Review of the “state of the art” and possibilities of the most significant approaches to the specific delivery of chemotherapy agents to tumor cells

Los principales problemas de la quimioterapia proceden esencialmente de la relativa falta de especificidad derivada de la extensa biodistribución de los agentes antitumorales y de los efectos secundarios generados por la acción inespecífica de éstos en tejidos y órganos sanos. La necesidad de encontrar tratamientos eficaces contra el cáncer ha hecho que se incrementen las líneas de investigación en esta materia. Una de las aproximaciones más prometedoras en este sentido es el desarrollo de sistemas coloidales biodegradables para el transporte de fármacos antitumorales. Gracias a éstos, se logra acumular específicamente la cantidad de fármaco administrada en el lugar de acción, logrando así un aumento significativo de la eficacia clínica, junto con una minimización de las reacciones adversas asociadas. En este trabajo, pretendemos analizar el estado actual en el diseño de coloides como transportadores de fármacos antitumorales, junto con la aplicación de las novedosas estrategias de transporte pasivo y activo de fármacos.The main problems related to chemotherapy mainly come from a relative lack of selectivity, that is associated to the extensive biodistribution of antitumor molecules, and to the severe side effects generated by the unspecific drug action on healthy tissues and organs. The need of finding out efficient treatments against cancer has led to an enhancement in the number of research lines in the field. In this way, one of the most promising approaches is the development of biodegradable colloids for the delivery of antitumor drugs. Thanks to them, it is possible to specifically concentrate the drug into the site of action. Therefore, a significant improvement of the chemotherapy effect is obtained along with a minimization of the related adverse side effects. In this review, we analyze the current “state of the art” in the development of colloidal systems for the efficient delivery of anticancer drugs. The possibilities of novel drug delivery strategies based on passive and active targeting mechanisms are also discussed

Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome

OBJECTIVE: To report the visual outcome after 4-year follow-up in a series of highly myopic eyes with choroidal neovascularisation (CNV) treated with antivascular endothelial growth factor (anti-VEGF) drugs. METHODS: A retrospective, non-randomised, multicentre, consecutive, interventional case series study was performed. 92 highly myopic eyes with subfoveal CNV were treated with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3 injections) was dictated by surgeons' preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyse BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives. RESULTS: The mean age of the patients was 57 years (SD 14, range 30-93). The mean number of letters read was 46.1 (SD 16.8, range 5-70) at baseline, 55.5 (SD 18.6, range 10-85) at 12 months, 50.1 (SD 20.1, range 5-82) at 24 months, 54.2 (SD 21.9, range 2-85) at 36 months and 53.1 (SD 22.5, range 1-83) at 48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months; Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4, range 1-29). SE and treating drug had no influence on the final visual outcome and number of injections required. CONCLUSIONS: Intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at 4-year follow-up

Sistemas transportadores de fármacos basados en el polímero poly(e- caprolactona) para el tratamiento del cáncer

Chemotherapy agents have little or no specificity over cancer cells, resulting in low therapeutic concentrations at the tumor site (a consequence of a broad systemic distribution), and severe side effects. With the aim of avoiding cancer therapy failure, several approaches such as design of new anticancer drugs, chemical engineering of conventional drugs and development of drug delivery systems have been proposed. The objective is to enhance drug localization at the tumor region (by controlling its biodistribution profile) and, therefore, to increase the anti-tumor efficacy (even in multi-drug resistant tumors), while reducing systemic side effects. One of the most promising approaches to the problem is the development of drug nanocarriers based on the polymer poly(e-caprolactone). In this review we will focus our attention on these polymeric colloids, particularly on the most significant characteristics and formulation procedures, and on their use as nanoplatforms for the delivery of chemotherapy agents to the tumor site. Furthermore, the most recent in vitro and in vivo investigations on the subject are extensively reviewed

Predicting Atrial Fibrillation Recurrence After Catheter Ablation Through Time Variability of P-wave Features

[EN] Nowadays, the first-line therapy for paroxysmal atrial fibrillation (PAF) is pulmonary vein isolation through catheter ablation. However, the success rate of this procedure is still not as high as desirable. Thus, preoperative prediction of early AF recurrence after ablation is a challenge to select optimal candidates for the intervention. To this end, some promising predictors based on the P-wave in short ECG signals have been proposed in the last years. However, evolution of the P-wave along the time has still not been analyzed. Hence, the present work studies how time variability of two features of the P-wave predicts midterm cryoablation failure. For 45 PAF patients, a standard 12-lead ECG signal was obtained for 5 minutes before ablation. An automatic algorithm was then used to delineate all P-waves in lead II, and duration and amplitude were computed. The resulting time series were characterized by their mean, standard deviation and coefficient of variation (CV). Correlating these measures with ablation outcome, the CV for both parameters obtained the best discrimination between patients. In fact, compared with the mean value, the CV for both features obtained accuracies 10% greater, thus achieving values of 70%. These outcomes entail that time variability of the P-wave can reveal new information about the proarrhythmic condition of the patients, thus improving predictions of ablation failure.Ruiz, A.; Arias, MA.; Puchol, A.; Pachon, MI.; Rieta, JJ.; Alcaraz, R. (2020). Predicting Atrial Fibrillation Recurrence After Catheter Ablation Through Time Variability of P-wave Features. IEEE. 1-4. https://doi.org/10.22489/CinC.2020.366S1

