132 results on '"Marc-Antoine Custaud"'
Search Results
2. Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation
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Adrien Robin, Angelique Van Ombergen, Claire Laurens, Audrey Bergouignan, Laurence Vico, Marie-Thérèse Linossier, Anne Pavy-Le Traon, Marc Kermorgant, Angèle Chopard, Guillaume Py, David Andrew Green, Michael Tipton, Alexander Choukér, Pierre Denise, Hervé Normand, Stéphane Blanc, Chantal Simon, Elisabeth Rosnet, Françoise Larcher, Peter Fernandez, Isabelle de Glisezinski, Dominique Larrouy, Isabelle Harant-Farrugia, Inês Antunes, Guillemette Gauquelin-Koch, Marie-Pierre Bareille, Rebecca Billette De Villemeur, Marc-Antoine Custaud, and Nastassia Navasiolava
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Science - Abstract
Abstract Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.
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- 2023
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3. Corrigendum: Editorial: Rising stars in environmental, aviation and space physiology: 2022
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Alina Saveko, Takuro Washio, Lonnie G. Petersen, Marc-Antoine Custaud, and Anna-Maria Liphardt
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weightlessness ,deconditioning ,countermeasures ,integrative physiology ,gravitational physiology ,Physiology ,QP1-981 - Published
- 2023
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4. Editorial: Rising stars in environmental, aviation and space physiology: 2022
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Alina Saveko, Takuro Washio, Lonnie G. Petersen, Marc-Antoine Custaud, and Anna-Maria Liphardt
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weightlessness ,deconditioning ,countermeasures ,integrative physiology ,gravitational physiology ,Physiology ,QP1-981 - Published
- 2023
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5. A dry immersion model of microgravity modulates platelet phenotype, miRNA signature, and circulating plasma protein biomarker profile
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Laura Twomey, Nastassia Navasiolava, Adrien Robin, Marie-Pierre Bareille, Guillemette Gauquelin-Koch, Arnaud Beck, Françoise Larcher, Gerardene Meade-Murphy, Sinead Sheridan, Patricia B. Maguire, Michael Harrison, Bernard Degryse, Niall M. Moyna, Claude Gharib, Marc-Antoine Custaud, and Ronan P. Murphy
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Medicine ,Science - Abstract
Abstract Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
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- 2021
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6. Running vs. resistance exercise to counteract deconditioning induced by 90-day head-down bedrest
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Adrien Robin, Linjie Wang, Marc-Antoine Custaud, Jiexin Liu, Min Yuan, Zhili Li, Jean-Christophe Lloret, Shujuan Liu, Xiaoqian Dai, Jianfeng Zhang, Ke Lv, Wenjiong Li, Guillemette Gauquelin-Koch, Huijuan Wang, Kai Li, Xiaotao Li, Lina Qu, Nastassia Navasiolava, and Yinghui Li
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maximal working capacity ,countermeasure ,microgravity ,HDBR ,cardiovascular deconditioning ,orthostatic tolerance ,Physiology ,QP1-981 - Abstract
Spaceflight is associated with enhanced inactivity, resulting in muscular and cardiovascular deconditioning. Although physical exercise is commonly used as a countermeasure, separate applications of running and resistive exercise modalities have never been directly compared during long-term bedrest. This study aimed to compare the effectiveness of two exercise countermeasure programs, running and resistance training, applied separately, for counteracting cardiovascular deconditioning induced by 90-day head-down bedrest (HDBR). Maximal oxygen uptake (V˙O2max), orthostatic tolerance, continuous ECG and blood pressure (BP), body composition, and leg circumferences were measured in the control group (CON: n = 8), running exercise group (RUN: n = 7), and resistive exercise group (RES: n = 7). After HDBR, the decrease in V˙O2max was prevented by RUN countermeasure and limited by RES countermeasure (−26% in CON p < 0.05, −15% in RES p < 0.05, and −4% in RUN ns). Subjects demonstrated surprisingly modest orthostatic tolerance decrease for different groups, including controls. Lean mass loss was limited by RES and RUN protocols (−10% in CON vs. −5% to 6% in RES and RUN). Both countermeasures prevented the loss in thigh circumference (−7% in CON p < 0.05, −2% in RES ns, and −0.6% in RUN ns) and limited loss in calf circumference (−10% in CON vs. −7% in RES vs. −5% in RUN). Day–night variations in systolic BP were preserved during HDBR. Decrease in V˙O2max positively correlated with decrease in thigh (r = 0.54 and p = 0.009) and calf (r = 0.52 and p = 0.012) circumferences. During this 90-day strict HDBR, running exercise successfully preserved V˙O2max, and resistance exercise limited its decline. Both countermeasures limited loss in global lean mass and leg circumferences. The V˙O2max reduction seems to be conditioned more by muscular than by cardiovascular parameters.
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- 2022
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7. Editorial: Cardio-vascular Dysfunction and Physiological Manifestations Induced by Environmental Conditions
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Marc-Antoine Custaud, Olga Vinogradova, Claude Gharib, Michael Delp, François Guerrero, and Ronan Murphy
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weightlessness ,diving ,deconditioning ,gravity ,extreme environment ,Physiology ,QP1-981 - Published
- 2022
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8. Vitamin D concentration and focal brain atrophy in older adults: a voxel‐based morphometric study
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Pauline Ali, Matthieu Labriffe, Nastassia Navasiolava, Marc‐Antoine Custaud, Mickaël Dinomais, Cédric Annweiler, and the SAM group
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Vitamin D is involved in brain health and function. Our objective was to determine whether lower 25‐hydroxyvitamin D (25OHD) concentration was associated with focal brain volume reduction in older adults. Serum 25OHD concentration was measured among 53 older adults (72 ± 5 years; 38% female; mean 25OHD = 67.3 ± 20.8 nmol/L). Gray matter volume (GMV) was automatically segmented using voxel‐based morphometry with CAT12 software. Covariables were age, gender, education, total intracranial volume, and season. Serum 25OHD was positively associated with GMV in left calcarine sulcus (P
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- 2020
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9. Determinants of Doppler-based renal resistive index in patients with septic shock: impact of hemodynamic parameters, acute kidney injury and predisposing factors
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François Beloncle, Natacha Rousseau, Jean-François Hamel, Alexis Donzeau, Anne-Lise Foucher, Marc-Antoine Custaud, Pierre Asfar, René Robert, and Nicolas Lerolle
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Acute kidney injury ,Shock ,Sepsis ,Resistive index ,Critical care ,Vasopressors ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Increased renal resistive index (RI) measured by Doppler ultrasonography has been shown to be associated with acute kidney injury (AKI) in septic patients. However, its clinical use is limited by poor sensitivity and specificity which may be explained by its numerous determinants [in particular mean arterial pressure (MAP)]. We measured, in patients with septic shock, RI at different MAP levels over a short period of time on the admission day to ICU (D1) and every 3 days until day 10 (D10) to define the determinants of RI and study specifically the relationship between RI and MAP. Results Consecutive patients with septic shock without preexisting chronic renal dysfunction were included in this prospective cohort study in two ICUs. Sixty-five patients were included in the study. Thirty-three (50.8%) and 15 (23.1%) patients had a history of chronic hypertension or diabetes, respectively. At D3, 35 patients presented AKI with AKIN 2 or 3 criteria (severe AKI, AKIN2-3 group) and 30 presented no AKIN or AKIN 1 criteria (AKIN0-1 group). As previously described, RI at D1 was higher in the AKIN2-3 group than in the AKIN0-1 group (0.73 interquartile range [0.67; 0.78] vs. 0.67 [0.59; 0.72], p = 0.001). A linear mixed model for predicting RI from D1 to D10 showed that an increase in pulse pressure, presence of severe AKI and additional day of ICU hospitalization were associated with an increase in RI. An increase in MAP and recovery from severe AKI were associated with a decrease in RI. In the presence of chronic hypertension or diabetes, an increase in MAP resulted in a lower decrease in RI, than in the absence of such factors. Presence of AKI at D3 did not impact the relationship between MAP and RI. Conclusions Severe AKI was associated with a reversible increase in RI without significant interaction with the relationship between MAP and RI. Conversely, the presence of chronic hypertension and/or diabetes interacted with this relationship.
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- 2019
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10. Vascular and Microvascular Dysfunction Induced by Microgravity and Its Analogs in Humans: Mechanisms and Countermeasures
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Nastassia Navasiolava, Ming Yuan, Ronan Murphy, Adrien Robin, Mickael Coupé, Linjie Wang, Asmaa Alameddine, Guillemette Gauquelin-Koch, Claude Gharib, Yinghui Li, and Marc-Antoine Custaud
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vascular deconditioning ,endothelium ,vascular remodeling ,vascular risk ,prevention ,shear stress ,Physiology ,QP1-981 - Abstract
Weightlessness and physical inactivity have deleterious cardiovascular effects. The space environment and its ground-based models offer conditions to study the cardiovascular effects of physical inactivity in the absence of other vascular risk factors, particularly at the macro- and microcirculatory levels. However, the mechanisms involved in vascular dysfunction and remodeling are not sufficiently studied in the context of weightlessness and its analogs including models of physical inactivity. Here, we summarize vascular and microvascular changes induced by space flight and observed in models of microgravity and physical inactivity and review the effects of prophylactic strategies (i.e., countermeasures) on vascular and microvascular function. We discuss physical (e.g., exercise, vibration, lower body negative pressure, and artificial gravity) and nutritional/pharmacological (e.g., caloric restriction, resveratrol, and other vegetal extracts) countermeasures. Currently, exercise countermeasure appears to be the most effective to protect vascular function. Although pharmacological countermeasures are not currently considered to fight vascular changes due to microgravity, nutritional countermeasures are very promising. Dietary supplements/natural health products, especially plant extracts, should be extensively studied. The best prophylactic strategy is likely a combination of countermeasures that are effective not only at the cardiovascular level but also for the organism as a whole, but this strategy remains to be determined.
