Anemia and erythropoietin in space flights.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.

Renal function in space: the link between osteoporosis, hypercalciuria, and aquaporins.

This article reviews bone adaptation to microgravity, during manned space missions, in humans undergoing Head Down Tilt (HDT) and in Hind-Limb-Suspended Rats. Under microgravity conditions, bone loss occurs in association with hypercalciuria, which in turn modulates Aquaporin 2 (AQP2) excretion in urine, thus avoiding stone forming in space. This report discloses the need to prevent bone loss in order to prepare for long stays at lunar bases or voyages to Mars.

History of fluid balance and kidney function in space.

During the last four decades, about 400 people have been in Space, since Yuri Gagarin was sent in 1961 as the first human into Earth orbit. From the very beginning, the circulatory system of astronauts (meaning heart, vascular system, body fluid distribution and balance, and the kidney) was central to the medical concerns of Space physiologists and physicians because of its gravity-dependence. The present manuscript puts emphasize on some key scientists who worked in the field of body fluid regulation and kidney function in the USA, in Russia and in Europe during recent decades. The manuscript in particular summarizes the outcome of this research and describes the present understanding of how the body fluid regulatory system adapts to the extreme environment of Space.

Low urinary albumin excretion in astronauts during space missions.

BACKGROUND: Physiological changes occur in man during space missions also at the renal level. Proteinuria was hypothesized for space missions but research data are missing. METHODS: Urinary albumin, as an index of proteinuria, and other variables were analyzed in 4 astronauts during space missions onboard the MIR station and on the ground (control). Mission duration before first urine collection in the four astronauts was 4, 26, 26, and 106 days, respectively. On the ground, data were collected 2 months before mission in two astronauts, 6 months after in the other astronauts. A total of twenty-two 24-hour urine collections were obtained in space (n per astronaut = 1-14) and on the ground (n per astronaut = 2-12). Urinary albumin was measured by radioimmunoassay. For each astronaut, mean of data in space and on the ground was defined as individual average. RESULTS: The individual averages of 24 h urinary albumin were lower in space than on the ground in all astronauts; the difference was significant (mean +/- SD, space and on the ground = 3.41 +/- 0.56 and 4.70 +/- 1.20 mg/24 h, p = 0.017). Dietary protein intake and 24-hour urinary urea were not significantly different between space and on the ground. CONCLUSIONS: Urinary albumin excretion is low during space mission compared to data on the ground before or after mission. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).

Changes in bone turnover in patients with anorexia nervosa during eleven weeks of inpatient dietary treatment.

BACKGROUND: Many adolescents with anorexia nervosa suffer from severe osteopenia and osteoporosis. We hypothesized that individualized nutrition therapy may improve bone turnover in anorectic patients. METHODS: We studied 19 female patients [mean age, 14.2 +/- 1.4 years; mean body weight, 39.3 +/- 5.4 kg; mean body mass index (BMI), 14.2 +/- 1.4 kg/m(2)] with anorexia nervosa (International Classification of Diseases-10: F50.0, F50.1) for a period of 3 months. Nutrition therapy began at the end of the first week and included individualized hypercaloric diets, high calcium intake (2000 mg/day), and administration of vitamin D (400 IU/day). Blood samples were taken at baseline and again in weeks 3, 7, and 11. We measured serum calcium, parathyroid hormone, bone formation and resorption markers, insulin-like growth factor 1 (IGF-1), and leptin. RESULTS: Mean BMI increased significantly, from 14.2 +/- 1.4 to 17.1 +/- 0.7 kg/m(2) (P = 0.000001), during the course of treatment, whereas serum total calcium and phosphate concentrations remained unchanged. The bone formation markers procollagen-I carboxy-terminal propeptide and bone alkaline phosphatase almost doubled (P = 0.006). Both IGF-1 (P = 0.00001) and leptin (P = 0.000005) increased significantly by week 11. Parallel to this, the serum concentration of C-telopeptide, a bone resorption marker, decreased significantly (P = 0.009). CONCLUSIONS: Nutritional rehabilitation, possibly as a result of increasing IGF-1 and leptin concentrations, may increase bone formation. It therefore provides additional objective evidence of the importance of nutrition for bone.

Influence of microgravity on plasma levels of gastroenteropancreatic peptides: a case study.

BACKGROUND: No data are available about the short- or long-term influences of microgravity in space on the release of gastroenteropancreatic peptides, although these peptides are involved in the regulation of gastrointestinal functions. METHODS: Fasting plasma samples were gained during the EUROMIR-94 mission from a European Space Agency (ESA) astronaut who experienced no signs of space motion sickness in orbit. Plasma concentrations of nine gastroenteropancreatic peptides were measured with sensitive and specific radioimmunoassays. RESULTS: Fasting plasma levels of motilin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), and secretin were increased and plasma level of cholecystokinin (CCK) was decreased by acute exposure of the astronaut to microgravity. Chronic (4 wk) exposure caused an enhancement of plasma CCK, motilin, neurotensin, VIP, and insulin whereas plasma concentrations of PP, secretin, gastrin, and somatostatin showed no changes. During the 25-d stay on MIR station plasma levels of CCK, motilin, and neurotensin increased. Short-time body rotations caused an elevation of plasma levels of PP but decreased plasma motilin. CONCLUSIONS: As the influence of microgravity on the peptide levels was not uniform, an effect due to other factors (e.g., change in fluid balance or body weight) is unlikely. Moreover, adaptive changes of some peptides occurred during the stay in orbit. The release of PP and motilin seems to be very sensitive to rotation forces. These results have to be confirmed in more subjects in space to be able to link changes of gastroenteropancreatic peptide release to alterations of gastrointestinal functions.

Urinary albumin in space missions.

Proteinuria was hypothesized for space mission but research data are missing. Urinary albumin, as index of proteinuria, was analyzed in frozen urine samples collected by astronauts during space missions onboard MIR station and on ground (control). Urinary albumin was measured by a double antibody radioimmunoassay. On average, 24h urinary albumin was 27.4% lower in space than on ground; the difference was statistically significant. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).

Urinary albumin in head-down bed rest.

Previous studies reported low urinary albumin excretion in astronauts during space missions, suggesting an effect of microgravity on renal albumin handling. To test this hypothesis, urinary albumin excretion was investigated with use of head-down bed rest at -6 degrees (HDBR), an experimental model of microgravity. Eight healthy young men underwent two phases. Each phase included 2 days of dietary adaptation (run-in), 4 days of baseline (light activities and bed rest), and 6 days of experiment: HDBR 24h every day for intervention light activities and bed rest for control. The study was done in metabolic ward (DLR, Cologne, Germany). Urine were collected in days 3-4 of baseline and days 4-6 of experiment. Urinary albumin was measured by a double antibody radioimmunoassay, creatininuria by automated colourimetry. Data are expressed as albumin/creatinine ratio to control for timing and completeness of urine collection. Compared to baseline, albumin/creatinine ratio decreased by 9.3% during HDBR and increased by 14.9% during control. The difference in changes over baseline was significant between HDBR and control (p < 0.01 by paired comparison). The data support the hypothesis that low gravity reduces renal albumin excretion.