7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's disease

Neuronal nitric oxide synthase (nNOS) is involved in the regulation of diverse intracellular messenger systems in the brain. Nitric Oxide (NO) contributes to inducing signaling cascades that involve a complex pattern of phosphorylation of DARPP-32 (in Thr-34), which controls the phosphoproteins involved in neuronal activation. However, the role of NO in the pathophysiology of Parkinson's disease (PD) and its effect in striatal neurons have been scarcely explored. In the present work, we investigate the effects of a nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI) in the nigrostriatal pathway of striatal 6-hydroxydopamine (6-OHDA) lesioned rats. Our quantitative histological findings show that treatment with 7-NI significantly reduced 6-OHDA-induced dopaminergic damage in the dorsolateral striatum and Substantia Nigra pars compacta (SNpc). Moreover, 6-OHDA lesioned rats show a significant increase of nNOS+ and Phospho-Thr34-DARPP-32+ cells, accompanied by a consequent decrease of total DARPP-32+ cells, which suggests an imbalance of NO activity in the DA-depleted striatum, which is also reflected in behavioral studies. Importantly, these effects are reverted in the group treated with 7-NI. These results show a clear link between the state of phosphorylation of DARPP-32 and parkinsonism, which is regulated by nNOS. This new evidence suggests a prominent role for nitric oxide in the neurotransmitter balance within the basal ganglia in the pathophysiology of experimental parkinsonism.This work was supported by grants from the Spanish Ministry of Science (SAF 2007-62262), FIS (PI/2010/02827) and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)

Persistent phagocytic characteristics of microglia in the substantia nigra of long-term Parkinsonian macaques

Patients with Parkinson's disease show persistent microglial activation in the areas of the brain where the degeneration of dopaminergic neurons takes place. The reason for maintaining this activated state is still unknown, but it is thought that this persistent microglial activation may contribute to the degeneration of dopaminergic neurons. In this study, we report the microanatomical details of microglia and the relationship between microglia and neurons in the substantia nigra pars compacta of Parkinsonian monkeys years after insult with MPTP. We observed that microglial cells appear polarized toward dopaminergic neurons in MPTP-treated macaques compared to untreated animals and present clear phagocytic characteristics, such as engulfing gliaptic contacts, an increase in Golgi apparatus protein machinery and ball-and-chain phagocytic buds. These results demonstrate that activated microglia maintain phagocytic characteristics years after neurotoxin insult, and phagocytosis may be a key contributor to the neurodegenerative process

CCL2-Expressing Astrocytes Mediate the Extravasation of T Lymphocytes in the Brain. Evidence from Patients with Glioma and Experimental Models In Vivo

CCL2 is a chemokine involved in brain inflammation, but the way in which it contributes to the entrance of lymphocytes in the parenchyma is unclear. Imaging of the cell type responsible for this task and details on how the process takes place in vivo remain elusive. Herein, we analyze the cell type that overexpresses CCL2 in multiple scenarios of T-cell infiltration in the brain and in three different species. We observe that CCL2+ astrocytes play a part in the infiltration of T-cells in the brain and our analysis shows that the contact of T-cells with perivascular astrocytes occurs, suggesting that may be an important event for lymphocyte extravasation

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson’s disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9+ glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism

Comparison of injury severity scores (ISS) obtained by manual coding versus ?Two-step conversion? from ICD-9-CM

Background: The International Classification of Diseases (ICD) is the standard diagnostic tool for classifying and coding diseases and injuries. The Abbreviated Injury Scale (AIS) is the most widely used injury severity scoring system. Although manual coding is considered the gold standard, it is sometimes unavailable or impractical. There have been many prior attempts to develop programs for the automated conversion of ICD rubrics into AIS codes. Objective: To convert ICD, Ninth Revision, Clinical Modification (ICD-9-CM) codes into AIS 2005 (update 2008) codes via a derived map using a two-step process and, subsequently, to compare Injury Severity Score (ISS) resulting from said conversion with manually coded ISS values. Methods: A cross-sectional retrospective study was designed in which medical records at the Hospital Universitario Marqués de Valdecilla of Cantabria (HUMV) and the Complejo Hospitalario of Navarra (CHN), both in Spain, were reviewed. Coding of injuries using AIS 2005 (update 2008) version was done manually by a certified AIS specialist and ISS values were calculated. ICD-9-CM codes were automatically converted into ISS values by another certified AIS specialist in a two-step process. ISS scores obtained from manual coding were compared to those obtained through this conversion process. Results: The comparison of obtained through conversion versus manual ISS resulted in 396 concordant pairs (70.2%); the analysis of values according to ISS categories (ISS24) showed 493 concordant pairs (87.4%). Regarding the criterion of ?major trauma? patient (i.e., ISS> 15), 538 matching pairs (95.2%) were obtained. The conversion process resulted in underestimation of ISS in 112 cases (19.9%) and conversion was not possible in 136 cases (19%) for different reasons. Conclusions: The process used in this study has proven to be a useful tool for selecting patients who meet the ISS>15 criterion for ?major trauma?. Further research is needed to improve the conversion process

Pulsed light for a cleaner dyeing industry: azo dye degradation by an advanced oxidation process driven by pulsed light