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- 2020
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11. MNX (Medium Duration Nutrition and Resistance-Vibration Exercise) Bed-Rest: Effect of Resistance Vibration Exercise Alone or Combined With Whey Protein Supplementation on Cardiovascular System in 21-Day Head-Down Bed Rest
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Patrick Guinet, James Patrick MacNamara, Matthieu Berry, Françoise Larcher, Marie-Pierre Bareille, Marc-Antoine Custaud, Anne Pavy-Le Traon, Benjamin D. Levine, and Nastassia Navasiolava
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countermeasures ,simulated microgravity ,cardiovascular deconditioning ,resistance vibration exercise ,whey protein supplementation ,cardiac MRI ,Physiology ,QP1-981 - Abstract
Current inflight countermeasures do not completely prevent bone and cardiovascular changes induced by microgravity. High load Resistance Exercise combined with whole body Vibration (RVE) demonstrated benefits on bone and cardiovascular system during previous Head-Down Bed Rest (HDBR) studies. We examined the effectiveness of RVE alone or combined with a nutritional supplementation of Whey protein (NeX) on cardiovascular deconditioning. Eight male subjects (age 34 ± 8 years) in a crossover design completed three 21-day HDBR campaigns (Control-CON, RVE, and NeX). Pre and post HDBR Orthostatic Tolerance (OT) was evaluated by a 15-min head-up tilt test followed by increasing levels of Lower Body Negative Pressure (LBNP). Heart rate (HR), blood pressure (BP), and Sympathetic Index (ΣI) through spectral analysis were measured during OT test. Plasma Volume (PV), and Maximal Oxygen Uptake (VO2max) were measured before and after each campaign. Left ventricular mass, left ventricular end diastolic (LVEDV), end systolic (LVESV), stroke (SV) volumes, and circumferential deformation at rest and during an orthostatic stress simulated by a 30 mmHg LBNP were measured by cardiac MRI. RVE failed to prevent any change in these variables and NeX did not have any additional effect over exercise alone. In the 3 groups, (1) OT time dropped similarly (bed rest p < 0.001), (2) HR and ΣI were increased at rest at the end of HDBR and HR increased markedly during LBNP-tilt test, with inability to increase further the ΣI, (3) PV dropped (bed rest p < 0.001), along with LVEDV, LVESV and SV (p = 0.08, p < 0.001, and p = 0.045, respectively), (4) Left ventricle mass did not change significantly, (5) Deformation of the heart assessed by global circumferential strain was preserved and early diastolic circumferential strain rate was increased during orthostatic stress at the end of HDBR, illustrating preserved systolic and diastolic function respectively, without any difference between groups. Despite the drop in PV and LV volumes, RVE and NeX tended to alleviate the decrease in VO2max. In conclusion, RVE and NeX failed to prevent the cardiovascular deconditioning induced by a 21 day-HDBR.
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- 2020
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12. The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory System
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Vasily B. Rusanov, Ludmila Kh. Pastushkova, Irina M. Larina, Anna G. Chernikova, Anna G. Goncharova, Andrei M. Nosovsky, Daria N. Kashirina, Alexander G. Brzhozovsky, Nastassia Navasiolava, Alexey S. Kononikhin, Anna R. Kussmaul, Marc-Antoine Custaud, and Evgeny N. Nikolaev
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circulatory system ,regulatory mechanisms ,proteomics ,dry immersion ,effects of microgravity ,Physiology ,QP1-981 - Abstract
The purpose of the study was to investigate the regulatory and metabolic changes in the circulatory system when simulating microgravity conditions in a five-day dry immersion. These changes reflect the adaptation processes characteristic for the initial stages of a space flight or a short-duration space flight. Studies were conducted with 13 healthy male volunteers aged 21 to 29 years. The assessment of regulatory and metabolic processes in the circulatory system was based on the heart rate variability (HRV) and urine proteomic profile analysis. It was found that the restructuring of hemodynamics during 5 days hypogravity begins with the inclusion of the nervous circuit of regulation, and for manifestations at the body fluids protein composition level and activation of the metabolic regulation, these periods are apparently insufficient. Perhaps this is due to the fact that the metabolic regulation, being evolutionarily ancient and genetically determined, is more stable and requires more time for its pronounced activation when stimulated by extreme life conditions.
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- 2020
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13. DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid Changes but Not Orthostatic Intolerance Induced by a 5-Day Dry Immersion
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Adrien Robin, Aline Auvinet, Bernard Degryse, Ronan Murphy, Marie-Pierre Bareille, Arnaud Beck, Claude Gharib, Guillemette Gauquelin-Koch, Aude Daviet, Françoise Larcher, Marc-Antoine Custaud, and Nastassia Navasiolava
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simulated microgravity ,thigh cuffs ,countermeasure ,fluid shift ,volemia ,bio-impedance ,Physiology ,QP1-981 - Abstract
Venoconstrictive thigh cuffs are used by cosmonauts to ameliorate symptoms associated with cephalad fluid shift. A ground simulation of microgravity, using the dry immersion (DI) model, was performed to assess the effects of thigh cuffs on body fluid changes and dynamics, as well as on cardiovascular deconditioning. Eighteen healthy men (25–43 years), randomly divided into two groups, (1) control group or (2) group with thigh cuffs worn 10 h/day, underwent 5-day DI. Cardiovascular responses to orthostatic challenge were evaluated using the lower body negative pressure (LBNP) test; body fluid changes were assessed by bio-impedance and hormonal assay; plasma volume evolution was estimated using hemoglobin-hematocrit; subjective tolerance was assessed by questionnaires. DI induced a decrease in plasma volume of 15–20%. Reduction in total body water of 3–6% stabilized toward the third day of DI. This reduction was derived mostly from the extracellular compartment. During the acute phase of DI, thigh cuffs limited the decrease in renin and the increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), the loss in total body water, and tended to limit the loss in calf volume, extracellular volume and plasma volume. At the later stable phase of DI, a moderate protective effect of thigh cuffs remained evident on the body fluids. Orthostatic tolerance time dropped after DI without significant difference between groups. Thigh cuff countermeasure slowed down and limited the loss of body water and tended to limit plasma loss induced by DI. These observed physiological responses persisted during periods when thigh cuffs were removed. However, thigh cuffs did not counteract decreased tolerance to orthostatic challenge.
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- 2020
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14. Cardiovascular System Under Simulated Weightlessness: Head-Down Bed Rest vs. Dry Immersion
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Liubov Amirova, Nastassia Navasiolava, Ilya Rukavishvikov, Guillemette Gauquelin-Koch, Claude Gharib, Inessa Kozlovskaya, Marc-Antoine Custaud, and Elena Tomilovskaya
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support unloading ,lower body negative pressure ,water balance ,orthostatic tolerance ,autonomous regulation ,microgravity models ,Physiology ,QP1-981 - Abstract
BackgroundThe most applicable human models of weightlessness are −6° head-down bed rest (HDBR) and head-out dry immersion (DI). A detailed experimental comparison of cardiovascular responses in both models has not yet been carried out, in spite of numerous studies having been performed in each of the models separately.ObjectivesWe compared changes in central hemodynamics, autonomic regulation, plasma volume, and water balance induced by −6° HDBR and DI.MethodsEleven subjects participated in a 21-day HDBR and 12 subjects in a 3-day DI. During exposure, measurements of the water balance, blood pressure, and heart rate were performed daily. Plasma volume evolution was assessed by the Dill–Costill method. In order to assess orthostatic tolerance time (OTT), central hemodynamic responses to orthostatic stimuli, and autonomous regulation, the 80° lower body negative pressure–tilt test was conducted before and right after both exposures.ResultsFor most of the studied parameters, the changes were co-directional, although they differed in their extent. The changes in systolic blood pressure and total peripheral resistance after HDBR were more pronounced than those after DI. The OTT was decreased in both groups: to 14.2 ± 3.1 min (vs. 27.9 ± 2.5 min before exposure) in the group of 21-day HDBR and to 8.7 ± 2.1 min (vs. 27.7 ± 1.2 min before exposure) in the group of 3-day DI.ConclusionsIn general, cardiovascular changes during the 21-day HDBR and 3-day DI were co-directional. In some cases, changes in the parameters after 3-day DI exceeded changes after the 21-day HDBR, while in other cases the opposite was true. Significantly stronger effects of DI on cardiovascular function may be due to hypovolemia and support unloading (supportlessness).
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- 2020
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15. Effects of Resistance Exercise and Nutritional Supplementation on Dynamic Cerebral Autoregulation in Head-Down Bed Rest
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Marc Kermorgant, Nathalie Nasr, Marc-Antoine Custaud, Nastassia Navasiolava, Philippe Arbeille, Patrick Guinet, Marc Labrunée, Florent Besnier, Dina N. Arvanitis, Marek Czosnyka, Jean-Michel Senard, and Anne Pavy-Le Traon
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cerebral autoregulation ,head-down bed rest ,microgravity ,resistance vibration exercise ,nutritional supplementation ,Physiology ,QP1-981 - Abstract
Head-down bed rest (HDBR) is commonly considered as ground-based analog to spaceflight and simulates the headward fluid shift and cardiovascular deconditioning associated with spaceflight. We investigated in healthy volunteers whether HDBR, with or without countermeasures, affect cerebral autoregulation (CA). Twelve men (at selection: 34 ± 7 years; 176 ± 7 cm; 70 ± 7 kg) underwent three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel, and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Cerebral blood flow velocity was assessed using transcranial Doppler ultrasonography. CA was evaluated by transfer function analysis and by the autoregulatory index (Mxa) in order to determine the relationship between mean cerebral blood flow velocity and mean arterial blood pressure. In RVE condition, coherence was increased after HDBR. In CON condition, Mxa index was significantly reduced after HDBR. In contrast, in RVE and NeX conditions, Mxa were increased after HBDR. Our results indicate that HDBR without countermeasures may improve dynamic CA, but this adaptation may be dampened with RVE. Furthermore, nutritional supplementation did not enhance or worsen the negative effects of RVE. These findings should be carefully considered and could not be applied in spaceflight. Indeed, the subjects spent their time in supine position during bed rest, unlike the astronauts who perform normal daily activities.
