Genets en l'art rupestre de les terres valencianes

En este trabajo se presenta una revisión de las figuras de jinetes documentadas en conjuntos de arte rupestre del territorio valenciano y se hace una valoración de su cronología y de su significado. Por sus caracteristicas técnicas y formales no pueden adscribirse a los artes rupestres Levantino y Esquematico, sino que se enmarcan en un horizonte gráfico de la Edad del Hiero y de época histórica.This paper present the painted and engraved riders located in the Valencian region. Technically and formally they are different from the human and animal figures dated to the Levantine and Schematic Art. This article describes the motifs and ascribes them a chronology of the Iron Age and historical times

Synthesis and characterization of nanoparticles of MFe2O4 (M=Fe, CO, Ni) for application in magnetic hyperthermia

Las nanopartículas magnéticas de óxido de hierro constituyen en la actualidad uno de los sistemas más prometedores dentro del campo de la biomedicina. Debido a las novedosas propiedades que presentan, su estudio se ha convertido en una actividad muy importante en la investigación de materiales magnéticos con carácter aplicativo. Por lo tanto, la motivación fundamental para la síntesis y estudio de coloides biocompatibles es el estudio de las propiedades magnéticas derivadas de las dimensiones nanométricas y la relación área superficial contra volumen existente. En el presente trabajo se ha estudiado la preparación de suspensiones coloidales de partículas de magnetita y ferritas de cobalto y níquel para aplicaciones biomédicas, abarcando tanto su síntesis como la caracterización de las propiedades. Para llevar a cabo la síntesis de las partículas se ha estudiado un método muy novedoso como es el de la descomposición térmica de precursores orgánicos de hierro en disolventes orgánicos y en presencia de surfactantes. Este método conduce a nanopartículas magnéticas monodispersas y muy cristalinas cuyo tamaño medio, forma y distribución pueden variar en función de parámetros experimentales como la naturaleza y concentración de los reactivos, además del control de la rampa de temperatura. Las propiedades estructurales de estas partículas son mejores que las obtenidas por métodos más convencionales como la coprecipitación o la pirolisis láser. Dado el carácter hidrófobo de las partículas sintetizadas, éstas no son aptas para su uso en biomedicina por lo que se ha estudiado la transferencia al medio acuoso, consiguiendo obtener suspensiones estables en agua menores de 100 nm. Las nanopartículas obtenidas se evaluaron in vitro como agentes de calentamiento para hipertermia magnética mediante la Absorción Específica de Potencia (SPA). Los valores obtenidos dependen tanto del tamaño de partícula como de la distribución de tamaños. El objetivo global está orientado al desarrollo de una nueva terapia de hipertermia magnética con aplicación en oncología

Long-term stability and reproducibility of magnetic colloids are key issues for steady values of specific power absorption over time

Virtually all clinical applications of magnetic nanoparticles (MNPs) require the formulation of biocompatible, water-based magnetic colloids. For magnetic hyperthermia, the requirements also include a high colloidal stability against precipitation and agglomeration of the constituent MNPs to maintain the heating efficiency of the ferrofluid in the long term. Agglomeration can change the heating efficiency by forming MNP clusters that modify the magnetic dipolar interactions between particles. Additionally, precipitation of the MNPs (i.e., the heating sources within the liquid) can change the measured heating rates of a colloid by altering the heat flow dynamics as the particles plunge to the precipitate. The specific power absorption (SPA) of single-domain MNPs depends critically on the average particle size and size distribution width and therefore first-rate reproducibility of different batches with respect to these parameters is also needed. We have studied the evolution of the SPA of highly reproducible and stable water-based colloids composed of polymer-coated Fe3O4 magnetic nanoparticles. By measuring the specific power absorption (SPA) values for 1 year as a function of field amplitude and frequency (H = 24 kA/m; 260 = f = 830 kHz), we have demonstrated that the SPA values of these samples can be reproduced in successive synthetic batches and stable for several months due to the in situ polymer coating that provides colloidal stability and keeps dipolar interactions negligible

Utilización de campos magnéticos y nanopartículas magnéticas para la orientación de células neuronales

