Lecturas canónicas de Calderón en la primera mitad del siglo XIX

En este trabajo se analiza la diversidad de criterios con los que en la primera mitad del siglo XIX se valoró el teatro de Calderón y la diferente concepción de canónico o modélico que se atribuyó a su obra dramática. Se realiza así un recorrido explicativo de los comentarios que suscitó para comprobar cómo, cuándo y por qué se convirtió en un canon, en qué sentido se le canoniza (poético, dramático, ideológico, religioso, moral), y también cómo se transformó ese canon a lo largo del siglo XIX por razones tanto de evolución del arte como de la utilización de un autor representativo de la literatura española para justifi car el respeto a la tradición literaria nacional sobre la base de la aceptación de un sentido del progreso poético y político de las naciones. El artículo se inicia estudiando cómo la imaginación poética calderoniana se eleva a la categoría de cualidad nacional de índole artística o ético-religiosa según los críticos. Se continúa con los planteamientos que exigen su relativización estético-política en función de la historia y como ello conlleva una canonización moral. Ello plantea el conflicto entre la estatización del canon o su dinamización en la historia y por la historia.This study analyses the diversity of criteria with which the plays by Calderón were assessed during the first half of the 19th century, and the different classification as canon or model to which his dramatic works were ascribed. We present an explanatory review of the comments to which his works gave rise in order to observe how, when and why they became part of the canon, in what sense they were canonized (poetically, dramatically, ideologically, religiously, morally), and also how that canon was transformed throughout the 19th century. This transformation took place both on the grounds of the evolution of art and of the use of an author who was representative of Spanish literature to justify the respect for national literary tradition based on the acceptance of a sense of poetic and political progress of nations. The article starts by analysing how the poetic imagination of Calderón is granted the category of a national artistic or ethical/religious feature, according to the critics. It continues by studying the approaches that required its aesthetic/political relativization depending on history, and how this fact implies a moral canonization. This, in turn, leads to the conflict between a static canon and a canon which is dynamic as part of history and because of history

Decoration of squalenoyl-gemcitabine nanoparticles with squalenyl-hydroxybisphosphonate for the treatment of bone tumors

Therapeutic perspectives of bone tumors such as osteosarcom are main restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancers qualene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bi-sphosphonatemoiety to the squalenechain. This amphiphilic compound was inserted onto squalenoyl-gemcitabinenano-particles using the nanoprecipitation method. The co-assemblyled to nanoconstructsof 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybi-sphosphonate enhanced the nanoparticles binding affinity for hydroxyapatite,a mineral present in the bone. Moreover, the in vitro anticancer activity was preserved when tested in commercial and patient-treated derived pedia tricoste osarcomacells. Furtherin vivo studies will shed lighton the potential of these nano medicines for the treatment of bones arcomas

Identification of importin (IPO-8) as the most accurate reference gene for the clinicopathological analysis of lung specimens

Abstract Background: The accurate normalization of differentially expressed genes in lung cancer is essential for the identification of novel therapeutic targets and biomarkers by real time RT-PCR and microarrays. Although classical "housekeeping" genes, such as GAPDH, HPRT1, and beta-actin have been widely used in the past, their accuracy as reference genes for lung tissues has not been proven. Results: We have conducted a thorough analysis of a panel of 16 candidate reference genes for lung specimens and lung cell lines. Gene expression was measured by quantitative real time RTPCR and expression stability was analyzed with the softwares GeNorm and NormFinder, mean of |ΔCt| (= |Ct Normal-Ct tumor|) ± SEM, and correlation coefficients among genes. Systematic comparison between candidates led us to the identification of a subset of suitable reference genes for clinical samples: IPO8, ACTB, POLR2A, 18S, and PPIA. Further analysis showed that IPO8 had a very low mean of |ΔCt| (0.70 ± 0.09), with no statistically significant differences between normal and malignant samples and with excellent expression stability. Conclusion: Our data show that IPO8 is the most accurate reference gene for clinical lung specimens. In addition, we demonstrate that the commonly used genes GAPDH and HPRT1 are inappropriate to normalize data derived from lung biopsies, although they are suitable as reference genes for lung cell lines. We thus propose IPO8 as a novel reference gene for lung cancer samples

Brain aging and Parkinson's disease: new therapeutic approaches using drugs delivery systems

ABSTRACT The etiology and pathogenesis of Parkinson’s disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alphasynuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration

Id2 leaves the chromatin of the E2F4-p130-controlled c-myc promoter during hepatocyte priming for liver regeneration

The Id (inhibitor of DNA binding or inhibitor of differentiation) helix-loop-helix proteins are involved in the regulation of cell growth, differentiation and cancer. The fact that the molecular mechanisms of liver regeneration are not completely understood prompted us to study the fate of Id2 in proliferating liver. Id2 increases in liver regeneration after partial hepatectomy, following the early induction of its gene. Co-immunoprecipitation shows that Id2 forms a complex with E2F4, p130 and mSin3A in quiescent liver and all these components are present at the c-myc promoter as shown using ChIP (chromatin immunoprecipitation). Activation of c-myc during hepatocyte priming (G0-G1 transition) correlates with the dissociation of Id2 and HDAC (histone deacetylase), albeit p130 remains bound at least until 6 h. Moreover, as the G0-G1 transition progresses, Id2 and HDAC again bind the c-myc promoter concomitantly with the repression of this gene. The time course of c-myc binding to the Id2 promoter, as determined by ChIP assays is compatible with a role of the oncoprotein as a transcriptional inducer of Id2 in liver regeneration. Immunohistochemical analysis shows that Id2 also increases in proliferating hepatocytes after bile duct ligation. In this case, the pattern of Id2 presence in the c-myc promoter parallels that found in regenerating liver. Our results may suggest a control role for Id2 in hepatocyte priming, through a p130 dissociation-independent regulation of c-my

