Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient Mice

The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning.

Cortistain is expressed in a distinct subset of cortical interneurons

Cortistatin is a presumptive neuropeptide that shares 11 of its 14 amino acids with somatostatin. In contrast to somatostatin, administration of cortistatin into the rat brain ventricles specifically enhances slow wave sleep, apparently by antagonizing the effects of acetylcholine on cortical excitability. Here we show that preprocortistatin mRNA is expressed in a subset of GABAergic cells in the cortex and hippocampus that partially overlap with those containing somatostatin. A significant percentage of cortistatin-positive neurons is also positive for parvalbumin. In contrast, no colocalization was found between cortistatin and calretinin, cholecystokinin, or vasoactive intestinal peptide. During development there is a transient increase in cortistatin-expressing cells in the second postnatal week in all cortical areas and in the dentate gyrus. A transient expression of preprocortistatin mRNA in the hilar region at P16 is paralleled by electrophysiological changes in dentate granule cells. Together, these observations suggest mechanisms by which cortistatin may regulate cortical activity.

Intestinal content detection in capsule endoscopy using robust features

This work covers two aspects. First, it generally compares and summarizes the similarities and differences of state of the art feature detector and descriptor and second it presents a novel approach of detecting intestinal content (in particular bubbles) in capsule endoscopy images. Feature detectors and descriptors providing invariance to change of perspective, scale, signal-noise-ratio and lighting conditions are important and interesting topics in current research and the number of possible applications seems to be numberless. After analysing a selection of in the literature presented approaches, this work investigates in their suitability for applications information extraction in capsule endoscopy images. Eventually, a very good performing detector of intestinal content in capsule endoscopy images is presented. A accurate detection of intestinal content is crucial for all kinds of machine learning approaches and other analysis on capsule endoscopy studies because they occlude the field of view of the capsule camera and therefore those frames need to be excluded from analysis. As a so called “byproduct” of this investigation a graphical user interface supported Feature Analysis Tool is presented to execute and compare the discussed feature detectors and descriptor on arbitrary images, with configurable parameters and visualized their output. As well the presented bubble classifier is part of this tool and if a ground truth is available (or can also be generated using this tool) a detailed visualization of the validation result will be performed.

Implication of Nerve Growth Factor in intestinal mucosal mast cell activity and colonic motor alterations in a model of ovalbumin-induced gut dysfunction in rats

We determined NGF involvement in MMCs and colonic motor alterations in an ovalbumin (OVA)-induced gut dysfunction model in rats. Animals received OVA (6 weeks), with/without simultaneous K252a (TrkA antagonist) treatment. MMCs, rat mast cell protease II (RMCPII) levels and colonic contractility in vitro were assessed. OVA increased MMC density and RMCPII concentration. Spontaneous contractility was similar in both groups and inhibited by K252a. Carbachol responses were increased by OVA in a K252a-independent manner. NO-synthase inhibition increased spontaneous activity in OVA-treated animals in a K252a-dependent manner. These observations support an involvement of NGF in the functional changes observed in this model.

Impacto de la fatiga en la percepción de salud en la enfermedad inflamatoria intestinal.

La salud de los pacientes con enfermedad inflamatoria intestinal (EII) está afectada por la fatiga, que condiciona una baja calidad de vida. Este estudio administró cuestionarios de calidad de vida y fatiga a 110 pacientes con EII, cuantificando fatiga y correlacionándola con la actividad, se determinó la afectación de la calidad de vida. Los resultados mostraron relación inversa entre fatiga y actividad de EII, con diferencias estadísticamente significativas según brote o remisión de la enfermedad. Las correlaciones entre actividad y fatiga con calidad de vida, fueron negativas. En conclusión, a mayor actividad, mayor fatiga que conlleva peor calidad de vida.

Estudi de l’efecte del tractament amb Adalimumab sobre la microbiota associada a la mucosa intestinal en pacients amb malaltia de Crohn.

La malaltia de Crohn és una malaltia inflamatòria intestinal en la qual s´ha observat que la densitat i la diversitat bacteriana difereixen dels subjectes sans. En els últims anys s’estan emprant tractaments biològics com els anti-TNFα (Adalimumab) de manera alternativa a tractaments ja existents. Els resultats obtinguts després de l’anàlisi de la composició bacteriana de la mucosa intestinal de pacients amb Malaltia de Crohn tractats amb Adalimumab, són esperançadors ja que apunten a una recuperació del patró normal a través de la recuperació d’espècies pròpies de persones sanes i la desaparició d’aquelles més prevalents en malalts de Crohn.