Este Trabajo Fin de Grado se centra en el estudio de la capacidad de nanopartículas de magnetita (MNPs) biocompatibles de orientar células cuando éstas las ingieren y son sometidas a un campo magnético estático. Se pretende desarrollar una configuración de campo que optimice la fuerza magnética que actúa sobre estas MNPs absorbidas. El papel de la fuerza es orientar los organismos celulares. Por tratarse de componentes del tejido nervioso, las células empleadas poseen unas ramificaciones cortas e irregulares en el cuerpo celular, en cuya observación nos centraremos para hablar de esa orientación. Tras un estudio teórico previo de los parámetros a optimizar de la fuerza, se simulará el campo magnético mediante un algoritmo de elementos finitos (FEMM). Este método proporcionará resultados numéricos de los diseños de perfiles magnéticos realizados, que servirán como modelo para la construcción de un aplicador de imanes de NdFeB. Se busca reproducir en el laboratorio del INA los valores simulados y terminar haciendo un análisis estadístico del ángulo de la orientación de las células neuronales con el campo magnético, para concluir que tal orientación existe

Determination of the blocking temperature of magnetic nanoparticles : The good, the bad, and the ugly

A numerically solved two-level Stoner-Wohlfarth model with thermal agitation is used to simulate Zero Field Cooling (ZFC)–Field Cooling (FC) curves of monosize and polysize samples and to determine the best method for obtaining a representative blocking temperature TB value of polysize samples. The results confirm a technique based on the T derivative of the difference between ZFC and FC curves proposed by Micha et al. (the good) and demonstrate its relation with two alternative methods: the ZFC maximum (the bad) and the inflection point (the ugly). The derivative method is then applied to experimental data, obtaining the TB distribution of a polysize Fe3O4 nanoparticle sample suspended in hexane with an excellent agreement with TEM characterization.Instituto de Física La Plat

Magnetic field-assisted gene delivery: achievements and therapeutic potential

The discovery in the early 2000’s that magnetic nanoparticles (MNPs) complexed to nonviral or viral vectors can, in the presence of an external magnetic field, greatly enhance gene transfer into cells has raised much interest. This technique, called magnetofection, was initially developed mainly to improve gene transfer in cell cultures, a simpler and more easily controllable scenario than in vivo models. These studies provided evidence for some unique capabilities of magnetofection. Progressively, the interest in magnetofection expanded to its application in animal models and led to the association of this technique with another technology, magnetic drug targeting (MDT). This combination offers the possibility to develop more efficient and less invasive gene therapy strategies for a number of major pathologies like cancer, neurodegeneration and myocardial infarction. The goal of MDT is to concentrate MNPs functionalized with therapeutic drugs, in target areas of the body by means of properly focused external magnetic fields. The availability of stable, nontoxic MNP-gene vector complexes now offers the opportunity to develop magnetic gene targeting (MGT), a variant of MDT in which the gene coding for a therapeutic molecule, rather than the molecule itself, is delivered to a therapeutic target area in the body. This article will first outline the principle of magnetofection, subsequently describing the properties of the magnetic fields and MNPs used in this technique. Next, it will review the results achieved by magnetofection in cell cultures. Last, the potential of MGT for implementing minimally invasive gene therapy will be discussed.Instituto de Investigaciones Bioquímicas de La Plat

Understanding the first Neolithic occupation of Cova d’En Pardo (Planes, Alicante): preliminary results of the multidisciplinary analysis of levels VIII and VIIIb

Se presentan los resultados de las excavaciones llevadas a cabo en la Cova d’En Pardo (Planes, Alicante), concretamente los niveles VIII y VIIIb. El desarrollo de un proyecto multidisciplinar ha permitido caracterizar la ocupación de una pequeña cavidad por parte de las primeras comunidades campesinas asociadas al inicio del proceso de neolitización del levante de la península Ibérica.We present the results of excavations carried out in the Cova d’En Pardo (Planes, Alicante), specifically the levels VIII and VIIIb. The development of a multidisciplinary project has allowed characterize the occupation of a small cavity by the first farming communities associated with the Neolithization process of the Levant of Iberian Peninsula.Este trabajo se ha realizado en el marco del proyecto Origins and Spread of Agriculture in the western Mediterranean región (ERC-2008-AdG 230561)

