Oeuvres posthumes de M. Bidault de Villiers,... renfermant : °1 Un Mémoire sur la topographie médicale et sur les maladies épidémiques de l'île Minorque, traduit de l'anglais de Cleghorn ; °2 des Remarques et observations pour servir à l'histoire des phlegmasies gangréneuses et spécialement de la pustule maligne ; °3 des Observations adressées à M. Guyton de Morveau, relativement à plusieurs passages de son Traité des moyens de désinfecter l'air

Comprend : Mémoire sur la topographie médicale et sur les maladies épidémiques de l'île Minorque, traduit de l'anglais

Noise-enhanced excitability in bistable activator-inhibitor media

We show that external fluctuations induce excitable behavior in a bistable spatially extended system with activator-inhibitor dynamics of the FitzHugh-Nagumo type. This can be understood as a mechanism for sustained signal propagation in bistable media. The phase diagram of the stochastic system is analytically obtained and numerically verified. For small-noise intensities, front propagation becomes unstable, and excitable pulses arise as the only possible spatiotemporal behavior of the system. For large-noise intensities, on the other hand, the system enters an effective regime of oscillatory behavior, where it exhibits spontaneous nucleation of pulses and synchronized firing.

Enhanced pulse propagation in non-linear arrays of oscillators

The propagation of a pulse in a nonlinear array of oscillators is influenced by the nature of the array and by its coupling to a thermal environment. For example, in some arrays a pulse can be speeded up while in others a pulse can be slowed down by raising the temperature. We begin by showing that an energy pulse (one dimension) or energy front (two dimensions) travels more rapidly and remains more localized over greater distances in an isolated array (microcanonical) of hard springs than in a harmonic array or in a soft-springed array. Increasing the pulse amplitude causes it to speed up in a hard chain, leaves the pulse speed unchanged in a harmonic system, and slows down the pulse in a soft chain. Connection of each site to a thermal environment (canonical) affects these results very differently in each type of array. In a hard chain the dissipative forces slow down the pulse while raising the temperature speeds it up. In a soft chain the opposite occurs: the dissipative forces actually speed up the pulse, while raising the temperature slows it down. In a harmonic chain neither dissipation nor temperature changes affect the pulse speed. These and other results are explained on the basis of the frequency vs energy relations in the various arrays

Enhanced oligonucleotide delivery to mouse retinal cells using iontophoresis.

PURPOSE: To study the combination of oligodeoxynucleotides (ODNs) intravitreous injection and saline transpalpebral iontophoresis on the delivery of ODNs to photoreceptors in the newborn rd1/rd1 mice. METHODS: Cathodal or anodal transpalpebral iontophoresis (1.43 mA/cm(2) for 5 min) was applied to eyes of postnatal day 7 (PN7) rd1/rd1 mice immediately before the intravitreous injection of ODNs. The effect of cathodal iontophoresis after ODNs injection was also evaluated. The influence of current intensity (0.5, 1.5, and 2.5 mA) was assayed with cathodal iontophoresis performed prior to ODNs injection. The duration of current-induced facilitation of ODNs delivery to photoreceptors was evaluated for 6 h following iontophoresis. One group of control eyes received cathodal iontophoresis prior to the intravitreous injection of phosphate buffered saline (PBS) or hexachlorofluorescein (Hex). The second control group received ODN or Hex intravitreous injection without iontophoresis. The penetration of fluorescent ODNs in the outer nuclear layer (ONL) was quantified by image analysis of the ONL fluorescence intensity on cryosection microphotographs. Integrity of ODN was assessed using acrylamide gel migration after its extraction from the retina of treated mice. The integrity of retinal structure, 1 and 24 h after iontophoresis, was analyzed using light and electron microscopy. RESULTS: Transpalpebral anodal or cathodal saline iontophoresis enhanced the penetration of ODNs in all retinal layers. Cathodal iontophoresis was more efficient than anodal iontophoresis in enhancing the tissue penetration of the injected ODN. Photoreceptor delivery of ODN was significantly higher when cathodal saline transpalpebral iontophoresis was applied prior than after the injection. The extent of enhanced tissue penetration decreased in parallel to the increased interval between iontophoresis application and the intravitreous injection. Current of 1.5 mA was safe and optimal for the delivery of ODNs to the ONL. One hour after iontophoresis followed by injection, ODN extracted from the retina of treated eyes remained intact. Histology and electron microscopy observations demonstrated that iontophoresis using the optimal parameters did not induce any permanent tissue alterations or structure damage. CONCLUSIONS: Saline transpalpebral iontophoresis facilitates the penetration of injected ODNs in photoreceptors for at least 3 h. This method may be considered for photoreceptor targeted gene therapy.