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- 2019
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16. Multi-System Adaptation to Confinement During the 180-Day Controlled Ecological Life Support System (CELSS) Experiment
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Ming Yuan, Marc-Antoine Custaud, Zi Xu, Jingyu Wang, Min Yuan, Carole Tafforin, Loïc Treffel, Philippe Arbeille, Michel Nicolas, Claude Gharib, Guillemette Gauquelin-Koch, Laurent Arnaud, Jean-Christophe Lloret, Yinghui Li, and Nastassia Navasiolava
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spaceflight analog ,CELSS ,Mars mission ,chronic stress ,adaptation ,ethological monitoring ,Physiology ,QP1-981 - Abstract
Confinement experiments are essential to prepare long-term space exploration. The 180-day Chinese CELSS (Controlled Ecological Life Support System) study is unique in its design, including a closed-loop system and mid-mission simulation of Mars-like day–night cycle of 24 h 40 min for 36 days (days 72–108). Our aim was to study physiological and psychological consequences of this confinement in four healthy volunteers (one female). CELSS platform consisted of six interconnected modules including four greenhouses. Life support systems were controlled automatically. Body composition, fluid compartments, metabolic state, heart, large vessels, endothelial function, and muscle tone were studied using biological, functional, and/or morphological measurements. Behavioral activities were studied by ethological monitoring; psychological state was assessed by questionnaires. Body weight decreased by ∼2 kg mostly due to lean mass loss. Plasma volume and volume-regulating hormones were mostly stable. Carotid intima-media thickness (IMT) increased by 10–15%. Endothelium-dependent vasodilation decreased. Masseter tone increased by 6–14% suggesting stress, whereas paravertebral muscle tone diminished by 10 ± 6%. Behavioral flow reflecting global activity decreased 1.5- to 2-fold after the first month. Psychological questionnaires revealed decrease in hostility and negative emotions but increase in emotional adaptation suggesting boredom and monotony. One subject was clearly different with lower fitness, higher levels of stress and anxiety, and somatic signs as back pain, peak in masseter tone, increased blood cortisol and C-reactive protein. Comparison of CELSS experiment with Mars500 confinement program suggests the need for countermeasures to prevent increased IMT and endothelial deconditioning. Daily activity in greenhouse could act as countermeasure against psycho-physiological deconditioning.
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- 2019
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17. DI-5-Cuffs: Lumbar Intervertebral Disc Proteoglycan and Water Content Changes in Humans after Five Days of Dry Immersion to Simulate Microgravity
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Loïc Treffel, Nastassia Navasiolava, Karen Mkhitaryan, Emmanuelle Jouan, Kathryn Zuj, Guillemette Gauquelin-Koch, Marc-Antoine Custaud, and Claude Gharib
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spine ,intradiscal proteins ,ADC diffusion ,T1-T2 mapping ,vertebral deconditioning ,space physiology ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Most astronauts experience back pain after spaceflight, primarily located in the lumbar region. Intervertebral disc herniations have been observed after real and simulated microgravity. Spinal deconditioning after exposure to microgravity has been described, but the underlying mechanisms are not well understood. The dry immersion (DI) model of microgravity was used with eighteen male volunteers. Half of the participants wore thigh cuffs as a potential countermeasure. The spinal changes and intervertebral disc (IVD) content changes were investigated using magnetic resonance imaging (MRI) analyses with T1-T2 mapping sequences. IVD water content was estimated by the apparent diffusion coefficient (ADC), with proteoglycan content measured using MRI T1-mapping sequences centered in the nucleus pulposus. The use of thigh cuffs had no effect on any of the spinal variables measured. There was significant spinal lengthening for all of the subjects. The ADC and IVD proteoglycan content both increased significantly with DI (7.34 ± 2.23% and 10.09 ± 1.39%, respectively; mean ± standard deviation), p < 0.05). The ADC changes suggest dynamic and rapid water diffusion inside IVDs, linked to gravitational unloading. Further investigation is needed to determine whether similar changes occur in the cervical IVDs. A better understanding of the mechanisms involved in spinal deconditioning with spaceflight would assist in the development of alternative countermeasures to prevent IVD herniation.
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- 2020
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18. Dry immersion as a model of deafferentation: A neurophysiology study using somatosensory evoked potentials.
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Blandine Acket, Liubov Amirova, Angelique Gerdelat, Pascal Cintas, Marc-Antoine Custaud, and Anne Pavy-LeTraon
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Medicine ,Science - Abstract
INTRODUCTION:Dry immersion is a ground-based experiment simulating the effects of weightlessness, and it is a model of acute symmetrical bilateral deafferentation. This exploratory study aimed to investigate the effects of three days of dry immersion (DI) on sensory thresholds and the functioning of lemniscal pathways, assessed by somatosensory evoked potentials (SEPs). METHODS:Twelve healthy male volunteers (32+/-4.8 years) participated in the study. Sensory thresholds and SEPs of the tibial nerve of both limbs were recorded before (D-1) and on the third day of dry immersion (D3). RESULTS:Sensory thresholds significantly decreased on D3 (-20.75 +/-21.7%; z = -2.54; p = 0.0109 on the right side and -22.18+/-17.28%; z = -3.059; p = 0.002 on the left side). The amplitude of P40 responses did not differ between D-1 and D3. Latencies of all central responses until P30 were shortened on D3 (N21 right:-0.57+/-0.31; z = -3.06; p = 0.002; N21 left -0.83+/-0.53; z = -2.94; p = 0.003; P30 right: -1.26+/-1.42; z = -3.059; p = 0.002; P30 left: -1.11+/-1.55; z = -2.27; p = 0.02). CONCLUSION:Three days of dry immersion can induce hyperexcitability of lemniscal pathways. SIGNIFICANCE:This may be explained by a change in the expression of membrane channels and/or medullar plasticity and/or hypersensitization of peripheral sensory receptors induced by this acute deafferentation. Additional studies are needed to further elucidate the mechanisms.
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- 2018
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19. Impacts of Simulated Weightlessness by Dry Immersion on Optic Nerve Sheath Diameter and Cerebral Autoregulation
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Marc Kermorgant, Florian Leca, Nathalie Nasr, Marc-Antoine Custaud, Thomas Geeraerts, Marek Czosnyka, Dina N. Arvanitis, Jean-Michel Senard, and Anne Pavy-Le Traon
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transcranial Doppler ,cerebral autoregulation ,optic nerve sheath diameter ,intracranial pressure ,dry immersion ,Physiology ,QP1-981 - Abstract
Dry immersion (DI) is used to simulate weightlessness. We investigated in healthy volunteers if DI induces changes in ONSD, as a surrogate marker of intracranial pressure (ICP) and how these changes could affect cerebral autoregulation (CA). Changes in ICP were indirectly measured by changes in optic nerve sheath diameter (ONSD). 12 healthy male volunteers underwent 3 days of DI. ONSD was indirectly assessed by ocular ultrasonography. Cerebral blood flow velocity (CBFV) of the middle cerebral artery was gauged using transcranial Doppler ultrasonography. CA was evaluated by two methods: (1) transfer function analysis was calculated to determine the relationship between mean CBFV and mean arterial blood pressure (ABP) and (2) correlation index Mxa between mean CBFV and mean ABP.ONSD increased significantly during the first day, the third day and the first day of recovery of DI (P < 0.001).DI induced a reduction in Mxa index (P < 0.001) and an elevation in phase shift in low frequency bandwidth (P < 0.05). After DI, Mxa and coherence were strongly correlated with ONSD (P < 0.05) but not before DI. These results indicate that 3 days of DI induces significant changes in ONSD most likely reflecting an increase in ICP. CA was improved but also negatively correlated with ONSD suggesting that a persistent elevation ICP favors poor CA recovery after simulated microgravity.
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- 2017
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20. Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise
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Steven De Abreu, Liubov Amirova, Ronan Murphy, Robert Wallace, Laura Twomey, Guillemette Gauquelin-Koch, Veronique Raverot, Françoise Larcher, Marc-Antoine Custaud, and Nastassia Navasiolava
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modeled weightlessness ,physical inactivity ,supportlessness ,cardiovascular deconditioning ,glucose intolerance ,muscle tone ,Physiology ,QP1-981 - Abstract
Dry immersion (DI) is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt). Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement.Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.
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- 2017
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21. Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines.
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Marie-Thérèse Linossier, Liubov E Amirova, Mireille Thomas, Myriam Normand, Marie-Pierre Bareille, Guillemette Gauquelin-Koch, Arnaud Beck, Marie-Claude Costes-Salon, Christine Bonneau, Claude Gharib, Marc-Antoine Custaud, and Laurence Vico
- Subjects
Medicine ,Science - Abstract
Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones.Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h). Markers of bone turnover, phosphocalcic metabolism, adipokines and associated factors were measured.Bone resorption as assessed by tartrate-resistant acid phosphatase isoform 5b and N-terminal crosslinked telopeptide of type I collagen levels increased as early as DI24h. At the same time, total procollagen type I N- and C-terminal propeptides and osteoprotegerin, representing bone formation markers, decreased. Total osteocalcin [OC] was unaffected, but its undercarboxylated form [Glu-OC] increased from DI24h to R+3h. The early and progressive increase in bone alkaline phosphatase activities suggested an increased mineralization. Dickkopf-1 and sclerostin, as negative regulators of the Wnt-β catenin pathway, were unaltered. No change was observed either in phosphocalcic homeostasis (calcium and phosphate serum levels, 25-hydroxyvitamin D, fibroblast growth factor 23 [FGF23]) or in inflammatory response. Adiponectemia was unchanged, whereas circulating leptin concentrations increased. Neutrophil gelatinase-associated lipocalin [lipocalin-2], a potential regulator of bone homeostasis, was found elevated by 16% at R+3h compared to DI24h. The secretory form of nicotinamide phosphoribosyl-transferase [visfatin] concentrations almost doubled after one day of DI and remained elevated. Serum insulin-like growth factor 1 levels progressively increased. Fasting insulin concentrations increased during the entire DI, whereas fasting glucose levels tended to be higher only at DI24h and then returned to BDC values. Changes in bone resorption parameters negatively correlated with changes in bone formation parameters. Percent changes of ultra-sensitive C-reactive protein positively correlated with changes in osteopontin, lipocalin-2 and fasting glucose. Furthermore, a positive correlation was found between changes in FGF23 and Glu-OC, the two main osteoblast-/osteocyte-derived hormones.Our results demonstrated that DI induced an unbalanced remodeling activity and the onset of insulin resistance. This metabolic adaptation was concomitant with higher levels of Glu-OC. This finding confirms the role of bone as an endocrine organ in humans. Furthermore, visfatin for which a great responsiveness was observed could represent an early and sensitive marker of unloading in humans.
