Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Graphene oxide-silver nanoparticle hybrid material: an integrated nanosafety study in zebrafish embryos.

This work reports an integrated nanosafety study including the synthesis and characterization of the graphene oxide-silver nanoparticle hybrid material (GO-AgNPs) and its nano-ecotoxicity evaluation in the zebrafish embryo model. The influences of natural organic matter (NOM) and a chorion embryo membrane were considered in this study, looking towards more environmentally realistic scenarios and standardized nanotoxicity testing. The nanohybrid was successfully synthesized using the NaBH4 aqueous method, and AgNPs (~ 5.8 nm) were evenly distributed over the GO surface. GO-AgNPs showed a dose-response acute toxicity: the LC50 was 1.5 mg L-1 for chorionated embryos. The removal of chorion, however, increased this toxic effect by 50%. Furthermore, the presence of NOM mitigated mortality, and LC50 for GO-AgNPs changed respectively from 2.3 to 1.2 mg L-1 for chorionated and de-chorionated embryos. Raman spectroscopy confirmed the ingestion of GO by embryos; but without displaying acute toxicity up to 100 mg L-1, indicating that the silver drove toxicity down. Additionally, it was observed that silver nanoparticle dissolution has a minimal effect on these observed toxicity results. Finally, understanding the influence of chorion membranes and NOM is a critical step towards the standardization of testing for zebrafish embryo toxicity in safety assessments and regulatory issues.

Fast and efficient electrochemical thinning of ultra-large supported and free-standing MoS2 layers on gold surfaces.

Molybdenum disulfide (MoS2) is a very promising layered material for electrical, optical, and electrochemical applications because of its unique and outstanding properties. To unlock its full potential, among different preparation routes, electrochemistry has gain interest due to its simple, fast, scalable and simple instrumentation. However, obtaining large-area monolayer MoS2 that will enable the fabrication of novel electronic and electrochemical devices is still challenging. In this work, we reported a simple and fast electrochemical thinning process that results in ultra-large MoS2 down to monolayer on Au surfaces. The high affinity of MoS2 by Au surfaces enables the removal of bulk layers while preserving the first layer attached to the electrode. With a proper choice of the applied potential, more than 90% of the bulk regions can be removed from large-area MoS2 crystals, as confirmed by atomic force microscopy, photoluminescence, and Raman spectroscopy. We further address a set of contributions that are helpful to elucidate the features of MoS2, namely, the hyphenation of electrochemistry and optical microscopy for real-time observation of the thinning process that was revealed to occur from the edges to the center of the flake, an image treatment to estimate the thinning area and thinning rate, and the preparation of free-standing MoS2 layers by electrochemically thinning bulk flakes on microhole-structured Ni/Au meshes.

Usos terapeuticos potenciales de los antagonistas opioides: Fisiopatologia y evidencia preclinica / Potential therapeutic uses of opioid antagonists: Pathophysiology and preclinical evidence

El sistema opioide, del cual forman parte los peptidos opioides endogenos y sus receptores (Miu, Kappa, delta y ORL), tiene un papel importante en la fisiologia de diferentes sistemas. Existe una creciente evidencia de su participacion en la fisiopatologia de multiples trastornos del sistema nervioso central, endocrino e inmunologico. La modulacion del sistema opioide mediante el uso de antagonistas especificos o inespecificos de sus receptores puede tener un papel terapeutico en el manejo sintomatico de diferentes contextos, incluyendo la intoxicacion aguda por opiaceos, la dependencia a opioides, y la reduccion de reacciones adversas de agonistas opioides utilizados en el manejo del dolor cronico. El presente trabajo tiene como objetivo revisar la farmacologia de los antagonistas opioides especificos e inespecificos, y realizar una actualizacion de sus posibles nuevas indicaciones y usos terapeuticos.

Opioid system, which involved endogenous opioid peptides and their receptors (Miu, Kappa, delta and ORL), has a main role in the physiology of several systems. At the same time, there is cumulating evidence in the role of the opioid system in the physiopathology of several disorders in the central nervous, endocrine and immunological system. The modulation of the opioid system using nonspecific antagonists may have a therapeutic role in the symptomatic management of several diseases, as well as, in the emergency management of opioid analgesic overdose, opioid dependence and to reduce the drug side effects of the opioid agonists used in chronic pain. This paper aims to review the pharmacology of specific and nonspecific opioid antagonists, and update on possible new indications and therapeutic uses of such antagonists.

Reacciones adversas a medicamentos como motivo de consulta en un servicio de atención prioritaria / Adverse drug reactions as the reason for visiting an emergency department

Objetivo El objetivo del presente estudio consistió en determinar la prevalencia de las reacciones adversas a medicamentos (RAM) como motivo de consulta a un servici -o de atención prioritaria. Métodos El estudio se realizó en el servicio de atención prioritaria del Centro de Atención Ambulatoria Central Luis de la ESE Luis Carlos Galán Sarmiento en Bo- gotá , del 20 de septiembre al 2 de octubre de 2004. Las RAM fueron identificadas por un evaluador, quien revisó todas las historias clínicas y cada vez que los médi -cos señalaron la sospecha de una RAM. Los pacientes fueron contactados. La eva - luación de la causalidad, prevenibilidad , y mecanismo de generación fue realizada por dos evaluadores. Resultados La prevalencia de RAM fue de 45 RAM en 1 395 consultas, en dos semanas (2,8 por ciento de las consultas). El reporte espontáneo modificado permitió de- tectar el 26,7 por ciento de las RAM identificadas por búsqueda activa. Del total de las RAM identificadas el 73,3 por ciento se presentó en mujeres, 64,9 por ciento en mayores de 60 años, 48,9 por ciento fueron no prevenibles, 22,2 por ciento prevenibles y 28,9 por ciento inclasificables. Conclusiones Las RAM representan una proporción significativa de la consulta ambulatoria y el sistema de reporte espontáneo modificado detectó un gran porcen -taje de RAM. La distribución y tipo de RAM fueron similares a las descritas en otras series. Aproximadamente 2 de cada 10 RAM pudieron haberse prevenido.

Objective Determining the prevalence of adverse drug reactions (ADR) as the reason for visiting an emergency department. Methods The study took place at the Luis Carlos Galán Sarmiento ESE's Emergency Department's Central Outpatient Centre in Bogotá. It was carried out from September 20 th to October 2 nd 2004. ADR were identified by an evaluator who reviewed all clinical histories, noting when physicians had indicated that an ADR had occurred. The patients were contacted. Two people evaluated causality, the degree of preventability and the mechanism producing the ADR. Results 45 ADR were recorded in 1,395 visits made during a two-week period (2.8 percent of the consultations). Modified spontaneous report detected 26.7 percent ADR identified by active search. 73.3 percent of all identified ADR occurred in females, 64.9 percent in people older than 60. 48.9 percent were non-preventable, 22.2 percent preventable and 28.9 percent were unclassifiable. Conclusions ADR represent a significant proportion of the reasons for outpatient consultation; the modified spontaneous report system detected a large percentage of ADR. There were no statistically significant differences between gender and ADR frequency. ADR occurred more frequently in elderly patients. Around 2 out of each 10 ADR could have been prevented.