Search PubMed⌕ Search

Biomedical subjects

P Vasseur

Publications and source records attributed to P Vasseur.

At least 37 records · Page 2Linked to original sources

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest.

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.

Adult↗

Effects of peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on intercellular communication and connexin43 in two hamster fibroblast systems.

Effects of 12-O-tetradecanoyl phorbol 13-acetate (TPA) and the hepatic peroxisome proliferators (HPPs) clofibrate, methyl clofenapate (MCP), di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate (MEHP) were studied in 2 gap junctional intercellular communication (GJIC) systems, metabolic cooperation in V79 cells and microinjection/dye transfer in Syrian hamster embryo (SHE) cells and V79 cells. TPA inhibited GJIC in both systems but was considerably more potent in V79 cells. SHE cells showed a rapid and transient inhibition of GJIC after exposure to HPPs, with maximal inhibition occurring at 5-15 min. The transient inhibition could be caused by metabolization of the compounds. Clofibrate and MEHP produced strong inhibition of metabolic cooperation in V79 cells at high concentrations, while the effect of MCP and DEHP was lower. However, DEHP, MEHP and clofibrate strongly inhibited dye transfer in V79 cells after a 30 min exposure. Clofibrate also showed a dose- and time-dependent effect on dye transfer in V79 cells. The phosphorylation status of the gap junction protein connexin43 (Cx43) changed minimally in SHE cells after exposure to TPA or HPPs. Cx43 from V79 cells was strongly affected by TPA, but not by HPPs. Immunofluorescence of Cx43 disappeared in both cell types when they were exposed to TPA and MEHP, but not to the other HPPs. Thus, there is no direct correlation between the inhibition of GJIC and changes in the phosphorylation status of Cx43 or the appearance of Cx43 in immunofluorescence experiments. The discrepancies may partly be explained by binding of accessory proteins to Cx43. We point out sequences that may be involved in such binding.

Animals↗

Glutathione reductase, selenium-dependent glutathione peroxidase, glutathione levels, and lipid peroxidation in freshwater bivalves, Unio tumidus, as biomarkers of aquatic contamination in field studies.

The aim of this study was to evaluate the usefulness of antioxidant parameters in the freshwater bivalve, Unio tumidus, as biomarkers of exposure to pollutants and to study their potential interest in predicting toxicity. Selenium-dependent glutathione peroxidase (Se-GPx), non-selenium-dependent glutathione peroxidase (non-Se-GPx), glutathione reductase (GRd), catalase, and superoxide dismutase (SOD) activities; reduced (GSH) and oxidized (GSSG) glutathione levels; and lipid peroxidation were measured in the gills and digestive glands of Unio. Control mussels were encaged and transplanted for 15 and 30 days to sites where the contamination of sediments was analyzed, along a river receiving domestic and industrial sources of pollution. After 15 days of exposure, all antioxidant parameters of the bivalves transferred to the most polluted sites had strongly decreased compared with control values. This was particularly true for Se-GPx and GRd activities, which were inhibited by 60 and 80% in the two tissues, and for GSH levels (80% reduction in the gills and 60% in digestive glands). These decreases were associated in the gills with lipid peroxidation (measured by malondialdehyde content) and with a high level of contamination of sediments by polycyclic aromatic hydrocarbons and polychlorinated biphenyls. In the mussels exposed at the least polluted sites, the same parameters decreased in the gills, but to a lesser extent: 50% for Se-GPx and 32% for GRd activities, and 45% for GSH levels. The gills appeared more sensitive than the digestive glands. After 30 days of exposure, while Se-GPx, GRd, and GSH remained reduced, a significant induction of non-Se-GPx and catalase activities was recorded in the gills, which reflected an adaptation of the transplanted species to their unsafe environment. All the results indicated that antioxidant defense components, namely, Se-GPx, GRd, and GSH, are sensitive parameters that could be useful biomarkers for the evaluation of contaminated aquatic ecosystems. The relationship between the degree of deficiency of antioxidant defenses and lipid peroxidation suggests that these parameters could also be biomarkers for toxicity.

Animals↗

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↗

Dysregulation of ornithine decarboxylase activity, apoptosis and Bcl-2 oncoprotein in Syrian hamster embryo cells stage-exposed to di(2-ethylhexyl)phthalate and tetradecanoylphorbol acetate.

