Thesis (M.S.)--University of Michigan, 1997. / Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1997. / Includes bibliographical references.

Introduction: Space is an extreme environment exposing astronauts to microgravity and cosmic radiation resulting in immune dysfunction. To overcome the complex challenges of studying astronauts in space, bed rest studies represent an alternative model simulating microgravity exposure on Earth. We sought to characterize the steady state transcriptome changes in leukocytes isolated from two microgravity models: (1) participants to 60 days of bed rest and (2) astronauts to ~6 months of spaceflight. Methods: The bed rest study recruited twenty healthy men receiving a nutritional supplement or not; the spaceflight study had fourteen male and female astronauts participate. For both studies, ten blood samples were collected over three study phases, leukocytes were isolated, and transcriptomes were quantified using high throughput RNA-sequencing. My pipeline of data analysis applied differential expression (DE) methods and functional enrichment to identify gene expression changes and pathways responding to the altered gravity environments of both bed rest and spaceflight models. Results: Temporal differential expression identified transcriptome modulation reflecting multisystem shifts and immune dysregulation in response to the transitions to and from bed rest (2,415 DE genes) and spaceflight (247 DE genes). Interestingly, later bed rest and in-flight timepoints trended towards stable RNA levels with no differential expression. The bed rest study found the nutritional intervention had no mitigating effects on transcriptome changes (0 DE genes), and the spaceflight study revealed down-regulation in response to spaceflight followed by an opposite up-regulation upon return to Earth. Conclusion: The altered gravity environments of bed rest and spaceflight significantly modulated leukocyte transcriptome compositions revealing immune dysfunction at the molecular level. Future analyses utilizing the higher quality bed rest dataset is required to isolate the effect of microgravity from other space stressors and apply validation experiments to develop gene biomarkers indicative of immune deconditioning.

This study was designed to test the hypothesis that 60 days continuous head down bed rest (HDBR), an Earth-based analogue of the effects of space flight, would elevate factors that increase vasoconstriction and would increase markers of vascular inflammation. The study incorporated countermeasures consisting of treadmill running within lower-body negative pressure and resistive "flywheel" exercise (exercise countermeasure, EX) or an increased protein intake of 0. 6 g/kg body weight/day (dietary countermeasures, DIET) to determine whether these interventions might prevent the vasoconstrictor and inflammatory responses when compared to a control (CON) group. Markers of vascular health measured in the study include the vasoactive molecules angiotensin II (Ang II), endothelin-1 (ET-1), and nitric oxide metabolites (NO_met); and markers of inflammation including C-reactive protein (CRP), and the adhesion molecules E-selectin (E-sel), intracellular adhesion molecule-1 (ICAM), and vascular cell adhesion molecule-1 (VCAM). Twenty four women were housed at the MEDES clinic in Toulouse, France, as part of a large international study (Women International Space Simulation for Exploration, WISE) in which various experimental protocols and countermeasures were integrated into a single experimental design completed during two campaigns. Each 100 day campaign included 20 days of pre-testing (pre-HDBR), 60 days of bed rest (HDBR), and 20 days of post-testing (post-HDBR). The experimental countermeasures were applied only during the 60-day HDBR period. Following 60 days of HDBR, many changes occurred in the concentrations of the measured molecules. Specifically, the concentration of Ang II significantly increased in the CON and DIET groups (52. 9%, p = 0. 014; and 124. 4%, p <0. 0001 respectively), but not in the EX group. Also, NO_met decreased in all groups, with reductions in the EX and DIET groups (p = 0. 013, and p = 0. 056 respectively). Markers used to assess vascular inflammation increased following the HDBR. The increase in CRP in the CON and DIET groups and the decrease in the EX group from pre- to post-HDBR were not significant; however, the directional changes resulted in an interaction between group and HDBR (p = 0. 052). The adhesion molecule E-sel was significantly increased in the DIET group (p = 0. 003), and VCAM was significantly increased in the CON group (p = 0. 016) with a smaller increase in the DIET group (p = 0. 08). No changes in adhesion molecules were observed in the EX group. This study demonstrated that 60 days of HDBR by young, healthy, women caused changes in several different molecules that are beginning to emerge as risk factors for the development of cardiovascular diseases. Further, it was observed that regular, vigorous exercise during HDBR prevented these changes. These results suggest that future studies of this kind should directly monitor the effects of simulated space flight on vascular health in men and women to obtain a greater understanding of the adaptations that might occur during long term space exploration missions. HDBR can be considered an extreme model of physical inactivity and could be used to provide insight into mechanisms of disease processes associated with the sedentary lifestyle that is prevalent in Western society.

