A study of iNOS and TNF-a participation in the evolution of experimental autoimmune neuritis in Lewis rats

Orientadores: Francesco Langone, Leonilda Maria Barbosa dos SantosTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: A isoforma induzível da sintase do óxido nítrico (iNOS) e o fator de necrose tumoral-alfa (TNF-a) estão envolvidos em processos inflamatórios desmielinizantes como a síndrome de Guillain Barré e seu modelo animal, a neurite experimental auto-imune (EAN). A presença dessas moléculas foi investigada no sistema nervoso periférico de ratos Lewis em diferentes fases da EAN. Raízes nervosas oriundas dos segmentos medulares torácico 12 (T12) a lombar 3 (L3) (raízes adjacentes à intumescência lombar), cauda eqüina e nervos ciáticos foram coletados e processados para dupla imunofluorescência. Paralelamente, esses espécimes foram analisados quanto à desmielinização e degeneração axonal, por meio de histoquímica de Sudan Black e imunofluorescência para neurofilamentos, respectivamente. Todos os animais com EAN apresentaram células inflamatórias com imunorreatividade para iNOS e TNF-a, correspondendo a macrófagos e polimorfonucleares (neutrófilos). Essas células contendo iNOS e TNF-a foram observadas nos ratos Lewis exibindo os primeiros sinais clínicos da EAN. Sua população tornou-se numerosa durante a fase de agravamento do quadro clínico, diminuiu no decorrer da fase de recuperação e não foi observada nos animais clinicamente recuperados. Conforme o estágio da EAN, essas células contendo iNOS e TNF-a foram encontradas nas diferentes regiões nervosas analisadas. No início dos sinais clínicos observou-se algumas células iNOS/TNF-a-imunorreativas em vasos da cauda eqüina e do nervo ciático. Na fase em que os animais apresentaram paraparesia, houve um aumento dessa população celular ao redor de vasos e infiltrados inflamatórios nos gânglios sensitivos, na cauda eqüina e nas raízes nervosas T12-L3. Alterações na bainha de mielina e nos neurofilamentos não foram detectadas. Com a evolução da EAN, os animais desenvolveram paraparesia severa. Nesta fase, numerosas células com imunorreatividade para iNOS e TNF-a distribuíram-se ao redor de infiltrados inflamatórios e no tecido endoneural das raízes espinhais e do nervo ciático. Próximo às regiões de infiltrado, algumas fibras nervosas apresentaram bainha de mielina fragmentada ou mais delgada. Alguns axônios no nervo ciático exibiram imunomarcação dos neurofilamentos menos intensa, fragmentada ou aglomerada. Na fase de recuperação, raras células iNOS/TNF-a-imunorreativas foram encontradas em vasos das raízes nervosas T12-L3 e do nervo ciático. Em algumas raízes da cauda eqüina, essas células foram observadas em maior número. O auge da desmielinização foi verificado no nervo ciático nesse estágio, com a presença de vários fragmentos e ovóides de mielina. Os neurofilamentos imunomarcados, por sua vez, apresentaram-se contínuos, porém mais delgados do que os normais. Na fase de resolução da EAN não foram evidenciadas células duplamente imunorreativas. A bainha de mielina recobrou seu aspecto normal nas raízes nervosas, enquanto que no nervo ciático, bainhas de mielina e neurofilamentos imunomarcados delgados foram observados em meio a bainhas e imunomarcação de neurofilamentos mais grossas. Nossos resultados sugerem uma correlação entre a presença da iNOS e TNF-a nas diferentes regiões nervosas e os sinais clínicos exibidos pelo animal com EAN. Além disso, o acentuado processo desmielinizante que ocorre no nervo ciático é capaz de promover alterações estruturais nos neurofilamentos, provavelmente afetando o funcionamento normal dos axôniosAbstract:Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-a) are involved in inflammatory processes such as Guillain Barré Syndrome and its animal model, Experimental Autoimmune Neuritis (EAN). In this study, the presence of these molecules was investigated in the peripheral nervous systems of Lewis rats at different stages of EAN. Thoracic 12 (T12) to lumbar 3 (L3) spinal roots adjacent to lumbar intumescence, cauda equina and sciatic nerves were obtained and processed for double immunofluorescence. These specimens were also analyzed for myelin and axonal degeneration using Sudan Black histochemistry and neurofilament immunolabelling, respectively. All the immunized animals showed double iNOS and TNF-a immunoreactivity in inflammatory cells such as macrophages and polymorphonuclears (neutrophils). These cells were observed in Lewis rats exhibiting the first clinical signs of EAN. Their population increased during the worsening of the disease, diminished during the recovery phase and had disappeared completely in clinically recovered rats. Depending on the EAN phase, iNOS and TNF-a bearing cells were found in the different regions of peripheral nervous system analyzed. At the onset of clinical signs, some iNOS and TNF-a immunoreactive cells were observed in vessels of the cauda equina and the sciatic nerve. In mildly paraparetic rats, an increase in the amount of these cells around vessels and inflammatory infiltrates in the dorsal root ganglia, cauda equina and T12-L3 spinal roots was observed. Changes in the myelin sheath and neurofilaments were not detected. As the EAN evolved, the rats developed severe paraparesis. At this stage, numerous iNOS and TNF-a bearing cells were observed around inflammatory infiltrates and in the endoneurium of the spinal roots and the sciatic nerve. Some nerve fibers near to infiltrated regions showed a thinner or even fragmented myelin sheath. Some sciatic nerve axons exhibited a less intense, fragmented or clustered neurofilament immunolabelling. During recovery stage, rare iNOS/TNF-a immunoreactive cells were detected in vessels of T12-L3 spinal roots and the sciatic nerve. An increased number of these cells was observed in some nerve fibers of cauda equina. The peak stage of demyelination was verified in the sciatic nerve by the presence of several myelin ovoids. Neurofilaments showed continuous immunolabelling, but were more slender than the neurofilaments in naïve rats. Double-immunoreactive cells were not evidenced during the recovery stage. In nerve roots, the myelin sheath recovered its normal appearance, while in sciatic nerves, slenderer myelin sheaths and immunolabelled neurofilaments were observed among thicker ones. Our results suggest that there is a close association between the presence of iNOS and TNF-a bearing cells in the various regions of the peripheral nervous system and the clinical signs exhibited by the animals. Furthermore, the acute demyelinating process in sciatic nerves also promotes structural changes, probably affecting the normal functioning of axonsDoutoradoBiologia CelularDoutor em Biologia Celular e Estrutura

