Search

The aim of the present study was to assess injection flow rates of metal syringes, with an emphasis on injection speed and the generation of flow pulsations. A cohort of 64 operators (32 practitioners and 32 students) performed 3 consecutive ex vivo simulated injections (SIs) of 1.8-mL cartridges of anesthetic solution. Two needle diameters were tested (27-gauge and 30-gauge). Each SI was filmed and analyzed using a computer. In most cases, the SI lasted longer than 60 seconds with the 30-gauge needle (75%) but not with the 27-gauge needle (47.9%) (P < .0001). Practitioners and men delivered a full cartridge significantly faster than students and women, respectively (P = .0007 in both cases). All operators generated 1 pulse in at least 1 of the 3 SIs with both types of needles, especially during the first 3 seconds (254/384; 66.1%). Pulses occurred more frequently with practitioners (P = .0176) and with the 27-gauge needle (P = .005). Within its methodological limits, the present study showed how difficult it is to control injection pressure when using a metal syringe, especially at the beginning of the injection. Computerized systems may help overcome this problem.

International audience; BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for stroke. Impairment of cerebral autoregulation may play a potential role in the pre-disposition to stroke of OSAS patients. In this study, we aimed to assess dynamic cerebral autoregulation (DCA) during wakefulness in OSAS patients and a group of matched controls. METHODS: Patients and controls were examined in the morning after an overnight complete polysomnography. Mean cerebral blood flow velocity (CBFV) in the middle cerebral artery and mean arterial blood pressure (ABP) were continuously recorded using transcranial Doppler and Finapres. DCA was assessed using the Mx autoregulatory index. Mx is a moving correlation coefficient between mean CBFV and mean ABP. More positive value of Mx indicates worse autoregulation. RESULTS: Eleven OSAS patients (mean age +/- SD; 52.6 +/- 7.9) and 9 controls (mean age +/- SD; 49.1 +/- 5.3) were enrolled. The mean apnea-hypopnea index (AHI) in the OSAS group was of 22.7 +/- 11.6. No significant difference was found between the two groups as for age, body mass index, mean ABP and endtidal CO(2) pressure. Cerebral autoregulation was impaired in OSAS patients compared with controls (Mx index: 0.414 +/- 0.138 vs. 0.233 +/- 0.100; P = 0.009). The severity of autoregulation impairment correlated to the severity of the sleep respiratory disturbance measured by the AHI (P = 0.003). CONCLUSION: Cerebral autoregulation is impaired in patients with OSAS during wakefulness. Impairment of cerebral autoregulation is correlated with the severity of OSAS.

International audience; The occurrence of nonspherical oscillations (or surface modes) of coated microbubbles, used as ultrasound contrast agents in medical imaging, is investigated using ultra-high-speed optical imaging. Optical tweezers designed to micromanipulate single bubbles in 3-D are used to trap the bubbles far from any boundary, enabling a controlled study of the nonspherical oscillations of free-floating bubbles. Nonspherical oscillations appear as a parametric instability and display subharmonic behavior: they oscillate at half the forcing frequency, which was fixed at 1.7 MHz in this study. Surface modes are shown to preferentially develop for a bubble radius near the resonance of radial oscillations. In the studied range of acoustic pressures, the growth of surface modes saturates at a level far below bubble breakage. With the definition of a single, dimensionless deformation parameter, the amplitude of nonspherical deformation is quantified as a function of the bubble radius (between 1.5 and 5 microm) and of the acoustic pressure (up to 200 kPa).

