Tres nuevos asentamientos altomedievales en la provincia de Madrid

Recientemente se han excavado tres nuevos asentamientos de carácter rural y época altomedieval en la provincia de Madrid. En todos los casos se trata de excavaciones de urgencia vinculadas a diversos proyectos de infraestructura. Se presentan los yacimientos de "Monte de la Villa" próximo al río Guadarrama y "Casas de Bahezuela II y III" y "Valdelayegua" en la margen izquierda del río Henares. Las intervenciones arqueológicas realizadas han permitido documentar parcialmente unos asentamientos caracterizados por cabañas de planta rectangular o irregular, de suelo rehundido, asociadas a silos subterráneos, cubetas de diversa morfología y hornos. En "Monte de la Villa" se ha localizado parcialmente la necrópolis asociada. En "Casas de Bahezuela III" la época visigoda presenta dos claros periodos de ocupación: edificios con zócalo de piedra y alzados de tapial se superponen a las cabañas de planta oval o rectangular excavadas en el subsuelo

La fortaleza de Qal‘at ‘Abd as-Salam. La recuperación de una dignidad perdida (Alcalá de Henares, Madrid)

The Muslim founded fortress, placed to the Southwest of Alcalá de Henares (Madrid), has been an archaeological site roughly handled by time and men. After having been firstly excavated and restored, this site was abandoned again until the undertaking of the current reassessment tasks. Excavation and conservation tasks overlap to each other along with previous historiographical studies and analyses of factors of variations and state of preservation. It is thus guaranteed that all these activities make sense and have a clear objective, including the respect to the site and the social display of a fortified enclosure with specific characteristics. These changes do not entail formal additional modifications on behalf of preserving the place. Those building and defensive features of the hill and the surrounding areas are explained considering the social display of a monument thought to be a model of al- Andalus architecture in the Iberian plateau. It is within this idea that it must recover its lost dignity.La fortaleza de fundación musulmana situada al suroeste de Alcalá de Henares (Madrid) ha sido un yacimiento arqueológico maltratado por el tiempo y por el hombre. Tras las primeras intervenciones de excavación y restauración realizadas, fue abandonado de nuevo hasta la puesta en práctica de las obras de revalorización que se realizan en la actualidad. Excavación y conservación se solapan en su ejecución con el apoyo de estudios previos historiográficos y del análisis de los factores de alteración o del estado de conservación. Se garantiza, de esta forma, que las actuaciones tengan un sentido, un objetivo claro donde prime el respeto al yacimiento y la exhibición social de un recinto fortificado con unas características propias que lo definen. Las actuaciones se ejecutan sin ocasionar alteraciones fisionómicas colaterales en nombre de la preservación del lugar. Se presentan dichas características constructivas y defensivas del cerro y del entorno al amparo de su exhibición al público como obra referente de la arquitectura andalusí en la meseta. Como tal debe recuperar su dignidad hasta hoy perdida

Polymeric Nanocapsules for Vaccine Delivery: Influence of the Polymeric Shell on the Interaction With the Immune System

The use of biomaterials and nanosystems in antigen delivery has played a major role in the development of novel vaccine formulations in the last few decades. In an effort to gain a deeper understanding of the interactions between these systems and immunocompetent cells, we describe here a systematic in vitro and in vivo study on three types of polymeric nanocapsules (NCs). These carriers, which contained protamine (PR), polyarginine (PARG), or chitosan (CS) in the external shell, and their corresponding nanoemulsion were prepared, and their main physicochemical properties were characterized. The particles had a mean particle size in the range 250–450 nm and a positive zeta potential (~30–40 mV). The interaction of the nanosystems with different components of the immune system were investigated by measuring cellular uptake, reactive oxygen species production, activation of the complement cascade, cytokine secretion profile, and MAP kinases/nuclear factor κB activation. The results of these in vitro cell experiments showed that the NC formulations that included the arginine-rich polymers (PR and PARG) showed a superior ability to trigger different immune processes. Considering this finding, protamine and polyarginine nanocapsules (PR and PARG NCs) were selected to assess the association of the recombinant hepatitis B surface antigen (rHBsAg) as a model antigen to evaluate their ability to produce a protective immune response in mice. In this case, the results showed that PR NCs elicited higher IgG levels than PARG NCs and that this IgG response was a combination of anti-rHBsAg IgG1/IgG2a. This work highlights the potential of PR NCs for antigen delivery as an alternative to other positively charged nanocarriersThis work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2011-30337-C02-02 and BIO2014-53091-C3-1-R). Financial support from the Xunta de Galicia (Centro singular de investigación de Galicia 2016–2019 and Grupo de referencia competitiva, ED431C 2016041) and the European Union (European Regional Development Fund—ERDF) is gratefully acknowledged. MP acknowledges fellowships from the Spanish Ministry of Education (FPU predoctoral grants program)S