Costo de infección de vías urinarias asociada a sonda vesical en un hospital universitario de Santander, Colombia

Objetivo Estimar el exceso de costos de la infección de vías urinarias asociada al uso de catéter y las intervenciones clínicas que más influyen en los costos.Métodos Se realizó un estudio de cohortes pareadas por tiempo de aparición del evento nosocomial. Los expuestos fueron pacientes con infección de vías urinarias asociada a catéter, y los no expuestos, pacientes sin infección nosocomial, con diagnóstico de ingreso similar al expuesto. En las dos cohortes se evaluaron los costos directos de atención hospitalaria.Resultados El exceso de costo total de atención de una Infección de vías urinarias asociada a catéter fue de $2 460 168 pesos colombianos para 2009. El mayor porcentaje fue atribuido a los días de hospitalización en sala general con un 71,8$2 460 168,9 pesos (1 329 dólares de 2009)

Iron-binding properties of sugar cane yeast peptides

AbstractThe extract of sugar-cane yeast (Saccharomyces cerevisiae) was enzymatically hydrolysed by Alcalase, Protex or Viscozyme. Hydrolysates were fractionated using a membrane ultrafiltration system and peptides smaller than 5kDa were evaluated for iron chelating ability through measurements of iron solubility, binding capacity and dialyzability. Iron-chelating peptides were isolated using immobilized metal affinity chromatography (IMAC). They showed higher content of His, Lys, and Arg than the original hydrolysates. In spite of poor iron solubility, hydrolysates of Viscozyme provided higher iron dialyzability than those of other enzymes. This means that more chelates of iron or complexes were formed and these kept the iron stable during simulated gastro-intestinal digestion in vitro, improving its dialyzability

Costo de neumonía nosocomial no asociada a ventilación en el hospital universitario de santander, 2007-2009

Objetivo Estimar el exceso de costos asociado a neumonía nosocomial no asociada a ventilación mecánica y las intervenciones clínicas que más influyen en él.Métodos Se realizó un estudio de cohortes pareadas por tiempo de aparición del evento nosocomial. Los expuestos fueron pacientes con neumonía nosocomial y los no expuestos pacientes sin infección nosocomial, con diagnóstico de ingreso similar al expuesto. El principal resultado evaluado en las dos cohortes fueron los costos directos de atención hospitalaria.Resultados El exceso de costo total de atención de una neumonía nosocomial no asociada ventilación fue de $7 771 583,50 (4 200 dólares de 2009). Los días de hospitalización en unidad de cuidado intensivo correspondieron al 39$2 980 000), los antibióticos aportaron el 33,7 % (mediana $2 571 953,60), la hospitalización en sala general el 19$1 473 760), y las valoraciones diarias 4,9 % (mediana $379 937,90). Las demás variables contribuyeron más o menos 1$7 771 583,50 pesos (4 200,80 dólares de 2009)