Perturbations of cell proliferation and death are considered as essential events in the process of carcinogenesis. Thus, two parameters, ornithine decarboxylase (ODC), an enzyme closely related to cell proliferation and transformation, and apoptotic phenomenon are profoundly modified. Using Syrian hamster embryo (SHE) cells, we have examined in the framework of two-stage carcinogenesis (initiation-promotion) the effects of a non-genotoxic [diethylhexylphthalate (DEHP)] or genotoxic [benzo[a]pyrene (BaP)] carcinogen or a non-carcinogenic compound [phthalic anhydride (AP)] on these parameters. Immunoreactive Bcl-2 and Bcl-xL proteins were also investigated following two-stage exposures. Whereas exposures to BaP, DEHP or AP alone did not provoke any modification of ODC activity, the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), strongly increased it. Using two-stage exposure protocol (xenobiotics first, then replacement by TPA-promoter), the ODC activity was higher than that obtained with TPA alone. This superinduction of ODC activity was observed only with the carcinogenic compounds DEHP and BaP. Following the same exposure protocol, spontaneous cellular apoptosis was decreased. Furthermore, Bcl-2 oncoprotein was also upregulated approximately 8- and 11-fold for BaP and DEHP respectively; meanwhile Bcl-xL protein rate did not change. The non-carcinogenic compound AP slightly inhibited spontaneous SHE cell death without ODC superinduction. Exogenous polyamines, putrescine, spermidine and spermine diluted in the medium did not inhibit spontaneous apoptosis. Although inhibition of apoptosis was not specific of carcinogenic compound, both superinduction of ODC activity and inhibition of apoptosis via Bcl-2 upregulation, may cooperate during early stages of the carcinogenic process.

Animals↗

Alteration in methyl-methanesulfonate-induced poly(ADP-ribosyl)ation by 2-butoxyethanol in Syrian hamster embryo cells.

The effects of 2-butoxyethanol (2-BE) on poly(ADP-ribosyl)ation were studied in Syrian hamster embryo (SHE) cells by measuring the cellular concentrations of the polymer poly(ADP-ribose) (pADPr) and of NAD+, the substrate of poly(ADP-ribose) polymerase (PARP). As biotransformation pathways of ethylene glycol ethers involve NAD+-dehydrogenases, it was hypothesized that 2-BE could reduce poly(ADP-ribosyl)ation by consuming NAD+. As a result DNA repair could be altered, which would explain that 2-BE had been shown to potentiate the effects of clastogenic substances such as methyl-methanesulfonate (MMS). In this study, the effects of 2-BE on MMS-induced pADPr metabolism were analyzed. The results indicated that: (i) 2-BE (5 mM) by itself did not influence significantly pADPr or NAD+ levels. (ii) 2-BE inhibited pADPr synthesis in MMS (0.2 mM)-pretreated cells, without any change in NAD+ concentrations. (iii) MMS treatment, which rapidly increased pADPr levels, also affected the poly(ADP-ribosyl)ation system as a secondary effect by damaging cell structures. Membrane permeabilization, which occurred at concentrations >1 mM MMS, led to a dramatic leakage of cellular NAD+ resulting in a strong reduction in pADPr levels. (iv) A bleomycin pulse (100 microM) applied after MMS and/or 2-BE treatment confirmed that 2-BE reduced poly(ADP-ribosyl)ation capacities of MMS-treated cells, though the glycol ether had no effect alone. This study confirmed that the inhibition of pADPr synthesis could be responsible for the synergistic effects of 2-BE with genotoxic substances. The mechanism of this inhibition cannot be explained by a lack of NAD+ at the concentrations of 2-BE tested.

Animals↗

Comparative effects of clofibrate and methyl clofenapate on morphological transformation and intercellular communication of Syrian hamster embryo cells.

The Syrian hamster embryo (SHE) cell system was used to evaluate the ability of two hepatocarcinogenic structurally related peroxisome proliferators (PPs) to induce morphological transformation (MT) of SHE colonies and to inhibit gap junctional intercellular communication (GJIC). Clofibrate and methyl clofenapate (MCP), which was shown to be a more active PP and a more potent carcinogen in vivo than clofibrate, were compared. MCP appeared slightly more active in vitro than clofibrate in affecting MT and GJIC of SHE cells. The morphological transformation of SHE colonies was induced by 50 microM MCP, against 100 microM clofibrate. Moreover, 50 microM MCP potentiated the transforming effects of both benzo[a]pyrene and 12-O-tetradecanoylphorbol-13-acetate. The inhibition of GJIC, measured by transfer of lucifer yellow, was transient and occurred at concentrations inducing morphological transformation. MCP inhibited dye transfer at 50 microM and the inhibition lasted up to 24 h at 100 microM. Inhibition of communication lasted only 4 h with clofibrate and occurred at a higher concentration (175 microM). This study showed that both the SHE cell transformation and dye transfer assays were able to display the different activities of the two PPs, even though the difference in potency observed was smaller than in vivo. It also revealed interactions between non-genotoxic carcinogens and the ability of the SHE cell transformation assay to detect these combined effects.