The TWIK related K+ channel TREK1 is an important member of the class of two-pore-domain K+ channels. It is a background K+ channel and is regulated by hormones, neurotransmitters, intracellular pH and mechanical stretch. This work shows that TREK1 is present both in mesenteric resistance arteries and in skin microvessels. It is particularly well expressed in endothelial cells. Deletion of TREK1 in mice leads to an important alteration in vasodilation of mesenteric arteries induced by acetylcholine and bradykinin. Iontophoretic delivery of acetylcholine and bradykinin in the skin of TREK1+/+ and TREK1−/− mice also shows the important role of TREK1 in cutaneous endothelium-dependent vasodilation. The vasodilator response to local pressure application is also markedly decreased in TREK1−/− mice, mimicking the decreased response to pressure observed in diabetes. Deletion of TREK1 is associated with a marked alteration in the efficacy of the G-protein-coupled receptor-associated cascade producing NO that leads to major endothelial dysfunction.

International audience; The hair bundles of cochlear hair cells play a central role in the auditory mechano-electrical transduction (MET) process. The identification of MET components and of associated molecular complexes by biochemical approaches is impeded by the very small number of hair cells within the cochlea. In contrast, human and mouse genetics have proven to be particularly powerful. The study of inherited forms of deafness led to the discovery of several essential proteins of the MET machinery, which are currently used as entry points to decipher the associated molecular networks. Notably, MET relies not only on the MET machinery but also on several elements ensuring the proper sound-induced oscillation of the hair bundle or the ionic environment necessary to drive the MET current. Here, we review the most significant advances in the molecular bases of the MET process that emerged from the genetics of hearing.

International audience; AIMS: The optic atrophy 1 (OPA1) protein is an essential protein involved in the fusion of the mitochondrial inner membrane. Despite its high level of expression, the role of OPA1 in the heart is largely unknown. We investigated the role of this protein in Opa1(+/-) mice, having a 50% reduction in OPA1 protein expression in cardiac tissue. METHODS AND RESULTS: In mutant mice, cardiac function assessed by echocardiography was not significantly different from that of the Opa1(+/+). Electron and fluorescence microscopy revealed altered morphology of the Opa1(+/-) mice mitochondrial network; unexpectedly, mitochondria were larger with the presence of clusters of fused mitochondria and altered cristae. In permeabilized mutant ventricular fibres, mitochondrial functional properties were maintained, but direct energy channelling between mitochondria and myofilaments was weakened. Importantly, the mitochondrial permeability transition pore (PTP) opening in isolated permeabilized cardiomyocytes and in isolated mitochondria was significantly less sensitive to mitochondrial calcium accumulation. Finally, 6 weeks after transversal aortic constriction, Opa1(+/-) hearts demonstrated hypertrophy almost two-fold higher (P< 0.01) than in wild-type mice with altered ejection fraction (decrease in 43 vs. 22% in Opa1(+/+) mice, P< 0.05). CONCLUSIONS: These results suggest that, in adult cardiomyocytes, OPA1 plays an important role in mitochondrial morphology and PTP functioning. These properties may be critical for cardiac function under conditions of chronic pressure overload.

How chronic pressure overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we used a connexin (Cx)40 knockout/enhanced green fluorescent protein knockin transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially located PCS would remodel after chronic pressure overload and therefore analyzed cell size, markers of hypertrophy, and PCS-specific Cx and ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical transaortic constriction. After transaortic constriction, we observed that PCS cardiomyocytes hypertrophied by 23% ( P < 0.05) and that microdissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Cx40-positive gap junction particles, with an associated twofold increase in gene expression ( P < 0.05). We also identified a 50% reduction in Cx43 gap junction particles located at the interface between PCS cardiomyocytes and the working cardiomyocyte. In addition, we measured a fourfold increase of an ion channel, hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, throughout the PCS ( P < 0.05). As a direct consequence of PCS remodeling, we found that pressure-overloaded hearts exhibited marked changes in ventricular activation patterns during normal sinus rhythm. These novel findings characterize PCS cardiomyocyte remodeling after chronic pressure overload. We identified significant hypertrophic growth accompanied by modified expression of Cx40, Cx43, and HCN4 within PCS cardiomyocytes. We found that a functional outcome of these changes is a failure of the PCS to activate the ventricular myocardium normally. Our findings provide a proof of concept that pressure overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS.

