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Mignardot J.-B.,University of Nantes | Mignardot J.-B.,Ecole Polytechnique Federale de Lausanne | Deschamps T.,University of Nantes | Barrey E.,CNRS Unit of Integrative Biology of Adaptation to Exercise | And 7 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Falls are common in the elderly, and potentially result in injury and disability. Thus, preventing falls as soon as possible in older adults is a public health priority, yet there is no specific marker that is predictive of the first fall onset. We hypothesized that gait features should be the most relevant variables for predicting the first fall. Clinical baseline characteristics (e.g., gender, cognitive function) were assessed in 259 home-dwelling people aged 66 to 75 that had never fallen. Likewise, global kinetic behavior of gait was recorded from 22 variables in 1036 walking tests with an accelerometric gait analysis system. Afterward, monthly telephone monitoring reported the date of the first fall over 24 months. A principal components analysis was used to assess the relationship between gait variables and fall status in four groups: non-fallers, fallers from 0 to 6 months, fallers from 6 to 12 months and fallers from 12 to 24 months. The association of significant principal components (PC) with an increased risk of first fall was then evaluated using the area under the Receiver Operator Characteristic Curve (ROC). No effect of clinical confounding variables was shown as a function of groups. An eigenvalue decomposition of the correlation matrix identified a large statistical PC1 (termed "Global kinetics of gait pattern"), which accounted for 36.7% of total variance. Principal component loadings also revealed a PC2 (12.6% of total variance), related to the "Global gait regularity." Subsequent ANOVAs showed that only PC1 discriminated the fall status during the first 6 months, while PC2 discriminated the first fall onset between 6 and 12 months. After one year, any PC was associated with falls. These results were bolstered by the ROC analyses, showing good predictive models of the first fall during the first six months or from 6 to 12 months. Overall, these findings suggest that the performance of a standardized walking test at least once a year is essential for fall prevention. © 2014 Mignardot, Deschamps, Barrey, Auvinet, Berrut, Cornu, Constans and de Decker.

Mesti T.,University of Paris Descartes | Savarin P.,University of Paris 13 | Triba M.N.,University of Paris 13 | Le Moyec L.,CNRS Unit of Integrative Biology of Adaptation to Exercise | And 3 more authors.
PLoS ONE | Year: 2014

Background: Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the existence of an autocrine loop. The direct impact on glioma cells metabolism of drugs targeting the VEGF pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), is poorly known. Material and Methods: U87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked with FACS flow cytometry and Quantitative Real-Time PCR. VEGF secretion into the medium was assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS). Results: U87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells. Conclusion: Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop. In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess drug cytotoxicity. © 2014 Mesti et al.

Capomaccio S.,University of Perugia | Cappelli K.,University of Perugia | Barrey E.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Barrey E.,French National Institute for Agricultural Research | And 3 more authors.
Animal Genetics | Year: 2010

It is known that moderate physical activity may have beneficial effects on health, whereas strenuous effort induces a state resembling inflammation. The molecular mechanisms underlying the cellular response to exercise remain unclear, although it is clear that the immune system plays a key role. It has been hypothesized that the physio-pathological condition that develops in athletes subjected to heavy training is caused by derangement of cellular immune regulation. The purpose of the present study was to obtain information on endurance horse gene transcription under strenuous conditions and to identify candidate genes causing immune system derangement. We performed a wide gene expression scan, using microarray technology, on peripheral blood mononuclear cells of ten horses chosen from high-level participants in national and international endurance races. The use of three different timepoints revealed changes in gene expression when post-effort samples (T1, taken immediately after the race; and T2, taken 24?h after the race) were compared with basal sample (T0, at rest). Statistical analysis showed no differences in gene expression between T0 and T2 samples, indicating complete restoration of homeostasis by 24?h after racing, whereas T1 showed strong modulation of expression, affecting 132 genes (97 upregulated, 35 downregulated). Ingenuity pathway analysis revealed that the main mechanisms and biofunctions involved were significantly associated with immunological and inflammatory responses. Real-time PCR was performed on 26 gene products to validate the array data. © 2010 Stichting International Foundation for Animal Genetics.

Martin V.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Nicol C.,Aix - Marseille University
Movement and Sports Sciences - Science et Motricite | Year: 2010

Eccentric- and stretch-shortening cycle (SSC) type exercises are of great functional interest for human locomotion. However, the repetition of such types of muscle actions during prolonged exercises or at high intensities may induce acute and delayed structuro-functional deficits, frequently associated with delayed onset muscle soreness (DOMS). These alterations are reversible owing to the intervention of an inflammatory process. The associated biochemical, thermal and mechanical changes are suggested to sensitize small diameter muscles afferents (type III and IV) that may then contribute to the DOMS generation and neural adjustments to the contractile failure. © ACAPS, EDP Sciences, 2010.

Van de Louw A.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Van de Louw A.,Intensive Care Unit | Medigue C.,Institute National Of Recherche En Informatique Et En Automatique | Papelier Y.,EA 3544 | Cottin F.,CNRS Unit of Integrative Biology of Adaptation to Exercise
Respiratory Research | Year: 2010

Background: Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity.Methods: We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices.Results: At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage.Conclusions: During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases. © 2010 Van de Louw et al; licensee BioMed Central Ltd.

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