Polymeric nanocapsules for vaccine delivery: influence of the polymeric shell on the interaction with the immune system

The use of biomaterials and nanosystems in antigen delivery has played a major role in the development of novel vaccine formulations in the last few decades. In an effort to gain a deeper understanding of the interactions between these systems and immunocompetent cells, we describe here a systematic in vitro and in vivo study on three types of polymeric nanocapsules (NCs). These carriers, which contained protamine (PR), polyarginine (PARG), or chitosan (CS) in the external shell, and their corresponding nanoemulsion were prepared, and their main physicochemical properties were characterized. The particles had a mean particle size in the range 250-450 nm and a positive zeta potential (~30-40 mV). The interaction of the nanosystems with different components of the immune system were investigated by measuring cellular uptake, reactive oxygen species production, activation of the complement cascade, cytokine secretion profile, and MAP kinases/nuclear factor κB activation. The results of these in vitro cell experiments showed that the NC formulations that included the arginine-rich polymers (PR and PARG) showed a superior ability to trigger different immune processes. Considering this finding, protamine and polyarginine nanocapsules (PR and PARG NCs) were selected to assess the association of the recombinant hepatitis B surface antigen (rHBsAg) as a model antigen to evaluate their ability to produce a protective immune response in mice. In this case, the results showed that PR NCs elicited higher IgG levels than PARG NCs and that this IgG response was a combination of anti-rHBsAg IgG1/IgG2a. This work highlights the potential of PR NCs for antigen delivery as an alternative to other positively charged nanocarriers.Ministerio de Ciencia e Innovación | Ref. SAF2011-30337-C02-02Ministerio de Economía y Competitividad | Ref. BIO2014-53091-C3-1-RXunta de Galicia | Ref. ED431C 201604

Revista de libros

Libros reseñados: * Max Scheler: Amor y conocimiento. Versión castellana de Ansgar Klein. Buenos Aires. Ed. Sur, 1960. Vol. rústica, 186 págs. * Nicola Abbagnano: Filosofía, Religión, Ciencia. Traducción directa de Angel Fausto Di Rissio. Editorial Nova. Buenos Aires, 1961. Vol. rústica, 162 págs. * Fryda Schultz de Mantovani: La mujer en la vida nacional. Ediciones Galatea Nueva Visión, Buenos Aires, 1960, 103 págs. * Carmelo M. Bonnet: La crítica literaria. Editorial Nova. Buenos Aires, 1959. Vol. rústica, 122 págs. * Juan Carlos Ghiano: Los géneros literarios. Editorial Nova. Buenos Aires, 1961. Vol. rústica, 112 págs. * Nórberto Rodríguez Bustamante: La filosofía social de Alberdi. Universidad Nacional de La Plata. Departamento de Filosofía. Instituto de Historia de la Filosofía y del Pensamiento Argentino. Cuaderno de Extensión Universitaria N° 5, 64 págs., La Plata, 1960. * Eduard Spranger: El educador nato. Traducción de Jorge Enrique Rothe. Estudio preliminar de Ricardo Nassif. Kapelusz, Buenos Aires, 1960. Vol. rústica de 38 págs. de prólogo y 96 páginas.Universidad Nacional de La Plat

Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA

Background Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions. Methods We evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR. Results LINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients. Conclusions Hypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Pre-clinical development of cyclodextrin-based nanoparticles for oral delivery of protein/peptide drugs-in vitro and in vivo evaluation

Over the past decades, oral protein delivery has become a major research area for pharmaceutical companies. Ideally, once the protein is orally administered, it should remain stable until it reaches the targeted site of absorption in spite of the myriad of factors that could hinder its stability, such as the harsh environment of the gastrointestinal tract, the possible pre-systemic degradation by enzymes, the wide range of pH and the poor permeability of the intestinal mucosa. The application of nanosystems, specifically cyclodextrin-based nanoparticles (NPs) to overcome these barriers is the focus of this project. The overall goal of this thesis has been to design and develop three different nanoparticle formulations including three different drug cargos, two human insulin analogues (insulin glulisine and Lola insulin) and the GLP-1 analogue named as liraglutide. In the first stage of the preclinical development of these formulations, the fabrication process of the three prototypes containing the different cargos was optimized. The resulting formulations showed suitable physico-chemical properties for an oral administration as well as suitable stability profiles, both upon contact with proteolytic enzymes and as a freeze-dried product. In addition, in vitro and ex vivo were carried out to evaluate the intestinal uptake mechanisms of the formulations. In vitro studies using the Caco-2 cell monolayer model and ex vivo (rat intestinal tissue) studies showed that insulin glulisine NPs enhanced the epithelial permeability of insulin. Lastly, the formulations were assessed in different animal models. Best results were obtained with the insulin glulisine NPs, where progressive and significant reduction in the glucose levels was achieved after the in situ instillation (50 IU/kg) to healthy anaesthetized Wistar rats (≈50 % after 45 minutes maintained up to 4 hours). Overall, the insulin glulisine NPs stands out as the most promising for further development of an effective insulin oral dosage form

Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin

Due to excellent efficacy, low toxicity, and well-defined selectivity, development of new injectable peptides is increasing. However, the translation of these drugs into products for effective oral delivery has been restricted due to poor oral bioavailability. Nanoparticle (NP) formulations have potential to overcome the barriers to oral peptide delivery through protecting the payload and increasing bioavailability. This study describes the rational design, optimization and evaluation of a cyclodextrin-based NP entrapping insulin glulisine for intestinal administration. A cationic amphiphilic cyclodextrin (click propyl-amine cyclodextrin (CD)) was selected as the primary complexing agent for NP development. Following NP synthesis, in vitro characterization was performed. The insulin glulisine NPs exhibited an average size of 109 ± 9 nm, low polydispersity index (0.272) negative zeta potential (−25 ± 3 mV), high association efficiency (71.4 ± 3.37%) and an insulin loading of 10.2%. In addition, the NPs exhibited colloidal stability in intestinal-biorelevant media (SIF, supplemented-SIF 1% (w/v) and FaSSIF-V2) for up to 4 h. Proteolysis studies indicated that the NPs conferred protection to the entrapped insulin relative to free insulin. In vivo rat jejunal instillation studies demonstrated that the NPs mediated systemic insulin absorption, accompanied by a decrease in blood glucose levels. The relative bioavailability of the instilled insulin (50 IU/kg) from the NP was 5.5% compared to subcutaneous administration of insulin solution (1 IU/kg). The pharmacodynamic and pharmacokinetic data indicate that this cyclodextrin-based formulation may have potential for further research as an oral insulin dosage form.European Commission - Seventh Framework Programme (FP7)European TRANS-INT Consortiu

Optimizacion de la produccion de biotensioactivos por Pseudomonas aeruginosa 44T1

En este trabajo se describen los resultados experimentales destinados a la optimización de la producción de biotensioactivos por Pseudomonas aeruginosa 44T1 en un medio mineral con glucosa como fuente de carbono. Se han ensayado diversos componentes del medio de cultivo y condiciones de incubación, siendo la relación C/N, la concentración de hierro así como la temperatura de incubación, los parámetros fundamentales que han incrementado los valores de CMC-1 como medida de la acumulación de tensioactivos