International audience; AIMS: The optic atrophy 1 (OPA1) protein is an essential protein involved in the fusion of the mitochondrial inner membrane. Despite its high level of expression, the role of OPA1 in the heart is largely unknown. We investigated the role of this protein in Opa1(+/-) mice, having a 50% reduction in OPA1 protein expression in cardiac tissue. METHODS AND RESULTS: In mutant mice, cardiac function assessed by echocardiography was not significantly different from that of the Opa1(+/+). Electron and fluorescence microscopy revealed altered morphology of the Opa1(+/-) mice mitochondrial network; unexpectedly, mitochondria were larger with the presence of clusters of fused mitochondria and altered cristae. In permeabilized mutant ventricular fibres, mitochondrial functional properties were maintained, but direct energy channelling between mitochondria and myofilaments was weakened. Importantly, the mitochondrial permeability transition pore (PTP) opening in isolated permeabilized cardiomyocytes and in isolated mitochondria was significantly less sensitive to mitochondrial calcium accumulation. Finally, 6 weeks after transversal aortic constriction, Opa1(+/-) hearts demonstrated hypertrophy almost two-fold higher (P< 0.01) than in wild-type mice with altered ejection fraction (decrease in 43 vs. 22% in Opa1(+/+) mice, P< 0.05). CONCLUSIONS: These results suggest that, in adult cardiomyocytes, OPA1 plays an important role in mitochondrial morphology and PTP functioning. These properties may be critical for cardiac function under conditions of chronic pressure overload.

Multiple modalities converge on a common gate to control K2P channel function K2P potassium channels play important roles in the regulation of neuronal excitability. K2P channels are gated chemical, thermal, and mechanical stimuli, and the present study identifies and characterizes a common molecular gate that responds to all different stimuli, both activating and inhibitory ones., Members of the K2P potassium channel family regulate neuronal excitability and are implicated in pain, anaesthetic responses, thermosensation, neuroprotection, and mood. Unlike other potassium channels, K2Ps are gated by remarkably diverse stimuli that include chemical, thermal, and mechanical modalities. It has remained unclear whether the various gating inputs act through separate or common channel elements. Here, we show that protons, heat, and pressure affect activity of the prototypical, polymodal K2P, K2P2.1 (KCNK2/TREK-1), at a common molecular gate that comprises elements of the pore-forming segments and the N-terminal end of the M4 transmembrane segment. We further demonstrate that the M4 gating element is conserved among K2Ps and is employed regardless of whether the gating stimuli are inhibitory or activating. Our results define a unique gating mechanism shared by K2P family members and suggest that their diverse sensory properties are achieved by coupling different molecular sensors to a conserved core gating apparatus.

International audience; How sensory organization for postural control matures in children is not clear at this time. The present study examined, in children aged 7 to 11 and in adults, the postural control modifications in quiet standing when somatosensory inputs from the ankle were disturbed. Since the reweighting of sensory inputs is not mature before 10, we hypothesized that postural stability was more affected in children than in adults when somatosensory inputs were altered and that this postural instability decreased as age increased during childhood. 37 children aged 7 to 11 years and 9 adults participated in the experiments. The postural task was a semi-tandem position with the right foot in front of the left one. Postural performance was measured by means of a force platform. Two experimental conditions were presented to the participants to maintain quiet standing: With or without altered somatosensory inputs (i.e., with or without ankles vibration). Results showed that postural stability--and thus how the reweighting process of the visual/somatosensory inputs matured--increased non-monotonically between 7 years of age and adult age: There was a linear improvement of postural stability from 7 to 10, followed by a more steady behaviour between 10 and 11 and then postural stability increased to reach the adults' level of performance.