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- 2017
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22. The Effects of Spaceflight Factors on the Human Plasma Proteome, Including Both Real Space Missions and Ground-Based Experiments
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Alexander G. Brzhozovskiy, Alexey S. Kononikhin, Lyudmila Ch. Pastushkova, Daria N. Kashirina, Maria I. Indeykina, Igor A. Popov, Marc-Antoine Custaud, Irina M. Larina, and Evgeny N. Nikolaev
- Subjects
spaceflight ,ground-based experiments ,mass-spectrometry ,astronauts ,head-down bed rest ,dry immersion ,proteomics ,extreme conditions ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The aim of the study was to compare proteomic data on the effects of spaceflight factors on the human body, including both real space missions and ground-based experiments. LC−MS/MS-based proteomic analysis of blood plasma samples obtained from 13 cosmonauts before and after long-duration (169−199 days) missions on the International Space Station (ISS) and for five healthy men included in 21-day-long head-down bed rest (HDBR) and dry immersion experiments were performed. The semi-quantitative label-free analysis revealed significantly changed proteins: 19 proteins were significantly different on the first (+1) day after landing with respect to background levels; 44 proteins significantly changed during HDBR and 31 changed in the dry immersion experiment. Comparative analysis revealed nine common proteins (A1BG, A2M, SERPINA1, SERPINA3, SERPING1, SERPINC1, HP, CFB, TF), which changed their levels after landing, as well as in both ground-based experiments. Common processes, such as platelet degranulation, hemostasis, post-translational protein phosphorylation and processes of protein metabolism, indicate common pathogenesis in ground experiments and during spaceflight. Dissimilarity in the lists of significantly changed proteins could be explained by the differences in the dynamics of effective development in the ground-based experiments. Data are available via ProteomeXchange using the identifier PXD013305.
- Published
- 2019
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23. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.
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Emilie Vessières, Abdallah Dib, Jennifer Bourreau, Eric Lelièvre, Marc-Antoine Custaud, Martine Lelièvre-Pégorier, Laurent Loufrani, Daniel Henrion, and Céline Fassot
- Subjects
Medicine ,Science - Abstract
Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside) relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.
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- 2016
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24. Craniomandibular System and Postural Balance after 3-Day Dry Immersion.
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Loïc Treffel, Liubov Dmitrieva, Guillemette Gauquelin-Koch, Marc-Antoine Custaud, Stéphane Blanc, Claude Gharib, and Catherine Millet
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Medicine ,Science - Abstract
The objective of the study was to determine the influence of simulated microgravity by exposure to dry immersion on the craniomandibular system. Twelve healthy male volunteers participated in a 3-day dry immersion study. Before and immediately after exposure we measured maximal bite force using piezoresistive sensors. The mechanical properties of the jaw and cervical muscles were evaluated before, during, and after dry immersion using MyotonPRO. Because recent studies reported the effects of jaw motor activity on the postural stability of humans, stabilometric measurements of center of pressure were performed before and after dry immersion in two mandibular positions: rest position without jaw clenching, and intercuspidal position during voluntary teeth clenching. Results revealed no significant changes of maximal bite force after dry immersion. All postural parameters were significantly altered by dry immersion. There were however no significant differences in stabilometric data according to mandibular position. Moreover the masseter tonicity increased immediately after the end of dry immersion period. Dry immersion could be used as a valid model for studying the effects of microgravity on human subjects. However, 3 days appear insufficient in duration to evaluate the effects of weightlessness on maximal bite force. Our research suggests a link between postural disturbance after dry immersion and masseter tonicity.
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- 2016
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25. Peripheral arterial and venous response to tilt test after a 60-day bedrest with and without countermeasures (ES-IBREP).
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Ming Yuan, Mickael Coupé, Yanqiang Bai, Guillemette Gauquelin-Koch, Shizhong Jiang, Patrick Aubry, Yumin Wan, Marc-Antoine Custaud, Yinghui Li, and Philippe Arbeille
- Subjects
Medicine ,Science - Abstract
UNLABELLED: We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. METHODS: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. RESULTS: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. CONCLUSION: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib.
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- 2012
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26. Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats.
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Darya Tsvirkun, Jennifer Bourreau, Aurélie Mieuset, Florian Garo, Olga Vinogradova, Irina Larina, Nastassia Navasiolava, Guillemette Gauquelin-Koch, Claude Gharib, and Marc-Antoine Custaud
- Subjects
Medicine ,Science - Abstract
The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.
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- 2012
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27. Pleiotropic Effects of Icariside II on the Cardiovascular System: Novel Applications of Ethnopharmacology in Targeting Vascular Remodeling
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Chunxu, Shan, Bernard, Degryse, Paul, Tolan, Marc-Antoine, Custaud, and Ronan P, Murphy
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Flavonoids ,Pharmacology ,Ethnopharmacology ,Humans ,Vascular Remodeling ,Cardiology and Cardiovascular Medicine ,Cardiovascular System - Published
- 2022
28. Permanent proteins in the urine of healthy humans during the Mars-500 experiment.
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Irina M. Larina, Lyudmila Kh. Pastushkova, Evgeny S. Tiys, Kirill S. Kireev, Alexey S. Kononikhin, Natalia L. Starodubtseva, Igor A. Popov, Marc-Antoine Custaud, Igor V. Dobrokhotov, Evgeny N. Nikolaev, Nikolay A. Kolchanov, and Vladimir A. Ivanisenko
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- 2015
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29. Associations between gait speed and brain structure in amnestic mild cognitive impairment: a quantitative neuroimaging study
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Marc Antoine Custaud, Pauline Ali, Mickael Dinomais, Cédric Annweiler, Paul Paisant, and Matthieu Labriffe
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medicine.medical_specialty ,Gait Disturbance ,business.industry ,Cognitive Neuroscience ,Neuropsychology ,STRIDE ,Motor control ,Frontal gyrus ,Statistical parametric mapping ,Behavioral Neuroscience ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Gait (human) ,Physical medicine and rehabilitation ,Neurology ,Neuroimaging ,Medicine ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,business ,human activities - Abstract
Patients with amnestic mild cognitive impairment (aMCI) present gait disturbances including slower speed and higher variability when compared to cognitively healthy individuals (CHI). Brain neuroimaging could explore higher levels of motor control. Our purpose was to look for an association between morphometrics and gait parameters in each group. We hypothesized that the relation between morphological cerebral alteration and gait speed are different following the group. Fifty-three participants (30 with aMCI and 23 CHI) were recruited in this French cross-sectional study (mean 72 ± 5 years, 38% female). Gait speed and gait variability (coefficients of variation of stride time (STV) and stride length (SLV)) were measured using GAITrite® system. CAT12 software was used to analyse volume and surface morphometry like gray matter volume (GMV) and cortical thickness (CT). Age, gender and education level were used as potential cofounders. aMCI had slower gait speed and higher STV when compared to CHI. In aMCI the full adjusted linear regression model showed that lower gait speed was associated with decreased GMV and lower CT in bilateral superior temporal gyri (p
- Published
- 2021
30. Spinal changes after 5-day dry immersion as shown by magnetic resonance imaging (DI-5-CUFFS)
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Adrien Robin, Nastassia Navasiolava, Guillemette Gauquelin-Koch, Claude Gharib, Marc-Antoine Custaud, and Loïc Treffel
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Male ,Lumbar Vertebrae ,Physiology ,Back Pain ,Physiology (medical) ,Immersion ,Lumbosacral Region ,Humans ,Intervertebral Disc ,Magnetic Resonance Imaging - Abstract
Astronauts frequently report microgravity-induced back pain, which is generally more pronounced in the beginning of a spaceflight. The dry immersion (DI) model reproduces the early effects of microgravity in terms of global support unloading and fluid shift, both of which are involved in back pain pathogenesis. Here, we assessed spinal changes induced by exposure to 5 days of strict DI in 18 healthy men (25–43-yr old) with ( n = 9) or without ( n = 9) thigh cuffs countermeasure. Intervertebral disk (IVD) height, spinal cord position, and apparent diffusion coefficient (ADC; reflecting global water motion) were measured using magnetic resonance imaging before and after DI. After DI, IVD height increased in thoracic (+3.3 ± 0.8 mm; C7–T12) and lumbar (+4.5 ± 0.4 mm; T12–L5) regions but not in the cervical region (C2–C7) of the spine. An increase in ADC after DI was observed at the L1 (∼6% increase, from 3.2 to 3.4 × 10−3 mm2/s; P < 0.001) and L2 (∼3% increase, from 3.4 to 3.5 × 10−3 mm2/s; P = 0.005) levels. There was no effect of thigh cuffs on spinal parameters. This change in IVD after DI follows the same “gradient” pattern of height increase from the cervical to the lumbar region as observed after bed rest and spaceflight. The increase in ADC at L1 level positively correlated with reported back pain. These findings emphasize the utility of the DI model for studying early spinal changes observed in microgravity.