Despite years of research, the role that hypovolemia plays in orthostatic intolerance after head down bed rest (BR) and spaceflight remains unclear. Additionally, the efficacy of oral saline countermeasures, employed in an attempt to restore plasma volume (PV) after BR is questionable. Several previous studies have suggested that a new homeostatic set point is achieved in space or during BR, making attempts to restore PV temporary at best. We tested the hypotheses that one day of BR would induce a transient increase in PV followed by hypovolemia and new hormonal balance; that a salt tablet and water fluid loading (FL) countermeasure would be ineffective in restoring PV; and also that the FL would not attenuate the exaggerated hormonal responses to orthostatic stress that are expected after 28hr of BR. Plasma volume, serum sodium and osmolarity, and plasma ANP, AVP, renin, angiotensin II, aldosterone, and catecholamines were measured in nine male subjects undergoing 5 different protocols (28hr Bed Rest without Fluid Loading = 28NFL, 28hr Bed Rest with Fluid Loading = 28FL, 4hr Seated Control = 4NFLS, 4hr Seated Control with Fluid Loading = 4FLS, and 4hr Bed Rest = 4BR) in a randomized repeated measures design. The FL countermeasure was 15 ml/kg of body weight of water with 1g of NaCl per 125ml of water. Orthostatic testing by lower body negative pressure (LBNP) was performed before and after all protocols. In agreement with our first hypothesis, we observed transient reductions in renin, angiotensin II, and aldosterone, which after 25.5hr were restored to baseline, slightly augmented, and suppressed, respectively. Also after 25.5hr, PV was reduced in the 28hr BR protocols and was not restored in 28FL; however, the FL protocol increased PV during 4FLS. We additionally observed augmented renin and aldosterone responses, as well as generally elevated angiotensin II after 28NFL, but not after 28FL or any of the 4hr protocols. Furthermore, no changes in plasma norepinephrine responses to LBNP were documented from Pre-Post test in any protocol. Our results indicate that: 1) PV is reduced after short term BR and is not restored by an oral FL; 2) renin-angiotensin-aldosterone system (RAAS) responses to orthostatic stress are augmented after 28hr of BR and the amplified response can be abrogated by FL; and 3) plasma norepinephrine responses during orthostatic stress are not affected by BR or FL, suggesting that RAAS activity may be modulated by FL independently of sympathetic activity and PV during orthostasis after bed rest.

This study was designed to test the hypothesis that 60 days continuous head down bed rest (HDBR), an Earth-based analogue of the effects of space flight, would elevate factors that increase vasoconstriction and would increase markers of vascular inflammation. The study incorporated countermeasures consisting of treadmill running within lower-body negative pressure and resistive "flywheel" exercise (exercise countermeasure, EX) or an increased protein intake of 0. 6 g/kg body weight/day (dietary countermeasures, DIET) to determine whether these interventions might prevent the vasoconstrictor and inflammatory responses when compared to a control (CON) group. Markers of vascular health measured in the study include the vasoactive molecules angiotensin II (Ang II), endothelin-1 (ET-1), and nitric oxide metabolites (NO_met); and markers of inflammation including C-reactive protein (CRP), and the adhesion molecules E-selectin (E-sel), intracellular adhesion molecule-1 (ICAM), and vascular cell adhesion molecule-1 (VCAM). Twenty four women were housed at the MEDES clinic in Toulouse, France, as part of a large international study (Women International Space Simulation for Exploration, WISE) in which various experimental protocols and countermeasures were integrated into a single experimental design completed during two campaigns. Each 100 day campaign included 20 days of pre-testing (pre-HDBR), 60 days of bed rest (HDBR), and 20 days of post-testing (post-HDBR). The experimental countermeasures were applied only during the 60-day HDBR period. Following 60 days of HDBR, many changes occurred in the concentrations of the measured molecules. Specifically, the concentration of Ang II significantly increased in the CON and DIET groups (52. 9%, p = 0. 014; and 124. 4%, p <0. 0001 respectively), but not in the EX group. Also, NO_met decreased in all groups, with reductions in the EX and DIET groups (p = 0. 013, and p = 0. 056 respectively). Markers used to assess vascular inflammation increased following the HDBR. The increase in CRP in the CON and DIET groups and the decrease in the EX group from pre- to post-HDBR were not significant; however, the directional changes resulted in an interaction between group and HDBR (p = 0. 052). The adhesion molecule E-sel was significantly increased in the DIET group (p = 0. 003), and VCAM was significantly increased in the CON group (p = 0. 016) with a smaller increase in the DIET group (p = 0. 08). No changes in adhesion molecules were observed in the EX group. This study demonstrated that 60 days of HDBR by young, healthy, women caused changes in several different molecules that are beginning to emerge as risk factors for the development of cardiovascular diseases. Further, it was observed that regular, vigorous exercise during HDBR prevented these changes. These results suggest that future studies of this kind should directly monitor the effects of simulated space flight on vascular health in men and women to obtain a greater understanding of the adaptations that might occur during long term space exploration missions. HDBR can be considered an extreme model of physical inactivity and could be used to provide insight into mechanisms of disease processes associated with the sedentary lifestyle that is prevalent in Western society.

