Biomedical subjects

A Güell

Publications and source records attributed to A Güell.

At least 19 recordsLinked to original sources

PubMed2000

Altered gravity downregulates aquaporin-1 protein expression in choroid plexus.

Aquaporin-1 (AQP1) is a water channel expressed abundantly at the apical pole of choroidal epithelial cells. The protein expression was quantified by immunocytochemistry and confocal microscopy in adult rats adapted to altered gravity. AQP1 expression was decreased by 64% at the apical pole of choroidal cells in rats dissected 5.5-8 h after a 14-day spaceflight. AQP1 was significantly overexpressed in rats readapted for 2 days to Earth's gravity after an 11-day flight (48% overshoot, when compared with the value measured in control rats). In a ground-based model that simulates some effects of weightlessness and alters choroidal structures and functions, apical AQP1 expression was reduced by 44% in choroid plexus from rats suspended head down for 14 days and by 69% in rats suspended for 28 days. Apical AQP1 was rapidly enhanced in choroid plexus of rats dissected 6 h after a 14-day suspension (57% overshoot, in comparison with control rats) and restored to the control level when rats were dissected 2 days after the end of a 14-day suspension. Decreases in the apical expression of choroidal AQP1 were also noted in rats adapted to hypergravity in the NASA 24-ft centrifuge: AQP1 expression was reduced by 47% and 85% in rats adapted for 14 days to 2 G and 3 G, respectively. AQP1 is downregulated in the apical membrane of choroidal cells in response to altered gravity and is rapidly restored after readaptation to normal gravity. This suggests that water transport, which is partly involved in the choroidal production of cerebrospinal fluid, might be decreased during spaceflight and after chronic hypergravity.

Animals↗

PubMed1999

Cardiac atrial natriuretic peptide (ANP) in rat dams and fetuses developed in space (NIH-R1 and NIH-R2 experiments).

NIH-R1 and R2 missions, conducted by NASA, allowed us to study the effects of the microgravitational environment 1) on cardiac ANP in pregnant rats, spaceflown for 11 days and dissected after a 2-day readaptation to Earth's gravity, after natural delivery, and 2) on maturation of cardiac ANP system in rat fetuses developed for 11 days in space and dissected on the day of landing, 2 days before birth. Immunocytochemical and electron microscopy analyses showed a typical formation of ANP-containing granules in atrial myocytes, in both dams and fetuses. Using competitive RT-PCR and radioimmunoassays, we observed that, after 2 days of readaptation to Earth's gravity, cardiac ANP biosynthesis of rat dams flown in space was increased by about twice, when compared to Synchronous and Vivarium Control rats. More obviously, rat fetuses developed in space and dissected on the day of landing displayed an altered maturation of cardiac ANP, evidenced by an increased mRNA biosynthesis (by about 6 fold, p<0.05), whereas the cardiac ANP storage was slightly reduced (by about twice, p<0.05) in both Flight and Synchronous Control groups, in comparison with Vivarium Control rats. These last results suggest that ANP metabolism during development is impacted by the microgravitational environment, but also by the housing conditions designed for space flight.

Animals↗

PubMed1999

Contributory factors to orthostatic intolerance after simulated weightlessness.

Various factors may contribute to orthostatic intolerance (OI) observed after space flights or simulated weightlessness such as bed rest experiments: individual physical and physiological factors (arterial blood pressure (BP), height), physiological changes induced by real or simulated weightlessness (hypovolaemia, increase in venous distensibility), and space flight or simulation conditions (duration and counter-measure application). Our purpose was to test which of these factors were dominant in contributing to the OI. This was assessed in 47 healthy men participating in bed rest experiments of 4, 14, 28, 30 and 42 days, with or without counter-measures (medical stockings, lower-body negative pressure (LBNP), LBNP + muscular exercise). Nineteen subjects did not finish the orthostatic test (60 degrees head-up tilt or stand test) after bed rest. The occurrence of OI was associated with greater height, low resting BP, greater changes in resting lower-limb venous distensibility throughout the bed rest, and absence of counter-measures.

Adult↗

PubMed1998

The transcription factor GHF-1, but not the splice variant GHF-2, cooperates with thyroid hormone and retinoic acid receptors to stimulate rat growth hormone gene expression.