- Published
- 2022
31. Development of dynamic cell and organotypic skin models, for the investigation of a novel visco-elastic burns treatment using molecular and cellular approaches
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Laura Twomey, Bernard Degryse, Aoife Morrin, Niall M. Moyna, Emer Duffy, Gerardene Meade-Murphy, Robert G. Wallace, Aidan J. Brady, Ronan P. Murphy, Mary-Rose Kenealy, Marc-Antoine Custaud, and David Caballero-Lima
- Subjects
Burn injury ,Human skin ,Inflammation ,In Vitro Techniques ,Critical Care and Intensive Care Medicine ,Bioinformatics ,Cicatrix ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Intensive care ,medicine ,Humans ,Barrier function ,Skin ,Biological Products ,Wound Healing ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,medicine.disease ,Emergency Medicine ,Surgery ,medicine.symptom ,Burns ,business ,Wound healing ,Total body surface area ,Bandages, Hydrocolloid - Abstract
Background Burn injuries are a major cause of morbidity and mortality worldwide. Despite advances in therapeutic strategies for the management of patients with severe burns, the sequelae are pathophysiologically profound, up to the systemic and metabolic levels. Management of patients with a severe burn injury is a long-term, complex process, with treatment dependent on the degree and location of the burn and total body surface area (TBSA) affected. In adverse conditions with limited resources, efficient triage, stabilisation, and rapid transfer to a specialised intensive care burn centre is necessary to provide optimal outcomes. This initial lag time and the form of primary treatment initiated, from injury to specialist care, is crucial for the burn patient. This study aims to investigate the efficacy of a novel visco-elastic burn dressing with a proprietary bio-stimulatory marine mineral complex (MXC) as a primary care treatment to initiate a healthy healing process prior to specialist care. Methods A new versatile emergency burn dressing saturated in a >90% translucent water-based, sterile, oil-free gel and carrying a unique bio-stimulatory marine mineral complex (MXC) was developed. This dressing was tested using LabSkin as a burn model platform. LabSkin a novel cellular 3D-dermal organotypic full thickness human skin equivalent, incorporating fully-differentiated dermal and epidermal components that functionally models skin. Cell and molecular analysis was carried out by in vitro Real-Time Cellular Analysis (RTCA), thermal analysis, and focused transcriptomic array profiling for quantitative gene expression analysis, interrogating both wound healing and fibrosis/scarring molecular pathways. In vivo analysis was also performed to assess the bio-mechanical and physiological effects of this novel dressing on human skin. Results This hybrid emergency burn dressing (EBD) with MXC was hypoallergenic, and improved the barrier function of skin resulting in increased hydration up to 24 h. It was demonstrated to effectively initiate cooling upon application, limiting the continuous burn effect and preventing local tissue from damage and necrosis. xCELLigence RTCA® on primary human dermal cells (keratinocyte, fibroblast and micro-vascular endothelial) demonstrated improved cellular function with respect to tensegrity, migration, proliferation and cell-cell contact (barrier formation) [ 1 ]. Quantitative gene profiling supported the physiological and cellular function finding. A beneficial quid pro quo regulation of genes involved in wound healing and fibrosis formation was observed at 24 and 48 h time points. Conclusion Utilisation of this EBD + MXC as a primary treatment is an effective and easily applicable treatment in cases of burn injury, proving both a cooling and hydrating environment for the wound. It regulates inflammation and promotes healing in preparation for specialised secondary burn wound management. Moreover, it promotes a healthy remodelling phenotype that may potentially mitigate scarring. Based on our findings, this EBD + MXC is ideal for use in all pre-hospital, pre-surgical and resource limited settings.
- Published
- 2020
32. Cardio-vascular Dysfunction and Physiological Manifestations Induced by Environmental Conditions
- Author
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Marc-Antoine Custaud, Ronan Padraic Murphy, Olga Vinogradova, Claude Gharib, François Guerrero, and Michael D. Delp
- Published
- 2022
- Full Text
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33. Research of the Plasma Protein Profile in Comparison with the Biochemical Parameters of Blood of Volunteers in a 21-Day Head Down Bed Rest
- Author
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D. N. Kashirina, A. G. Goncharova, A. G. Brzhozovskiy, Irina M. Larina, A. M. Nosovsky, Marc-Antoine Custaud, E. N. Nikolaev, Alexey S. Kononikhin, Nastassia Navasiolava, and L. Kh. Pastushkova
- Subjects
medicine.medical_specialty ,Aldosterone ,Physiology ,business.industry ,05 social sciences ,Blood volume ,Carbohydrate metabolism ,medicine.disease ,Blood proteins ,050105 experimental psychology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Platelet degranulation ,chemistry ,Physiology (medical) ,Internal medicine ,Renin–angiotensin system ,Blood plasma ,medicine ,0501 psychology and cognitive sciences ,business ,030217 neurology & neurosurgery - Abstract
Study of changes in the proteome of extracellular body fluids under conditions of simulated weightlessness of medium duration (21 days) remains relevant for clarifying the physiological mechanisms of homeostasis regulation and is important for gravitational physiology and medicine. Plasma samples of 8 healthy volunteers participating in head down bed rest (HDBR –6°) experiment were studied using semi-quantitative proteomics methods. Each volunteer participated both in the control session and in the session with physical training for negative changes prevention. By the end of HDBR, significant changes in the concentration of proteins involved in platelet degranulation, blood coagulation, fibrinolysis, proteolysis regulation, complement activation, and the immune response were detected in both sessions. The following changes in biochemical parameters of carbohydrate metabolism and regulation of circulating blood volume were shown: a significant increase in renin concentration and a tendency to an increase in aldosterone; an increase in fasting insulin concentration and a tendency to an increase in the insulin resistance index. Physical training did not have a significant effect on biochemical parameters, except for the representation of cholesterol fractions, un which a significant decrease in the concentration of high-density lipoprotein cholesterol observed in HDBR became statistically insignificant in session with physical training. However, the protein composition in blood plasma of volunteers in the prophylaxis session changed less compared to HDBR. Physical training resulted in increase in the concentration of proteins involved in the normalization of carbohydrate and lipid metabolism, such as a macrophage stimulating protein and phosphatidylinositol-glycan-specific phospholipase D, which indicates the effectiveness of preventive measures.
- Published
- 2020
34. A dry immersion model of microgravity modulates platelet phenotype, miRNA signature, and circulating plasma protein biomarker profile
- Author
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Guillemette Gauquelin-Koch, Niall M. Moyna, Nastassia Navasiolava, Françoise Larcher, Patricia B. Maguire, Arnaud Beck, Laura Twomey, Bernard Degryse, Ronan P. Murphy, Adrien Robin, Marie-Pierre Bareille, Sinead Sheridan, Gerardene Meade-Murphy, Marc-Antoine Custaud, Michael Harrison, and Claude Gharib
- Subjects
Proteomics ,Adult ,Blood Platelets ,Male ,Science ,030204 cardiovascular system & hematology ,Models, Biological ,Article ,Non-coding RNAs ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,Humans ,Platelet ,Epigenetics ,030304 developmental biology ,Hemostasis ,0303 health sciences ,Multidisciplinary ,Weightlessness ,Microarray analysis techniques ,Chemistry ,Microarray analysis ,Thrombosis ,Blood Proteins ,Phenotype ,Blood proteins ,MicroRNAs ,Mechanisms of disease ,Cancer research ,Medicine ,Biomarker (medicine) ,Biomarkers - Abstract
Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
- Published
- 2021
35. Specific age-correlated activation of top hierarchical motor control areas during gait-like plantar stimulation: An fMRI study
- Author
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Henry, Jeanvoine, Matthieu, Labriffe, Thomas, Tannou, Nastassia, Navasiolava, Aram, Ter Minassian, Jean-Baptiste, Girot, Louis-Marie, Leiber, Marc-Antoine, Custaud, Cédric, Annweiler, and Mickaël, Dinomais
- Subjects
Adult ,Male ,Brain Mapping ,Aging ,brain ,Putamen ,Prefrontal Cortex ,Forefoot, Human ,functional neuroimaging ,Middle Aged ,Globus Pallidus ,gait ,Magnetic Resonance Imaging ,functional magnetic resonance imaging ,Young Adult ,Thalamus ,motor cortex ,Physical Stimulation ,Humans ,Female ,human activities ,Research Articles ,Research Article ,Aged ,Visual Cortex - Abstract
A better understanding of gait disorders that are associated with aging is crucial to prevent adverse outcomes. The functional study of gait remains a thorny issue due to technical constraints inherent to neuroimaging procedures, as most of them require to stay supine and motionless. Using an MRI‐compatible system of boots reproducing gait‐like plantar stimulation, we investigated the correlation between age and brain fMRI activation during simulated gait in healthy adults. Sixty‐seven right‐handed healthy volunteers aged between 20 and 77 years old (49.2 ± 18.0 years; 35 women) were recruited. Two paradigms were assessed consecutively: (a) gait‐like plantar stimulation and (b) chaotic and not gait‐related plantar stimulation. Resulting statistical parametric maps were analyzed with a multiple‐factor regression that included age and a threshold determined by Monte‐Carlo simulation to fulfill a family‐wise error rate correction of p, Gait decline during normal aging is a key public health concern. This fMRI study addresses the question of brain activation evolution with advance in age in healthy adults. We highlight a gradual and specific overactivation of top hierarchical cortical motor control areas in simulated gait during advance in age. Our results support the theory of a progressive loss of automation of gait in older healthy adults.