International audience; The HIV-1 envelope glycoprotein 41 (gp41) undergoes large-scale conformational changes in order to induce the fusion of the virus and cell membranes. Thus, we investigated a possible structure transit at the air-water interface for the tryptophan-rich peptide of gp41 (gp41W). The synthetic peptide (KWASLWNWFNITNWLWYIK), corresponding to gp41W, shows interfacial properties on pure water and Tris buffer at pH 8.5. Isotherm measurements and Brewster angle microscopy (BAM) imaging showed that the behavior of the peptide monolayer was dependent on the subphase composition. A homogenous film was formed on buffer during the peptide monolayer compression, while the appearance of condensed domains on pure water could indicate the oligomerization of gp41W during the surface pressure increase. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) showed that, whatever the subphase, gp41W adopts an α-helix structure at the air-water interface and does not transit for any other structure even at high surface pressures.

International audience; Recent studies have demonstrated the feasibility of transcranial high-intensity focused ultrasound (HIFU) therapy in the brain using adaptive focusing techniques. However, the complexity of the procedures imposes provision of accurate targeting, monitoring and control of this emerging therapeutic modality in order to ensure the safety of the treatment and avoid potential damaging effects of ultrasound on healthy tissues. For these purposes, a complete workflow and setup for HIFU treatment under magnetic resonance (MR) guidance is proposed and implemented in rats. For the first time, tissue displacements induced by the acoustic radiation force are detected in vivo in brain tissues and measured quantitatively using motion-sensitive MR sequences. Such a valuable target control prior to treatment assesses the quality of the focusing pattern in situ and enables us to estimate the acoustic intensity at focus. This MR-acoustic radiation force imaging is then correlated with conventional MR-thermometry sequences which are used to follow the temperature changes during the HIFU therapeutic session. Last, pre- and post-treatment magnetic resonance elastography (MRE) datasets are acquired and evaluated as a new potential way to non-invasively control the stiffness changes due to the presence of thermal necrosis. As a proof of concept, MR-guided HIFU is performed in vitro in turkey breast samples and in vivo in transcranial rat brain experiments. The experiments are conducted using a dedicated MR-compatible HIFU setup in a high-field MRI scanner (7 T). Results obtained on rats confirmed that both the MR localization of the US focal point and the pre- and post-HIFU measurement of the tissue stiffness, together with temperature control during HIFU are feasible and valuable techniques for efficient monitoring of HIFU in the brain. Brain elasticity appears to be more sensitive to the presence of oedema than to tissue necrosis.

International audience; Blebs are spherical membrane protrusions often observed during cell migration, cell spreading, cytokinesis, and apoptosis, both in cultured cells and in vivo. Bleb expansion is thought to be driven by the contractile actomyosin cortex, which generates hydrostatic pressure in the cytoplasm and can thus drive herniations of the plasma membrane. However, the role of cortical tension in bleb formation has not been directly tested, and despite the importance of blebbing, little is known about the mechanisms of bleb growth. In order to explore the link between cortical tension and bleb expansion, we induced bleb formation on cells with different tensions. Blebs were nucleated in a controlled manner by laser ablation of the cortex, mimicking endogenous bleb nucleation. Cortical tension was modified by treatments affecting the level of myosin activity or proteins regulating actin turnover. We show that there is a critical tension below which blebs cannot expand. Above this threshold, the maximal size of a bleb strongly depends on tension, and this dependence can be fitted with a model of the cortex as an active elastic material. Together, our observations and model allow us to relate bleb shape parameters to the underlying cellular mechanics and provide insights as to how bleb formation can be biochemically regulated during cell motility.

International audience; Brain treatment through the skull with high-intensity focused ultrasound can be achieved with multichannel arrays and adaptive focusing techniques such as time reversal. This method requires a reference signal to be either emitted by a real source embedded in brain tissues or computed from a virtual source, using the acoustic properties of the skull derived from computed tomography images. This noninvasive computational method focuses with precision, but suffers from modeling and repositioning errors that reduce the accessible acoustic pressure at the focus in comparison with fully experimental time reversal using an implanted hydrophone. In this paper, this simulation-based targeting has been used experimentally as a first step for focusing through an ex vivo human skull at a single location. It has enabled the creation of a cavitation bubble at focus that spontaneously emitted an ultrasonic wave received by the array. This active source signal has allowed 97 +/- 1.1% of the reference pressure (hydrophone-based) to be restored at the geometrical focus. To target points around the focus with an optimal pressure level, conventional electronic steering from the initial focus has been combined with bubble generation. Thanks to step-by-step bubble generation, the electronic steering capabilities of the array through the skull were improved.

This work was supported by the Institut National de la Recherche Agronomique (doctoral fellowship to C.E. and grant no. AIP300), the French Ministry of Research (grant no. ACI2003 [Biologie du Développement et Physiologie Intégrative] to C.M. and T.S.), and Agence Nationale de la Recherche Génoplante (award to F.T.).; International audience; Root hydraulic conductivity in plants (Lp(r)) exhibits large variations in response to abiotic stimuli. In this study, we investigated the impact of dynamic, aquaporin-mediated changes of Lp(r) on leaf growth, water potential, and water flux throughout the plant. For this, we manipulated Lp(r) by subjecting roots to four independent treatments, with aquaporin inhibitors applied either to transpiring maize (Zea mays) plants grown in hydroponics or to detopped root systems for estimation of Lp(r). The treatments were acid load at pH 6.0 and 5.0 and hydrogen peroxide and anoxia applied for 1 to 2 h and subsequently reversed. First, we established that acid load affected cell hydraulic conductivity in maize root cortex. Lp(r) was reduced by all treatments by 31% to 63%, with half-times of about 15 min, and partly recovered when treatments were reversed. Cell turgor measured in the elongating zone of leaves decreased synchronously with Lp(r), and leaf elongation rate closely followed these changes across all treatments in a dose-dependent manner. Leaf and xylem water potentials also followed changes in Lp(r). Stomatal conductance and rates of transpiration and water uptake were not affected by Lp(r) reduction under low evaporative demand. Increased evaporative demand, when combined with acid load at pH 6.0, induced stomatal closure and amplified all other responses without altering their synchrony. Root pressurization reversed the impact of acid load or anoxia on leaf elongation rate and water potential, further indicating that changes in turgor mediated the response of leaf growth to reductions in Lp(r).

Our understanding of chronic thromboembolic pulmonary hypertension (CTEPH), in terms of both its natural history and pathophysiology, has greatly improved since the landmark descriptions given by Moser and Braunwald 1 more than 40 yrs ago. At that time, small case series were available, depicting the clinical features of patients suffering from “long-standing thromboembolic pulmonary hypertension”, “chronic massive thromboembolic obstruction” or “chronic obstruction of large pulmonary arteries”. These patients shared a history of long-term dyspnoea on exertion with normal spirometry values, evidence of pulmonary hypertension, and right ventricular dysfunction in association with the presence of marked defects at the ventilation/perfusion scan; the occurrence of a single or multiple venous thromboembolism episodes, usually several years previously, was constantly mentioned in the diagnostic work-up 2–5. The success of a surgical procedure, namely pulmonary endarterectomy, has transformed this lethal disorder into a potentially curable form of pulmonary hypertension 1. As a consequence, the referral of cases suitable for surgery has gradually increased with time: at the University of San Diego (San Diego, CA, USA) there were 41 operated cases in 1980, rising to 323 cases in 1992 6, 7. This has enabled us to broaden our knowledge, with the help of further involvement from European centres 8–11]. Forty years ago, the frequency of CTEPH was estimated to be 0.1% of patients who survived an episode of pulmonary embolism 12 …

International audience; A new fabrication method to produce homogeneously fluorescent nanodiamonds with high yields is described. The powder obtained by high energy ball milling of fluorescent high pressure, high temperature diamond microcrystals was converted in a pure concentrated aqueous colloidal dispersion of highly crystalline ultrasmall nanoparticles with a mean size less than or equal to 10 nm. The whole fabrication yield of colloidal quasi-spherical nanodiamonds was several orders of magnitude higher than those previously reported starting from microdiamonds. The results open up avenues for the industrial cost-effective production of fluorescent nanodiamonds with well-controlled properties.

