Institute Of Recherche Biomedicale Des Armees Irba

Brétigny-sur-Orge, France

Institute Of Recherche Biomedicale Des Armees Irba

Brétigny-sur-Orge, France
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Blatteau J.-E.,Institute Of Recherche Biomedicale Des Armees Irba | Gempp E.,Expertise Plongee SMHEP | Constantin P.,Expertise Plongee SMHEP | Louge P.,Expertise Plongee SMHEP
Diving and Hyperbaric Medicine | Year: 2011

Background: This study was designed to examine the influence of short delay to recompression and other risk factors associated with the development of severe neurological decompression sickness (DCS) in military divers. Methods: Fifty-nine divers with DCS treated in less than 6 hours from onset of symptoms to hyperbaric recompression were included retrospectively. Diving parameters, Symptom latency and recompression delay were analysed. Clinical symptoms were evaluated for both the acute event and one month later. Results: Median delay to hyperbaric treatment was 35 min (2-350 min). Resolution was incomplete after one month in 25.4% of divers with DCS. Multivariate analysis demonstrated that severe symptoms, classifiedas sensory and motor deficits or the presence of bladder dysfunction, were predictors of poor recovery with adjusted odds ratios (OR) of 4.1 (1.12 to and 9.99 (1.5 to 66.34) respectively. There was a relationship between a longer delay to treatment and incomplete recovery, but the increased risk appeared negligible with an adjusted OR of 1.01 (1-1.02). Conclusion: Our results suggest that neurological severity upon occurrence is the main independent risk factor associated with a poor outcome in military divers with DCS. Clinical recovery was not dramatically improved in this series when recompression treatment was performed promptly.


Drouet J.-B.,Institute Of Recherche Biomedicale Des Armees Irba | Fauvelle F.,Institute Of Recherche Biomedicale Des Armees Irba | Maunoir-Regimbal S.,Institute Of Recherche Biomedicale Des Armees Irba | Fidier N.,Institute Of Recherche Biomedicale Des Armees Irba | And 5 more authors.
Neuroscience | Year: 2015

In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by 1H high-resolution magic angle spinning magnetic resonance spectroscopy (1H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed in the stressed animals may participate in shaping individual differences in psychophysiological reactions. © 2014 IBRO.


Chennaoui M.,Institute Of Recherche Biomedicale Des Armees Irba | Chennaoui M.,University of Paris Descartes | Arnal P.J.,Institute Of Recherche Biomedicale Des Armees Irba | Arnal P.J.,University of Paris Descartes | And 4 more authors.
Sleep Medicine Reviews | Year: 2015

Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a person's cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen. © 2014 Elsevier Ltd.


Lamkowski A.,University of Ulm | Forcheron F.,Institute Of Recherche Biomedicale Des Armees Irba | Agay D.,Institute Of Recherche Biomedicale Des Armees Irba | Ahmed E.A.,University of Ulm | And 4 more authors.
PLoS ONE | Year: 2014

Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (±66%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after IR exposure. © 2014 Lamkowski et al.


Dorey R.,French National Center for Scientific Research | Dorey R.,Institute Of Recherche Biomedicale Des Armees Irba | Pierard C.,Institute Of Recherche Biomedicale Des Armees Irba | Chauveau F.,Institute Of Recherche Biomedicale Des Armees Irba | And 2 more authors.
Neuropsychopharmacology | Year: 2012

The present study was aimed at determining the relative contribution of the dorsal (DH) and ventral (VH) hippocampus in stress-induced memory retrieval impairments. Thus, we studied the temporal involvement of corticosterone and its receptors, i.e. mineralocorticoid (MR) and glucocorticoid (GR) in the DH and VH, in relation with the time-course evolution of stress-induced memory retrieval impairments. In a first experiment, double microdialysis allowed showing on the same animal that an acute stress (electric footshocks) induced an earlier corticosterone rise in the DH (1560 min post-stress) and then in the VH (90105 min post-stress). The return to baseline was faster in the DH (105 min) than in the VH (120 min). Memory deficits assessed by delayed alternation occurred at 15-, 60-, and 105-min delays after stress and were closely related to the kinetic of corticosterone rises within the DH and VH. In a second experiment, the GR antagonist RU-38486 and the MR antagonist RU-28318 were administered in the DH or VH 15 min before stress. RU-38486 restored memory at 60 but not at 105 min post-stress delays in the DH, whereas the opposite pattern was observed in the VH. By contrast, RU-28318 had no effect on memory impairments at both the 60- and 105-min post-stress delays, showing that MR receptors are not involved at these delays. However, RU-28318 administered in the DH restored memory when administered at a shorter post-stress delay (15 min). Overall, our data are first to evidence that stress induces a functional switch from the DH to VH via different corticosterone time-course evolutions in these areas and the sequential GR receptors involvement in the DH and then in the VH, as regards the persistence of stress-induced memory retrieval deficits over time. © 2012 American College of Neuropsychopharmacology. All rights reserved.