The rat growth hormone (GH) promoter was significantly activated in non-pituitary cells by the expression of unliganded trioodothyronine (T3) and retinoic acid (RA) receptors. Furthermore, a strong ligand-dependent activation was found in the presence of the pituitary-specific transcription factor GHF-1. When compared with GHF-1, the splice variant GHF-2 showed a decreased ability to bind the cognate site in the GH promoter. As a consequence, expression of GHF-2 had little stimulatory effect on the GH promoter and did not show cooperation with T3 or RA receptors even in the presence of ligands. Furthermore, over-expression of GHF-2 inhibited the response to T3 and RA in pituitary cells. These results show that alternative splicing of the GHF-1 gene gives rise to two isoforms that differ in their transactivating properties and in their ability to synergize with the nuclear thyroid hormone and retinoic acid receptors on GH gene expression.

Alternative Splicing↗

PubMed1997

Effects of an 11-day spaceflight on the choroid plexus of developing rats.

Cellular distributions of ezrin, a cytoskeletal protein involved in apical cell differentiation in choroid plexus, and carbonic anhydrase II, which is partly involved in the cerebrospinal fluid production, were studied by immunocytochemistry, at the level of choroidal epithelial cells from the lateral, third and fourth ventricles in normal or experimental fetuses, in parallel with the ultrastructure of apical microvilli, observed by transmission electron microscopy. We compared choroid plexuses from developing normal rats (gestational day 15 to birth) with choroid plexuses from 20-day-old rat fetuses, developed for 11 days in space, aboard a space shuttle (NASA STS-66 mission, NIH-R1 experiments), from gestational day 9 to day 20. The main changes observed in fetuses developed in space were demonstrated by immunocytochemistry and concerned the distribution of ezrin and carbonic anhydrase II. Thus, in fetuses developing in space, ezrin was strongly detected in the choroidal cytoplasm and weakly associated to the membrane in the apical domain of the choroid plexus from the fourth ventricle. Such alterations suggested that choroid plexus from rat fetal brain displays a delayed maturation under a micro-gravitational environment. In contrast, intense immunoreactions to anti-carbonic anhydrase II antibodies showed that this enzyme is very abundant in rats developed in space, compared to ground control fetuses.

Animals↗

PubMed1997

Pharmacology in space: pharmacotherapy.

This chapter summarized the information available on the pharmacological kits onboard spacecraft and on the use of drugs in space, while the next chapter is dedicated to the impacts of weightlessness on drug pharmacokinetics. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights has been discussed. Recommendations are made for a Space Pharmacopoeia as well as for the areas of research needed to adapt medication to the weightlessness of the space environment. Although the usefulness of these drugs has been clearly demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. Inflight data obtained by salivary drug monitoring have shown changes in the distribution of scopolamine and a significant change in the disposition of the common pain-relief agent acetaminophen taken inflight, in both drug concentration and time course. The authors of this study emphasize, however, that their data are preliminary and as yet incomplete. Further simulation studies and, if possible, inflight experiments are required. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. The possible consequences of these findings for the treatment of infections contracted by astronauts are yet to be elucidated. There is still a lack of pharmacological countermeasures, particularly for preventing the progressive bone demineralization occurring in weightlessness. The treatment of space motion sickness with drugs carries with it the problem of undesirable side-effects on psychomotor performance. In order to arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Aerospace Medicine↗

PubMed1997

Pharmacology in space: pharmacokinetics.

The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.

Biological Availability↗

PubMed1997

Orthostatic tests after a 4-day confinement or simulated weightlessness.

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6 degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower-body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D-1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT and LBNP without difference between D-1 and R1. This experiment showed that a 4-day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.

Adult↗

PubMed1997

Changes in leg vein filling and emptying characteristics and leg volumes during long-term head-down bed rest.