Water pollution by wastewater containing dyes is an environmental issue that can be mitigated by the use of advanced oxidation processes (AOP). Pulsed light (PL) is an emerging food processing technology that uses eco-friendly lamps and can potentially be adapted as light source of an UV-based AOP. In the present work, a PL/H2O2 process was tested for the decolourization of two azo dyes, and a pulsed light/H2O2/ferrioxalate process was tested for the decolourization of one azo dye. The efficiency of the PL/H2O2 process in a batch reactor under different parametric values: dye concentration, pH, H2O2 and salt doses was followed by spectrophotometry and fitted to first-order kinetics; and several degradation products were detected. In the PL/H2O2 process, decolourization rates increased at low dye concentrations and high H2O2 doses, were pH-dependent and were inhibited by the addition of NaCl, Na2SO3 or Na2CO3. More than 50 % decolouration was achieved with the PL/H2O2 process for both dyes after applying 54 J/cm2 (25 light pulses). The PL/H2O2/ferrioxalate process achieved > 95 % decolouration for Methyl orange when applying 21 J/cm2 (10 pulses); that level of energy can be supplied by PL commercial systems in nine and four seconds respectively. No known toxic degradation products were detected. Results show that a PL/H2O2 process has potential to be used for the efficient degradation of dyes from wastewater. Furthermore, the efficacy of this process can be improved by the use of ferrioxalate. PL technology could become an alternative light source to contribute to decrease the environmental impact of wastewater produced by the dyeing industry.Ciencias de la Alimentació

Enfoques metodológicos en el proceso de enseñanza-aprendizaje de la revisión de traducciones

Se presenta la memoria del Proyecto de Innovación docente sobre actividades y métodos para enseñar a los estudiantes de Traducción e Interpretación a auto revisar y corregir sus traducciones

Inclusión de la perspectiva de género en las asignaturas de Didáctica

El profesorado de la Facultad de Educación de la Universidad de Alicante somos conscientes de la responsabilidad de integrar la perspectiva de género en la docencia universitaria si no queremos seguir transmitiendo conocimiento científico y usos sociales que perpetúen las injusticias de una socialización por géneros; con el añadido de saber que nuestro alumnado universitario es además el futuro personal docente de etapas educativas preuniversitarias. Nos integramos como Red de Innovación en Docencia Universitaria a tal efecto, y en esta primera edición hemos empezado por el análisis de las Guías Docentes de nuestras asignaturas. A tal efecto hemos diseñado un sencillo instrumento de análisis, que nos ha permitido analizar la presencia o no de objetivos y/o contenidos específicamente coeducativos, el uso o no de un lenguaje inclusivo en las guías, y el sexo de las autoras y autores de las referencias recomendadas en las asignaturas. Los resultados muestran la escasa integración de la perspectiva de género a través de alguno de dichos elementos, la necesidad de reparar esta situación, y nos animan a analizar con perspectiva de género otros aspectos de nuestra docencia universitaria en futuras ediciones de las Redes ICE

Educar para la transparencia y una ciudadanía informada: diseño, aplicación y evaluación del programa IRIS para alumnado de Bachillerato de la Región de Murcia (España)

In order to develop a validated model to teach key conceptsand values on the right to information and transparency to young people, the "IRIS" program was designed during the 2017-2018 academic year, which was applied as part of the "Philosophy" course of the First Year of High School students of six Secondary Education Institutes of five municipalities of the Region of Murcia. Its objectives were: a) Prepare and teach a Learning Unit on Transparency and Right to Information, in accordance with the standards of the Philosophy curriculum of the Region of Murcia. b) Identify initial perceptions of the students of the Region regarding concepts as Transparency and Open Government. c) Design a Contest on dissertations and videos on transparency and good governance, aimed at the students participating in the project. e) Evaluate results and identify recommendations to improve the program. After the evaluation we concluded that objectives had been achieved, and have proposed some recommendations to generalize and consolidate the acquisition of this citizen competence: a specific training plan for teachers, the inclusion of this standard on transparency in the autonomic curriculum, and that is necessary to develop a set of materials, texts and practical tasks to make easier the application to the teaching staff

Educar para la transparencia y una ciudadanía informada: diseño, aplicación y evaluación del programa IRIS para alumnado de Bachillerato de la Región de Murcia (España)

In order to develop a validated model to teach key conceptsand values on the right to information and transparency to young people, the "IRIS" program was designed during the 2017-2018 academic year, which was applied as part of the "Philosophy" course of the First Year of High School students of six Secondary Education Institutes of five municipalities of the Region of Murcia. Its objectives were: a) Prepare and teach a Learning Unit on Transparency and Right to Information, in accordance with the standards of the Philosophy curriculum of the Region of Murcia. b) Identify initial perceptions of the students of the Region regarding concepts as Transparency and Open Government. c) Design a Contest on dissertations and videos on transparency and good governance, aimed at the students participating in the project. e) Evaluate results and identify recommendations to improve the program. After the evaluation we concluded that objectives had been achieved, and have proposed some recommendations to generalize and consolidate the acquisition of this citizen competence: a specific training plan for teachers, the inclusion of this standard on transparency in the autonomic curriculum, and that is necessary to develop a set of materials, texts and practical tasks to make easier the application to the teaching staff