Leger D.,University of Paris Descartes | Bayon V.,University of Paris Descartes | Ohayon M.M.,University of Paris Descartes | Ohayon M.M.,Stanford University | And 6 more authors.
Journal of Sleep Research | Year: 2014

Summary: The link between sleepiness and the risk of motor vehicle accidents is well known, but little is understood regarding the risk of home, work and car accidents of subjects with insomnia. An international cross-sectional survey was conducted across 10 countries in a population of subjects with sleep disturbances. Primary care physicians administered a questionnaire that included assessment of sociodemographic characteristics, sleep disturbance and accidents (motor vehicle, work and home) related to sleep problems to each subject. Insomnia was defined using the International Classification of Sleep Disorders (ICSD-10) criteria. A total of 5293 subjects were included in the study, of whom 20.9% reported having had at least one home accident within the past 12 months, 10.1% at least one work accident, 9% reported having fallen asleep while driving at least once and 4.1% reported having had at least one car accident related to their sleepiness. All types of accident were reported more commonly by subjects living in urban compared to other residential areas. Car accidents were reported more commonly by employed subjects, whereas home injuries were reported more frequently by the unemployed. Car accidents were reported more frequently by males than by females, whereas home accidents were reported more commonly by females. Patients with insomnia have high rates of home accidents, car accidents and work accidents related to sleep disturbances independently of any adverse effects of hypnotic treatments. Reduced total sleep time may be one factor explaining the high risk of accidents in individuals who complain of insomnia. © 2013 European Sleep Research Society.


Dorey R.,French National Center for Scientific Research | Dorey R.,Institute Of Recherche Biomedicale Des Armees Irba | Pierard C.,Institute Of Recherche Biomedicale Des Armees Irba | Shinkaruk S.,French Institute of Health and Medical Research | And 5 more authors.
Neuropsychopharmacology | Year: 2011

This study was aimed at determining the type of the glucocorticoid membrane receptors (mineralocorticoid receptors (MRs) or glucocorticoid receptors (GRs)) in the dorsal hippocampus (dHPC) involved in the rapid effects of corticosterone or stress on memory retrieval. For that purpose, we synthesized corticosterone-3-O-carboxymethyloxime-bovine serum albumin conjugate (Cort-3CMO-BSA) conjugate (a high MW complex that cannot cross the cell membrane) totally devoid of free corticosterone, stable in physiological conditions. In a first experiment, we evidenced that an acute stress (electric footshocks) induced both a dHPC corticosterone rise measured by microdialysis and memory retrieval impairment on delayed alternation task. Both the endocrinal and cognitive effects of stress were blocked by metyrapone (a corticosterone synthesis inhibitor). In a second experiment, we showed that bilateral injections of either corticosterone or Cort-3CMO-BSA in dHPC 15 min before memory testing produced impairments similar to those resulting from acute stress. Furthermore, we showed that anisomycin (a protein synthesis inhibitor) failed to block the deleterious effect of Cort-3CMO-BSA on memory. In a third experiment, we evidenced that intra-hippocampal injection of RU-28318 (MR antagonist) but not of RU-38486 (GR antagonist) totally blocked the Cort-3CMO-BSA-induced memory retrieval deficit. In a fourth experiment, we demonstrated that RU-28318 administered 15 min before stress blocked the stress-induced memory impairments when behavioral testing occurred 15 min but not 60 min after stress. Overall, this study provides strong in vivo evidence that the dHPC membrane GRs, mediating the rapid and non-genomic effects of acute stress on memory retrieval, are of MR but not GR type. © 2011 American College of Neuropsychopharmacology. All rights reserved.


