Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Background and aims: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. Patients and methods: Serum PAP levels were determined in healthy controls (n¿=¿29), inflammatory controls (n¿=¿14), and IBD patients (n¿=¿171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor ¿B (NF¿B) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. Results: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn¿s disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-¿ induced NF¿B activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. Conclusions: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NF¿B activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.

Arva: prospecciones en un centro productor de ánforas Dressel 20 (Alcolea del Río, Sevilla)

La campaña de excavación realizada en 1991 en las proximidades de sector termal de la ciudad romana de Arva (Alco1ea del Río, Sevilla) ha permitido localizar tres hornos dedicados a la producción de ánforas Dressel20. Uno de ellos se data en época flavio-trajanea; los dos restantes se sitúan en un momento post-severiano. El conjunto parece formar parte del sector artesanal de Arva, situado junto al Guadalquivir.

Nuevo epígrafe métrico de Lora del Río (Sevilla)

El presente articulo edita por primera vez y comenta brevemente una inscripci6n métrica latina encontrada en Lora del Río (Sevilla)

Roman amphora trade across the Straits of Gibraltar: An ancient 'anti-economic practice'?

Summary. Olive oil and fish products from the south of Hispania and North Africa played an important role in the Roman economy. The authors call attention to the asymmetrical distribution of archaeological data available on this subject, in particular the location of amphora kilns, and try to give an explanation, based on the evolution of European archaeology in the twentieth century.

Arva: Prospección en un centro productor de ánforas Dressel 20 (Alcolea del Río, Sevilla)

La campaña de excavación realizada en 1991 en las proximidades de sector termal de la ciudad romana de Arva (Alco1ea del Río, Sevilla) ha permitido localizar tres hornos dedicados a la producción de ánforas Dressel20. Uno de ellos se data en época flavio-trajanea; los dos restantes se sitúan en un momento post-severiano. El conjunto parece formar parte del sector artesanal de Arva, situado junto al Guadalquivir.

El profesor Juan Maluquer de Motes y la investigación protohistórica en el curso inferior del río Ebro

La publicación en 1954 y 1958 de los Estudios Críticos 1 y JI dedicados al poblado de la primera Edad del Hierro del Alto de la Cruz (Cortes de Navarra) supuso, sin ningún género de dudas, el arranque de la sistematización de la secuencia cultural y poblacional del área del valle medio del Ebro en el período correspondiente al Bronce Final y las fases más antiguas de la Edad del Hierro.

Detección por el satélite LANDSAT-4 de los efectos de la riada del 8-XI-82 en el río Segre

Por medio de técnicas de tratamiento de imágenes digitales se realiza un estudio de los efectos producidos por una inundación ocurrida a finales del año 1982 en el valle del río Segre, en Catalunya, a partir de la información multiespectral captada por el sensor TM del satélite LANDSAT-4. Utilizando un programa de clasificación no supervisada basado en la distancia euclídea, se diferencian cuatro tipos de suelo o de cubiertas en el rea de estudio (3.8 x 2.3 km). Se efecta un análisis cuantitativo de la calidad de los resultados, usando como referencia la información obtenida en un estudio de campo. Este análisis muestra un alto grado de correspondencia entre el mapa de campo (verdad terreno) y la cartografía realizada a partir de los datos multiespectrales.

Estudio tectónico del Paleozoico inferior del Pirineo entre la Cerdaña y el río Ter (resumen)

El análisis estructural del domo del río Freser (Pirineos Orientales, España) permite poner de manifiesto una sucesión de tres fases de plegamiento hercinianas. Se describen las características de las mismas y se comparan con las descritas por otros autores en regiones vecinas.

Mineralogía y elementos pesados de 1os sedimentos actuales del río Llobregat (Barcelona

El objetivo del presente trabajo es la adquisición de conocimientos previos acerca de la evolución mineralógica y de la distribución de elementos pesados en 1os sedimentos actuales del rio Llobregat (Barcelona, España). El análisis mineralógico se ha realizado por difracción de rayos X. Las concentraciones de Ba, Pb, Cr, Cu, Ni, Rb, Sr y Zn han sido determinadas por medio de espectrometria de fluorescencia de rayos X. Los resultados obtenidos permiten apreciar un marcado aumento del contenido en elementos pesados hacia el curso bajo el rio atribuible al mayor grado de contaminación. Pb y Cu presentan una notable relación en su comportamiento geoquímico mientras que otros elementos contaminantes como Zn y Cr, con notable aumento en la desembocadura del rio, siguen una distinta dinámica de reparto.

Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2 cell line was observed. Based on these results we developed 5C3, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.