Specialized physiological studies in support of manned space flight

Research in aerospace medicine is presented. The reports discussed include: circulatory and respiratory transients during and after orthostasis and the effects of beta adrenergic blockade; the determination of total body water by an ethanol dilution method; and increased total respiratory conductance breathing 100% oxygen (forced oscillation method)

Rats, Salt, and History

The Dahl salt-sensitive rat is a 50-year-old enigma in hypertension research. How does salt increase blood pressure? One hypothesis put forward is the involvement of reactive oxygen species produced in the renal outer medulla. A novel rat gene-deletion model in this issue of Cell Metabolism supports this argument

Biomarkers and predicting acute kidney injury

Aim: How can we convert biomarkers into reliable, validated laboratory tests? Glomerular filtration rate (GFR) estimators exist for more than a century. The first utilitarian biomarkers were endogenously produced urea and creatinine. Clinicians then developed simple tests to determine whether or not renal tubular function was maintained. Are there faster and better tests that reflect decreased renal function and increased acute kidney injury (AKI) risk? Methods: We inspect earlier, and recently propagated biomarkers. Cystatin C reflects GFR and is not confounded by muscle mass. Direct GFR and plasma volume can now be measured acutely within 3 hours. Better yet would be tests that give information before GFR decreases and prior to urea, creatinine, and cystatin C increases. Prospective tests identifying those persons likely to develop AKI would be helpful. Even more utilitarian would be a test that also suggests a therapeutic avenue. Results: A number of highly provocative biomarkers have recently been proposed. Moreover the application of big data from huge electronic medical records promise new directions in identifying and dealing with AKI. Conclusions: Pipedreams are in the pipeline; the novel findings require immediate testing, verification, and perhaps application. Future research promises to make such dreams come true

Specialized physiological studies in support of manned space flight

The effects of a diuretic (Lasix) induced dehydration on the cardiovascular and hematological responses to lower body negative pressure (LBNP) were analyzed and compared to previous observations on dehydration following exercise in the heat. During LBNP runs the subjects were monitored for changes in blood volume, heart rate, blood pressure, and variations in the volume of the left calf. It was concluded that Lasix dehydration produced a depletion of the body electrolytes at the expense of both the plasma and extravascular compartments. Striking differences were found between those subjects who were physically active (Runners: R) and those who did not engage in any regular physical activity (Non-runners: NR). Tolerance to LBNP (Torr x min) was significantly lower in the R's than the NR's before and after dehydration, however the R's lost more of their tolerance after dehydration with Lasix than after exercise in the heat for about the same fluid loss. The opposite was true for the NR's. Two factors appear to be responsible for the lower LBNP tolerance in R's: parasympathetic inhibition of cardiac activity during LBNP and a greater propensity to pool blood in the lower extremities

Specialized physiological studies in support of manned space flight

The reversible changes that take place in the cardiovascular system during weightlessness were investigated. Particular attention was given to the assessment of cardiovascular functions during and after space missions. One of the most important of these functions is the amount of blood pumped by the heart per min at rest and during exercise of gravitational stress

Research report on: Specialized physiological studies in support of manned space flight

An investigation of the role of 02 fluctuations in oxygen uptake observed with changing posture is reported. A comparison of the closing volume test with other pulmonary function measurements is presented along with a comparison of hydrostatic weighing, and a stereophotogrammetric method for determining body volume

Specialized physiological studies in support of manned space flight

Subjects were tested for tolerance to lower body negative pressure (LBNP) before and after acute dehydration by working intermittenly for two hours without fluid replacement. On the second day there-after the LBNP tests were repeated before and after acute dehydration. The LBNP test consisted of 5 min long consective stages at -20, -30, -40, -50 and -60 Torr. Tests were terminated when syncope was imminent or the full sequence was completed. Tolerance was expressed in terms of cumulative stress in Torr x min. Measurements of body mass, density, fat fraction and total body water (TBW) were made before and after acclimation. Blood volume and its constituents were determined before and after each of the four LBNP tests. During LBNP, heart rate, blood pressure, and changes in calf and forearm volume were recorded every minute. Results showed: acute dehydration caused a significant loss in average LBNP tolerance on all subjects. Acclimation to heat did not significantly affect LBNP tolerance in hydrated subjects but significantly improved it on dehydrated subjects

Role of walking-exercise therapy after stroke

Stroke commonly leads to reduced mobility, which leads to deconditioning and a worsening of vascular risk factors, such as diabetes. The worsened risk profile leads to further strokes and disability--a vicious cycle for the stroke survivor. Exercise (walking) therapy may break this cycle by providing adequate stimuli for improving gait through plastic adaptation in the brain and through increasing fitness. Randomized, controlled data demonstrate the efficacy for gains in fitness and walking speed, the latter being related to lasting changes in activation patterns of the brainstem and cerebellum. Diabetes and muscle inflammation can also be improved by aerobic exercise training. The scope of this review summarizes these data and identifies unresolved issues related to optimization, intensity and maintenance of therapy effects. Exercise should be an integral part of every rehabilitation program

Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets

CD177 presents antigens in allo- and autoimmune diseases on the neutrophil surface. Individuals can be either CD177-deficient or harbor distinct CD177(neg) and CD177(pos) neutrophil subsets. We studied mechanisms controlling subset-restricted CD177 expression in bimodal individuals. CD177(pos), but not CD177(neg) neutrophils, produced CD177 protein and mRNA. Haplotype analysis indicated a unique monoallelic CD177 expression pattern, where the offspring stably transcribed either the maternal or paternal allele. Hematopoietic stem cells expressed both CD177 alleles and silenced one copy during neutrophil differentiation. ChIP and reporter assays in HeLa cells with monoallelic CD177 expression showed that methylation reduced reporter activity, whereas demethylation caused biallelic CD177 expression. HeLa cell transfection with c-Jun and c-Fos increased CD177 mRNA. Importantly, CD177(pos) human neutrophils, but not CD177(neg) neutrophils, showed a euchromatic CD177 promoter, unmethylated CpGs, and c-Jun and c-Fos binding. We describe epigenetic mechanisms explaining the two distinct CD177 neutrophil subsets and a novel monoallelic CD177 expression pattern that does not follow classical random monoallelic expression or imprinting