Animals↗

Cardiovascular and hormonal changes induced by a simulation of a lunar mission.

BACKGROUND: This is the first simulation of a 14-d lunar mission including 6 d on the Moon. HYPOTHESIS: We hypothesized that a lunar gravity simulation in the middle of a head-down tilt (HDT) might result in some reversal of body fluid/hormonal responses, and influence cardiovascular deconditioning. METHODS: Six men (28 +/- 2.5 yr) were placed in bed rest (BR): in (HDT) (-6 degrees) to simulate microgravity during the travel (two 4-d periods), and in head-up tilt (HUT) (+10 degrees) (6-d period) to simulate lunar gravity (1/6 g). Muscular exercise was performed during the HUT period to simulate 6 h of lunar EVA. Heart rate variability (HRV) and hormonal responses were studied. RESULTS: An orthostatic arterial hypotension was observed after the BR (tilt test) in 4 of the 6 subjects. Plasma volume measured at D14 decreased by -11.1% (vs. D-3, sitting position). A decrease in atrial natriuretic peptide (26 +/- 3.5 pg.ml-1 (D14) vs. 37.9 +/- 3.5 pg.ml-1 (D-3, sitting) and an increase in plasma renin activity (198 +/- 9.2 mg.L-1.min-1 (D14) vs. 71 +/- 9.2 mg.L-1.min-1 (D-3, sitting) were observed during the BR, more pronounced in HUT at 7:00 p.m. Sympathetic-parasympathetic balance (HRV) at rest showed a decrease in parasympathetic indicator and an increase in sympathetic indicator in BR (p < 0.05), without differences within HDT and HUT periods. CONCLUSION: These changes were mostly similar to those reported in spaceflights, and HDT. Although the exposure to 1/6 g with exercise modified some hormonal and body fluid responses, this partial gravity simulation was not sufficient to prevent the decrease in orthostatic tolerance observed here as well as after Apollo lunar missions.

Adult↗

Glycol ethers induce death and necrosis in human leukemia cells.

Ethylene glycol ethers are common solvents. Some isomers are toxic for the reproduction and immunity functions of humans and laboratory animals and are antileukemic for rodents. The health hazards of ethylene glycol ethers may result from their ability to induce cell death in various organs or tissues. To study this possibility, the human leukemia cell lines HL-60, Molt3, and K562 were treated with ethylene glycol ethers. 2-Ethoxyethanol and 2-butoxyethanol were selected because they are among the most commonly used ethelyne glycol ethers, but little is known about their individual toxicity. Cell death was detected by trypan blue uptake, flow cytometry, DNA electrophoresis, and poly(ADP-ribose) polymerase proteolysis. The treatments lasted up to 72 h with doses ranging from 1 to 20 mM, which are high relative to the concentrations found in biological fluids of exposed workers. The highest dose of 2-butoxyethanol (20 mM) induced apoptosis in Molt3 cells after 72 h incubation. Other treatments had no effect, induced necrosis, or blocked the cells in the G1 phase of the cell cycle.

Apoptosis↗

Nongenotoxic carcinogens: development of detection methods based on mechanisms: a European project.

