The use of microindentation for the study of bone properties in type 1 diabetes mellitus patients.

Diabetes mellitus is associated with a higher risk of fracture. In this study, we analysed the bone quality of premenopausal women with type 1 diabetes mellitus by microindentation. No differences in bone quality were identified between patients and healthy controls, suggesting that intensive insulin therapy can preserve bone health. PURPOSE: To compare the bone quality of women with type 1 diabetes mellitus (T1DM) and healthy controls, and to determine the relationship with bone mineral density (BMD). METHODS: This was a cross-sectional study of 45 premenopausal women with T1DM and 21 healthy controls, matched according to age and BMI. Clinical parameters, BMD and bone tissue mechanical properties (assessed using the bone material strength index [BMSi]) were evaluated in each group using microindentation. In T1DM patients, glycosylated haemoglobin (HbA1c), the number of hypoglycaemic events and the status of chronic complications were also analysed. RESULTS: No differences in BMSi or BMD between T1DM patients and healthy controls were identified. In the T1DM patients, the mean HbA1c was 7.52% ± 1.00% and the mean time elapsed since diagnosis was 22.6 ± 12.2 years. Eight patients (17.7%) met the criteria for metabolic syndrome (MetS), and microvascular complications were present in 12 patients (26.7%). Neither the number of features of MetS present nor the presence of microangiopathy was found to be associated with BMSi. CONCLUSIONS: T1DM premenopausal patients showed bone tissue properties comparable to those shown by controls. Further larger-scale studies should be conducted to confirm these results.

Reversibility of hemodynamic hypofrontality in schizophrenia.

Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia.

Cerebral blood flow studied by Xenon-133 inhalation technique in parkinsonism: loss of hyperfrontal pattern.

Cerebral blood flow (grey matter flow) in parkinsonism requires further investigation. The noninvasive method of 133Xe inhalation permits study of larger numbers of subjects than previously used invasive techniques such as the intracarotid 133Xe injection method. Measurements were made in this laboratory in 30 subjects having Parkinson's disease. Mean hemispheric blood flow (F1) values were 70.4 +/- 9.3 ml/100 g/min, compared to 76.3 for a group of age-matched normal subjects, which is a decrease of -7.8%. The most striking difference was the loss of the "hyperfrontal distribution" in parkinsonism. The prefrontal F1 values were only 1.8% greater than the hemisphere grey matter flow, compared with 8.5% in controls of a similar age group.

Effects of a dopaminergic agonist (piribedil) on cerebral blood flow in man.

In baboons, the intravenous administration of piribedil, a dopaminergic agonist, was associated with marked dose dependent increases in CBF and cerebral oxygen consumption. We have studied the effects of piribedil on CBF in 20 normal, human volunteers of comparable ages. Ten received 0.1 mg/kg piribedil intravenously for 30 min; the other ten received 0.2 mg/kg. In the first group, CBF did not vary significantly, in the second group, there was a mean increase in CBF of 21.8% (p less than or equal to 0.005). In man, as in animals, piribedil provokes an increase of CBF.

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.

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.

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.

Epinephrine, norepinephrine, and dopamine during a 4-day head-down bed rest.

Head-down bed rest at an angle of 6 degrees was used as an experimental model to simulate the hemodynamic effects of microgravity, i.e., the shift of fluids from the lower to the upper part of the body. The sympathoadrenal activity during acute (from 0.5 to 10 h) and prolonged (4 days) head-down bed rest was assessed in eight healthy men (24 +/- 1 yr) by measuring epinephrine (E), norepinephrine (NE), dopamine (DA), and methoxylated metabolite levels in their plasma and urine. Catecholamine (CA) and methoxyamine levels were essentially unaltered at any time of bed rest. Maximal changes in plasma were on the second day (D2): NE, 547 +/- 84 vs. 384 +/- 55 pg/ml; DA, 192 +/- 32 vs. 141 +/- 16 pg/ml; NS. After 24 h of bed rest, heart rate decreased from 71 +/- 1 to 63 +/- 3/min (P less than 0.01). Daily dynamic leg exercise [50% maximum O2 uptake (VO2 max)] used as a countermeasure did not alter the pattern of plasma CA during bed rest but resulted in a higher urinary NE excretion during postexercise recovery (+45% on D2; P less than 0.05). The data indicate no evident relationship between sympathoadrenal function and stimulation of cardiopulmonary receptors or neuroendocrine changes induced by central hypervolemia during head-down bed rest.

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)

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)

Changes in apical organization of choroidal cells in rats adapted to spaceflight or head-down tilt.

Structural changes observed in choroid plexuses from rats dissected aboard a space shuttle, on day 13 of an orbital flight (NASA STS-58 mission, SLS-2 Experiments) demonstrated that choroidal epithelial cells display a modified organization in a microgravitational environment. Results were compared with ultrastructural observations of choroid plexus from rats maintained under anti-orthostatic restraint (head-down tilt) for 14 days. In both experiment types, the main alterations observed by transmission electron microscopy, at the level of choroidal epithelial cells from the third and fourth ventricles, concerned the formation and the organization of apical microvilli, whereas pseudopod-like structures appeared. Immunocytochemical distribution of ezrin, a cytoskeletal protein involved in apical cell differentiation in choroid plexus, confirmed the structural alteration of microvilli in head-down tilted rats, Kinocilia tended to disappear from the apical surface, suggesting a partial loss of cell polarization. In addition, large amounts of clear vesicles were gathered in the apical cytoplasm of choroidal epithelial cells. Disorganization of apical microvilli accumulations of apical vesicles and partial loss of cell polarity showed that long-stays in weightlessness induced alterations in the fine structure of choroid plexus, consistent with a marked reduction of cerebrospinal fluid production.

