Altered Mechanisms Underlying the Abnormal Glutamate Release in Amyotrophic Lateral Sclerosis at a Pre-Symptomatic Stage of the Disease.

Abnormal Glu release occurs in the spinal cord of SOD1(G93A) mice, a transgenic animal model for human ALS. Here we studied the mechanisms underlying Glu release in spinal cord nerve terminals of SOD1(G93A) mice at a pre-symptomatic disease stage (30days) and found that the basal release of Glu was more elevated in SOD1(G93A) with respect to SOD1 mice, and that the surplus of release relies on synaptic vesicle exocytosis. Exposure to high KCl or ionomycin provoked Ca(2+)-dependent Glu release that was likewise augmented in SOD1(G93A) mice. Equally, the Ca(2+)-independent hypertonic sucrose-induced Glu release was abnormally elevated in SOD1(G93A) mice. Also in this case, the surplus of Glu release was exocytotic in nature. We could determine elevated cytosolic Ca(2+) levels, increased phosphorylation of Synapsin-I, which was causally related to the abnormal Glu release measured in spinal cord synaptosomes of pre-symptomatic SOD1(G93A) mice, and increased phosphorylation of glycogen synthase kinase-3 at the inhibitory sites, an event that favours SNARE protein assembly. Western blot experiments revealed an increased number of SNARE protein complexes at the nerve terminal membrane, with no changes of the three SNARE proteins and increased expression of synaptotagmin-1 and \u3b2-Actin, but not of an array of other release-related presynaptic proteins. These results indicate that the abnormal exocytotic Glu release in spinal cord of pre-symptomatic SOD1(G93A) mice is mainly based on the increased size of the readily releasable pool of vesicles and release facilitation, supported by plastic changes of specific presynaptic mechanism

Restoration by ketamine of stress-induced maladaptive changes in synaptic function and brain architecture

n/

Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab

Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. Objective: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. Methods: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. Results: According to the criteria, 39–52% of patients experienced complete remission in the first year, increasing to 51–73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Conclusions: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission

Diabetes mellitus: el desafío periodontal, sistémico y oclusal en la resolución de un caso

Introducción: Paciente de 57 años concurre desde el año 2010 a la Asignatura de Periodoncia “A” de la Facultad de Odontología de la U.N.L.P. En 2016, sufre una descompensación glucémica, traduciéndose en un cuadro periodontal con abscesos periodontales, pérdida de piezas dentarias, y movilidad grado II y III en la mayoría de sus piezas. Objetivos: Rehabilitar estética, fonética y masticatoriamente a un paciente diabético con periodontitis crónica severa generalizada, realizando un tratamiento periodontal y una posterior confección e instalación protética.Facultad de Odontologí

Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways

<p>Abstract</p> <p>Background</p> <p>Agomelatine is a melatonergic receptor agonist and a 5HT_2Creceptor antagonist that has shown antidepressant efficacy. In order to analyze separately the effect of the two receptorial components, rats were chronically treated with agomelatine, melatonin (endogenous melatonergic agonist), or S32006 (5-HT_2Cantagonist), and then subjected to acute footshock-stress.</p> <p>Results</p> <p>Only chronic agomelatine, but not melatonin or S32006, completely prevented the stress-induced increase of glutamate release in the rat prefrontal/frontal cortex.</p> <p>Conclusions</p> <p>These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.</p

Knocking down metabotropic glutamate receptor 1 improves survival and disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1G93A), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1G93A background (SOD1G93AGrm1crv4/+), by crossing the SOD1G93A mutant mouse with the Grm1crv4/+ mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1G93AGrm1crv4/+ mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1G93A mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1G93AGrm1crv4/+compared to SOD1G93A mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors

Prevalencia del canal MB2 en molares superiores

Introducción: Es indispensable conocer en detalle la anatomía radicular interna de los molares superiores debido a la presencia de un segundo conducto mesiobucal para asegurar el éxito del tratamiento endodóntico. Objetivo General: Conocimiento de la anatomía dentaria para arribar un eficaz tratamiento. Objetivo Específico: Localización e instrumentación del conducto MB2 en molares superiores.Facultad de Odontologí

