. The OTT was decreased in both groups: to 14.2 ± 3.1 min (vs. 27.9 ± 2.5 min before exposure) in the group of 21-day HDBR and to 8.7 ± 2.1 min (vs. 27.7 ± 1.2 min before exposure) in the group of 3-day DI.ConclusionsIn general, cardiovascular changes during the 21-day HDBR and 3-day DI were co-directional. In some cases, changes in the parameters after 3-day DI exceeded changes after the 21-day HDBR, while in other cases the opposite was true. Significantly stronger effects of DI on cardiovascular function may be due to hypovolemia and support unloading (supportlessness).
| S-EPMC7248392 | biostudies-literature
Project description:IntroductionProlonged confinement to head-down bed rest (HDBR) results in musculoskeletal losses similar to those observed during long-duration space flight. Exercise countermeasures by themselves have not completely prevented the deleterious losses in muscle mass or function in HDBR or space flight.PurposeThe objective was to investigate the safety and efficacy of intermittent, low-dose testosterone treatment in conjunction with NASA exercise (SPRINT) countermeasures during 70 d of 6° HDBR.MethodsHealthy men (35 ± 8 yr) were randomized into one of three groups that remained inactive (CON) or performed exercise 6 d·wk in addition to receiving either placebo (PEX) or testosterone treatment (TEX, 100 mg·wk). Testosterone/placebo injections were administered once a week for 2 wk, followed by 2 wk off and so on, during HDBR.ResultsTotal, leg, and trunk lean body mass (LBM) consistently decreased in CON, increased in TEX, and had little or no changes in PEX. Total, leg, and trunk fat mass consistently increased in CON and PEX and decreased in TEX. Leg strength decreased in CON, whereas PEX and TEX were protected against loss in strength. Changes in leg LBM correlated positively with changes in leg muscle strength.ConclusionsAddition of a testosterone countermeasure enhanced the preventative actions of exercise against body composition changes during long-term HDBR in healthy eugonadal men. This is the first report to demonstrate that cycled, low-dose testosterone treatment increases LBM under conditions of strict exercise control. These results are clinically relevant to the development of safe and effective therapies against muscle atrophy during long-term bed rest, aging, and disease where loss of muscle mass and strength is a risk. The potential space flight applications of such countermeasure combinations deserve further investigations.
| S-EPMC6095739 | biostudies-literature
Project description:ImportanceOptic disc edema among astronauts after long-duration spaceflight is associated with 1-carbon pathway single-nucleotide polymorphisms and B vitamin status. A recent strict 6° head-down tilt bed rest (HDTBR) study documented development of optic disc edema and increased total retinal thickness in participants exposed to carbon dioxide, 0.5%, for 30 days, but genetic risk factors have not been explored in the cohort.ObjectiveTo examine whether peripapillary retinal thickness measures obtained from optical coherence tomography images during HDTBR and carbon dioxide, 0.5%, exposure are associated with B vitamin status and single-nucleotide polymorphisms involved in folate-dependent and vitamin B12-dependent 1-carbon metabolism pathways.Design, setting, and participantsThis study was conducted with a cohort of healthy volunteers at the Institute of Aerospace Medicine at the German Aerospace Center in Cologne, Germany. Data collection occurred from October 2017 to November 2017. After a 14-day ambulatory phase without carbon dioxide, participants maintained strict HDTBR with carbon dioxide, 0.5%, for 30 days, followed by a 13-day ambulatory phase without carbon dioxide.Main outcomes and measuresBlood samples were collected before HDTBR to assess vitamin levels and single-nucleotide polymorphism status. Optical coherence tomographic images were collected before HDTBR; at days 1, 15, and 30 of the resting period; and 6 and 13 days after the period ended. Total retinal thickness was measured from a radial-24 B-scan centered over the optic disc, and global retinal nerve fiber layer thickness was measured from a circle scan. The changes in total retinal thickness and retinal nerve fiber layer thickness were evaluated against the number of risk alleles (defined as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [MTRR] 66 G and serine hydroxymethyltransferase 1 [SHMT1] 1420C alleles), along with folate, vitamin B6 (pyridoxine), and vitamin B12 (cobalamin) status.ResultsEleven heathy volunteers (6 men and 5 women) had a mean (SD) age of 33.4 (8.0) years and a mean (SD) body mass index of 23.4 (2.2). After statistical adjustment for B vitamin status, total retinal thickness at the end of HDTBR in participants with 3 or 4 risk alleles was 40 um (SE, 19 μm) greater than in participants with 0 to 2 risk alleles. In addition, the baseline retinal nerve fiber layer thickness was 14 um (SE, 2 μm) greater in those with 3 or 4 risk alleles compared with those with 0 to 2 risk alleles.Conclusions and relevanceThe magnitude of optic disc edema in individuals experiencing HDTBR and exposed to a chronic headward fluid shift in a mild hypercapnic environment was higher in participants with more MTRR 66 G and SHMT1 1420C alleles, even when this finding was statistically adjusted for B vitamin status. These findings may help explain the variability in magnitude of optic disc edema observed during bed rest and spaceflight and thereby improve efforts to counteract this phenomenon.
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