Tissue damage modeling in gene electrotransfer: the role of pH.

Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson-Nernst-Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase+GET protocol.

[Electrical alternans, electrocardiogram pattern in the diagnosis of a severe heart disease]. / Alternancia eléctrica, patrón electrocardiográfico en el diagnóstico de enfermedad cardiaca grave.

Electrical alternans is a broad term that describes alternate-beat variation in the direction, amplitude and duration of any component of the ECG wave-form. It is associated with cardiac tamponade, serious ventricular arrhythmias, and sudden death. We present the clinical case of a 77-year-old female with electrical alternans, from which a diagnosis of cardiac tamponade was established.

Alternancia eléctrica, patrón electrocardiográfico en el diagnóstico de enfermedad cardiaca grave / Electrical alternans, electrocardiogram pattern in the diagnosis of a severe heart disease

La alternancia eléctrica es un amplio concepto que describe las variaciones, latido a latido, en la dirección, amplitud y/o duración de cualquier componente del electrocardiograma. Se asocia a taponamiento cardiaco, arritmias malignas y muerte súbita. Presentamos el caso de una paciente de 77 años con alternancia eléctrica a partir de la cual se llegó al diagnóstico de taponamiento cardiaco (AU)

Electrical alternans is a broad term that describes alternate-beat variation in the direction, amplitude and duration of any component of the ECG wave-form. It is associated with cardiac tamponade, serious ventricular arrhythmias, and sudden death. We present the clinical case of a 77-year-old female with electrical alternans, from which a diagnosis of cardiac tamponade was established (AU)

Simulations of transport regime in electrodeposition in different viscosity scenarios.

In this work we study the effects of viscosity variations in thin-layer electrochemical deposition (ECD) under galvanostatic conditions through experimental measurements and theoretical modeling. The theoretical model, written in terms of dimensionless quantities, describes diffusive, migratory and convective ion transport in a fluid under galvanostatic conditions. Experiments reveal that as viscosity increases, convection decreases when the cell resistance remains constant. Our numerical model predicts that as viscosity increases, electroconvection becomes less relevant and concentration and convective fronts slow down. The time scaling of this phenomenon is studied and compared to previously reported low viscosity solution studies.

Ion transport in tumors under electrochemical treatment: in vivo, in vitro and in silico modeling.

The electrochemical treatment of cancer (EChT) consists in the passage of a direct electric current through two or more electrodes inserted locally in the tumor tissue. The extreme pH changes induced have been proposed as the main tumor destruction mechanism. Here, we study ion transport during EChT through a combined modeling methodology: in vivo modeling with BALB/c mice bearing a subcutaneous tumor, in vitro modeling with agar and collagen gels, and in silico modeling using the one-dimensional Nernst-Planck and Poisson equations for ion transport in a four-ion electrolyte. This combined modeling approach reveals that, under EChT modeling, an initial condition with almost neutral pH evolves between electrodes into extreme cathodic alkaline and anodic acidic fronts moving towards each other, leaving the possible existence of a biological pH region between them; towards the periphery, the pH decays to its neutral values. pH front tracking unveils a time scaling close to t(1/2), signature of a diffusion-controlled process. These results could have significant implications in EChT optimal operative conditions and dose planning, in particular, in the way in which the evolving EChT pH region covers the active cancer cells spherical casket.