Direccionamiento neuronal remoto utilizando nanopartículas y campos magnéticos

La regeneración del sistema nervioso, como tratamiento para las lesiones nerviosas traumáticas o enfermedades degenerativas, ha sido una idea perseguida a lo largo de décadas. El surgimiento de la nanotecnología ha permitido nuevas estrategias para la regeneración nerviosa, a través de enfoques innovadores basados en materiales nanoestructurados. Varias terapias de guiado neuronal se basan en estos ‘andamios’ nano-estructurados que sirven como "canales de guía de nervios " que proporcionan un conducto eficaz durante el proceso de regeneración del nervio. El presente trabajo se ha desarrollado en el marco de una nueva metodología, mínimamente invasiva, para el guiado físico de neuritas y axones basada en el uso de nanopartículas magnéticas y campos magnéticos aplicados remotamente. Esta estrategia se basa en la hipótesis de que las células neuronales pueden, bajo la aplicación de una fuerza de tracción producida y aplicada externamente, guiar el proceso de crecimiento de las neuritas y el alargamiento del axón a lo largo de la dirección impuesta por dichos campos magnéticos. El objetivo central de este trabajo ha sido demostrar que las nanopartículas magnéticas (NPMs) pueden utilizarse para generar estas fuerzas de tracción bajo el efecto de un gradiente de campo magnético externo, y estas fuerzas puede a su vez provocar la orientación de las neuritas a lo largo de la dirección del campo magnético. Las NPMs utilizadas están compuestas por un núcleo magnético de Fe3O4 recubierto por polietilenimina (PEI-NPMs), con tamaños de 25 ± 5 nm. Células de la línea PC12 fueron seleccionadas como modelo neuronal para los experimentos in vitro. Las PEI-NPMs mostraron una baja toxicidad en células PC12, y su cuantificación se llevó a cabo a través de ensayos de absorción colorimétrica mediante un complejo de hierro-tiocianato. El estudio de la distribución intracelular de las NPMs mediante técnicas de doble haz (FIB / SEM) y TEM reveló la coexistencia de aglomerados de NPMs internalizados en el espacio intracelular, junto con otros aglomerados parcialmente internalizados, es decir, atravesando la membrana celular. Cuando las células PC12 cargadas con PEI-NPMs fueron expuestas a un campo magnético estático se observó que el crecimiento de las neuritas ocurría preferencialmente en la dirección de la fuerza magnética externa aplicada. Simultáneamente, se observó un incremento estadísticamente significativo en la longitud promedio de las neuritas cuando éstas se encontraban cargadas con NPMs y sometidas al campo magnético externo. Hemos demostrado que la orientación de los axones producida tiene su origen en la fuerza magnética que actúa sobre las NPMs previamente incorporadas a las neuritas. Por otra parte, se ha observado un efecto adicional de las NPMs incorporadas, específicamente que las NPMs pueden estimular el proceso de crecimiento de las neuritas, abriendo la posibilidad de una terapia bi-funcional: la orientación remota en conjunto con la estimulación del crecimiento axonal. Estos resultados abren la posibilidad de nuevas terapias multifuncionales no invasivas para lesiones nerviosas severas, mediante el uso de NPMs y de campos magnéticos externos

