Sébastien Leclerc

Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock.

Background:Lactic acidosis is associated with cardiovascular failure. Buffering with sodium bicarbonate is proposed in severe lactic acidosis. Bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. The authors thus investigated the cardiovascular and metabolic effects of an adapted sodium bicarbonate therapy, including prevention of carbon dioxide increase with hyperventilation and ionized calcium decrease with calcium administration. Methods:Lactic acidosis was induced by hemorrhagic shock. Twenty animals were randomized into five groups: (1) standard resuscitation with blood retransfusion and norepinephrine (2) adapted sodium bicarbonate therapy (3) nonadapted sodium bicarbonate therapy (4) standard resuscitation plus calcium administration (5) hyperventilation. Evaluation was focused in vivo on extracellular pH, on intracellular pH estimated by P31 nuclear magnetic resonance and on myocardial contractility by conductance catheter. Aortic rings and mesenteric arteries were isolated and mounted in a myograph, after which arterial contractility was measured. Results:All animals in the hyperventilation group died prematurely and were not included in the statistical analysis. When compared with sham rats, shock induced extracellular (median, 7.13; interquartile range, [0.10] vs. 7.30 [0.01]; P = 0.0007) and intracellular acidosis (7.26 [0.18] vs. 7.05 [0.13]; P = 0.0001), hyperlactatemia (7.30 [0.01] vs. 7.13 [0.10]; P = 0.0008), depressed myocardial elastance (2.87 [1.31] vs. 0.5 [0.53] mmHg/&mgr;l; P = 0.0001), and vascular hyporesponsiveness to vasoconstrictors. Compared with nonadapted therapy, adapted bicarbonate therapy normalized extracellular pH (7.03 [0.12] vs. 7.36 [0.04]; P < 0.05), increased intracellular pH to supraphysiological values, improved myocardial elastance (1.68 [0.41] vs. 0.72 [0.44] mmHg/&mgr;l; P < 0.05), and improved aortic and mesenteric vasoreactivity. Conclusions:A therapeutic strategy based on alkalinization with sodium bicarbonate along with hyperventilation and calcium administration increases pH and improves cardiovascular function.

Effect of potassium on the mechanisms of biomass pyrolysis studied using complementary analytical techniques

Complementary analytical methods have been used to study the effect of potassium on the pyrolysis mechanisms of cellulose and lignocellulosic biomasses. Thermogravimetry, calorimetry, high-temperature (1) H NMR spectroscopy (in situ and real-time analysis of the fluid phase formed during pyrolysis), and water extraction of quenched char followed by size-exclusion chromatography coupled with mass spectrometry have been combined. Potassium impregnated in cellulose suppresses the formation of anhydrosugars, reduces the formation of mobile protons, and gives rise to a mainly exothermic signal. The evolution of mobile protons formed from K-impregnated cellulose has a very similar pattern to the evolution of the mass loss rate. This methodology has been also applied to analyze miscanthus, demineralized miscanthus, miscanthus re-impregnated with potassium after demineralization, raw oak, and Douglas fir. Hydrogen mobility and transfer are of high importance in the mechanisms of biomass pyrolysis.

NMR relaxometry study of the interaction of water with a Nafion membrane under acid, sodium, and potassium forms. Evidence of two types of bound water.

Through (1)H NMR relaxometry techniques (determination of the spin-lattice relaxation time as a function of the NMR measurement frequency), we have investigated, on a molecular scale, the water behavior in Nafion NRE 212 under acid, sodium, and potassium forms, the latter arising from different chemical treatments (with and without EDTA). Quantitatively, it turns out that (i) EDTA removes unwanted cations that may affect water mobility and (ii) the natural countercations (sodium and potassium) also affect water mobility according to their size. In order to go further, we have developed a new methodology that rests on the comparison between samples prepared with H2O and D2O. For the latter, residual protons allow us to exclusively access intermolecular contribution to proton relaxation and, thus, enable us to deduce the intramolecular contribution of proton relaxation in H2O. The analysis of this contribution reveals, for the first time, two types of bound water in Nafion.

Vibration-induced compaction of granular suspensions

We investigate the compaction dynamics of vibrated granular suspensions using both digital imaging technique and MRI measurements. Starting from initialy loose packings, our experimental data suggest the existence of two stages in the compaction dynamics: a fast stage at short times where a rising compaction front propagates through the granular suspension and a slow stage at large times where the packing compacts slowly and homogeneously. The compaction dynamics in each stage can be well fitted to usual stretched exponential laws with stretching exponents equal to 2 and 0.45, respectively. The transition time between these two stages, τc, depends on the fluid viscosity, vibration intensity and grain diameter. We show that τc−1 and the velocity of the front decrease roughly linearly with the lubrication Peclet number, Pelub related to the competition between the lubrication stress induced by vibrations and the granular pressure.Graphical abstract

Phthalimido–ferrocidiphenol cyclodextrin complexes: Characterization and anticancer activity