International audience; A new fabrication method to produce homogeneously fluorescent nanodiamonds with high yields is described. The powder obtained by high energy ball milling of fluorescent high pressure, high temperature diamond microcrystals was converted in a pure concentrated aqueous colloidal dispersion of highly crystalline ultrasmall nanoparticles with a mean size less than or equal to 10 nm. The whole fabrication yield of colloidal quasi-spherical nanodiamonds was several orders of magnitude higher than those previously reported starting from microdiamonds. The results open up avenues for the industrial cost-effective production of fluorescent nanodiamonds with well-controlled properties.

Background and Purpose— To analyze the postural behavior of standing stroke patients: (1) To differentiate between postural impairment attributable to the neurological condition (deficits attributable to the cerebral lesion) and postural impairment attributable to new mechanical constraints caused by body weight asymmetry; (2) To assess the involvement of each limb in the postural impairment; (3) To better understand which clinical deficits underlie the postural impairment. Methods— The posturographic characteristics of each limb in 41 stroke patients (first hemispheric stroke: 16 left, 25 right cerebral lesions) required to stand in their preferred posture were compared to those in 40 matched healthy individuals required to stand asymmetrically. Results— Compared to normal individuals in a similar asymmetrical posture, stroke patients were more unstable. The weight bearing asymmetry and the lateral postural instability were mainly related to spatial neglect. The paretic limb was unable to bring into play a normal longitudinal pattern of the center of pressure, which reflects an impaired stabilization control. Overall postural instability occurred when the strong limb was unable to compensate for the postural impairment of the paretic limb. Conclusions— The weight bearing asymmetry of standing stroke patients is not the primary cause of their postural imbalance, which is rather the consequence of impaired control of postural stabilization involving both limbs. Weight bearing asymmetry may not be the principle target of rehabilitation programs aiming at restoring standing balance after stroke. Instead it is suggested that more account should be taken of the compensatory role of the strong limb.

Background and Purpose— Posturography in patients with stroke is widely based on the use of a single force platform and the weightbearing asymmetry quantified from the lateral shift of the center of pressure toward the sound leg. Because the percentage of body weight on each side is a more concrete variable, the present study analyzed the possibility of inferring percentage of body weight from center of pressure. Methods— Forty-five hemiparetic subjects were asked to stand on a dual platform in a standardized position 3 months after a hemispheric stroke. First, the relationship between the %BW on each foot and the lateral shift of center of pressure was established. Second, the model was tested with a healthy subject standing on a single force platform. Results— The percentage of body weight may be simply modeled from the center of pressure shift, a center of pressure displacement of 10 mm corresponding to a 5% increase in body weight on this side ( r =0.97, P Conclusions— This finding should be useful for constructors and users of single force platforms, especially those involved in posturographic assessments of asymmetric conditions such as hemiparesis.

International audience; PURPOSE: We determined whether urinary leakage in some circumstances is associated with intrinsic sphincter deficiency, defined by a low maximum urethral closure pressure of 30 cm H(2)O or less, in women presenting for urinary incontinence. MATERIALS AND METHODS: We retrospective analyzed the records of 100 consecutive women who underwent complete urodynamic evaluations for complaints of urinary leakage. RESULTS: Logistic regression adjusted for age showed that leakage while running or during physical exertion, leakage while walking and leakage with no obvious reason were associated with intrinsic sphincter deficiency, while leakage upon coughing or sneezing was not. CONCLUSIONS: These results suggest that different mechanisms may govern incontinence during prolonged vs brief stress. Low maximum urethral closure pressure may be a sign of abnormal sphincter fatigability.

