Design, manufacture and initial tests of a drug-eluting coronary stent.

INTRODUCTION: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. OBJECTIVE: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs' antiproliferative activity and histological results. METHOD: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. RESULTS: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. CONCLUSIONS: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

INTRODUCCIÓN: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. OBJETIVO: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. MÉTODO: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. RESULTADOS: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. CONCLUSIONES: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.

Metabolic syndrome and nonalcoholic fatty liver disease. The role of endothelial progenitor cells.

BACKGROUND: Endothelial dysfunction has been previously described in metabolic syndrome patients. The levels of circulating endothelial progenitor cells (EPCs) inversely correlates with the incidence of cardiovascular disease. The aim of this study was to investigate the association between NAFLD, metabolic syndrome and EPC levels. MATERIAL AND METHODS: A cross-sectional pilot study was performed at a university hospital in Mexico. Two groups of patients without previously known chronic diseases were studied and classified according to the presence of NAFLD. Anthropometric, dietary, and biochemical variables, and circulating EPC number were measured and compared between the groups. RESULTS: Forty subjects were included and classified into two groups: patients with NAFLD (n = 20) and a control group (n = 20). The overall prevalence of insulin resistance and metabolic syndrome was 25% and 17.5%, respectively. EPC levels were found to be higher in the NAFLD group (p < 0.05) as in the patients with insulin resistance (p < 0.01) and metabolic syndrome (p < 0.01). These levels showed correlation with the severity of steatosis. CONCLUSIONS: Patients with NAFLD have increased levels of EPC, such levels are associated with the severity of NAFLD. These findings may suggest that these cells may play a role in the early natural history of NAFLD. EPC might be increased in an attempt to repair the endothelial damage resulting from metabolic alterations accompanying NAFLD. Further studies are needed to establish the dynamics of these cells in NAFLD.

Effect of dietary chia supplementation on glucose metabolism and adipose tissue function markers in non-alcoholic fatty liver disease subjects.

Introduction: Background: adipose tissue dysfunction is a key factor for diabetes and non-alcoholic fatty liver disease (NAFLD) development. Chia (Salvia hispanica) is an abundant source of omega-3 fatty acids, antioxidants, and fiber which could improve adipose tissue functionality. Aim: to analyze the effect of an isocaloric chia-supplemented diet on glucose metabolism, adipose tissue inflammation, and endothelial function markers in patients with NAFLD and early stages of diabetes. Methods: in 32 patients with previous NAFLD diagnosis, without known diabetes, the effect of a diet supplemented with ground chia (25 g/day/8 weeks) was evaluated. Visceral (VAF) and liver fat, plasma lipids, fatty acids, and cytokine profiles, oral glucose tolerance test (OGTT), insulinogenic index (IGI30), insulin disposition index (DIO), and endothelial progenitor cells (EPC) were analyzed. Before and after eight weeks of diet supplementation. Results: chia supplementation promoted increases in plasma alpha-linolenic acid (75 %) and fiber consumption (55 %), and a higher number of EPC (+126 %). Basal OGTT showed that nine patients had normal OGTT, 17 pre-diabetes, and six newly diagnosed diabetes. In patients with diabetes, chia favored a healthier adipose tissue (VAF -7 %, NAFLD -100 %, adiponectin +47 %, resistin -30 %, IL-6 -44 %, IL-1ß -22 %) and upturn glucose metabolism through the improvement of beta-cell function (IGI30 +50 %, DIO +66 %). Conclusions: dietary supplementation with 25 g/day of ground chia may promote a healthier adipose tissue and improve pancreatic ß-cell and endothelial function. Among patients with early metabolic abnormalities, phytochemical properties of chia may retard diabetes progression and advanced stages of liver damage.

Introducción: Antecedentes: la disfunción del tejido adiposo es un factor clave para el desarrollo de diabetes e hígado graso no alcohólico (HGNA). La chía (Salvia hispanica) es una fuente abundante de ácidos grasos omega-3, antioxidantes y fibra, que podrían mejorar la funcionalidad del tejido adiposo. Objetivo: analizar el efecto de una dieta isocalórica suplementada con chía sobre el metabolismo de glucosa y los marcadores de inflamación del tejido adiposo y de función endotelial en pacientes con HGNA y etapas tempranas de diabetes. Métodos: en 32 pacientes con diagnóstico previo de HGNA, pero sin diabetes conocida, se evaluó el efecto de una dieta suplementada con chía molida (25 g/día) sobre la grasa visceral (GAV) y hepática, el perfil de lípidos, los ácidos grasos y las citoquinas en plasma, la prueba de tolerancia oral a la glucosa (OGTT), el índice insulinogénico (IGI30), el índice de disposición de insulina (DIO) y las células progenitoras endoteliales (EPC), antes y después de ocho semanas de suplementación. Resultados: la suplementación con chía promovió aumentos en el consumo de ácido alfa-linolénico en plasma (75 %) y fibra de alta viscosidad (55 %) y un mayor número de EPC (+126 %). La OGTT basal mostró que nueve pacientes tenían curva normal, 17 tenían prediabetes y seis, diabetes de recién diagnóstico. En los pacientes con diabetes, la chía favoreció un tejido adiposo más sano (GAV -7 %, NAFLD -100 %, adiponectina +47 %, resistina -30 %, IL-6 -44 %, IL-1ß -22 %) y un aumento del metabolismo de la glucosa a través de la mejora de la función de las células beta (IGI30 +50 %, DIO +66 %). Conclusiones: la suplementación de la dieta con 25 g/día de chía molida puede promover un tejido adiposo más saludable y mejorar la función endotelial y de las células ß pancreáticas. Entre los pacientes con anomalías metabólicas tempranas, las propiedades fitoquímicas de la chía pueden retrasar la progresión de la diabetes y el desarrollo de etapas avanzadas de daño hepático.

Design, manufacture and initial tests of a drug-eluting coronary stent / Diseño, fabricación y pruebas iniciales de una endoprótesis coronaria liberadora de fármaco

Abstract Introduction: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. Objective: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs’ antiproliferative activity and histological results. Method: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. Results: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. Conclusions: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

Resumen Introducción: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. Objetivo: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. Método: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. Resultados: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. Conclusiones: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.