While the accumulation of genetic changes in a somatic cell is considered essential for the genesis of a cancer, it has become clear that not all carcinogens are genotoxic, suggesting that some carcinogens indirectly participate in the generation of genetic changes during carcinogenesis. A European project funded by the European Community was thus conceived to study mechanisms of nongenotoxic aspects of carcinogenesis. Two main strategical approaches were adapted: (i) to study whether and how Syrian hamster embryo (SHE), Syrian hamster dermal (SHD) and BALB/c 3T3 cell transformation systems simulate in vivo carcinogenesis, and to examine whether they can detect nongenotoxic carcinogens; (ii) to study, refine and validate mechanisms-based end-points for detection of nongenotoxic carcinogens. For mechanisms-based research, the proposed end-points included gap junctional intercellular communication (GJIC) inhibition, altered expression of critical genes, immortalization and aberrant cell proliferation. We also selected model compounds commonly usable for various endpoints. Our major results can be summarized as follows: (1) SHE and BALB/c 3T3 transformation systems reflect both genotoxic and nongenotoxic carcinogenic events; they detect not only genotoxic but also many although not all, nongenotoxic carcinogens. This is further supported by the fact that both genotoxic and nongenotoxic carcinogens were able to immortalize SHD cells. (2) Many nongenotoxic carcinogens, although not all, inhibit GJIC in vitro as well as in vivo. Mechanistic studies suggest an important role of blocked GJIC in carcinogenesis and that different mechanisms are involved in inhibition of the communication by different agents used. However, inhibition of GJIC is not a prerequisite for the enhancement (or induction) of transformation of SHE or BALB/c 3T3 cells. (3) Among compounds examined, there was a good correlation between induction of micronuclei and cell transformation in SHE cells while no such correlation was found between the induction of cell transformation and ornithine decarboxylase activity. (4) Two transgenic mouse mutation assays (lacI and lacZ) were established and validated. The genotoxin dimethylnitrosamine was shown to be mutagenic to the liver in both assays. Ortho-anisidine, a bladder-specific carcinogen that was inactive in standard rodent genetic toxicity assays was uniquely mutagenic to the bladder of the transgenic mice. The peroxisome proliferator methyl clofenipate was established as nonmutagenic to the liver of both transgenic mice. That eliminated DNA damage as a cause of the liver tumours produced by this chemical and weakened the idea that induced cell division leads to mutation induction. (5) With an in vitro DNA replication model, it was found that DNA damage induced by genotoxic agents can be responsible for inhibition of DNA replication, while certain nongenotoxic agents such as phorbol esters increase DNA replication. (6) An attempt to use structure-activity relationship for subfamilies of nongenotoxic carcinogens, e.g., receptor-mediated carcinogens, has been initiated with some promising results. Our results support the idea that there are multiple nongenotoxic mechanisms in carcinogenesis, and that working hypothesis-oriented approaches are encouraged rather than simple screening of chemicals in developing test systems for the detection of nongenotoxic carcinogens.

3T3 Cells↗

The genotoxicity of iron and chromium in electroplating effluents.

Electroplating effluents were tested for their genotoxicity with the micronucleus test on newt larvae. The metallic content of the tested samples was responsible for the induction of micronuclei in red blood cells (RBC). Then, iron (Fe3+), chromium (Cr3+, Cr6+) and zinc (Zn2+) which were identified in these samples, were tested either separately or combined, at their concentrations in the electroplating effluents. Fe3+ induced a high level of micronuclei at 12.5 and 25 mg/l (nominal concentrations). Both soluble and non-soluble forms of iron were responsible for these genotoxic effects. At lower concentrations (0.6 and 4.5 mg/l) Fe3+ was not systematically genotoxic. Zinc could not be considered genotoxic on newt. Cr3+ gave negative responses, but exposure to Cr6+ (1 mg/l) could result in a significant number of micronucleated RBC in some cases. The most dramatic genotoxic effects were registered when Fe3+ and Cr6+ were combined. This study demonstrates that interactions between pollutants and the effects of non-soluble chemicals on aquatic vertebrates and invertebrates can no longer be neglected.

Animals↗

Synergistic effects of chlordane and TPA in multistage morphological transformation of SHE cells.

The cyclodiene pesticide chlordane has been reported to be a non-genotoxic carcinogen in rodents. The effects of chlordane on SHE cell transformation were investigated in this study. It appeared that chlordane exhibited a weak transforming activity when applied repeatedly at 8 micrograms/ml. No effect resulted from the combination of benzo[a]pyrene-chlordane. In contrast, chlordane in the range 5-20 micrograms/ml and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 micrograms/ml) highly potentiated each other when applied sequentially. The synergistic effects could be inhibited by dexamethasone. These results led us to study the genotoxicity of chlordane on SHE cells: no DNA adduct formation could be detected in SHE cells treated with chlordane at a concentration potentiating the transforming effect of TPA. We also confirmed that this pesticide markedly inhibited intercellular communication between SHE as well as V79 cells. These results support literature data on the non-genotoxicity of chlordane. Overall, this study highlights the fact that interaction between-non genotoxic carcinogens may enhance the transformation frequency of SHE cells. Thus, combined effects must be taken into account in the evaluation of carcinogenic risk.

Animals↗

Mutagenicity of ethylene glycol ethers and of their metabolites in Salmonella typhimurium his-.

Ethylene glycol ethers, their aldehyde and their acid metabolites were evaluated for their mutagenicity with the Ames test. The Salmonella typhimurium his- tester strains TA 97a, TA 98, TA 100 and TA 102 were used with and without rat S9 mix. Ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol n-butyl ether and their corresponding aldehyde and acid derivatives were tested up to 10(-4) mol/plate (around 10 mg/plate) or up to cytotoxic concentrations. All tested substances gave negative results with TA 98, TA 100 and TA 102 either with or without S9 mix. In contrast, ethylene glycol n-butyl ether (EGBE) and the aldehyde metabolite of ethylene glycol monomethyl ether, methoxyacetaldehyde (MALD), displayed mutagenic potency in strain TA 97a with and without S9 mix at high concentrations. A significant number of revertants was obtained from 19 mumol/plate EGBE (2.2 mg/plate) and from 34 mumol/plate MALD (2.5 mg/plate). At these concentrations the level of revertants reached up to 7-fold and 3-fold the control values for EGBE and MALD respectively.