International audience; We report on the neutral-to-ionic (N-I) phase transition in the one-dimensional organic complex (BEDT-TTF)-(ClMeTCNQ). The X-ray studies at room temperature show that the neutral phase of (BEDT-TTF)-(ClMeTCNQ) is already characterized by a polar long-range ordering, at variance with other charge-transfer compounds comprising noncentrosymmetric molecules. From a detailed neutron diffraction study of this complex under high pressure, we present the phase diagram of the N-I transition down to the quantum limit. We discuss the symmetry breaking associated with the transition and the evolution of its first-order character under pressure.

International audience; In this work, calcium-deficient apatites (CDA) were synthesized by ammonia hydrolysis reaction of dicalcium phosphate dihydrate (DCPD; CaHPO4 x 2 H2O) to obtain biphasic calcium phosphates (BCP) without any extraionic substitution. The influence of three parameters was studied: temperature of the reaction (70 and 100 degrees C), time of the reaction (4 and 18 h), and the pressure (open and closed system). Experiments were made according to a factorial design method (FDM) allowing optimization of the number of samples as well as statistical analysis of results. Moreover, the influence of temperature (until 200 degrees C) was investigated. The crystal size of CDA was determined according to the Scherrer's formula and from Rietveld refinements taking the CDA anisotropy into account. The last method seems to be a reliable method to determine crystallite sizes of CDA, since crystallite sizes of CDA along and directions were accessible. The results describe the hydroxyapatite % (HA%) in BCP by a first-order polynomial equation in the experimental area studied and the HA content was found to increase by raising time and temperature of the reaction. Moreover, the type of reaction system (open/closed vessel) appeared to have little influence on HA%.

The purpose of the present experiment was to investigate whether, with vision, the magnitude of the effect of calf muscles fatigue on postural control during bipedal quiet standing depends on the eye-visual target distance. Twelve young university students were asked to stand upright as immobile as possible in three visual conditions (No vision, Vision 1m and Vision 4m) executed in two conditions of No fatigue and Fatigue of the calf muscles. Centre of foot pressure displacements were recorded using a force platform. Similar increased variances of the centre of foot pressure displacements were observed in the fatigue relative to the No fatigue condition for both the No vision and Vision 4m conditions. Interestingly, in the vision 1m condition, fatigue yielded: (1) a similar increased variance of the centre of foot pressure displacements to those observed in the No vision and Vision 4m conditions along the medio-lateral axis and (2) a weaker destabilising effect relative to the No vision and Vision 4m conditions along the antero-posterior axis. These results evidence that the ability to use visual information for postural control during bipedal quiet standing following calf muscles fatigue is dependent on the eye-visual target distance. More largely, in the context of the multisensory control of balance, the present findings suggest that the efficiency of the sensory reweighting of visual sensory cues as the neuro-muscular constraints acting on the subject change is critically linked with the quality of the information the visual system obtains.

Background and Purpose— CADASIL is an inherited small-vessel disease responsible for lacunar strokes and cognitive impairment. The disease is caused by highly stereotyped mutations in Notch3 , the expression of which is highly restricted to vascular smooth muscle cells (VSMCs). The underlying vasculopathy is characterized by degeneration of VSMCs and the accumulation of granular osmiophilic material (GOM) and Notch3 protein within the cell surface of these cells. In this study, we assessed early functional changes related to the expression of mutant Notch3 in resistance arteries. Methods— Vasomotor function was examined in vitro in arteries from transgenic mice that express a mutant Notch3 in VSMC. Tail artery segments from transgenic and normal wild-type male mice were mounted on small-vessel arteriographs, and reactivity to mechanical (flow and pressure) forces and pharmacological stimuli were determined. Mice were studied at 10 to 11 months of age when VSMC degeneration, GOM deposits, and Notch3 accumulation were not yet present. Results— Passive arterial diameter, contraction to phenylephrine, and endothelium-dependent relaxation to acetylcholine were unaffected in transgenic mice. By contrast, flow-induced dilation was significantly decreased and pressure-induced myogenic tone significantly increased in arteries from transgenic mice compared with wild-type mice. Conclusions— This is the first study to our knowledge providing evidence that mutant Notch3 impairs selectively the response of resistance arteries to flow and pressure. The data suggest an early role of vascular dysfunction in the pathogenic process of the disease.

