J. Dufaux

A new experimental method for the evaluation of the release profiles of drug-loaded microbeads designed for embolisation

Abstract The development of a galenical form must take into account the drugs physico-chemical properties as well as the external conditions that govern its performances. In the case of loaded microbeads designed for embolisation, the drug-release kinetics strongly depends on the local hydrodynamic conditions. Currently the apparatuses recommended by the European Pharmacopoeia allow the measurement in vitro of these kinetics; but the measured kinetics are very different from those met in the in vivo embolisation procedures. A new methodology is presented for evaluating the controlled release of a drug from ion exchange resins for embolisation. Experimental and numerical data are reported on the release kinetics of two closely related galenical formulations (DEAE Trisacryl LS and QAE Trisacryl LS).

Effects of Contrast Media on Blood Rheology: Comparison in Humans, Pigs, and Sheep

AbstractPurpose: To compare whole blood viscosity and erythrocyte aggregation in humans, pigs, and sheep, before and after adding water-soluble iodinated contrast medium (CM). Methods: Two CMs were studied: iopromide (nonionic) and ioxaglate (ionic). The blood-CM viscosity was measured with a Couette viscometer. Erythrocyte aggregation was measured with an erythroaggregometer. Results: The blood-CM viscosity was increased up to +20% (relative to pure blood) with a CM concentration of 0%–10%. At CM concentrations from 10% to 50%, the viscosity decreased. The disaggregation shear stress was increased (relative to pure blood) at low CM concentration (0%–10%). When the CM concentration increased from 10% to 20%, the disaggregation shear stress was decreased, except with the pig blood–ioxaglate mixture. Conclusion: At low CM concentration the blood viscosity was increased in pig, sheep, and humans and the disaggregation shear stress was increased in pig and humans. The aggregation of sheep blood was too low to be detected by the erythroaggregometer. This rise can be explained by the formation of poorly deformable echinocytes. At higher CM concentration, the viscosity and the disaggregation shear stress decreased in relation to the blood dilution. We conclude that pig blood and sheep blood can both be used to study the effect of CM injection on blood viscosity. Nevertheless, the rheologic behavior of pig blood in terms of erythrocyte aggregation is closer to that of human blood than is sheep blood when mixed with CM. Pigs could thus be more suitable than sheep for in vivo studies of CM miscibility with blood during selective cannulation procedures.

AN EXPERIMENTAL AND THEORETICAL STUDY OF MASS TRANSFER FROM LOADED EMBOLISATION MICROBEADS: POSSIBLE OPTIMISATION

The development of loaded galenical formulations requires specific tests leading to a sharp discrimination of kinetics release. We have presented an experimental protocol where particular hydrodynamic conditions are implemented, permitting the drug to be transported by a controlled diffusive-convective process, after chemical liberation from the microbeads. This study shows that the procedure leads to satisfactory results regarding the characterization of closely related galenical formulations. A two dimensional phenomenological approach leads to the promising possibility of optimizing the procedure.

Diffuse Laser Doppler Velocimetry from Multiple Scattering Media and Flowing Suspensions

A study of the Doppler frequency spectrum (DFS) of the light multiply scattered from a random collection of moving anisotropic scatterers is presented. The analytical approach based on photon diffusion approximation and statistical models yields functional forms of DFS for random or simple shear flow consistent both with experiments in a backscatter geometry and predictions from the Diffusing Wave Spectroscopy theory (DWS). Homodyne and heterodyne detection modes are further analyzed and the potential applications of the Doppler heterodyne analysis in the field of suspension dynamics are investigated.

Extracorporeal cephalic blood autoperfusion method in the rat. Hemorrheological evaluation and proposed pharmacological uses.

We propose a constant cephalic blood perfusion method especially suitable to the rat. Cerebrovascular blood pressure is artificially regulated by an extracorporeal circuit with a perfusion pump and a Starling valve. A hemorrheological evaluation allows one to demonstrate an extracorporeal circuit that shows a growing pathological evolution, which can be purposely accelerated by iterative ischemic episodes. This method can be used (as shown by some examples) as a model for cerebrovascular failure or to study deleterious effects of the extracorporeal circuit.

Velocity Profile Measurements by Laser-Doppler Velocimetry (LDV) in Plane Capillaries. Comparison with Theoretical Profiles from a Two-Fluid Model

Since the yeh and CUMMINS’ work 1 the velocity measurement of suspension flow with Laser Doppler Velocimeter has been widely developped. There are no important problems when the suspension concentration is low and when the tube dimensions are greater than those of the volume where the light beams interfere.

Optical flow detection and imaging

Abstract In this paper we provide functional forms for Laser Doppler Velocimetry (LDV) and Diffusing Wave Spectroscopy (DWS) based on multiply scattered light by a random distribution of moving anisotropic centres. These results are based on statistical models and applied to single shear flows or random flows, and are compared to Monte Carlo simulations and in vitro experiments in back-scattered geometry. Finally LDV and DWS results are used to characterise red blood cell aggregation and to determine the perfusion flow rate of various human tissues.

Aggregation and deformation of red blood cells as probed by a laser light scattering technique in a concentrated suspension: methodology

A light scattering technique is presented which investigates the backscattered and transmitted flux of He-Ne laser light illuminating a concentrated suspension of red blood cells (RBC) submitted to a simple shear flow. Our experiments show that the angular distributions of scattered light are closely related to the state of the suspension (at rest, or submitted to a simple shear flow) and the rheological parameters of the suspension such as viscosity and volume concentration. Transmitted and reflected light measurements demonstrated reproducible and predictable changes in scattering cross sections of oriented and deformed RBCs by shear flow. Additionally, it is shown that the scattering cross-section of aggregated RBCs is different from disaggregated RBCs. A theoretical model, substantiated by Monte- Carlo simulations, is proposed which relates the changes in shape of the angular distribution of scattered light to the rate of aggregation and the gradients of deformation of RBCs.

Holographic visualization of the thermal perturbation around a hot wire in a thermally stratified medium heated from above

Abstract We show and discuss some examples of thermal plumes generated by hot wires in a thermally stratified medium heated from above. The use of a holographic bench allows the visualization of either the thermal distribution around the wire or only the thermal perturbation brought by the wire in the thermally stratified medium.

The Influence of the Internal Viscosity of Washed Red Blood Cells on Their Rheological Behaviour

The rheological characterization of washed RBC suspensions has been performed both using a low shear viscosimeter and a optical light back scattering system. Changing the volume of the cells and in such a way the hemoglobin concentration in the cells and/or the structure of the cell membrane by treatments with the antibiotic Amphotericin B and different pH, osmotic pressure or ionic strengths of the medium it was found that the rheological behaviour (relative viscosity in dependence on the shear rate,.02 s−1 – 128 s−1; intrinsic viscosities and the relaxation time corresponding to the orientation and desorientation) seems to be mainly connected with the change of the internal hemoglobin concentration.