La imagen y la narrativa como herramienta para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena

Se considera violencia el uso de la fuerza física para causar daño a otra persona con el fin de lograr un objetivo. Actualmente existen diversos tipos de violencia en diferentes contextos, el presente artículo, se enmarcará en el conflicto armado, violencia sexual, violencia física y violencia basada en género, todas estas como consecuencia a la problemática del conflicto armado o grupos ilegales. En los últimos dos siglos, Colombia ha experimentado múltiples incidentes de violencia, causando daño psicosocial irreparable en el tejido familiar y social del individuo y la comunidad, sin embargo, se evidencia la resiliencia de estas poblaciones, buscan la manera de transformar la realidad que les tocó vivir y presenciar en sus territorios. Conocer la perspectiva que tienen las víctimas, acerca de los procesos estratégicos que se implementan mediante leyes es de gran importancia; saber que consideraciones tienen ellos acerca de las posibles soluciones que buscan mejorar la calidad de vida. Las condiciones particulares del conflicto en Colombia demandan, la creatividad para la formulación de mecanismos de justicia que permitan la defensa y promoción de los derechos de las víctimas y, de ninguna manera, la mera postergación de esta agenda en nombre de circunstancias particulares. Uribe, M (2009) p.8 Las múltiples estrategias que se aplican en la actualidad han contribuido a que los afectados tengan un mayor interés en participar en los programas de construcción de memoria colectiva para ellos es muy importante ser escuchados y comprendidos.Violence is considered the use of physical force to cause harm to another person in order to achieve an objective. Currently we manage to visualize various types of violence in different contexts every day, but, in this article, we are going to focus on the armed conflict, sexual violence, physical violence and gender-based violence, all of these as a consequence of the problem of armed conflict or illegal groups. In the last two centuries, our country has experienced multiple incidents of violence. All this violence causes irreparable psychosocial damage to the family and social fabric of these communities, however, these communities are very resilient and every day they look for a way to transform that reality that they had to live and witness in their territories. Knowing the thinking of the affected people about the strategies that are implemented through laws is of great importance, knowing what consideration they have about those possible solutions that seek to improve the quality of life of the victims. The particular conditions of the conflict in Colombia demand creativity for the formulation of justice mechanisms that allow the defense and promotion of the rights of victims and, in no way, the mere postponement of this agenda." in the name of particular circumstances. Uribe, M (2009) (p.8) The multiple strategies that are currently applied have contributed to those affected having a greater interest in participating in programs for the construction of collective memory. For them, it is very important to be heard and understood

Strengthening reading competence supported by the use of Information and Communication Technologies

La presente investigación surge de la problemática que se evidencia, en cuanto a la adquisición y desarrollo de las competencias lectoras en los estudiantes, teniendo en cuenta los bajos resultados obtenidos en las pruebas internas y externas que se aplican a los estudiantes de la Institución. El objetivo de la investigación corresponde a fortalecer la comprensión lectora de los estudiantes de la Institución Educativa Departamental de Guáimaro Magdalena, mediante la lúdica apoyada en las Tecnologías de la Información y Comunicación. La investigación se basa en una metodología cualitativa, empleando técnicas como la observación, la encuesta y la prueba diagnóstica. Los resultados obtenidos demuestran que la articulación de las TIC dentro del contexto educativo es de vital importante no sólo desde una perspectiva didáctica sino también como dinamizadora del quehacer pedagógico.A través del proceso investigativo y dando respuesta al objetivo general en cual se busca impulsar la comprensión lectora a través del uso de herramientas tecnológicas.The present investigation arises from the problematic that is evidenced, in terms of the acquisition and development of the reading competences in the students, taking into account the low results obtained in the internal and external tests that are applied to the students of the Institution. The objective of the research corresponds to strengthen the reading comprehension of the students of the Departmental Educational Institution of Guáimaro Magdalena, through the ludic supported on ICT. The research is based on a qualitative methodology, using techniques such as observation, the survey and the diagnostic test. The results show that the articulation of ICT within the educational context is vitally important not only from a didactic perspective but also as a catalyst for pedagogical work. Through the investigative process and responding to the general objective in which it seeks to promote understanding reader through the use of technological tools

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements