Search

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte concentrations and cytokine profiles. METHODS: The study was conducted during the Ultra-Trail du Mont Blanc® ultra-marathon running event, and included 11 runners who completed the 40 km trail run and 12 runners who completed the 171 km ultra-trail. Blood samples were taken before and after the races. RESULTS: Leukocyte concentrations significantly increased after both races. Circulating levels of IL-6, IL-1β, MCP-1, and IFN-γ were significantly higher after the longer race compared to the shorter race. Furthermore, while both races resulted in significant increases in IL-6 and IL-8, only the longer race resulted in significant increases in MIP-1β, IL-7, IL-17a, and IL-4. CONCLUSIONS: These results illustrate that a 171 km ultra-trail race results in greater modulations in cytokine profiles than a traditional trail race.

International audience; Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity. Several parameters were compared between processed RBCs loaded with l-asparaginase (“eryaspase”), processed RBCs without drug and non-processed RBCs. Processed RBCs were less hydrated and displayed a reduction of intracellular content. We observed a change in the metabolomic but not in the proteomic profile of processed RBCs. Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release. Despite a decrease in deformability, processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance. Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.

International audience; This research in progress aims to understand the governance of managerial intercultural relations in the context of a merger of two SMEs in Luxembourg financed by a British Private Equity firm. An analysis of the intercultural environment of the company and of the structure of the forces at play exposes the influence of the multicultural factor on the implementation of the merger. The literature review, focused on intercultural management and approaches in terms of varieties of capitalism, highlights the cultural behavioral variables of the relationship between the decision-makers of the merged company. These perspectives allow us to build a framework explaining the relationship between intercultural strength and governance mechanisms in a company merger process. The qualitative methodology used is based on four interviews and a study of contextual elements in order to provide material for a content analysis. The results highlight the tensions exacerbated by the SME merger context in the exercise of governance by its actors and show the influence of the intercultural forces on the implementation mechanism of the merger project. We conclude by underlining the limits of the study and related other research opportunities.; Cette recherche en cours vise à comprendre la gouvernance des relations interculturelles managériales dans le cadre d'une fusion de deux PME luxembourgeoises financée par une société britannique de Private Equity. L'analyse de l'environnement interculturel de l'entreprise et de la structure des forces en présence met en évidence l'influence du facteur multiculturel sur la mise en œuvre de la fusion. La revue de la littérature, centrée sur le management et les approches interculturelles en termes de variétés de capitalisme, met en évidence les variables comportementales culturelles de la relation entre les décideurs de l'entreprise fusionnée. Ces perspectives nous permettent de construire un cadre expliquant la relation entre la force interculturelle et les mécanismes de gouvernance dans un processus de fusion d'entreprises. La méthodologie qualitative utilisée est basée sur quatre entretiens et une étude des éléments contextuels afin de fournir des éléments pour une analyse de contenu. Les résultats mettent en évidence les tensions exacerbées par le contexte de la fusion de PME dans l'exercice de la gouvernance par ses acteurs et montrent l'influence des forces interculturelles sur le mécanisme de mise en œuvre du projet de fusion. Nous concluons en soulignant les limites de l'étude et les autres possibilités de recherche qui y sont liées.

Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny&ndash, Combes &agrave, Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.