Acetaldehyde↗

Femoral flow response to lower body negative pressure: an orthostatic tolerance test.

UNLABELLED: The objective was to check, during a lower body negative pressure (LBNP) test, new vascular parameters for the detection of orthostatic intolerance induced by head-down-tilt (HDT) and spaceflight. METHODS: The lower-limb volume flow and vascular resistance were evaluated by Doppler ultrasound. The HDT population consisted of two groups: control [6 subjects resting in a HDT (-6 degrees) position for 28 d] and countermeasure (6 subjects also in HDT for 28 d, but with repeated LBNP and exercise). The LBNP orthostatic test (four steps: -20, -30, -40, -50 mm Hg, of 3 min each) was performed before, during, and after the HDT. For the 14-d spaceflight (Antares) the cosmonaut underwent the LBNP test (10 min at -25 mm Hg and 10 min at -45 mm Hg), at preflight (3 times), inflight (day 11), and postflight (twice). RESULTS: HDT--As the LBNP pressure decreased, the femoral blood flow decreased and the lower-limb vascular resistances increased in both HDT groups. In the control group the femoral flow was less reduced, at each of the 4 levels of depressure (p < 0.01). The amplitude of the leg vascular resistances was reduced at -40 mm Hg, and at -50 mm Hg, on HDT day 15 in both groups (before LBNP, after 1 week's exercise for the countermeasure group), and on post-HDT day 1 (p < 0.01) only in the control group. The femoral vascular resistance response had completely recovered in the countermeasure group on post-HDT day 1. During the post-HDT tilt table test, all 6 controls had a drop in blood pressure of 20 mm Hg (4 subjects) or 10 mm Hg (2 subjects); 3 had pre-syncopal symptoms. The HDT countermeasure subjects had neither any clinical signs of orthostatic intolerance nor any blood pressure drop. 14d-Spaceflight--During the flight, the cosmonaut did not use any countermeasures (exercise, LBNP). On flight day +11, and on postflight day 3, the femoral vascular resistance response to LBNP was decreased as observed in the control group on HDT day +15 and post HDT. On postflight day 7, the femoral response had completely recovered. The middle cerebral flow response to the various pre-, in-, and postflight LBNP tests consisted of a slight decrease of the cerebral flow together with resistances of comparable amplitude (-10 to -20%) to those measured during the same LBNP test in the HDT control group. CONCLUSION: The femoral hemodynamics are much more disturbed than the cerebral ones in vascular deconditioning. The assessment of the lower limb vascular reactivity will be of interest in predicting orthostatic intolerance, and checking the efficiency of counter-measures.

Cardiovascular Deconditioning↗

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↗

[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↗

The environmental risks of industrial waste disposal: an experimental approach including acute and chronic toxicity studies.

The toxicity of 15 leachates of various solid industrial wastes accepted in an engineered landfill has been studied. A cost-effective battery of tests allowing evaluation of acute and chronic toxicity, as well as genotoxicity, and investigations on different trophic levels in the aquatic environment has been used. Acute toxicity was tested on bacteria (Microtox assay with Photobacterium phosphoreum) and microcrustaceans (Daphnia magna immobilization assay). A growth inhibition test of microalgae was carried out on Raphidocelis subcapitata. A 28-day chronic test with Daphnia magna was used to detect effects on reproduction. Genotoxicity was evaluated by means of the Ames test conducted on the crude aqueous phase and also on the concentrated fractions of water-extractable micropollutants (liquid-liquid and freeze-dried extracts). Chemical analyses of leachates were carried out simultaneously. The toxicity varied greatly between the different wastes. Toxic effects were observed in the short and/or in the long term. Four samples were potentially genotoxic. In most cases, toxicity registered could not be correlated with results of the chemical analyses. This study demonstrates the usefulness of associating a toxicological monitoring with chemical analyses in waste management.

Animals↗

European isolation and confinement study. Lower body negative pressure tests.

From the LBNP experiment carried out during the ISEMSI project, we can conclude that there was no indication of the cardiac deconditioning syndrome in any of the six subjects. The absence of such effects can probably be ascribed to the following two conditions: (1) the subjects were not in inactive conditions; and (2) there was only a slight overpressure in the hyperbaric chamber.

Adult↗