How does stent expansion alter drug transport properties of the arterial wall?

Stents have become the most successful device to treat advanced atherosclerotic lesions. However, one of the main issues with these interventions is the development of restenosis. The coating of stents with antiproliferative substances to reduce this effect is now standard, although such drugs can also delay re-endothelialization of the intima. The drug release strategy is therefore a key determinant of drug-eluting stent efficacy. Many mathematical models describing drug transport in arteries have been developed and, usually separately, models describing the mechanics of arterial tissue have been devised. However, the literature is lacking a comprehensive model that adequately takes into account both the mechanical deformation of the porous arterial wall and the resulting impact on drug transport properties. In this paper, we provide the most comprehensive study to date of the effect of stent mechanical expansion on the drug transport properties of a three-layer arterial wall. Our model incorporates the state-of-the art description of the mechanical properties of arterial tissue though an anisotropic, hyperelastic material model and includes a nonlinear saturable binding model to describe drug transport in the arterial wall. We establish relationships between mechanical force generated through device expansion and alteration in diffusion within the arterial wall and perform simulations to elucidate the impact of such alterations in spatio-temporal drug release and tissue uptake. Mechanical deformation of the arterial wall results in modified drug transport properties and tissue drug concentrations, highlighting the importance of coupling solid mechanics with drug transport

The mucosal immune system and its regulation by autophagy

The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a “self-eating” survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders

Modelo computacional acoplado de la expansión mecánica de dispositivos intravasculares y liberación de fármaco asociada

Como punto de partida se realizó un exhaustivo estudio bibliográfico (sec. “Introducción”) obteniendo nociones básicas de aterosclerosis (“Anatomía e histología de la arteria coronaria”, “Aterosclerosis”) y los tratamientos contra la misma (“Dispositivos intravasculares de difusión de fármaco”, “Tipos de fármaco”). Adicionalmente, se estudió la teoría de transporte de fármaco, los distintos modelos de comportamiento de material y el acoplamiento entre las dos físicas. Respecto al software utilizado, fue necesario un aprendizaje previo de su funcionamiento y un análisis de las funciones de cada física (sec.“Material y Métodos”). Una vez determinado el marco teórico, se desarrollaron los modelos computacionales de elementos finitos mediante el software COMSOL Multiphysics. Tras la realización de los modelos, se extrajeron los resultados, estudiando el comportamiento de los mismos y analizando los efectos de la mecánica (sec.”Resultados”). Como conclusiones (sec.”Conclusiones”) se obtuvieron resultados del efecto de la expansión del dispositivo en el transporte de fármaco, donde la deformación de las paredes arteriales es un parámetro que afecta notablemente al pico de concentración máxima de fármaco. Así mismo, se realizó una comparativa entre dispositivos, en la cual el stent presentó un control más eficiente del fármaco. La diferencia entre coeficientes de difusión entre la placa y la capa media fue clave en el modelo desarrollado en arteria afectada por placa de ateroma. El estudio comparativo de fármacos mostró comportamientos de difusión y adhesión al tejido muy diferente. Por último, los modelos 3D y 2D arrojaron resultados similares

Computational Modelling of the Effect of Mechanical Expansion on Drug Delivery from Endovascular Devices

No abstract available

Computational Modelling of the Effect of Mechanical Expansion on Drug Delivery from Endovascular Devices

No abstract available