Blood rheology is a key determinant of blood flow and tissue perfusion. There are still large discrepancies regarding the effects of an acute running exercise on blood rheological properties and red blood cell (RBC) physiology. We investigated the effect of a 10 km running trial on markers of blood rheology and RBC physiology in endurance trained athletes. Blood was sampled before and after the exercise to measure lactate and glucose, hematological and hemorheological parameters (blood viscosity, RBC deformability, and aggregation), eryptosis markers (phosphatidylserine and CD47 exposure, RBC reactive oxygen species), RBC-derived microparticles (RBC-MPs), and RBC electrophysiological activity. Weight was measured before and after exercise. Peripheral oxygen saturation and heart rate were monitored before and during the trial. Blood lactate and glucose levels increased after exercise and subjects significantly lost weight. All athletes experienced a significant fall in oxygen saturation. Mean corpuscular volume (MCV) was increased from 95.1 ± 3.2 to 96.0 ± 3.3 and mean corpuscular hemoglobin concentration (MCHC) decreased after exercise suggesting a slight RBC rehydration. Exercise increased RBC deformability from 0.344 ± 0.04 to 0.378 ± 0.07, decreased RBC aggregates strength and blood viscosity, while hematocrit (Hct) remained unaffected. While RBC electrophysiological recording suggested a modulation in RBC calcium content and/or chloride conductance, eryptosis markers and RBC-MPs were not modified by the exercise. A 10 km acute running exercise had no effect on RBC senescence and membrane blebbing. In contrast, this exercise increased RBC deformability, probably through rehydration process which resulted in a decrease in blood viscosity.

International audience; Uranium (U) is the heaviest naturally occurring element ubiquitously present in the Earth’s crust. Human exposure to low levels of U is, therefore, unavoidable. Recently, several studies have clearly pointed out that the brain is a sensitive target for U, but the mechanisms leading to the observed neurological alterations are not fully known. To deepen our knowledge of the biochemical disturbances resulting from U(VI) toxicity in neuronal cells, two complementary strategies were set up to identify the proteins that selectively bind U(VI) in human dopaminergic SH-SY5Y cells. The first strategy relies on the selective capture of proteins capable of binding U(VI), using immobilized metal affinity chromatography, and starting from lysates of cells grown in a U(VI)-free medium. The second strategy is based on the separation of U-enriched protein fractions by size-exclusion chromatography, starting from lysates of U(VI)-exposed cells. High-resolution mass spectrometry helped us to highlight 269 common proteins identified as the urano-proteome. They were further analyzed to characterize their cellular localization and biological functions. Four canonical pathways, related to the protein ubiquitination system, gluconeogenesis, glycolysis, and the actin cytoskeleton proteins, were particularly emphasized due to their high content of U(VI)-bound proteins. A semi-quantification was performed to concentrate on the ten most abundant proteins, whose physico-chemical characteristics were studied in particular depth. The selective interaction of U(VI) with these proteins is an initial element of proof of the possible metabolic effects of U(VI) on neuronal cells at the molecular level.

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

Neoliberalism, or faith in the capacity of markets to solve social and economic problems, is a key element of the prevailing public policy orthodoxy in G20 countries. Throughout the 1980s, key proponents of the Neoliberal message such as UK Prime Minister Margaret Thatcher and American President Ronald Regan spoke optimistically about the philosophy’s inevitability and its benefits. During that period, the metaphor of a “rising tide lifting all boats” was offered as a way of envisaging the natural consequence of a supply-side strategy deployed with little or no state intervention. This project examines the shifting neoliberal message through two epochs: the closing decade of the industrial age from approximately 1980 to the early 1990s; and the period of the post-industrial age of e-commerce and the Internet. These eras can be viewed as steps along a path of diminishing comparative commercial advantage for G20 countries relative to emerging economies in Asia, and Latin America. Insofar as neoliberalism is concerned, early proponents of the ideology have realized their objective of reduced state involvement in Western countries but generally have not been able to produce evidence that a “rising tide lifts all boats”. Against this background, the modern G20 neoliberal message has changed from being one of optimism, opportunity and growing advantage to being one of survival. This paper explores why the message has changed and offers two interpretations of the relevance of a less bullish view of the advantages of neoliberalism.

The conversion of propargylic trimethylsilyl ether 3 into (Z)-1-bromo-3-benzoxy-1-butene 1 was achieved by hydroboration with pinacolborane followed by successive treatment with bromine and DBU. The key step of the chiral synthesis involves the asymmetric reduction of the α,β-unsaturated ketone 7 with (−)-diisopinocampheylchloroborane [(−)-Ipc2BCl].