- Published
- 2021
36. Function, Proteomic and miRomic Study of a Dry Immersion Model of Microgravity implicates the Wnt/Dkk1/AXIN1 axis in Prothrombotic Platelet Phenotype
- Author
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Ronan P. Murphy, Marie-Pierre Bareille, Gerardene Meade-Murphy, Nastassia Navasiolava, Michael R. Harrison, Patricia B. Maguire, Niall M. Moyna, Adrien Robin, Sinead Sheridan, Marc-Antoine Custaud, Claude Gharib, Françoise Larcher, Guillemette Gauquelin-Koch, Arnaud Beck, Laura Twomey, and Bernard Degryse
- Subjects
DKK1 ,Chemistry ,AXIN1 ,Wnt signaling pathway ,Immersion (virtual reality) ,Platelet ,Phenotype ,Function (biology) ,Cell biology - Abstract
Objective: Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and biomarker expression.Approach and Results: The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers whose expression levels were altered after DI. 22 “DI/PI” related miRNA were identified, of which five have potential targets in the Wnt pathway associated with platelet biogenesis and function. These findings are supported by increased circulating Axin1 and DKK1.Conclusions: Circulating biomarker and miRomic analysis implicates miRNA regulation of Wnt/Dkk1/AXIN1 axis in DI/PI induced primed platelet phenotype. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
- Published
- 2021
37. Associations between gait speed and brain structure in amnestic mild cognitive impairment: a quantitative neuroimaging study
- Author
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Pauline, Ali, Matthieu, Labriffe, Paul, Paisant, Marc Antoine, Custaud, Cédric, Annweiler, and Mickaël, Dinomais
- Subjects
Male ,Cross-Sectional Studies ,Brain ,Humans ,Cognitive Dysfunction ,Female ,Neuroimaging ,Magnetic Resonance Imaging ,Walking Speed - Abstract
Patients with amnestic mild cognitive impairment (aMCI) present gait disturbances including slower speed and higher variability when compared to cognitively healthy individuals (CHI). Brain neuroimaging could explore higher levels of motor control. Our purpose was to look for an association between morphometrics and gait parameters in each group. We hypothesized that the relation between morphological cerebral alteration and gait speed are different following the group.Fifty-three participants (30 with aMCI and 23 CHI) were recruited in this French cross-sectional study (mean 72 ± 5 years, 38% female). Gait speed and gait variability (coefficients of variation of stride time (STV) and stride length (SLV)) were measured using GAITrite® system. CAT12 software was used to analyse volume and surface morphometry like gray matter volume (GMV) and cortical thickness (CT). Age, gender and education level were used as potential cofounders.aMCI had slower gait speed and higher STV when compared to CHI. In aMCI the full adjusted linear regression model showed that lower gait speed was associated with decreased GMV and lower CT in bilateral superior temporal gyri (p 0.36). In CHI, no association was found between gait speed and brain structure. Higher SLV was correlated with reduced GMV in spread regions (p 0.05) and thinner cortex in the middle right frontal gyrus (p = 0.001) in aMCI. In CHI, higher SLV was associated with reduced GMV in 1 cluster: the left lingual (p = 0.041).These findings indicate that lower gait speed is associated with specific brain structural changes as reduced GMV and CT during aMCI.
- Published
- 2021
38. A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19
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Bruno Vielle, Olivier Robineau, Patrick Rispal, Caroline Lefeuvre, Sophie Boucher, Pierre-Marie Roy, Chadi Abbara, Sylvain Diamantis, Vincent Dubée, Astrid Darsonval, Emma d’Anglejean, Elsa Parot-Schinkel, Odile Blanchet, Isabelle Pellier, Marc-Antoine Custaud, Edouard Devaud, Thomas Guimard, and Alain Mercat
- Subjects
medicine.medical_specialty ,education.field_of_study ,Randomization ,business.industry ,medicine.medical_treatment ,Population ,Hydroxychloroquine ,medicine.disease ,Placebo ,Comorbidity ,Internal medicine ,Relative risk ,Oxygen therapy ,medicine ,Clinical endpoint ,education ,business ,medicine.drug - Abstract
BackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.
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- 2020
39. The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory System
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Anna R. Kussmaul, Evgeny N. Nikolaev, Irina M. Larina, A. G. Goncharova, Marc-Antoine Custaud, Alexander G Brzhozovsky, Alexey S. Kononikhin, A. M. Nosovsky, A. G. Chernikova, Ludmila Kh. Pastushkova, Vasily B. Rusanov, Nastassia Navasiolava, and D. N. Kashirina
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0301 basic medicine ,Proteomic Profile ,lcsh:QP1-981 ,Physiology ,Hemodynamics ,Protein composition ,030204 cardiovascular system & hematology ,Biology ,effects of microgravity ,lcsh:Physiology ,regulatory mechanisms ,dry immersion ,03 medical and health sciences ,proteomics ,030104 developmental biology ,0302 clinical medicine ,Metabolic regulation ,Physiology (medical) ,Circulatory system ,Immersion (virtual reality) ,Heart rate variability ,Hypogravity ,circulatory system ,Original Research - Abstract
The purpose of the study was to investigate the regulatory and metabolic changes in the circulatory system when simulating microgravity conditions in a five-day dry immersion. These changes reflect the adaptation processes characteristic for the initial stages of a space flight or a short-duration space flight. Studies were conducted with 13 healthy male volunteers aged 21 to 29 years. The assessment of regulatory and metabolic processes in the circulatory system was based on the heart rate variability (HRV) and urine proteomic profile analysis. It was found that the restructuring of hemodynamics during 5 days hypogravity begins with the inclusion of the nervous circuit of regulation, and for manifestations at the body fluids protein composition level and activation of the metabolic regulation, these periods are apparently insufficient. Perhaps this is due to the fact that the metabolic regulation, being evolutionarily ancient and genetically determined, is more stable and requires more time for its pronounced activation when stimulated by extreme life conditions.
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- 2020
40. Deciphering the Mechanisms Behind Cardiovascular Disease: Long Noncoding RNAs as Key Molecular Signaling Hubs and Biomarkers of Atherosclerosis
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Nastassia Navasiolava, Ronan P. Murphy, Niall M. Moyna, Bernard Degryse, and Marc-Antoine Custaud
- Subjects
Pharmacology ,Molecular signaling ,Cardiovascular Diseases ,Key (cryptography) ,Humans ,RNA, Long Noncoding ,Disease ,Computational biology ,Biology ,Cardiology and Cardiovascular Medicine ,Atherosclerosis ,Biomarkers ,Signal Transduction - Published
- 2020
41. Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial
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Vincent Dubée, Pierre-Marie Roy, Bruno Vielle, Elsa Parot-Schinkel, Odile Blanchet, Astrid Darsonval, Caroline Lefeuvre, Chadi Abbara, Sophie Boucher, Edouard Devaud, Olivier Robineau, Patrick Rispal, Thomas Guimard, Emma d’Anglejean, Sylvain Diamantis, Marc-Antoine Custaud, Isabelle Pellier, Alain Mercat, Antoine Brangier, Philippe Codron, Jean Michel Lemée, Virginie Pichon, Robin Dhersin, Geoffrey Urbanski, Christian Lavigne, Roxane Courtois, Hélène Danielou, Jonathan Lebreton, Rémi Vatan, Nicolas Crochette, Jean-Baptiste Lainé, Lucia Perez, Sophie Blanchi, Hikombo Hitoto, Louis Bernard, François Maillot, Sylvain Marchand Adam, Jean-Philippe Talarmin, Emeline Gaigneux, Pauline Motte-Vincent, Marine Morrier, Dominique Merrien, Yves Bleher, Maxime Flori, Amélie Ducet-Boiffard, Orane Colin, Ronan Février, Pauline Thill, Macha Tetart, François Demaeght, Barthelemy Lafond-Desmurs, Maxime Pradier, Agnes Meybeck, Marjorie Picaud, Thierry Prazuck, Guillaume Chapelet, Agnès Rouaud, Paul Le Turnier, Simon Sunder, Aurélien Lorleac'h, Christophe Dollon, Antoine Jacquet, Francois Le Vely, Pierre Gazeau, Séverine Ansart, Hélène Roger, François Laterza, Rodolphe Buzelé, Fella Tahmi, Raphael Lepeule, Karine Lacombe, Bénédicte Lefebvre, Thomas Célarier, Amandine Gagneux-Brunon, Elisabeth Botelho-Nevers, Marc Bernard, Camille Garnier, Morgane Mourguet, Gregory Pugnet, Sara Vienne-Noyes, Guillaume Martin-Blondel, Pierre Delobel, Gaspard Grouteau, Alexa Debard, Laurent Guilleminault, Pauline Arias, Catherine Chakvetadze, Clara Flateau, Aude Kopp, Alain Putot, Jeremy Barben, Suzanne Mouries Martin, Valentine Nuss, Lionel Piroth, Yann-Erick Claessens, Veronique Hentgen, Martin Martinot, Maxime Bach-Bunner, Thomas Bonijoly, Simon Gravier, Jean-Marc Michel, Mathilde Andreu, Mélanie Roriz, Aurélie Baldolli, Julia Brochard, Olivier Grossi, Samuel Pineau, Josselin Brisset, Edouard Desvaux, Guillaume Gondran, Jean-François Faucher, Paul-Antoine Quesnel, Holy Bezanahary, Clément Danthu, Blandine Gutierrez, Kim Ly, Yannick Simonneau, Anne Cypierre, Pauline Pinet, Hélène Durox, Sophie Ducroix-Roubertou, Claire Genet, Guillaume Beraud, Gwenael Le Moal, Blandine Rammaert, Jean-Philippe Lanoix, Claire Andrejak, Cédric Joseph, Sandrine Soriot-Thomas, Robin Dhote, Sébastien Abad, Ruben Benainous, Jean-François Boitiaux, Guillaume Briend, Celine Gonfroy, Stanislas Harent, Aurore Lagrange, Alina Tone, Laura Wayenberg, Sophie Desoutter, Nicolas Ettahar, Thomas Gey, Vincent Leroy, Sacha Gaillard, Andrea Toma, Amaury Broussier, Sandrine Etienne, Yann Spivac, Benoit Martha, Nathalie Roch, Pierre Diaz, Danièle N’guyen Baranoff, Stanislas Rebaudet, François Jourda, Valérie Zeller, Boris Bienvenu, Arnaud Boyer, Marie Briet, Bertrand Guidet, Patrick Mismetti, Eric Vicaut, Olivier Sanchez, Philippe Girard, Antoine Elias, Francis Couturaud, Béatrice Gable, Sybille Lazareff, Loïc Carballido, Catherine Hue, Jean-Marie Chrétien, Adrien Goraguer, Lucie van Eeckhoutte, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Pharmacie [CHU d'Angers], Laboratoire de virologie [CHU Angers], Département de Pharmacologie-Toxicologie [CHU Angers], Centre Hospitalier René Dubos [Pontoise], Centre Hospitalier Tourcoing, Service de Médecine Interne [Agen], Centre Hospitalier d'Agen, Centre Hospitalier Départemental Vendée (CHDV), Centre Hospitalier de Versailles André Mignot (CHV), Groupe Hospitalier Sud, Université d'Angers (UA), HYCOVID study group, HYCOVID investigators, Angers University Hospital, Cholet Hospital, Laval Hospital, Le Mans Hospital, Tours University Hospital, Quimper Hospital, La Roche sur Yon Hospital, Tourcoing Hospital, Orléans Hospital, Nantes University Hospital, Niort Hospital, Lorient Hospital, Brest University Hospital, Cherbourg Hospital, Saint-Brieuc Hospital, Créteil – APHP University Hospital, Saint-Antoine – APHP University Hospital, Saint-Etienne University Hospital, Toulouse University Hospital, Melun Hospital, Dijon University Hospital, Princesse Grace – Monaco Hospital, Versailles Hospital, Colmar Hospital, Agen-Nerac Hospital, Caen University Hospital, Saint-Nazaire Hospital, Nantes – Confluent Hospital, Limoges University Hospital, Poitiers University Hospital, Amiens University Hospital, Bobigny – APHP University Hospital, Cergy-Pontoise Hospital, Valencienne Hospital, Valencienne – Clinique Tessier Hospital, Henri-Mondor – APHP University Hospital, Chalon-sur-Saône Hospital, Marseille European Hospital, Auxerre Hospital, Diaconnesses Croix-Saint-Simon Hospital, Marseille – Saint Joseph Hospital, Composition of the HYCOVID management team, Steering committee, Independant data safety and monitoring board, Independent adjudication of clinical events committee, Study management Coordination, Data management., Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service des maladies infectieuses et tropicales [CHU Angers], and Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC)
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Population ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,law ,Interquartile range ,Intensive care ,Internal medicine ,medicine ,Clinical endpoint ,030212 general & internal medicine ,education ,Severe acute respiratory syndrome coronavirus 2 ,education.field_of_study ,Coronavirus disease 2019 ,business.industry ,Hydroxychloroquine ,General Medicine ,Placebo-controlled ,3. Good health ,Infectious Diseases ,Relative risk ,business ,medicine.drug - Abstract
Objectives To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. Trial registration ClinicalTrials.gov Identifier: NCT04325893 ( https://clinicaltrials.gov/ct2/show/NCT04325893 ).
