Five decades of cuprizone, an updated model to replicate demyelinating diseases

Abstract: Introduction: Demyelinating diseases of the central nervous system (CNS) comprise a group of neurological disorders characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter tracts. Some of myelin disorders include: Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others. To date, the etiology of these disorders is not well known and no effective treatments are currently available against them. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology and clinical signs of these diseases. Herein, we describe the model of toxic demyelination induced by cuprizone (CPZ), a copper chelator that reduces the cytochrome and monoamine oxidase activity into the brain, produces mitochondrial stress and triggers the local immune response. These biochemical and cellular responses ultimately result in selective loss of oligodendrocytes and microglia accumulation, which conveys to extensive areas of demyelination and gliosis in corpus callosum, superior cerebellar peduncles and cerebral cortex. Remarkably, some aspects of the histological pattern induced by CPZ are similar to those found in multiple sclerosis. CPZ exposure provokes behavioral changes, impairs motor skills and affects mood as that observed in several demyelinating diseases. Upon CPZ removal, the pathological and histological changes gradually revert. Therefore, some authors have postulated that the CPZ model allows to partially mimic the disease relapses observed in some demyelinating diseases. Conclusion: for five decades, the model of CPZ-induced demyelination is a good experimental approach to study demyelinating diseases that has maintained its validity, and is a suitable pharmacological model for reproducing some key features of demyelinating diseases, including multiple sclerosis.UAEME

Madurez ciudadana. Requisito para la consolidación de una democracia ética

La ciudadanía, decían los filósofos griegos, es la condición por la que el hombre puede, en lugar de limitarse a vivir, aspirar a una vida buena. La teoría política enseña que los ciudadanos son importantes sencillamente porque son la esencia y existencia de todo Estado. Sin ciudadanos no hay Estado. ¿Cuál es la situación del ciudadano en la actualidad? ¿Cuál es su nivel de participación y compromiso con los fines del Estado? Ser ciudadano supone desarrollar el sentido de identidad y pertenencia en el lugar en el que se interactúa socialmente; implica desenvolverse con responsabilidad, lo cual nos conduce al meollo de la ciudadanía: la participación política. La participación ciudadana en política se asocia estrechamente al concepto de democracia, la cual se caracteriza por la necesidad de conciliar las exigencias de la participación con la gobernabilidad. Pero para lograr una actitud de compromiso y participación se requiere de una ciudadanía madura. En la antigüedad se decía que el “ciudadano virtuoso” era aquel ciudadano libre y bien formado, con capacidad crítica, que actuaba con ética y responsabilidad, participando en la decisión sobre los derroteros de su comunidad. Para volver a ese ciudadano virtuoso, libre y activo, que se evocaba en la antigüedad, es necesario desenmarañar el entramado actual y salir del laberinto creado por la sociedad de consumo. Indudablemente, es fundamental que cada individuo encuentre o recupere su libertad. Quienes participamos en la obra Madurez ciudadana y gobernanza para la consolidación de una democracia ética invitamos a la ciudadanía a caminar en ese sentido

EGF-Coupled Gold Nanoparticles Increase the Expression of CNPase and the Myelin-Associated Proteins MAG, MOG, and MBP in the Septal Nucleus Demyelinated by Cuprizone

ARTICULO DE ACCESO ABIERTOCurrent pharmacological therapies against demyelinating diseases are not quite satisfactory to promote remyelination. Epidermal growth factor (EGF) can expand the population of oligodendrocyte precursor cells (OPCs) that may help with the remyelination process, but its delivery into the injured tissue is still a biomedical challenge. Gold nanoparticles (GNPs) may be a useful tool for drug delivery into the brain. To evaluate remyelination in the septal nucleus, we administered intracerebral GNPs coupled with EGF (EGF–GNPs). C57BL6/J mice were demyelinated with 0.4% cuprizone (CPZ) and divided into several groups: Sham, Ctrl, GNPs, EGF, and EGF–GNPs. We evaluated the remyelination process at two time-points: 2 weeks and 3 weeks post-injection (WPI) of each treatment. We used the rotarod for evaluating motor coordination. Then, we did a Western blot analysis myelin-associated proteins: CNPase, MAG, MOG, and MBP. EGF–GNPs increase the expression of CNPase, MAG, and MOG at 2 WPI. At 3 WPI, we found that the EGF–GNPs treatment improves motor coordination and increases MAG, MOG, and MBP. EGF–GNPs enhance the expression of myelin-associated proteins and improve the motor coordination in mice. Thus, EGF-associated GNPs may be a promising pharmacological vehicle for delivering long-lasting drugs into the brain.S/

Caracterización de la logística en la cadena de suministro de cosméticos y productos de aseo

The sector of cosmetics and toiletries is a world class sector, consolidated in Colombia with 690 companies of which 420 are in Bogotá D.C. Taking into account that logistics management generates competitive advantage in organizations as factor of success in a global economy, this paper proposes a logistics analysis applied to the case of cosmetics and toiletries supply chain. The results include the diagnosis of logistics processes and resources, which they were studied with an own methodology proposal. The methodology allowed study the logistics factors and variables, elements that recognized the logistical behaviour in the different links of the supply chain.El sector de cosméticos y productos de aseo de talla mundial, consolidado en Colombia con 690 empresas de las cuales 420 se encuentran en Bogotá, D.C. Al considerar que la gestión logística genera ventaja competitiva en las organizaciones como factor de éxito en una economía globalizada, este artículo presenta una propuesta metodológica, que permite estudiar factores y variables logísticas, elementos que identifican el comportamiento de la cadena de suministro en los diferentes eslabones, la cual es aplicada al caso de la cadena de suministro de cosméticos y productos de aseo. El resultado incluye el diagnóstico de los procesos logísticos y recursos.

Added Value of Transluminal Attenuation Gradient to Qualitative CCTA Ischemia Detection as Determined by N-13-ammonia PET Quantitative Myocardial Perfusion

Transluminal attenuation gradient (TAG) represents the slope of intraluminal contrast that decreases along a coronary vessel during coronary computed tomography angiography (CCTA). The aim of this study was to determine the added value of TAG to qualitative CCTA assessment of significant stenosis (>50%) detecting ischemia as determined by stress myocardial blood flow (MBF) or myocardial flow reserve (MFR) measured by positron emission tomography (PET). Individual contributions of TAG, qualitative assessment and the impact of calcium score were also investigated. METHODS: We studied 38 consecutive patients that were referred due to suspected or known coronary artery disease (CAD). All patients underwent a two-phase hybrid 13N-ammonia PET/CT and CCTA. RESULTS: TAG and presence of qualitatively assessed significant stenosis, but not calcium score, were associated with stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). The area under the curves (AUC) of the linear predictor model including qualitative assessment and TAG was superior to the AUC of separate qualitative assessment or TAG for the detection of ischemia according to stress MBF (AUCs were: 88% vs. 79% and 77%; p = 0.01 and p = 0.01, respectively). CONCLUSIONS: TAG combined with qualitative CCTA assessment improved ischemia detection