Biosecurity In Rural Areas

Introducción El Protocolo de Bioseguridad del Voluntariado FOLP tiene como finalidad reducir el riesgo de transmisión de enfermedades infectocontagiosas a través de la sangre, secreciones orales y/o respiratorias desde el paciente hacia los profesionales y colaboradores, de estos al paciente y entre pacientes del servicio odontológico Objetivos Establecer las medidas de prevención para evitar las enfermedades de riesgo profesional y la infección cruzada entre el profesional odontólogo, personal auxiliar, pacientes. Establecer la conducta a seguir frente a un accidente con exposición a sangre y otros fluidos corporales.Introduction: The FOLP Volunteering Biosecurity Protocol aims to reduce the risk of transmission of infectious diseases through blood, oral and / or respiratory secretions from the patient to professionals and collaborators, from these to the patient and between patients of the dental service Aim To establish the preventive measures to avoid the diseases of professional risk and the crossed infection between the professional dentist, auxiliary personnel, patients. Establish the behaviour to follow in the event of an accident with exposure to blood and other body fluids.Facultad de Odontologí

Single-Cell Redox Imaging Demonstrates a Distinctive Response of Dopaminergic Neurons to Oxidative Insults

Producción CientíficaAims: The study of the intracellular oxido-reductive (redox) state is of extreme relevance to the dopamine (DA) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production, and they selectively degenerate in Parkinson's disease under oxidative stress conditions. To test the hypothesis that these cells display a unique redox response to mild, physiologically relevant oxidative insults when compared with other neuronal populations, we sought to develop a novel method for quantitatively assessing mild variations in intracellular redox state. Results: We have developed a new imaging strategy to study redox variations in single cells, which is sensitive enough to detect changes within the physiological range. We studied DA neurons' physiological redox response in biological systems of increasing complexity--from primary cultures to zebrafish larvae, to mammalian brains-and identified a redox response that is distinctive for substantia nigra pars compacta DA neurons. We studied simultaneously, and in the same cells, redox state and signaling activation and found that these phenomena are synchronized. Innovation: The redox histochemistry method we have developed allows for sensitive quantification of intracellular redox state in situ. As this method is compatible with traditional immunohistochemical techniques, it can be applied to diverse settings to investigate, in theory, any cell type of interest. Conclusion: Although the technique we have developed is of general interest, these findings provide insights into the biology of DA neurons in health and disease and may have implications for therapeutic intervention

Multiplicar es salud

Introducción: El agente multiplicador de salud tiene como fin, asegurar que la educación para la salud bucal sea de forma constante y duradera, sin la necesidad de la presencia del equipo de trabajo de esa escuela. A través de los agentes multiplicadores de salud logramos un constante incentivo a la incorporación del hábito de higiene oral, como así también un control y evaluación constante y permanente de la salud bucal y la posibilidad de reforzar esa motivación. Por eso es de suma importancia que el docente, director, padre o tutor esté presente. Objetivos: Identificar al líder comunitario, el cual debe tener contacto directo con la comunidad afectada por el programa. Capacitar al líder y proveerlo de cepillos y pasta dental, flúor, y material didáctico. Instalar conciencia y compromiso sobre la salud individual y comunitaria. Promover la prevención en la comunidad Metodología: Charlas educativas sobre prevención de la salud en grupos reducidos de niños de edad escolar y sus respectivos maestros; Uso de material didáctico para fijar de mejor manera el concepto de salud; Concientizar respecto a la acción de los alimentos en relación a la caries, racionalización de la dieta e indicación de posibles sustitutos, adaptándose a características y costumbres de cada comunidad en particular; Interiorizar el concepto de responsabilidad sobre la tarea asignada. Resultados: A través de los agentes multiplicadores de salud logramos un constante incentivo a la incorporación del hábito de higiene oral, como así también un control y evaluación constante y permanente de la salud bucal; y la posibilidad de reforzar esta motivación. Su tarea es fundamental, manteniendo los niveles de salud y disminuyendo el riesgo a contraer enfermedades bucodentales. Conclusiones: Existen mejorías años tras año en las bocas de los niños, gracias al compromiso asumido por los agentes multiplicadores de salud. La incidencia de los mismos sobre la comunidad resulta de fundamental importancia para mantener los hábitos de higiene oral. De tal manera, tiene vital importancia en el resultado mediato del programa de salud.Facultad de Odontologí