Régulation de la prolifération des cellules musculaires lisses vasculaires par l’activation in vivo du récepteur natriurétique de type C

Le remodelage vasculaire dû à l’hyper-prolifération cellulaire des cellules musculaires lisses vasculaires (CMLVs) observé chez les rats spontanément hypertendus (RSH) est associé à l’hypertension artérielle. Nous avons précédemment démontré que le traitement in vivo des RSH par l’agoniste spécifique du récepteur du peptide natriurétique de type C (NPR-C), le C-ANP4-23 atténue l’hyper-prolifération des CMLVs. Nous avons entrepris cette étude afin d’investiguer si l’effet antiprolifératif du C-ANP4-23 agit par l’entremise de l’inhibition de la surexpression des protéines du cycle cellulaire, et afin d’en explorer les mécanismes sous-jacents. Pour cette étude, des RSH et des rats Wistar Kyoto (WKYs) âgés de deux semaines ont été injectés en intra-péritonéale par le C-ANP4-23 de 2 jusqu’à 8 semaines d’âge, deux fois par semaine et sacrifiés à la 9ème semaine. La pression artérielle a été mesurée par méthode Queue-coiffe, la prolifération des CMLVs a été déterminée par incorporation de thymidine et par test MTT, et l’expression des protéines a été quant à elle déterminée par technique d’immunobuvardage de type Western. Les CMLVs des RSH ont démontré une prolifération élevée en comparaison avec celles des WKYs, et le traitement par le C-ANP4-23 a atténué l’hyperprolifération à un niveau de contrôle. De plus, la surexpression des cyclines D1/A/E, des kinases cyclines dépendantes 2 et 4 (cdk2, cdk4), de la forme phosphorylée de la protéine du rétinoblastome et des protéines Gαi des CMLV des RSH a été atténuée à un niveau de contrôle. Par ailleurs, l’hyperphosphorylation d’ERK1/2, AKT, EGF-R, PDGF-R, IGF-R et de c-Src a significativement diminué par le traitement au C-ANP4-23. En outre, le niveau élevé de l’anion superoxyde (O2-), l’activité de la NADP(H) oxydase et de ses sous unités chez les RSH ont été atténués par le C-ANP4-23 .Ces résultats indiquent que l’activation in vivo de NPR-C atténue la surexpression des protéines du cycle cellulaire via l’inhibition de l’activité élevée du stress oxydatif, de c-Src et de l’activation de EGF-R, PDGF- R, IGF-R, de la signalisation de MAPK et la surexpression des protéines Gαi résultant ainsi en l’inhibition de l’hyperprolifération des CMLVs des RSH. Ainsi, il peut être suggéré que le C-ANP4-23 pourrait être utilisé comme agent thérapeutique pour le traitement des complications vasculaires associées à l’hypertension et à l’athérosclérose.

Measurements of adipocity and high blood pressure among children and adolescents living in Belo Horizonte

Objective: To verify an association, if it exists, between obesity and blood pressure raised beyond the 90th percentile in children and adolescents, and to determine the measure of adiposity that best correlates with blood pressure in these subjects. Design: Cross-sectional study. Setting: A school-based study in Belo Horizonte, Brazil. Participants: We selected randomly 1,403 students, aged from 6 to 18 years, from 545,046 students attending 521 public and private schools. Those selected completed the study. Main measures of outcome: We recorded the weight, height, skin fold in the triceps, subscapular, and suprailiac areas, waist and hip circumference, body-mass index, and resting systolic and diastolic blood pressures using a mercury sphygmomanometer. Results: In univariate analyses, body mass index greater or lesser than 85th percentile, measurements of skin thickness in the subscapular and suprailiac areas, and the sum of all measurements of skinfold thickness, were associated with both systolic and diastolic measurements of blood pressure. After multivariate analyses that adjusted for all measurements of adiposity except itself, and age, race, and socioeconomic state, we found that the increased body mass index was associated with a 3.6-fold increased frequency of elevated systolic measurements of blood pressure, with 9596 confidence intervals from 2.2 to 5.8, and a 2.7-fold increased frequency of elevated measurements of diastolic blood pressure, with 95% confidence intervals from 1.9 to 4.0. Conclusions: Body-mass index serves as a better predictor of elevated blood pressure among children than do local measurements of adiposity.

Validity of an arterial pressure waveform analysis device: does the puncture site play a role in the agreement with intermittent pulmonary artery catheter thermodilution measurements?