Leg venous hemodynamics [venous distensibility index (VDI), arterial flow index (AFI), half-emptying time (T1/2)], and leg volumes (LV) were assessed by mercury strain-gauge plethysmography with venous occlusion and volometry, respectively, in seven men before, during, and after 42 days of 6 degrees head-down bed rest. Results showed a high increase in VDI up to day 26 of bed rest (+50% vs. control at day 26, P < 0.05), which tended to subside thereafter (+20% increase vs. control value at day 41, P < 0.05). VDI changes were associated with parallel changes in T1/2 (+54% vs. control at day 26 of bed rest, P < 0.05, and +25% vs. control at day 41, P < 0.05) and with a decrease in AFI (-49% at day 41 vs. P < 0.05). LV continuously decreased throughout bed rest (-13% vs. control at day 41, P < 0.05) but was correlated with VDI only during the first month of bed rest. These results show that during long-term 6 degrees head-down bed rest alterations of leg venous compliance are associated with impairment of venous emptying capacities and arterial flow. Changes in skeletal muscle mass and fluid shifts may account for venous changes during the first month of bed rest but, subsequently, other physiological factors, to be determined, may also be involved in leg venous hemodynamic alterations.

Adult↗

PubMed1997

Unusual vestibular and visual input in human dynamic balance as a motion sickness susceptibility test.

BACKGROUND: Motion sickness (MS) is commonly thought to arise from a sensory conflict. However, few quantitative methods based on this theory are available to detect MS susceptibility. HYPOTHESIS: It was asked whether the standardized unusual stimulation of a single sensory channel under quantified dynamic balance conditions in man could elicit a sensory conflict and therefore trigger motion sickness (MS) METHODS: Vestibular and visual channels were stimulated by galvanic current and rotating prismatic glasses, respectively. The moving platform used to create the requirements for dynamic balance conditions was chosen not only to worsen the malaise but also to obtain an objective measurement of the balance consequences of the stimulations. RESULTS: Both vestibular and visual stimulation, applied separately, elicited MS-like symptoms (in 56% and 73% of subjects, respectively) and stereotyped balance reactions. A relationship was found between subjective MS-like symptoms and objective measurements of dynamic balance performance. Subjects sensitive to unusual vestibular messages differed from the others by a greater increase in the parameters indicating a difficulty of balance whereas subjects sensitive to unusual visual messages were recognized by the strategy they used to balance themselves. CONCLUSIONS: These results demonstrated that a sensory conflict can trigger MS-like symptoms. We conclude that the measured parameters of a global somatomotor activity, such as the dynamic balance task proposed here, could be useful for objectively detecting subjects predisposed to MS, for training them and testing the efficiency of anti-MS drugs.

Adult↗

PubMed1995

Impact of a four-day head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as probe to evaluate hepatic blood flow.

The impact of a microgravity simulation using a head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7-day study, including a 4-day head-down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidocaine on days 1 through 5 and 7. Blood sampling, cardiac output, and hepatic artery blood flow velocity measurements were done within 6 hours after administration. Cardiac output increased significantly during head-down tilt, and returned to basal values during the recovery period. Blood flow velocity in the hepatic artery increased during the first day of the down tilt. Slight side effects (buzzing noise in the ears and sleepy feeling) were reported within minutes after the injection of lidocaine. Lidocaine disposition was modified during head-down tilt: a significant decrease in maximal concentration (1.47 +/- 0.26 mg/L on day 1 and 0.96 +/- 0.30 mg/L on day 2); an increase in elimination clearance from 8.24 +/- 3.22 mL/kg.minutes-1 to 11.63 +/- 3.00 mL/kg.minutes-1; an increase in volume of distribution on day 2 and a decrease to lower than basal value on the other days (2.77 +/- 1.73 L/kg on day 1 and 2.33 +/- 0.48 L/kg on day 7). Half-life regularly decreased from 264 +/- 210 minutes to 160 +/- 60 minutes between day 1 and day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Muscle strength during bedrest with and without muscle exercise as a countermeasure.

Bedrest is known to be a useful experimental model for simulating weightlessness and studying its effects on human skeletal muscle activity. We therefore conducted a study in which 12 healthy male subjects underwent 28 days of continuous exposure to 6 degrees head-down bedrest. Our main objective was to test a set of preventive countermeasures for maintaining the stability of the human body. Of the subjects 6 performed deadlifts in the supine position for 30 to 45 min each day. The isometric actions were performed for 5-30 s at 90, 120 and 150 degrees knee angles and isokinetic training at speeds of 30 and 180 degrees.s-1. In vivo quadriceps muscle strength was measured under controlled experimental conditions with a commercial dynamometer. The hypothesis that intense daily isometric and isokinetic leg exercise and lower body negative pressure (LBNP) might serve to maintain muscle strength under conditions of weightlessness was tested. Of the subjects 6, who did not perform any exercise, served as the control population under conditions of simulated weightlessness. The results showed that a significant reduction (P < or = 0.0001) in the muscle force [-10.3 (SD 6.7%)] occurred in the control group whereas no significant changes were observed in the trained group [+3.9 (6.8%)]. From these studies we conclude that intense muscle training and LBNP constitute efficient countermeasures to compensate for the biomechanical effects of weightlessness on human lower limbs and to limit other factors such as cardiovascular deconditioning.