Tractament preoperatori de l’oclusió intestinal amb pròtesis de còlon en malalts amb càncer de còlon no metastàsic

S’evalua la supervivència lliure de progressió i la supervivència global dels pacients amb càncer de còlon que han debutat amb oclusió intestinal i com a primer tractament s’ha col.locat una pròtesis metàl.lica autoexpandible al còlon prèviament a la cirurgia del tumor primari. És un estudi retrospectiu i unicèntric on s’inclouen 45 pacients. Els resultats de l’estudi demostren que el fet de col.locar una pròtesis en la fase aguda de l’oclusió no empitjora el pronòstic a llarg termini d’aquests pacients.

Análisis de la alteración de la permeabilidad intestinal en pacientes con insuficiencia cardiaca aguda o crónica reagudizada.

Análisis de la alteración de la permeabilidad intestinal (P.I.) en pacientes críticos afectos de insuficiencia cardiaca aguda o crónica descompensada empleando la prueba de lactulosa/manitol administrada por vía enteral con recogida de la diuresis siguiente para calcular su ratio. Conclusiones: Existe una alteración funcional aunque no se ha podido relacionar con la gravedad del paciente, una relación entre la alteración y la hipoperfusión sistémica, una asociación entre la mejora de la función intestinal y la supervivencia y una relación entre la elevación de procalcitonina y la alteración de la permeabilidad que explicaría la traslocación bacteriana como fuente de los signos de infección que suelen presentar.

Anemia en la enfermedad inflamatoria intestinal: Prevalencia y factores que influyen.

La anemia es una complicación muy importante de la enfermedad inflamatoria intestinal (EII). Actualmente desconocemos la prevalencia de anemia en los pacientes afectos por dicha enfermedad. Para ello se ha realizado un estudio retrospectivo de revisión del historial clínico de pacientes con EII registrados en la Unidad de Atención Crohn-Colitis, con el objetivo de determinar la prevalencia de anemia en nuestro medio y analizar los factores que influyen en la aparición de la misma. La prevalencia de anemia en la EII en el año 2007 fue del 26,3%. El factor más importante para desarrollarla fue la presencia de actividad clínica.

Conocimiento de la fisiopatología de la Enfermedad Inflamatoria Intestinal a partir del estudio de su incidencia (Departamento de Salud 6 de Valencia).

La Enfermedad Inflamatoria Intestinal (Enfermedad de Crohn,EC; Colitis Ulcerosa,CU; Colitis inclasificable, CI) ha sufrido variaciones de incidencia, su estudio permite conocer los factores fisiopatológicos implicados y tratamientos específicos. Se ha realizado un estudio observacional retrospectivo de los casos diagnosticados de EII en el Departamento de Salud 6 de Valencia relacionando resultados con los obtenidos en España y otros países. La incidencia estandarizada a la población europea, ajustada a sexo y edad fue: 3.89(EC),6.635(CU) y de 2.845(CI). La incidencia de CU fue más elevada que la de EC, excepto en los más jóvenes, superior para CU y CI en hombres.

Influència del tabac en la resposta a azatioprina en malaltia inflamatòria intestinal corticodepenent

Disposem d’evidència sobre la influència negativa del tabac en la malaltia de Crohn i el seu efecte positiu en la Colitis ulcerosa. Per altra banda, no s’ha avaluat una potencial interacció entre el tabaquisme i la resposta a determinats fàrmacs. En el present treball hem avaluat l’eficàcia de les tiopurines en la malaltia inflamatòria intestinal corticodepenent, en relació a l’existència d’hàbit tabàquic a l’inici del tractament i la seva influència en el seguiment dels pacients amb resposta inicial al fàrmac, valorant la necessitat de teràpies de rescat o de tractament quirúrgic durant la seva evolució segons l’hàbit tabàquic.

Respuesta motora intestinal a la sobrecarga de quimo

Els pacients amb crisis suboclusives recurrents o amb símptomes digestius que impideixen mantenir el seu pes normal, en absència d´una causa estructural que justifique els símptomes, poden estar afectes d´un trastorn de la motilitat del budell prim. La manometría gastrointestinal es la tècnica d´ elecció per l´ estudi de la motilidad del tracte gastrointestinal i en aquests pacients pot mostrar patrons aberrants que justifiquin els símptomes. No obstant, la manometría gastrointestinal és una tècnica específica però poc sensible. L´objetiu general d´aquest treball es determinar la resposta motora intestinal a una sobrecàrrega de quimo. Per a això s´estudiarà un grup de subjectes sans i es mesurarà l´ activitat motora del budell prim mitjançant manometría durant la infusió contínua de una solució de nutrients solos o espesats amb un compost no absobible.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Chronic intestinal pseudoobstruction and ophthalmoplegia in a patient with mitochondrial myopathy

A 38 year old woman having chronic intestinal pseudoobstruction associated with mitochondrial myopathy is reported. The clinical and radiographic features suggested the diagnosis of chronic intestinal pseudoobstruction. Muscular atrophy and ophthalmoplegia led to muscle biopsy, which disclosed accumulation of normal and abnormal mitochondria ('ragged red fibres'), characteristic of mitochondrial myopathy.