OBJECTIVE: The measurement of cardiac output is a key element in the assessment of cardiac function. Recently, a pulse contour analysis-based device without need for calibration became available (FloTrac/Vigileo, Edwards Lifescience, Irvine, CA). This study was conducted to determine if there is an impact of the arterial catheter site and to investigate the accuracy of this system when compared with the pulmonary artery catheter using the bolus thermodilution technique (PAC). DESIGN: Prospective study. SETTING: The operating room of 1 university hospital. PARTICIPANTS: Twenty patients undergoing cardiac surgery. INTERVENTIONS: CO was determined in parallel by the use of the Flotrac/Vigileo systems in the radial and femoral position (CO_rad and CO_fem) and by PAC as the reference method. Data triplets were recorded at defined time points. The primary endpoint was the comparison of CO_rad and CO_fem, and the secondary endpoint was the comparison with the PAC. MEASUREMENTS AND MAIN RESULTS: Seventy-eight simultaneous data recordings were obtained. The Bland-Altman analysis for CO_fem and CO_rad showed a bias of 0.46 L/min, precision was 0.85 L/min, and the percentage error was 34%. The Bland-Altman analysis for CO_rad and PAC showed a bias of -0.35 L/min, the precision was 1.88 L/min, and the percentage error was 76%. The Bland-Altman analysis for CO_fem and PAC showed a bias of 0.11 L/min, the precision was 1.8 L/min, and the percentage error was 69%. CONCLUSION: The FloTrac/Vigileo system was shown to not produce exactly the same CO data when used in radial and femoral arteries, even though the percentage error was close to the clinically acceptable range. Thus, the impact of the introduction site of the arterial catheter is not negligible. The agreement with thermodilution was low.

Measurements of seismic attenuation and transient fluid pressure in partially saturated Berea sandstone: Evidence of fluid flow on the mesoscopic scale

A novel laboratory technique is proposed to investigate wave-induced fluid flow on the mesoscopic scale as a mechanism for seismic attenuation in partially saturated rocks. This technique combines measurements of seismic attenuation in the frequency range from 1 to 100?Hz with measurements of transient fluid pressure as a response of a step stress applied on top of the sample. We used a Berea sandstone sample partially saturated with water. The laboratory results suggest that wave-induced fluid flow on the mesoscopic scale is dominant in partially saturated samples. A 3-D numerical model representing the sample was used to verify the experimental results. Biot's equations of consolidation were solved with the finite-element method. Wave-induced fluid flow on the mesoscopic scale was the only attenuation mechanism accounted for in the numerical solution. The numerically calculated transient fluid pressure reproduced the laboratory data. Moreover, the numerically calculated attenuation, superposed to the frequency-independent matrix anelasticity, reproduced the attenuation measured in the laboratory in the partially saturated sample. This experimental?numerical fit demonstrates that wave-induced fluid flow on the mesoscopic scale and matrix anelasticity are the dominant mechanisms for seismic attenuation in partially saturated Berea sandstone.

High-resolution thermal expansion measurements under helium-gas pressure

We report on the realization of a capacitive dilatometer, designed for high-resolution measurements of length changes of a material for temperatures 1.4K ≤ T ≤ 300K and hydrostatic pressure P ≤ 250MPa. Helium ( 4He) is used as a pressure-transmitting medium, ensuring hydrostatic-pressure conditions. Special emphasis has been given to guarantee, to a good approximation, constant-pressure conditions during temperature sweeps. The performance of the dilatometer is demonstrated by measurements of the coefficient of thermal expansion at pressures P ≃ 0.1MPa (ambient pressure) and 104MPa on a single crystal of azurite, Cu 3(CO 3) 2(OH) 2, a quasi-one-dimensional spin S = 1/2 Heisenberg antiferromagnet. The results indicate a strong effect of pressure on the magnetic interactions in this system. © 2012 American Institute of Physics.

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans.