- Published
- 2020
42. Modification of the Urine Proteome in Healthy Human during 21-day Bed Rest
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E. S. Tiis, A. G. Brzhozovsky, A. S. Kononikhin, L. E. Dmitrieva, Irina M. Larina, L. Kh. Pastushkova, I. V. Dobrokhotov, and Marc-Antoine Custaud
- Subjects
Physiology ,Chemistry ,medicine.medical_treatment ,Urine ,Computational biology ,Human physiology ,030204 cardiovascular system & hematology ,Mass spectrometry ,Proteomics ,Bed rest ,Tandem mass spectrometry ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Proteome ,Healthy volunteers ,medicine ,030217 neurology & neurosurgery - Abstract
Mass spectrometry–based proteomics was employed to analyze urine from eight healthy volunteers during a 21-day bed rest (BR) study. The analysis included trypsinolysis in solution prior to liquid chromatography and tandem mass spectrometry (LC-MS/MS), and spectrum processing using the bioinformatic tools. Relying on 221 IPI indices with scores from 24 to 1700, 169 different proteins were identified. Molecular functions, biological processes, and cell components as the loci of certain protein functioning were determined with the help of UniProt-GOA. Associative interactions networks were constructed using BiNGO. There were 14 proteins identified that were functional in the cardiovascular system mostly. They were annotated, and the dynamics of their occurrence throughout the experiment was considered. Grounding on the biological functions of these proteins and an assumption of eligible activation of different biological processes during BR was made.
- Published
- 2017
43. Effect of 21-day head down bed rest on urine proteins related to endothelium: Correlations with changes in carbohydrate metabolism
- Author
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D. N. Kashirina, A. G. Brzhozovsky, A. M. Nosovsky, Lyudmila Ch. Pastushkova, I. V. Dobrokhotov, Marc-Antoine Custaud, Irina M. Larina, N. Navasiolava, A. S. Kononikhin, and E. N. Nikolaev
- Subjects
0301 basic medicine ,Endothelial protein C receptor ,medicine.medical_specialty ,biology ,Endothelium ,Chemistry ,Albumin ,Aerospace Engineering ,Urine ,030204 cardiovascular system & hematology ,Carbohydrate metabolism ,Receptor tyrosine kinase ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,Proteome ,biology.protein ,medicine ,Osteopontin - Abstract
We performed liquid chromatography-mass spectrometric study of the urine proteome in 8 healthy volunteers aged between 20 and 44 y.o. who have completed 21-day head-down bed rest. ANDSystem software which builds associative networks was used to identify the urinary proteins functionally related to the endothelium. We identified 7 endothelium-related biological processes, directly linked to 13 urine proteins. We performed manual annotation of the proteins which were the most important in terms of endothelial functions. Analysis of the correlations with biochemical variables revealed a positive correlation between fasting blood glucose and the following urine proteins: albumin, CD44 antigen, endothelial protein C receptor, mucin-1, osteopontin, receptor tyrosine kinase. As well, we found a positive correlation between HOMA-insulin resistance index and the following urine proteins: endothelial protein C receptor and syndecan-4. These results might suggest the involvement of above-mentioned proteins in glucose metabolism and their participation in the response to changes in blood glucose level.
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- 2017
44. Adaptation to a blood pressure telemetry system revealed by measures of activity, agility and operant learning in mice
- Author
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Olga Vinogradova, Darya Tsvirkun, Evgeniia Lagereva, Jeffrey R. Alberts, Anfisa Popova, Alexander Andreev-Andrievskiy, Oleg Dolgov, Konstantin V. Anokhin, Guillemette Gauquelin-Koch, and Marc-Antoine Custaud
- Subjects
Male ,0301 basic medicine ,Adult male ,Blood Pressure ,Toxicology ,Open field ,Automated data ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Telemetry ,Animals ,Learning ,Medicine ,Operant conditioning ,Simulation ,Pharmacology ,business.industry ,Continuous monitoring ,Adaptation, Physiological ,Mice, Inbred C57BL ,030104 developmental biology ,Blood pressure ,Anesthesia ,Conditioning, Operant ,Grip force ,business ,Locomotion ,030217 neurology & neurosurgery - Abstract
Introduction Implantable telemetry enables continuous monitoring of physiological functions in freely moving animals and can greatly complement pharmacological research. Despite its miniaturization, a sensor/transmitter constitutes 5% or more of a mouse's bodyweight. The aim of the present study was to evaluate whether factors related to the presence of a probe/transmitter influence the ambulatory activity, strength, agility, or operant, motivated behaviors of this small rodent. Methods Adult male mice (C57BL/6 N, 22–25 g, 9–10 weeks; implanted n = 26, intact n = 45) were evaluated during week-long tests, conducted three and eight weeks after surgical implantation of the PA-C10 blood pressure probe. An open field test, grip force measurement, Rotarod test were performed, followed by 7-day continuous monitoring of spontaneous wheel running activity and positively reinforced operant conditioning in an automated data collection system. Results An implanted blood pressure transmitter did not affect behavior of mice in the open field test, on the Rotarod or their grip force, compared to unoperated controls. Voluntary wheel running distance was reduced three, but not eight weeks after implantation. Three weeks after the surgery, performance in the positively reinforced operant conditioning in operated mice was slightly decreased compared to intact animals, while retention and acquisition of a 2nd, reversal-learning task eight weeks after the surgery were unaffected. Discussion We conclude that an implantable transmitter may have detectable effects in the first few weeks following implantation on some elements of mouse behavior. With sufficient recovery, mice perform comparably to unoperated controls in tests of strength, endurance, agility and learned operant behavior.
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- 2017
45. Constant urinary proteins in healthy humans in a 520-day isolation experiment
- Author
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Nikolay A. Kolchanov, Irina M. Larina, Igor Popov, I. V. Dobrokhotov, Marc-Antoine Custaud, E. N. Nikolaev, E. S. Tiys, K. S. Kireev, V. I. Pochuev, Vladimir A. Ivanisenko, A. S. Kononikhin, and L. Kh. Pastushkova
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0301 basic medicine ,biology ,Physiology ,Chemistry ,Urinary system ,Serum albumin ,Urine ,Plasma Serine Protease Inhibitor ,Andrology ,03 medical and health sciences ,030104 developmental biology ,Epidermal growth factor ,Physiology (medical) ,Immunology ,Proteome ,biology.protein ,Alpha-1-microglobulin ,Polymeric immunoglobulin receptor - Abstract
The aim of this study was the search of permanent proteins of the urinary proteome during a 520-day isolation experiment at the Institute of Biomedical Problems (IBMP) Ground-Based Test Facility in controlled conditions, using an autonomous life support system. The object of the study was urine sampled from 6 normal male subjects aged 25 to 37. The biological material samples (the second morning urine fractions) were collected for proteomic investigations against the background, on the 50th, 93rd, 124th, 153rd, 180th, 251st, 274th, 303rd, 330th, 371st, 400th, and 427th days of isolation, and on the 7th day after its completion. The samples were analyzed using chromatography–mass spectrometry, while the obtained results were analyzed using bioinformatics resources. The following seven permanent proteins were identified and observed during the entire period of urine investigations: epidermal growth factor, polymeric immunoglobulin receptor, plasma serine protease inhibitor, Alpha 1 microglobulin/bikunin precursor (AMBP), keratin (type II cytoskeletal 1), collagen alpha-1 (VI) chain, and serum albumin.