Several ferrocenyl analogues of tamoxifen have already showed strong antiproliferative activity in experimental glioma models. Nevertheless, these compounds are very poorly soluble in water and an adapted formulation is needed. In this work, we have tailored and optimized methylated cyclodextrin soluble complexes of phthalimido-ferrocidiphenol for the first time. The complexes were characterized, and the optimized formulation was tested for in vitro efficacy and cell proliferation assays on U87, human glioblastoma cancer cells. Molecular modeling can provide accurate information about the inclusion process. The inclusion of all the moieties at the same time (i.e., ferrocene, phthalimidylpropyl, 2 phenols) is not possible due to the steric hindrance of the 1:4 system. The 1:3 systems are possible but do not seem very relevant. However, various 1:2 and 1:1 complexes are mostly present in aqueous solutions. Some experiments have confirmed our hypothesis. First, interactions between the phenol, phthalimidylpropyl and ferrocenyl groups have been observed in our NMR experiments. Second, the inclusion of phthalimidylpropyl was detected by UV-vis spectrophotometry with an apparent 1:1 interaction, which was observed through the Benesi-Hildebrand method. The complex is readily soluble in water and keeps its pharmacological activity against U87 tumor cells (IC50=0.028 ± 0.007 μM vs. 0.018 ± 0.003 μM for PhtFerr).

Off-resonance effects and selectivity profiles in pulsed nitrogen-14 nuclear quadrupole resonance

In order to alleviate base-line distortions in nitrogen-14 NQR spectra originating from pulse breakthrough, low power radio-frequency (rf) pulses were applied. It is recalled that the required power is four times lower than that for an equivalent NMR experiment. This is easily explained by the fact that, in NMR, half the amplitude of the rf field is active. Moreover, the selectivity profile (i.e. the peak amplitude as a function of the difference between the carrier frequency and the resonance frequency) exhibits a shape which is, in most cases, more favorable in NQR than in NMR. An appropriate theory has been developed for explaining these experimental observations. It is concluded that low power NQR is perfectly feasible and should even be recommended for most applications, provided that the line-width of the NQR signal is not too large.

Self‐diffusion coefficients obtained from proton‐decoupled carbon‐13 spectra for analyzing a mixture of terpenes

In the limit of sufficient sensitivity, natural abundance 13C offers a much better spectral resolution than proton NMR. This is due to an important chemical shift range and to proton‐decoupling conditions that yield one peak per carbon with practically no overlap. However, pulsed gradient spin echo experiments, which lead to the diffusion coefficient associated with each peak, have scarcely been employed. In this article, we present and compare different ways to access this quantity and we have effectively verified that, without any precaution, diffusion coefficients cannot be properly determined from standard procedures. The cause of such a failure is decoupling during the gradient pulses. We have used a very simple remedy that proved to be very successful on a model mixture of three monoterpenes and that appears as being of general applicability. Copyright

Simulations of NMR experiments employing static and/or radio-frequency field gradients: application to slice selection by the inhomogeneous radio-frequency field of a standard coil

A general computer program has been developed in order to simulate any nuclear magnetic resonance (NMR) experiment. It includes, in addition to the action of radio-frequency (rf) pulses and of gradients of both the static and the rf magnetic fields, the effects of inhomogeneity of the latter. It has been used here for devising a slice selection procedure on the basis of the inhomogeneity of the rf field delivered by a standard coil (e.g., a saddle-shaped coil). Two sequences have been investigated, a DANTE-like pulse train and a very simple one (named S2P for slice selection with 2π pulses), (2π - τ)n, where 2π corresponds to the flip angle of the region to be selected, whereas τ has to be chosen according to the relaxation time values;n, the number of cycles, must be sufficiently large, its actual value being uncritical. Simulations show that performances (in terms of selectivity) of both sequences are comparable, while experimental verifications favor S2P for its robustness and for the absence of any signal loss.

Single-sided radio-frequency field gradient with two unsymmetrical loops: Applications to nuclear magnetic resonance

Magnetic field gradients are nowadays indispensable to most nuclear magnetic resonance experiments and are at the basis of magnetic resonance imaging (MRI). Most of the time, gradients of the static magnetic field are employed. Gradients of the radio-frequency (rf) field may constitute an interesting alternative. Until now, they were produced by a single loop. We demonstrate in this paper how two unsymmetrical series loops can be optimized to produce rf gradients of much better performances. This optimization is based on a thorough theoretical approach and the gradient uniformity is studied through accurate simulations. Two prototypes were devised: one for a 2.34 T horizontal magnet (used in MRI), and the other for a 4.7 T vertical magnet (used for pure spectroscopic applications). These two-loop systems were designed for proton resonance frequencies (100 and 200 MHz, respectively). Performances of both systems were verified (versus theoretical predictions) by means of experiments employing gradients in view of the determination of the self-diffusion coefficients of liquids.

Simulation of radio-frequency field inhomogeneity effects: application to pulse trains aimed at the determination of CSA-dipolar interference terms

The cross‐correlation relaxation rate constant between dipolar interaction and chemical shift anisotropy (interference term) is of considerable interest for structural and dynamical determinations. The present study focuses on methods related to its impact on longitudinal nuclear relaxation, and especially to a procedure based on the applications of a train of π pulses applied to both nuclei involved in such a process (Levitt MH, Di Bari L. Bull. Magn. Reson. 1994; 16: 94–114). The resulting steady state leads, in principle, to a straightforward determination of the relevant interference term. Simulations taking into account inhomogeneity of the radio‐frequency (RF) field show that artifacts are responsible for instabilities which in practice preclude such a determination. An alternative method making use of a very limited number of RF pulses, combined with an appropriate filter, proves to be rather robust in view of achieving a proper measurement of the required interference term. Copyright