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.

Cortical atrophy in Parkinson disease: correlation between clinical and CT findings with special emphasis on prefrontal atrophy.

Thirty-seven patients with Parkinson disease were evaluated clinically and with computed tomography in order to determine the incidence of prefrontal atrophy. An age-matched healthy control group was also scanned. The computed tomographic criteria used were the width of cortical sulci and ventriculocerebral indices. Parkinsonian patients with frontal cortical atrophy represent only one patient out of three. They are much older than parkinsonian patients with normal computed tomographic scans, and the onset of their illness occurs later. No significant difference was found according to gender, parkinsonian clinical triad, psychomotor study, or mean duration of illness and/or dopatherapy to the time of computed tomography. This work seems to separate two Parkinson diseases: one beginning before 65 years and damaging the nigrostriate system, and another beginning after 65 years and damaging both the nigrostriate system and the cortex, particularly the frontal cortex.

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.

Pharmacological exploration of dopamine hypersensitivity in migraine patients.

Patients with migraine show a hypersensitivity to dopamine or its agonists. One of these, piribedil, was administered as 0.1 mg/kg intravenously over 30 min to subjects with either migraine or other types of headache. This test provoked in migraine patients an increase of the cerebral blood flow and the peripheral signs of dopamine hypersensitivity:- nausea or vomiting and a rapid fall in blood pressure. In contrast, in those subjects with chronic non-migrainous headache, the administration of piribedil had no effect. The piribedil test appears to possess good specificity vis à vis migraine, enabling a differential diagnosis from atypical periodic headache, a condition difficult to consider as migraine or psychogenic headache on clinical grounds alone.

[Acebutolol and cerebral blood flow of the moderately hypertensive aged subject]. / Acébutolol et débit sanguin cérébral du sujet âgé moyennement hypertendu.

In 17 moderate hypertensive patients (mean age = 67 +/- 8.8) the effects of a chronic oral administration of the beta blocking agent acebutolol on regional cerebral blood flow (rCBF) was studied using the non invasive 133 Xenon inhalation technique. The results was compared to the rCBF obtained in an age matched normal control group. Our study shows that during long term therapy low doses of acebutolol (200 mg/daily) the rCBF is unaffected by a decrease (20 mmHg) of the mean arterial blood pressure. The relative hypofrontality of the elderly hypertensive patients leads to be corrected by acebutolol.

Voice analysis to predict the psychological or physical state of a speaker.

A vocal message, apart from its semantic content, carries information on the psychological and physiological condition of the speaker. Physical fatigue and especially psychological stress are the pathological elements of the condition. The accepted term for the cause of these effects is the "workload." This article describes the main research carried out since the 1940's to measure the acoustic modifications of the voice brought about by a workload. It concludes by a critical analysis of the studies and a short description of the perspectives for research. Their results mainly concern astronauts and pilots involved in specific high-stress tasks and possible users of voice recognition systems. All the studies show an excellent approach to this field of research but deserve to be widened, deepened, and made more accurate to enable estimating the nature or level of reaction to a workload.

Astronaut behavior in an orbital flight situation: preliminary ethological observations.

Following the ethological approach, astronaut behavior is divided into "observable" motor acts which make possible its quantitative description. Frame-by-frame analysis of current videotape recordings shows that the behavioral adaptation to weightlessness is achieved through various processes. Among these are new motor acts and stereotyped movements (successive movements of head, eye, arm, and hand), reversal and reorganization of the sequence of the motor acts to form new patterns (head and eye movements upward or downward), construction of a particular cognitive image of the astronaut's own world (more compensatory regulations than anticipatory processes), and the relationship between postures and orientations according to the proximate visual environment. Furthermore, the present analysis confirms physiological data showing a redistribution of activity between flexor and extensor muscles, and a differential adaptation of vestibulo-ocular reflexes. Thus, this approach suggests new physiological experiments and enables the prediction of behavioral changes occurring during adaptation in microgravity.

Cardiovascular adaptation during simulated microgravity: lower body negative pressure to counter orthostatic hypotension.

The cardiovascular function is one of the main functions disturbed by microgravity. It is particularly affected by the astronaut's return to Earth, where one of the symptoms of the cardiovascular adaptation syndrome is orthostatic hypotension; the clinical consequence can be presyncopal state or a syncope. Lower body negative pressure (LBNP) is intended to stimulate the venous system of the lower limbs. Studies performed in the U.S. have shown that LBNP constitutes an efficient countermeasure, but this approach is impractical because 4 to 6 h/d of application are required. Five volunteers took part in two recent antiorthostatic bed rest experiments for 30 days. In the first experiment, three subjects were submitted to several sessions of LBNP per day and two others were controls; in the second, the LBNP group of the first experiment became control and vice versa. Two orthostatic investigations were performed: 5 d before bed rest; and at the end of the 30-d bed rest period. The results showed that: 1) when the subjects were controls, a high orthostatic hypotension post bed rest with three syncopes and one presyncopal state during the first minutes of the tilt test appeared; 2) when the subjects were submitted to LBNP sessions, no orthostatic hypotension was noted. These two experiments proved the beneficial effects of the LBNP as a countermeasure against orthostatic hypotension.

Effects of acute exercise on attenuated vagal baroreflex function during bed rest.

We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 degrees head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4% (p < 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p < 0.05) by 10.7 +/- 3.7% above pre-bed rest levels and 34.3 +/- 7.9% above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.