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- 2016
46. Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study
- Author
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Valérie Daniel, Yoanna Onillon, Chadi Homedan, Pascal Reynier, Clara Locher, Loukman Omarjee, Juan-Manuel Chao de la Barca, Isabelle Laporte, Pierre Abraham, Jean-Marie Chretien, Manuela Ripoche, Vincent Jaquinandi, Alain Renault, Vincent Azzola, Marc-Antoine Custaud, Cedric Fontaine, Estelle Le Pabic, Céline Barbeau-Terrier, Guillaume Mahé, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Redon (CH Redon), Centre Hospitalier de Cholet, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Angers University Hospital, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Jonchère, Laurent
- Subjects
0301 basic medicine ,Male ,Time Factors ,Physiology ,[SDV]Life Sciences [q-bio] ,Walking ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Clinical endpoint ,Medicine ,Prospective Studies ,Treadmill ,ComputingMilieux_MISCELLANEOUS ,Cross-Over Studies ,Exercise Tolerance ,Absolute walking time ,Middle Aged ,3. Good health ,Walking time ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,Anesthesia ,Molecular Medicine ,Exercise oximetry ,Female ,France ,medicine.symptom ,Sildenafil ,Treadmill walking test ,Walk Test ,Placebo ,Sildenafil Citrate ,03 medical and health sciences ,Peripheral Arterial Disease ,Double-Blind Method ,Humans ,Aged ,Pharmacology ,Peripheral artery disease ,business.industry ,Oxygenation ,Recovery of Function ,Intermittent Claudication ,Phosphodiesterase 5 Inhibitors ,respiratory tract diseases ,Clinical trial ,030104 developmental biology ,chemistry ,Claudication ,business ,Biomarkers - Abstract
Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication.The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied.Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women.The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication.This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).
- Published
- 2019
47. Determinants of Doppler-based renal resistive index in patients with septic shock: impact of hemodynamic parameters, acute kidney injury and predisposing factors
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Pierre Asfar, François Beloncle, Nicolas Lerolle, Alexis Donzeau, Anne-Lise Foucher, Jean-François Hamel, Marc-Antoine Custaud, René Robert, Natacha Rousseau, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
- Subjects
medicine.medical_specialty ,Vasopressors ,[SDV]Life Sciences [q-bio] ,Critical Care and Intensive Care Medicine ,Sepsis ,Clinical study ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Diabetes mellitus ,medicine ,Prospective cohort study ,Septic shock ,business.industry ,Research ,Acute kidney injury ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,030208 emergency & critical care medicine ,Shock ,lcsh:RC86-88.9 ,Resistive index ,medicine.disease ,Pulse pressure ,critical care ,030228 respiratory system ,Shock (circulatory) ,Cardiology ,medicine.symptom ,business - Abstract
International audience; BACKGROUND: Increased renal resistive index (RI) measured by Doppler ultrasonography has been shown to be associated with acute kidney injury (AKI) in septic patients. However, its clinical use is limited by poor sensitivity and specificity which may be explained by its numerous determinants [in particular mean arterial pressure (MAP)]. We measured, in patients with septic shock, RI at different MAP levels over a short period of time on the admission day to ICU (D1) and every 3days until day 10 (D10) to define the determinants of RI and study specifically the relationship between RI and MAP.RESULTS: Consecutive patients with septic shock without preexisting chronic renal dysfunction were included in this prospective cohort study in two ICUs. Sixty-five patients were included in the study. Thirty-three (50.8%) and 15 (23.1%) patients had a history of chronic hypertension or diabetes, respectively. At D3, 35 patients presented AKI with AKIN 2 or 3 criteria (severe AKI, AKIN2-3 group) and 30 presented no AKIN or AKIN 1 criteria (AKIN0-1 group). As previously described, RI at D1 was higher in the AKIN2-3 group than in the AKIN0-1 group (0.73 interquartile range [0.67; 0.78] vs. 0.67 [0.59; 0.72], p = 0.001). A linear mixed model for predicting RI from D1 to D10 showed that an increase in pulse pressure, presence of severe AKI and additional day of ICU hospitalization were associated with an increase in RI. An increase in MAP and recovery from severe AKI were associated with a decrease in RI. In the presence of chronic hypertension or diabetes, an increase in MAP resulted in a lower decrease in RI, than in the absence of such factors. Presence of AKI at D3 did not impact the relationship between MAP and RI.CONCLUSIONS: Severe AKI was associated with a reversible increase in RI without significant interaction with the relationship between MAP and RI. Conversely, the presence of chronic hypertension and/or diabetes interacted with this relationship.
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- 2019
48. Effects of Resistance Exercise and Nutritional Supplementation on Dynamic Cerebral Autoregulation in Head-Down Bed Rest
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Dina N. Arvanitis, Marc Labrunee, Florent Besnier, Marc-Antoine Custaud, Nastassia Navasiolava, Marc Kermorgant, Marek Czosnyka, Jean-Michel Senard, Patrick Guinet, Philippe Arbeille, Anne Pavy-Le Traon, Nathalie Nasr, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie Vasculaire [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Neurosciences [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nuclear Medicine and Ultrasonography [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Addenbrooke's Hospital, Cambridge University NHS Trust, Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [CHU Angers] (PXE - le PseudoXanthome Elastique), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Détoxication et réparation tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Réeducation Cardio-Vasculaire et Pulmonaire [Clinique de Saint-Orens], Clinique Saint-Orens, Centre de biologie du développement (CBD), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de référence de l'atrophie multisystématisée [Toulouse] (AMS), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], HAL UR1, Admin, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
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medicine.medical_specialty ,resistance vibration exercise ,Supine position ,Nutritional Supplementation ,cerebral autoregulation ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Physiology ,medicine.medical_treatment ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,030204 cardiovascular system & hematology ,Spaceflight ,Bed rest ,Cerebral autoregulation ,lcsh:Physiology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Physiology (medical) ,Internal medicine ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cardiovascular Deconditioning ,ComputingMilieux_MISCELLANEOUS ,Original Research ,lcsh:QP1-981 ,business.industry ,microgravity ,head-down bed rest ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Blood pressure ,Cerebral blood flow ,Cardiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,nutritional supplementation ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,030217 neurology & neurosurgery - Abstract
International audience; Head-down bed rest (HDBR) is commonly considered as ground-based analog to spaceflight and simulates the headward fluid shift and cardiovascular deconditioning associated with spaceflight. We investigated in healthy volunteers whether HDBR, with or without countermeasures, affect cerebral autoregulation (CA). Twelve men (at selection: 34 ± 7 years; 176 ± 7 cm; 70 ± 7 kg) underwent three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel, and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Cerebral blood flow velocity was assessed using transcranial Doppler ultrasonography. CA was evaluated by transfer function analysis and by the autoregulatory index (Mxa) in order to determine the relationship between mean cerebral blood flow velocity and mean arterial blood pressure. In RVE condition, coherence was increased after HDBR. In CON condition, Mxa index was significantly reduced after HDBR. In contrast, in RVE and NeX conditions, Mxa were increased after HBDR. Our results indicate that HDBR without countermeasures may improve dynamic CA, but this adaptation may be dampened with RVE. Furthermore, nutritional supplementation did not enhance or worsen the negative effects of RVE. These findings should be carefully considered and could not be applied in spaceflight. Indeed, the subjects spent their time in supine position during bed rest, unlike the astronauts who perform normal daily activities.
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- 2019
49. WISE‐2005: Exercise countermeasure protects against changes in cardiovascular response to sublingual nitroglycerin after 56‐d bed rest
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Kathryn A Zuj, Kenneth S Dyson, Heather Edgell, Marc‐Antoine Custaud, and Richard L Hughson
- Published
- 2006
- Full Text
- View/download PDF
50. Effects of plantar stimulation on cardiovascular response to orthostatism
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Nastassia Navasiolava, L.E. Amirova, Guillemette Gauquelin-Koch, Claude Gharib, Marc-Antoine Custaud, Elena Tomilovskaya, Arnaud Beck, Marie-Pierre Bareille, and Inessa B. Kozlovzkaya
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Adult ,Male ,medicine.medical_specialty ,Sympathetic nervous system ,Cardiac output ,Sympathetic Nervous System ,Physiology ,Posture ,Blood Pressure ,Stimulation ,Walking ,030204 cardiovascular system & hematology ,Baroreflex ,03 medical and health sciences ,Orthostatic vital signs ,0302 clinical medicine ,Heart Rate ,Parasympathetic Nervous System ,Physical Stimulation ,Physiology (medical) ,Internal medicine ,Heart rate ,medicine ,Humans ,Orthopedics and Sports Medicine ,Cardiac Output ,Postural Balance ,Foot ,business.industry ,Public Health, Environmental and Occupational Health ,General Medicine ,Adaptation, Physiological ,Autonomic nervous system ,Blood pressure ,medicine.anatomical_structure ,Touch ,Physical therapy ,Cardiology ,business ,Mechanoreceptors ,030217 neurology & neurosurgery - Abstract
Walking is a complex locomotor process that involves both spinal cord reflexes and cortical integration of peripheral nerve input. Maintaining an upright body position requires not only neuromuscular activity but also cardiovascular regulation. We postulated that plantar mechanical stimulation might modulate autonomic nervous system activity and, thereby, impact blood pressure adaptation during standing. Twelve healthy subjects underwent three randomly ordered 45-min 70°-saddle tilt tests while the plantar surfaces of the feet were stimulated using specially engineered Korvit boots in the following modes: (1) no stimulation, (2) disrupted stimulation, and (3) walking mode. Orthostatic tolerance time was measured for each trial. During testing, we obtained an electrocardiogram and measured blood pressure, skin blood flow, and popliteal vein cross-sectional area. We estimated central hemodynamics, baroreflex sensitivity and heart rate variability. Orthostatic tolerance time was not found to differ significantly between test conditions (37.2 ± 10.4, 40.9 ± 7.6, and 41.8 ± 8.2 min, for no stimulation, disrupted stimulation, and walking mode, respectively). No significant differences between treatment groups were observed for stroke volume or cardiac baroreflex sensitivity, both of which decreased significantly from baseline during tilt testing in all groups. Cardiac sympathetic index and popliteal vein cross-sectional area increased at the end of the tilt period in all groups, without significant differences between treatments. Plantar mechanical stimulation is insufficient for immediate modulation of cardiac sympathetic and parasympathetic activity under orthostatic stress.
- Published
- 2016
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