We investigated the effect of performing a mental arithmetic task with two levels of difficulty on the regulation of centre of foot pressure (COP) displacements during bipedal quiet standing in young healthy individuals. There was also a control condition in which no concurrent task was required. A space-time-domain analysis showed decreased COP displacements, along the antero-posterior axis, when participants concurrently performed the most difficult mental arithmetic task. Frequency-domain and stabilogram-diffusion analyses further suggested these decreased COP displacements to be associated with an increased stiffness and a reduction of the exploratory behaviours in the short term, respectively.

International audience; The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

International audience; Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.

International audience; The aim of this study was to investigate the effects of a high ambient pressure of He on vascular contraction induced by noradrenaline and to distinguish the effects of ambient pressure per se from those of increased pressure of inert gas. Rings of thoracic aorta were isolated from male Wistar rats. Isometric tension was measured in preparations exposed to 7.1 MPa (absolute pressure) of He. Dose-response curves for noradrenaline and contractions elicited by 120 mM KCl were compared with time-matched experiments performed at atmospheric pressure. The same protocol was also carried out under 7.1 MPa of N2. At the high pressure of He, the contraction elicited by noradrenaline was increased with no change in the response to K(+)-evoked depolarization. The tension developed in response to noradrenaline also increased under 7.1 MPa of N2 but the effects were less marked than during the He experiments. Moreover, the response to KCl was reduced in this circumstance. Hyperbaric conditions enhance the noradrenaline-induced contraction of rat aorta in vitro. This effect probably results from an action of pressure per se on activation of adrenoceptors. However, the hyperbaric-induced increase in vascular smooth muscle contraction is partially counteracted by high pressures of inert gases (N2, but also probably He), which impair the efficiency of the contractile machinery.

International audience; Nucleoside Diphosphate Kinases (NDPKs) have long been considered merely as housekeeping enzymes. The discovery of the NME1 gene, an anti-metastatic gene coding for NDPK-A, led the scientific community to re-evaluate their role in the cell. It is now well established that the NDPK family is more complex than what was first thought, and despite the increasing amount of evidence suggesting the multifunctional role of nm23/NDPKs, the specific functions of each family member are still elusive. Among these isoforms, NDPK-D is the only one to present a mitochondria-targeting sequence. It has recently been shown that this protein is able to bind and cross-link with mitochondrial membranes, suggesting that NDPK-D can mediate contact sites and contributes to the mitochondrial intermembrane space structuring. To better understand the influence of NDPK-D on mitochondrial lipid organisation, we analysed its behaviour in different lipid environments. We found that NDPK-D not only interacts with CL or anionic lipids, but is also able to bind in a non negligible manner to zwitterionic PC. NDPK-D alters membrane organisation in terms of fluidity, hydration and lipid clustering, effects which depend on lipid structure. Changes in the protein structure after lipid binding were evidenced, both by fluorescence and infrared spectroscopy, regardless of membrane composition. Taking into account all these elements, a putative mechanism of interaction between NDPK-D and zwitterionic or anionic lipids was proposed.

International audience; A fluid-fiber-collagen stress tensor is used to describe the rheology of the left ventricle of the heart. Linear theory is used to find the equilibrium solutions for the end-diastolic and end-systolic states of general axisymmetric shapes that are small perturbations of a thick-walled finite cylinder. The general problem can be studied by superposing the effects of variable midwall radius but constant wall thickness with those of variable wall thickness but constant midwall radius. A Fourier series representation is used to describe the midwall radius and thickness functions. Numerical calculations are performed to determine the deformed geometry and spatial distributions of tissue pressure, stresses, and fiber strains. The calculations proved to be highly accurate when compared to an analytical solution obtained for the special case of no fibers. The results show significant longitudinal differences when compared to results for the cylindrical geometry, with more sensitivity to variation in wall thickness than to variation in midwall radius.