Adult↗

PubMed1995

Venous distensibility and venous emptying in the legs during a 42-day -6 degrees head-down bedrest.

Exposure to actual or simulated microgravity is known to result in changes in lower limb venous compliance or distensibility which may play a role in post-bedrest or postflight orthostatic intolerance. Venous deconditioning has only been described in terms of changes in vascular compliance or distensibility. But a complete understanding of changes in venous hemodynamics and cardiovascular regulation occurring under these conditions has to take into account changes in emptying capacities of the veins which influence venous return, cardiac filling, and cardiac output regulation. Moreover, few data are available about the course of changes in venous hemodynamics for periods of simulated microgravity longer than 4 weeks. The purpose of this investigation was to measure parameters of venous compliance and venous emptying before, during, and after a 42-day period of bedrest at -6 degrees head-down tilt for a better understanding of long term venous physiological adaptation to microgravity.

Adult↗

PubMed1995

Characteristics of the venous hemodynamics of the leg under simulated weightlessness: effects of physical exercise as countermeasure.

In order to test the hypothesis that increases in calf venous distensibility in microgravity are partly due to the changes affecting the surrounding skeletal muscles (muscular atrophy), 12 healthy volunteers were exposed for 28 d to microgravity simulated by -6 degrees head-down bed rest. Half these subjects were exposed to countermeasures during bed rest: a) repeated LBNP (Lower Body Negative Pressure) sequences starting on the 15th d with one 15 min sequence at -35 mb, every other day from the 15th until the 21st d, and then every day until the end of bed rest; b) physical training including isotonic type exercise and isometric or isokinetic work by all muscle mass of upper and lower limbs (from the 8th until the 28th d). The other six subjects forming the control group were not subjected to any countermeasure. Calf venous hemodynamics were determined by mercury strain gauge plethysmography with venous occlusion. Distensibility (delta Vmax) and venous emptying (venous outflow at the 6th s of emptying: VO6, half-emptying time: T1/2, maximum venous outflow (MVO) could also be measured. Nuclear magnetic resonance (NMR) was used to study changes in volume of calf muscles. Plethysmographic measurements made for each subject prior to, during (once a week), and after bed rest show a parallel increase in calf venous distensibility in both groups of subjects until the 20th d of bed rest. Filling and emptying times then tended to stabilize in the group treated with countermeasures (group CM) whereas high venous distensibility was observed until the end of bed rest and 5 d thereafter in the control group (group C).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Effects of 28-day head-down tilt with and without countermeasures on lower body negative pressure responses.

This study was performed to determine the effects of 28 d of head-down tilt (HDT) (simulated weightlessness) on cardiovascular responses to orthostatic stress induced by lower body negative pressure (LBNP) (before, during, and after HDT) and +60 degrees head-up tilt (before and after HDT) in 12 subjects. Half of them underwent countermeasures (CM) of regular muscular exercise (isometric and isokinetic training) and LBNP sessions (-30 mm Hg) as generally performed during spaceflight; the other six were a control group (C). The countermeasure effect on the orthostatic responses to LBNP and tilt test was assessed by studying the changes after HDT in the two groups. Essentially, blood pressure was better maintained in group CM in the tilt test after HDT (MBP at the end of the tilt vs. baseline value: +16% (CM); -19% (C)). LBNP and muscular exercise may have contributed to this improvement. One of the probable contributing factors is the relative conservation of plasma volume, at the end of HDT, in group CM (-2.2%), compared to group C (-11.2%). Transcranial Doppler (TCD) recordings of middle cerebral artery (MCA) velocities permitted indirect evaluation of cerebral blood flow changes during the orthostatic tests. MCA velocities decreased significantly although slightly (-7 to -12%) during LBNP sessions without changes along the HDT showing that the cerebral circulation was well preserved in each group. On the other hand, subjects undergoing presyncopal symptoms presented a drop in MCA velocities, suggesting a decrease in cerebral blood flow.