Synthesis of computations and experiments for obtaining pulsatile gas flow rates from dynamic pressure difference measurements across an orifice-plate meter

The use of conventional orifice-plate meter is typically restricted to measurements of steady flows. This study proposes a new and effective computational-experimental approach for measuring the time-varying (but steady-in-the-mean) nature of turbulent pulsatile gas flows. Low Mach number (effectively constant density) steady-in-the-mean gas flows with large amplitude fluctuations (whose highest significant frequency is characterized by the value fF) are termed pulsatile if the fluctuations have a direct correlation with the time-varying signature of the imposed dynamic pressure difference and, furthermore, they have fluctuation amplitudes that are significantly larger than those associated with turbulence or random acoustic wave signatures. The experimental aspect of the proposed calibration approach is based on use of Coriolis-meters (whose oscillating arm frequency fcoriolis >> fF) which are capable of effectively measuring the mean flow rate of the pulsatile flows. Together with the experimental measurements of the mean mass flow rate of these pulsatile flows, the computational approach presented here is shown to be effective in converting the dynamic pressure difference signal into the desired dynamic flow rate signal. The proposed approach is reliable because the time-varying flow rate predictions obtained for two different orifice-plate meters exhibit the approximately same qualitative, dominant features of the pulsatile flow.

SOLAR RADIATION PRESSURE AND LOCAL INTERSTELLAR MEDIUM FLOW PARAMETERS FROM INTERSTELLAR BOUNDARY EXPLORER LOW ENERGY HYDROGEN MEASUREMENTS

Neutral hydrogen atoms that travel into the heliosphere from the local interstellar medium (LISM) experience strong effects due to charge exchange and radiation pressure from resonant absorption and re-emission of Lyα. The radiation pressure roughly compensates for the solar gravity. As a result, interstellar hydrogen atoms move along trajectories that are quite different than those of heavier interstellar species such as helium and oxygen, which experience relatively weak radiation pressure. Charge exchange leads to the loss of primary neutrals from the LISM and the addition of new secondary neutrals from the heliosheath. IBEX observations show clear effects of radiation pressure in a large longitudinal shift in the peak of interstellar hydrogen compared with that of interstellar helium. Here, we compare results from the Lee et al. interstellar neutral model with IBEX-Lo hydrogen observations to describe the distribution of hydrogen near 1 AU and provide new estimates of the solar radiation pressure. We find over the period analyzed from 2009 to 2011 that radiation pressure divided by the gravitational force (μ) has increased slightly from μ = 0.94 ± 0.04 in 2009 to μ = 1.01 ± 0.05 in 2011. We have also derived the speed, temperature, source longitude, and latitude of the neutral H atoms and find that these parameters are roughly consistent with those of interstellar He, particularly when considering the filtration effects that act on H in the outer heliosheath. Thus, our analysis shows that over the period from 2009 to 2011, we observe signatures of neutral H consistent with the primary distribution of atoms from the LISM and a radiation pressure that increases in the early rise of solar activity.

Denaturant-induced movement of the transition state of protein folding revealed by high-pressure stopped-flow measurements

The small all-β protein tendamistat folds and unfolds with two-state kinetics. We determined the volume changes associated with the folding process by performing kinetic and equilibrium measurements at variable pressure between 0.1 and 100 MPa (1 to 1,000 bar). GdmCl-induced equilibrium unfolding transitions reveal that the volume of the native state is increased by 41.4 ± 2.0 cm3/mol relative to the unfolded state. This value is virtually independent of denaturant concentration. The use of a high-pressure stopped-flow instrument enabled us to measure the activation volumes for the refolding (ΔVf0‡) and unfolding reaction (ΔVu0‡) over a broad range of GdmCl concentrations. The volume of the transition state is 60% native-like (ΔVf0‡ = 25.0 ± 1.2 cm3/mol) in the absence of denaturant, indicating partial solvent accessibility of the core residues. The volume of the transition state increases linearly with denaturant concentration and exceeds the volume of the native state above 6 M GdmCl. This result argues for a largely desolvated transition state with packing deficiencies at high denaturant concentrations and shows that the structure of the transition state depends strongly on the experimental conditions.

Grain size measurements in Mg-Al high pressure die castings using electron back-scattered diffraction (EBSD)

Optical metallographic techniques for grain-size measurement give unreliable results for high pressure diecast Mg-Al alloys and electron back-scattered diffraction mapping (EBSD) provides a good tool for improving the quality of these measurements. An application of EBSD mapping to this question is described, and data for some castings are presented. Ion-beam milling was needed to prepare suitable samples, and this technique is detailed. As is well-known for high pressure die castings, the grain size distribution comprises at least two populations. The mean grain size of the fine-grained population was similar in both AZ91 and AM60 and in two casting thicknesses (2 mm and 5 mm) and, contrary to previously published reports, it did not vary with depth below the surface.