Determination of the stability of Kollicoat MAE 30D by means of differential scanning calorimetry

Se estudia la estabilidad de Kollicoat MAE 30D mediante determinaciones calorimétricas y microscópicas. Se estudian los efectos que producen pH, temperatura y agitación sobre las propiedades fi sicoquímicas de las partículas de este latex comercial. Se comprueba que el factor que mas infl uencia ejerce es el pH, siendo máxima la estabilidad a pH ácidos, y modifi cándose con un decrecimiento de la misma, a partir de pH 6. Se determina la forma y tamaño de partícula mediante medidas microfotográfi cas de SEM, realizando el recuento de 200 partículas de una muestra del latex previamente desecado. Se comprueba que la dispersión acuosa de Kollicoat MAE 30 D a su pH natural (2.5), da lugar a una población de partículas con un diámetro medio de 1.56 nm.The stability of Kollicoat MAE 30 D was studied with differential scanning calorimetric, and scanning electron microscopy. We investigated the effects of pH, temperature and shaking on physicochemical properties of the latex particles. Stability of the polymer as most strongly affected by pH; hence, we conclude that the stability of this latex reaches a maximum at acid pH values, where as stability is lost to pH 6. The particle shape and the mean diameter were determined by means of SEM microphotographs on 200 particles in a sample of dry latex. The aqueous Kollicoat MAE 30 D dispersion, at its natural pH (2.5), presented one population of particles with a mean diameter of 1.56 nm

Importancia de la polietilenimina en biomedicina y sus aplicaciones en terapia génica

Therapy is a branch of health science that deals with the means used and the manner of application in the treatment of diseases in order to relieve symptoms or produce a cure. Today there are many therapeutic tools available to combat the diverse health problems faced daily. With this evolution of medicine, it is inevitable that more and better strategies emerge leading to a more innovative therapeutic spectrum. Within the new strategies, we find that gene therapy is currently one with most potential. This type of therapy is based on using genetic material as an active substance against various pathologies and it is on which this literary review is focused. With the high demand for systems that vehiculize genetic material, diverse forms of carrying said material have emerged in the past decade. One of these forms consists of the use of non-viral vectors. The non-viral vectors act as transfectants that evade problems inherent to the use of viral structures such as immunological reactions. Polyethylenimine has emerged as the most promising polymer in this field for many reasons which will be illustrated in this paper. The objectives of this review are to give the reader an understanding of what Polyethylenimine is, why it has produced so much interest today in gene therapy, and what its applications are, with special emphasis on cancer treatment.La Terapéutica es la rama de las ciencias de la salud, que se ocupa de los medios empleados y su forma de aplicarlos en el tratamiento de las enfermedades con el fin de aliviar los síntomas o de producir la curación. Hoy en día existen al alcance multitud de herramientas terapéuticas para combatir los diversos problemas de salud a los que se hace frente día a día. Con esta evolución de la Medicina, es inevitable que vayan surgiendo cada vez más y mejores estrategias que conducen a un espectro terapéutico más innovador. Dentro de las nuevas estrategias, nos encontramos con la Terapia Génica que es una de las que más potencial tiene actualmente. Este tipo de terapia se basa en utilizar material genético como sustancia activa frente a diversas patologías y es aquí donde se encuentra el centro de atención de la presente revisión bibliográfica. Con la gran demanda de sistemas que vehiculizan el material génico han surgido en la última década, diversas formas de transportar dicho material. Una de estas formas consiste en el empleo de vectores no virales. Los cuales no son más que transfectores que eluden los problemas inherentes al empleo de estructuras víricas, como son las reacciones inmunológicas. La polietilenimina ha emergido como el polímero más prometedor en este ámbito por múltiples razones las cuales serán ilustradas en el presente trabajo. Los objetivos de la presente revisión son otorgar al lector un conocimiento sobre qué es la polietilenimina, porqué suscita tanto interés hoy en día en terapia génica, y cuáles son algunas de sus aplicaciones, haciendo especial hincapié en el tratamiento del cáncer.Proyecto FIS 11/02571 (Instituto de Salud Carlos III, España)

Myopic maculopathy: Current status and proposal for a new classification and grading system (ATN)

Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic myopia is especially common in East Asian countries. Ocular alterations associated with pathologic myopia, especially those involving the macular area—defined as myopic maculopathy—are the leading causes of vision loss in patients with pathologic myopia. High myopia is defined as the presence of a highly negative refractive error (>−6 to −8 diopters) in the context of eye elongation (26–26.5 mm). Although the terms high myopia and pathologic myopia are often used interchangeably, they do not refer to the same eye disease. The two key factors driving the development of pathologic myopia are: 1) elongation of the axial length and 2) posterior staphyloma. The presence of posterior staphyloma, which is the most common finding in patients with pathologic myopia, is the key differentiating factor between high and pathologic myopia. The occurrence of staphyloma will, in most cases, eventually lead to other conditions such as atrophic, traction, or neovascular maculopathy. Posterior staphyloma is for instance, responsible for the differences between a myopic macular hole (MH)—with and without retinal detachment—and idiopathic MH. Posterior staphyloma typically induces retinal layer splitting, leading to foveoschisis in myopic MH, an important differentiating factor between myopic and emmetropic MH. Myopic maculopathy is a highly complex disease and current classification systems do not fully account for the numerous changes that occur in the macula of these patients. Therefore, a more comprehensive classification system is needed, for several important reasons. First, to more precisely define the disease stage to improve follow-up by enabling clinicians to more accurately monitor changes over time, which is essential given the progressive nature of this condition. Second, unification of the currently-available classification systems would establish standardized classification criteria that could be used to compare the findings from international multicentric studies. Finally, a more comprehensive classification system could help to improve our understanding of the genetic origins of this disease, which is clearly relevant given the interchangeable—but erroneous—use of the terms high and pathologic myopia in genetic researc

Evaluation of two MM5-PBL parameterizations for solar radiation and temperature estimation in the South-Eastern area of the Iberian Peninsula

We study the relative performance of two different MM5-PBL parameterizations (Blackadar and MRF) simulating hourly values of solar irradiance and temperature in the south-eastern part of the Iberian Peninsula. The evaluation was carried out throughout the different seasons of the year 2005 and for three different sky conditions: clear-sky, broken-clouds and overcast conditions. Two integrations, one per PBL parameterization, were carried out for every sky condition and season of the year and results were compared with observational data. Overall, the MM5 model, both using the Blackadar or MRF PBL parameterization, revealed to be a valid tool to estimate hourly values of solar radiation and temperature over the study area. The influence of the PBL parameterization on the model estimates was found to be more important for the solar radiation than for the temperature and highly dependent on the season and sky conditions. Particularly, a detailed analysis revealed that, during broken-clouds conditions, the ability of the model to reproduce hourly changes in the solar radiation strongly depends upon the selected PBL parameterization. Additionally, it was found that solar radiation RMSE values are about one order of magnitude higher during broken-clouds and overcast conditions compared to clear-sky conditions. For the temperature, the two PBL parameterizations provide very similar estimates. Only under overcast conditions and during the autumn, the MRF provides significantly better estimates

Entrenamiento perceptivo en la portera de balonmano ante la trayectoria del tiro

This study aimed to analyze the application of a perceptive-motor training program effect in the handball goalkeeper and value the efficacy according to the shot trajectories, differentiating the moments of its application, under conditions of real practice. Two female goalkeepers were selected deliberately. A quasi-experimental case design of type A-B-A was utilized. The trained specialist registered the data in real time individually and after, watching the games recorded, out agreed by consensus. For the statistical processing the t of Student test for independent measures was carried out, an averages meaning contrast test and an anova followed by the post hoc Tukey test. The application of the program allowed to improve the effectiveness in the shot interception for the trajectories analyzed except those of half height.Este estudio ha analizado el efecto de la aplicación de un programa de entrenamiento perceptivo-motor en la portera de balonmano y valorado su eficacia en función de las trayectorias de lanzamiento, diferenciando los momentos de su aplicación, bajo condiciones de práctica real. Se seleccionaron dos porteras de forma intencionada. Se utilizó un diseño cuasiexperimental de caso único tipo A-B-A. Los observadores entrenados registraron los datos a tiempo real de forma individual y a posteriori, visionando los vídeos grabados, de forma consensuada. Para el tratamiento estadístico se realizó la prueba t de Student para medidas independientes, una prueba de contraste de significación de medias y un anova seguido por la prueba post hoc de Tukey. La aplicación del programa permitió mejorar la efectividad en la interceptación de los lanzamientos para las trayectorias analizadas salvo los de media altura

Observation of spontaneous self-channelling of light in air below the collapse threshold

We report the observation of the self-guided propagation of 120 fs, 0.56 mJ infrared radiation in air for distances greater than one meter. In contrast to the known case of filamentation, in the present experiment the laser power is lower than the collapse threshold. Therefore the counter balance between Kerr self focussing and ionization induced defocussing as the stabilizing mechanism is ruled out. Instead, we find evidences of a process in which the transversal beam distribution reshapes into a form similar to a Townes soliton. We include numerical support for this conclusion