Speciation analysis of aqueous nanoparticulate diclofenac complexes by solid-phase microextraction.

The dynamic sorption of an organic compound by nanoparticles (NPs) is analyzed by solid-phase microextraction (SPME) for the example case of the pharmaceutical diclofenac in dispersions of impermeable (silica, SiO(2)) and permeable (bovine serum albumin, BSA) NPs. It is shown that only the protonated neutral form of diclofenac is accumulated in the solid phase, and hence this species governs the eventual partition equilibrium. On the other hand, the rate of the solid/water partition equilibration is enhanced in the presence of the sorbing nanoparticles of SiO(2) and BSA. This feature demonstrates that the NPs themselves do not enter the solid phase to any appreciable extent. The enhanced rate of attainment of equilibrium is due to a shuttle-type of contribution from the NP-species to the diffusive supply of diclofenac to the water/solid interface. For both types of nanoparticulate complexes, the rate constant for desorption (k(des)) of bound diclofenac was derived from the measured thermodynamic affinity constant and a diffusion-limited rate of adsorption. The computed k(des) values were found to be sufficiently high to render the NP-bound species labile on the effective time scale of SPME. In agreement with theoretical prediction, the experimental results are quantitatively described by fully labile behavior of the diclofenac/nanoparticle system and an ensuing accumulation rate controlled by the coupled diffusion of neutral, deprotonated, and NP-bound diclofenac species.

Effects of hypercapnia and hypocapnia on ventilatory variability and the chaotic dynamics of ventilatory flow in humans.

In humans, lung ventilation exhibits breath-to-breath variability and dynamics that are nonlinear, complex, sensitive to initial conditions, unpredictable in the long-term, and chaotic. Hypercapnia, as produced by the inhalation of a CO(2)-enriched gas mixture, stimulates ventilation. Hypocapnia, as produced by mechanical hyperventilation, depresses ventilation in animals and in humans during sleep, but it does not induce apnea in awake humans. This emphasizes the suprapontine influences on ventilatory control. How cortical and subcortical commands interfere thus depend on the prevailing CO(2) levels. However, CO(2) also influences the variability and complexity of ventilation. This study was designed to describe how this occurs and to test the hypothesis that CO(2) chemoreceptors are important determinants of ventilatory dynamics. Spontaneous ventilatory flow was recorded in eight healthy subjects. Breath-by-breath variability was studied through the coefficient of variation of several ventilatory variables. Chaos was assessed with the noise titration method (noise limit) and characterized with numerical indexes [largest Lyapunov exponent (LLE), sensitivity to initial conditions; Kolmogorov-Sinai entropy (KSE), unpredictability; and correlation dimension (CD), irregularity]. In all subjects, under all conditions, a positive noise limit confirmed chaos. Hypercapnia reduced breathing variability, increased LLE (P = 0.0338 vs. normocapnia; P = 0.0018 vs. hypocapnia), increased KSE, and slightly reduced CD. Hypocapnia increased variability, decreased LLE and KSE, and reduced CD. These results suggest that chemoreceptors exert a strong influence on ventilatory variability and complexity. However, complexity persists in the quasi-absence of automatic drive. Ventilatory variability and complexity could be determined by the interaction between the respiratory central pattern generator and suprapontine structures.

Ventilatory support: a dynamical systems approach.

Misunderstanding of the dynamical behavior of the ventilatory system, especially under assisted ventilation, may explain the problems encountered in ventilatory support monitoring. Proportional assist ventilation (PAV) that theoretically gives a breath by breath assistance presents instability with high levels of assistance. We have constructed a mathematical model of interactions between three objects: the central respiratory pattern generator modelled by a modified Van der Pol oscillator, the mechanical respiratory system which is the passive part of the system and a controlled ventilator that follows its own law. The dynamical study of our model shows the existence of two crucial behaviors, i.e. oscillations and damping, depending on only two parameters, namely the time constant of the mechanical respiratory system and a cumulative interaction index. The same result is observed in simulations of spontaneous breathing as well as of PAV. In this last case, increasing assistance leads first to an increase of the tidal volume (VT), a further increase in assistance inducing a decrease in VT, ending in damping of the whole system to an attractive fixed point. We conclude that instabilities observed in PAV may be explained by the different possible dynamical behaviors of the system rather than changes in mechanical characteristics of the respiratory system.