Color changes and acrylamide formation in fried potato slices

Disorders of the retina and RPE tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. Long-term delivery of biologically active molecules to the RPE is problematic and remains a challenge. The cornea/sclera constitutes a static barrier severely limiting ocular bioavailability of surface instilled drugs and retinal-blood barrier prevent ocular drug diffusion after systemic administration. Intravitreal (IVT) and subretinal injections are considered as the most effective ways of delivering material to the back of the eye. In particular, subretinal injection seems to be the only effective option to target RPE but are very invasive with reduced patient compliance compared to IVT injections. IVT injection involves injection of drug in solution directly into the vitreous which is far from optimal for three reasons: short term complications caused by the initial high drug concentration, very short retention time and lack of tissue specificity. In the present study, we provide a method for exclusive and fast localization of drugs to RPE, with the use of magnetic nanoparticles (MNPs), by IVT injection. MNPs form a powerful drug delivery system because their reactive surface can be easily functionalized with biocompatible coatings and bioactive molecules to prevent interaction with healthy tissues and increase their target specificity . In addition to their established role as molecular carriers, MNPs have two other advantages. They can be controlled by noncontact forces and tracked by magnetic resonance imaging (MRI) . Furthermore, different MNPs have FDA approval for clinical use e.g., Endorem® (MRI contrast agent for diagnosis of liver tumors). Although the MNPs have not yet been tested on humans for ocular applications, there are evidences from studies in rats, that the iron oxide MNPs are non-toxic to the ocular structures . We have investigated the ability of MNPs to target RPE by IVT injection, using wild type Xenopus laevis as model system. Xenopus offers favorable features, such as external development, large supply of embryos with each fecundation, a very short early development time (3 days to reach tadpole) and close homology with human genes. A remarkable similarity in the molecular signaling processes, cellular structure, anatomy, and physiology of eye has been observed among Xenopus and other high-order vertebrates, including humans . Their relatively large size (from 1-1.2 mm (zygote) to 1 cm (5 days old)) enables an easy manipulation and IVT microinjection. Finally, the use of this model generates minor ethical issue compared to mammals because these embryos are considered to not be sufficiently sentient or experience nociceptive sensations when subjected to experimental procedures. We used commercial fluorescent MNPs with a negative surface charge and a hydrodynamic size of 252 nm to analyze their biodistribution after intravitreal injection, i.e., in the anterior part of the eye and, specifically, in a region behind the lens surrounded by the vitreous humor, into the left eye of Xenopus embryo. 24 h after the injection, we observed, by Prussian blue staining of paraffin sections, that MNPs are specifically retained in the ocular tissues without any diffusion to the other tissues, including the contralateral eye. Quantitative analysis of the iron content by thiocyanate colorimetric assay was used to confirm that all the MNPs were retained in the injected eye. The average ferric iron content in the injected eyes was significantly higher than in the control eyes. These results, together with the histochemical observations, demonstrate that the MNPs are retained exclusively inside the injected eye. We did not observe any toxic effects on the ocular structures caused by MNPs: no death or embryonic malformations were observed and the injected eye exhibited completely normal development. Even if the particles were injected in the anterior part of the eye they localized preferentially in the posterior segment, in a region corresponding to the RPE. The RPE is a single layer of pigmented cuboidal epithelial cells adjacent to the neural retina. In order to define precisely the MNP localization after one day from the injection, we studied the fluorescence of MNPs on cryostat sections without pigment bleaching, to highlight RPE. In this way we established the precise localization of the MNPs, as red spots, in RPE. The moderate red background is most likely due to a partially degradation of the MNPs linked fluorophore, as confirmed by the histological staining (Prussian Blue) of particles which were found to co-localize only with RPE layer. In order to characterize the kinetics of the migration process, we monitored the localization of MNPs at different time points starting from 5 min to 24 h after injection. Just 5 min after injection, the particles started to spread out from the vitreous chamber (VC), adhering to the neural retina (NR) and only few were in RPE . After the MNPs continue to progressively migrate at RPE from the vitreous chamber and the migration process is completed within 24 h. Another crucial factor for efficient drug delivery is permanence at the intended target site. For this reason, we monitored the retention of MNPs in embryos for periods up to 20 days. The MNP localization follows RPE during its development, included in the later stages (20 days) where RPE microvilli interdigit with the outer segment of photoreceptors. It is known that NPs size and surface charge influence the movement of nanoparticle-based ocular drug delivery systems. We investigated the effect of size and charge on MNP movement by comparing the localization of our MNPs (250 nm, -17 mV) with the localization of particles of similar size but more negatively charged (MNP-), or positively charged (MNP+), or particles with neutral charge but small size (MNPs). Surprisingly, the results were the same with all kinds of MNPs, i.e., they localized in RPE one day after injection with only a small fraction in NR and no particles diffusion to extra-ocular tissues. For the first time we demonstrated that charge surface, beyond the size, does not influence the localization of nanoparticles in RPE. We speculate that MNPs, with different charge and size, can diffuse in the vitreous, infiltrate among retinal neurons without cells engulfing until their reach RPE. These cells have a strong phagocytic activity, required for maintaining constant renewal process of the photoreceptor outer segments. In order to understand if the capability of MNPs to localize in RPE is species specific, we injected MNP in the left eye of zebrafish embryos at 48 hour post fertilization. We found that after 1 day from injection the MNPs localize specifically in RPE also in zebrafish. This datum suggests that the localization of MNPs in RPE is not species-specific. In conclusion, we have developed a protocol for fast and specific localization of magnetic nanocarriers in RPE layer, in an embryo model for the study of vertebrate diseases as a first step for therapeutic proof-of-concept studies, replacing or drastically reducing the use of mammals. We demonstrated that MNPs localize autonomously and specifically in RPE after IVT injection independently by particle size and surface charge. Moreover, this process seems to be not specie-specific. The MNPs have the potential for development as an ocular drug delivery, capable of targeting RPE with sustained controlled drug release providing MRI tracking for a variety of retinopathies. Moreover, the MNPs could be exploited also for magnetic hyperthermia treatments of ocular iper-proliferative diseases. Additionally there are other challenging applications which could be explored on the use of MNPs, such as magnetic targeting of RPE in the treatment of retinal detachment by applying external magnetic forces. REFERENCE Giannaccini M, Giannini M, Calatayud MP, Goya GF, Cuschieri A, Dente L, Raffa V. Magnetic nanoparticles as intraocular drug delivery system to target Retinal Epithelium (RPE). Int. J. Mol. Sci. 2014, 15:1590-1605