Despite years of research, the role that hypovolemia plays in orthostatic intolerance after head down bed rest (BR) and spaceflight remains unclear. Additionally, the efficacy of oral saline countermeasures, employed in an attempt to restore plasma volume (PV) after BR is questionable. Several previous studies have suggested that a new homeostatic set point is achieved in space or during BR, making attempts to restore PV temporary at best. We tested the hypotheses that one day of BR would induce a transient increase in PV followed by hypovolemia and new hormonal balance; that a salt tablet and water fluid loading (FL) countermeasure would be ineffective in restoring PV; and also that the FL would not attenuate the exaggerated hormonal responses to orthostatic stress that are expected after 28hr of BR. Plasma volume, serum sodium and osmolarity, and plasma ANP, AVP, renin, angiotensin II, aldosterone, and catecholamines were measured in nine male subjects undergoing 5 different protocols (28hr Bed Rest without Fluid Loading = 28NFL, 28hr Bed Rest with Fluid Loading = 28FL, 4hr Seated Control = 4NFLS, 4hr Seated Control with Fluid Loading = 4FLS, and 4hr Bed Rest = 4BR) in a randomized repeated measures design. The FL countermeasure was 15 ml/kg of body weight of water with 1g of NaCl per 125ml of water. Orthostatic testing by lower body negative pressure (LBNP) was performed before and after all protocols. In agreement with our first hypothesis, we observed transient reductions in renin, angiotensin II, and aldosterone, which after 25.5hr were restored to baseline, slightly augmented, and suppressed, respectively. Also after 25.5hr, PV was reduced in the 28hr BR protocols and was not restored in 28FL; however, the FL protocol increased PV during 4FLS. We additionally observed augmented renin and aldosterone responses, as well as generally elevated angiotensin II after 28NFL, but not after 28FL or any of the 4hr protocols. Furthermore, no changes in plasma norepinephrine responses to LBNP were documented from Pre-Post test in any protocol. Our results indicate that: 1) PV is reduced after short term BR and is not restored by an oral FL; 2) renin-angiotensin-aldosterone system (RAAS) responses to orthostatic stress are augmented after 28hr of BR and the amplified response can be abrogated by FL; and 3) plasma norepinephrine responses during orthostatic stress are not affected by BR or FL, suggesting that RAAS activity may be modulated by FL independently of sympathetic activity and PV during orthostasis after bed rest.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Introduction: Space exploration has been a dream of mankind since ancient times, this dream became a reality with the launch of Sputnik in 1957. Since then, significant advances in space technology have enabled humans to travel beyond the Earth's atmosphere. Although some of the health risks are well known, the effect of changes in the pharmacokinetics of drugs and their effectiveness is not yet fully understood. Aim and Method: This study aims to investigate the effect of space travel on the pharmacokinetics of antibiotics. A scoping review method was employed to investigate the changes in the pharmacokinetics of antibiotics during space travel. A search of the PubMed database was performed using the relevant terms. Inclusion criteria included available English full-text articles. A three-step selection process was employed, followed by data analysis and evaluation, to select relevant original scientific articles. Results: The findings suggest that the pharmacokinetics of some antibiotics, such as ciprofloxacin penicillin and benzylpenicillin, may not be significantly altered in microgravity environments. Further research is needed to better understand the implications of space travel on antibiotic efficacy and safety. Conclusion: Current research on the pharmacokinetic changes of antibiotics in microgravity simulations shows little change compared to Earth. However, further research is crucial to understand their bioavailability, durability, and performance in space environments, ensuring the health and safety of space travelers.

Critically ill patients can be prescribed bed rest as a therapeutic intervention. Immobility from bed rest can cause neuromuscular deconditioning and weakness. Preventing immobility by implementing mobilization activities may prevent these complications from occurring. Currently, mobility protocols are lacking. The purpose of this literature review is to analyze the evidence related to mobilizing patients in the Intensive Care Unit (ICU). In the future, a standard mobility protocol should be instituted for critically ill patients indicating when and how to begin mobilization. The efficacy of mobility protocols relies on an interdisciplinary team for positive outcomes to prevent complications of inactivity and promote patient safety. Future implementation of mobilization can decrease patients' lengths of stay and extensive rehabilitation from inactivity. Nursing education, practice and research should focus on interventions to prevent complications of immobility by identifying mobilization techniques, safety approaches and the use of protocols.