Mathieu J.,Institute Of Recherche Biomedicale Des Armees Irba | Mathieu J.,Institute Pasteur Paris
Toxins | Year: 2015

Autophagy is a physiological process involved in defense mechanisms for clearing intracellular bacteria. The autophagic pathway is finely regulated and bacterial toxins interact with this process in a complex manner. Bacterial toxins also interact significantly with many biochemical processes. Evaluations of the effects of bacterial toxins, such as endotoxins, pore-forming toxins and adenylate cyclases, on autophagy could support the development of new strategies for counteracting bacterial pathogenicity. Treatment strategies could focus on drugs that enhance autophagic processes to improve the clearance of intracellular bacteria. However, further in vivo studies are required to decipher the upregulation of autophagy and potential side effects limiting such approaches. The capacity of autophagy activation strategies to improve the outcome of antibiotic treatment should be investigated in the future. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Holy X.,Institute Of Recherche Biomedicale Des Armees Irba | Collombet J.-M.,Institute Of Recherche Biomedicale Des Armees Irba | Labarthe F.,Center Medical Of Lescadrille Des Sous Marins Nucleaires Lanceurs Dengins | Granger-Veyron N.,Center Medical Of Lescadrille Des Sous Marins Nucleaires Lanceurs Dengins | Begot L.,Institute Of Recherche Biomedicale Des Armees Irba
Journal of Applied Physiology | Year: 2012

The aim of the study was to determine the seasonal influence of vitamin D status on bone metabolism in French submariners over a 2-mo patrol. Blood samples were collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively. Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for acidbase balance (PCO 2, pH, and bicarbonate), bone metabolism (bone alkaline phosphatase and COOH-terminal telopeptide of type I collagen), and mineral homeostasis (parathyroid hormone, ionized calcium and phosphorus) were scrutinized. As expected, SP vitamin D status was higher than WP vitamin D status, regardless of the considered experimental time. A mild chronic respiratory acidosis (CRA) was identified in both SP and WP submariners, up to patrol day 41. Such an occurrence paired up with an altered bone remodeling coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of type I collagen ratio). At the end of the patrol (day 58), a partial compensation of CRA episode, combined with a recovered normal bone remodeling coupling, was observed in SP, not, however, in WP submariners. The mild CRA episode displayed over the initial 41-day submersion period was mainly induced by a hypercapnia resulting from the submarine-enriched CO 2 level. The correlated impaired bone remodeling may imply a physiological attempt to compensate this acidosis via bone buffering. On patrol day 58, the discrepancy observed in terms of CRA compensation between SP and WP may result from the seasonal influence on vitamin D status. Copyright © 2012 the American Physiological Society.


Leger D.,University of Paris Pantheon Sorbonne | Beck F.,University of Paris Pantheon Sorbonne | Richard J.-B.,University of Paris Pantheon Sorbonne | Sauvet F.,University of Paris Pantheon Sorbonne | And 2 more authors.
PLoS ONE | Year: 2014

Background: A significant U-shaped association between sleep duration and several morbidity (obesity, diabetes or cardiovascular disease) and mortality risks has been regularly reported. However, although the physiological pathways and risks associated with "too short sleep" (<5 hours/day) have been well demonstrated, little is known about "too much sleeping".Purpose: To explore socio-demographic characteristics and comorbidities of "long sleepers" (over 10 hours/day) from a nationally representative sample of adults.Methods: A cross-sectional nationally representative sample of 24,671 subjects from 15 to 85-year-old. An estimated total sleep time (TST) on non-leisure days was calculated based on a specifically designed sleep log which allows to distinguish "long sleepers" from "short sleepers" (<5 hours/day). Insomnia was assessed according to the International classification of sleep disorders (ICSD-2).Results: The average TST was 7 hours and 13 minutes (+/-17 minutes). Six hundred and twelve subjects were "long sleepers" (2.7%) and 1969 "short sleepers" (7.5%). Compared to the whole group, "long sleepers" were more often female, younger (15-25 year-old) or older (above 65 year-old), with no academic degree, mostly clerks and blue collar workers. "Long sleepers" were significantly more likely to have psychiatric diseases and a greater body mass index (BMI). However, long sleep was not significantly associated with the presence of any other chronic medical disease assessed. Conversely, short sleep duration was significantly associated with almost all the other chronic diseases assessed.Conclusions: In the general population, sleeping too much was associated with psychiatric diseases and higher BMI, but not with other chronic medical diseases. © 2014 Léger et al.

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