Adult↗

PubMed1994

[Orthostatic hypotension after space flight].

Cardiovascular changes occur during spaceflight. Because of the loss of hydrostatic pressure there is, during weightlessness, a fluid shift of extra- and intra-vascular volumes to the upper part of the body. This provokes objective and subjective symptoms, especially in the first days of spaceflight. The fluid shift is perceived by baroreceptors as a relative central hypervolaemia and induces neuro-hormonal mechanisms which provoke a real hypovolaemia. Cardiovascular deconditioning exists during spaceflight with the following symptoms when astronauts return to earth: decreased orthostatic tolerance with possible tendency towards spontaneous syncope and decreased effort capacity. The mechanisms of orthostatic intolerance are not well known. Several factors are probably involved, including hypovolaemia, modifications of the venous system, baroreflex changes, etc. Various countermeasures have been tested in microgravity simulations on the ground, then in flight.

Cardiovascular Deconditioning↗

PubMed1994

Altered autonomic regulation of cardiac function during head-up tilt after 28-day head-down bed-rest with counter-measures.

The effects of 28 days continuous 6 degrees head-down tilt bed-rest on heart rate variability and the slope of the spontaneous arterial baroreflex were evaluated during supine rest and the first 10 min of 60 degrees head-up tilt. Twelve healthy men were assigned to either a no counter-measure (No-CM), or a counter-measure (CM) group so that there was no difference in maximal oxygen uptake. Counter-measures consisted of short-term, high resistance exercise for 6 days per week from days 7-28, and lower body negative pressure (-28 mmHg) for 15 min on days 16, 18, 20 and 22-28. In spite of balanced between-group fitness, mean RR-interval was different between the No-CM and the CM group prior to bed-rest, but neither this nor any other variables showed significant counter-measure by bed-rest interaction effects. Therefore, all data presented are from the main effects of bed-rest or tilt from the analysis of variance. RR-interval was reduced significantly by bed-rest and by tilt (P < 0.0001). Indicators from spectral analysis of heart-rate variability suggested reduced parasympathetic nervous system activity with bed-rest (P < 0.01) and head-up tilt (P < 0.05), and increased sympathetic nervous system activity after bed-rest (P < 0.01). An indicator of complexity of cardiovascular control mechanisms, taken from the slope (beta) of log spectral power vs. log frequency relationship, suggested reduced complexity with bed-rest (P < 0.05) and head-up tilt (P < 0.01). The spontaneous baroreflex slope was reduced significantly by bed-rest (P < 0.03) and by head-up tilt (P < 0.04). Taken together, these data support the concept of altered autonomic nervous system function in the aetiology of cardiovascular deconditioning with bed-rest or space travel; and it would appear that no benefit is derived from these specific counter-measures.

Adult↗

PubMed1994

Reduced spontaneous baroreflex response slope during lower body negative pressure after 28 days of head-down bed rest.

Effects of 28 days of continuous 6 degrees head-down tilt bed rest on spontaneous vagally mediated baroreflex response slope were evaluated from beat-by-beat relationships between R-R interval and systolic arterial blood pressure. Twelve healthy men (age 27-42 yr) were assigned to either countermeasure (CM) or no-countermeasure (no-CM) groups. CM consisted of strenuous short-term exercise once per day 6 days/wk from days 7 to 28 and lower body negative pressure (LBNP) for 15 min on days 16, 18, 20, and 22-28. Spontaneous baroreflex slope was evaluated by application of linear regression to sequences of at least three beats in which systolic blood pressure and R-R interval changed in the same direction. Measurements were made pre-, mid- (day 15), and post-bed rest at rest and during progressive LBNP tests (3 min at each of -20, -30, -40, and -50 mmHg). R-R interval decreased progressively and significantly (P < 0.0001) over duration of bed rest. Spontaneous baroreflex slope at rest in pre-bed rest was 18.5 +/- 2.1 ms/mm Hg for CM and 14.9 +/- 1.6 ms/mmHg for no-CM. There was a significant reduction in baroreflex slope as a function of bed rest, and it was further reduced during LBNP (P < 0.0001). Between CM and no-CM groups differences existed, but these were present pre-bed rest and appeared unaffected by countermeasures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