The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus

The G protein-coupled receptor 39 (GPR39) has recently been identified as the receptor for obestatin, a peptidic hormone involved in energy homeostasis. However, the expression levels of this receptor in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) remain unknown. Therefore, we evaluated the actual presence of GPR39 mRNA in human adipose tissue and whether GPR39 expression levels are altered in obesity and obesity-associated T2DM. DESIGN: Omental adipose tissue biopsies obtained from 15 women were used in the study. Patients were classified as lean (body mass index 20.8 +/- 1.0 kg/m(2)), obese normoglycaemic (body mass index 48.4 +/- 2.1 kg/m(2)) and obese T2DM patients (body mass index 52.6 +/- 4.9 kg/m(2)). Anthropometric measurements and biochemical profiles were assessed for each subject. Real-time RT-PCR analyses were performed to quantify transcript levels of GPR39 and adiponectin. RESULTS: Obese T2DM patients exhibited significantly lower GPR39 expression levels compared to lean (P = 0.016) and obese normoglycaemic subjects (P = 0.008), while no differences between lean and obese normoglycaemic patients were observed. The mRNA expression levels of GPR39 were negatively correlated to fasting glucose concentrations (r = -0.581, P = 0.023), while exhibiting a positive correlation to adiponectin mRNA expression levels (r = 0.674, P = 0.006). CONCLUSION: GPR39 is expressed in human adipose tissue. The reduced expression levels of GPR39 in omental adipose tissue observed in obese patients with T2DM suggest an involvement of obestatin signalling in glucose homeostasis and T2DM development

Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation

Caveolin-1 (CAV-1) plays important roles in many aspects of cellular biology, including vesicular transport, cholesterol homeostasis and signal transduction. The aim of the present study was to explore gene expression levels of CAV-1 in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to analyse its potential implication in the inflammatory state associated with obesity. DESIGN AND METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) obtained from 15 females were used in the study. Patients were classified as lean (BMI 20.8 +/- 1.0 kg/m(2)) or obese (BMI 50.5 +/- 2.6 kg/m(2)). The obese group was further subclassified as normoglycaemic (NG) or patients with T2DM. Anthropometric measurements as well as circulating metabolites, hormones and adipokines were determined. Real-time polymerase chain reaction (PCR) analyses were performed to quantify transcript levels of CAV-1 and monocyte chemoattractant protein (MCP-1). RESULTS: The presence of CAV-1 protein was detected in VAT and SAT by immunohistochemistry. Both obese NG and with T2DM patients exhibited significantly higher CAV-1 expression levels in VAT and SAT compared with lean subjects (P < 0.05). No differences between obese NG and T2DM patients were observed in VAT. However, obese T2DM patients were found to have higher CAV-1 expression levels in SAT (P < 0.05) compared with obese NG patients. A significant correlation was found between CAV-1 mRNA expression levels in VAT and different circulating inflammatory markers such as sialic acid (SA) (P < 0.001) and fibrinogen (P < 0.001) as well as with MCP1 mRNA expression (P < 0.05). CONCLUSION: Our findings show for the first time the upregulation of mRNA CAV-1 expression levels in VAT and SAT of obese NG and obese T2DM patients compared with lean controls, suggesting a role for CAV-1 in obesity and T2DM development. The association with different inflammatory markers further suggests an implication of CAV-1 in the low-grade inflammation accompanying obesity

Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass

Context: Plasma YKL-40 is elevated in patients with type 2 diabetes. The potential role of visceral adipose tissue (VAT) as a significant source of YKL-40 is unknown. Objective: In the study circulating and expression levels of YKL-40 were examined in VAT analyzing the contribution of adipocytes and stromovascular fraction cells (SVFCs).Wealso explored YKL-40’s implication in insulin resistance and inflammation and the effect of weight loss on plasma YKL-40 concentrations. PatientsandMethods: Samples obtained from 53 subjects were used in the study.Geneandprotein expression levels of YKL-40 were analyzed in VAT as well as in both adipocytes and SVFCs. In addition, circulating YKL-40 concentrations were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (n 26) or after a conventional dietetic program (n 20). Results: Circulating concentrations and VAT expression of YKL-40 were increased in obese patients with type 2 diabetes (P 0.01) as well as associated with variables of insulin resistance and inflammation. No differences in YKL-40 expression levels between adipocytes and SVFCs were detected. Monocyte chemoattractant protein-1 and homeostasis model assessment emerged (P 0.01) as independent factors predicting circulating YKL-40. Elevated levels of YKL-40 in obese patients decreased after weight loss following a conventional hypocaloric diet (P 0.05) but not via a surgery-induced negative energy balance mediated by the Roux-en-Y gastric bypass. Conclusions: The association of increased YKL-40 mRNA and protein levels in VAT with its circulating concentrations indicates an important contribution of VAT in YKL-40 regulation. Furthermore, our data suggest a relevant role of glucose metabolism and inflammation on YKL-40 regulation

Tomografía por emisión de positrones en el cáncer de mama

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer