Comercio exterior y mediación lingüística en el sector vitivinícola de Castilla y León

Comercio exterior y mediación lingüística en el sector vitivinícola de Castilla y Leó

Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells

Limbal epithelial stem cells (LESCs) are responsible for the renewal of corneal epithelium. Cultivated limbal epithelial transplantation is the current treatment of choice for restoring the loss or dysfunction of LESCs. To perform this procedure, a substratum is necessary for in vitro culturing of limbal epithelial cells and their subsequent transplantation onto the ocular surface. In this work, we evaluated poly-L/DL-lactic acid 70:30 (PLA) films functionalized with type IV collagen (col IV) as potential in vitro carrier substrata for LESCs. We first demonstrated that PLA-col IV films were biocompatible and suitable for the proliferation of human corneal epithelial cells. Subsequently, limbal epithelial cell suspensions, isolated from human limbal rings, were cultivated using culture medium that did not contain animal components. The cells adhered significantly faster to PLA-col IV films than to tissue culture plastic (TCP). The mRNA expression levels for the LESC specific markers, K15, P63α and ABCG2 were similar or greater (significantly in the case of K15) in limbal epithelial cells cultured on PLA-col IV films than limbal epithelial cells cultured on TCP. The percentage of cells expressing the corneal (K3, K12) and the LESC (P63α, ABCG2) specific markers was similar for both substrata. These results suggest that the PLA-col IV films promoted LESC attachment and helped to maintain their undifferentiated stem cell phenotype. Consequently, these substrata offer an alternative for the transplantation of limbal cells onto the ocular surface.This work was supported by the Carlos III National Institute of Health, Spain (CIBER-BBN and Spanish Network on Cell Therapy, (TerCel RD12/0019/0036), MINECO/FEDER, EU), and the Castilla y León Regional Government, Spain (Regional Center for Regenerative Medicine and Cell Therapy, SAN673/VA/28/08 and SAN126/VA11/09)

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage

Producción CientíficaLimbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble the different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improves corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses.This work was supported by Instituto de Salud Carlos III, CIBER‐BBN, Spain (CB06/01/003 MINECO/FEDER, EU); Regional Center for Regenerative Medicine and Cell Therapy, Castilla y León, Spain; Ministry of Science and Innovation, Spain (SAF2010–14900); Ministry of Economy and Competitiveness and European Regional Development Fund, Spain (SAF2015–63594‐R MINECO/FEDER, EU

La evolución reciente del crédito al sector privado en España : algunas implicaciones

Artículo de revistaEl objetivo de este articulo es analizar la evolucion del credito bancario, a partir de su distribucion por finalidades -actividades productivas, vivienda, consumo- y las implicaciones que se derivan de la misma. Describe la evolucion reciente del credito, su distribucion por finalidades y su relacion con el ciclo economico, a la vez que se destacan algunos aspectos que diferencia a las cajas de ahorros y a los bancos. Se discuten las posibles implicaciones de esta distribucion del credito sobre la situcacion financiera del sector privado y sobre la estabilidad de precios. (arl) (igg

Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria

This work is licensed under the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License.-- et al.Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential and apoptosis in human cervical carcinoma HeLa cells, both responses being abrogated by Bcl-xL overexpression. We synthesized a number of new fluorescent edelfosine analogs, which preserved the proapoptotic activity of the parent drug, and colocalized with mitochondria in HeLa cells. Edelfosine induced swelling in isolated mitochondria, indicating an increase in mitochondrial membrane permeability. This mitochondrial swelling was independent of reactive oxygen species generation. A structurally related inactive analog was unable to promote mitochondrial swelling, highlighting the importance of edelfosine molecular structure in its effect on mitochondria. Raft disruption inhibited mitochondrial localization of the drug in cells and edelfosine-induced swelling in isolated mitochondria. Edelfosine promoted a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. Our data suggest that direct interaction of edelfosine with mitochondria eventually leads to mitochondrial dysfunction and apoptosis. These observations unveil a new framework in cancer chemotherapy that involves a link between lipid rafts and mitochondria in the mechanism of action of an antitumor drug, thus opening new avenues for cancer treatment.This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF2008-02251, BQU2003-4413 and RD06/0020/1037 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), Fondo de Investigación Sanitaria and European Commission (FIS-FEDER 06/0813, 08/1434, PS09/01915), European Community's Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986), Junta de Castilla y León (CSI052A11-2, GR15-Experimental Therapeutics and Translational Oncology Program, Biomedicine Project 2009 and Biomedicine Project 2010-2011), Fundación para la Investigación Sanitaria en Castilla-La Mancha (FISCAM, PI-2006/10) and Junta de Comunidades de Castilla-La Mancha (I1I09-0163-4002). CG is supported by the Ramón y Cajal Program from the Spanish Ministerio de Ciencia e Innovación. MF is recipient of a postdoctoral fellowship from Fondo de Investigación Sanitaria. VH is recipient of a predoctoral fellowship from the Spanish Ministerio de Ciencia e Innovación.Peer reviewe

Authentication of strawberry tree (Arbutus unedo L.) honeys from southern Europe based on compositional parameters and biological activities

Strawberry-tree (Arbutus unedo L.) honey is expensive and difficult to characterize by melissopalinology. This study aimed to authenticate strawberry-tree (A. unedo L.) honeys from southern Europe, determining arbutin, groups of polyphenols, volatile and semivolatile compounds, as well as biological activities such as trolox equivalent antioxidant capacity, antioxidant activities against both hydroxyl (AOA) and superoxide radicals (SRS), oxygen radical absorbance capacity, anti-inflammatory activity, and antimicrobial activity against 7 microorganisms (Escherichia coli, Streptococcus mutans, Staphylococcus aureus, Aspergillus flavus, Aspergillus niger, Fusarium sp., and Penicillium commune). Arbutin, analyzed using HPLC-UV, was quantified in 83% of the samples. Polyphenols' contents were high. Norisoprenoids and benzene derivatives were the major compounds determined using gas chromatography-mass spectrometry. Theobromine was detected in 67% of samples. 2,6,6-Trimetyl-4-oxo-2-cyclohexen-1-carboxaldehyde, 3,4,5 trimethylphenol and 2-hydroxycyclopent-2-en-1-one were proposed as potential strawberry-tree floral markers. Antioxidant and anti-inflammatory activities were significant. Honeys’ extracts showed higher AOA and SRS, and better antimicrobial activities than the honeys. This study highlights the potential of strawberry-tree honeys and/or their phenolic extracts for food, pharmaceutical and cosmetic uses.Spanish Junta de Castilla y León, Spain (BU041G18

Consecutive Expansion of Limbal Epithelial Stem Cells from a Single Limbal Biopsy

Producción CientíficaPurpose: Corneal epithelium is maintained by limbal epithelial stem cells (LESCs), the loss of which can be catastrophic for corneal transparency. Effective therapies include the transplantation of cultivated LESCs, requiring optimization of in vitro cultivation protocols. Unfortunately, optimization studies are hampered by the limited number of ocular tissue donors. We investigated the feasibility of obtaining more than one limbal primary culture (LPC) from the same 1-2 mm2 limbal explant (LE). Methods: LEs were plated and maintained until outgrowth surrounded each, being removed at this point. LPCs were allowed to reach confluence (LPC0). The same removed LE was plated again, following the same procedure, obtaining LPC1. This procedure was repeated as often as possible up to 6 times. LPCs from each passage were analysed by real time RT-PCR and immunofluorescence-microscopy. Results: LPCs from LPC0 to LPC2 presented an heterogeneous cell population, with cells positive for LESC markers K14, K15, ABCG2 and p63, differentiated corneal epithelial cell-specific markers K3 and K12, and for the fibroblast marker S100A4. These cells had an epithelial-like morphology. In LPC3-LPC4, elongated cell morphology appeared, and the presence of LESC markers decreased, while the presence of differentiated corneal epithelial-cell and fibroblast markers increased. Conclusion: one LE can be successfully cultivated up to three consecutive times while maintaining the LESC phenotype in the LPC cells. This protocol provides several homologous LPCs for basic research. Additionally, by using a cell-carrier, the resulting LPCs could serve reservoirs for potential autologous expanded LESC transplantations and/or for making correlations between laboratory and clinical outcomes.This study was supported by CIBER-BBN, Spain and Network Center for Regeneration Medicine and Cell Therapy, Castile and Leon Government (SAN673/VA/28/08 and SAN/103/2011). M. L-P. and S. G. were supported by scholarships co-financed by the Castile and Leon Government and the European-Social-Fond

Food and beverage can coatings: a review on chemical analysis, migration, and risk assessment

The internal surface of food and beverage cans is generally covered with polymeric coatings to preserve food and protect metal substrate from corrosion. Coating materials are complex formulations that contain different starting substances (e.g., monomers, prepolymers, additives, etc.) and in addition during the manufacture of the material several compounds can be formed (e.g., reaction products, degradation products, etc.). These substances have the potential to migrate into the food. Many of them have not been identified and only some have been toxicologically evaluated. This article aims to provide a comprehensive review on the analytical methods used for the identification of potential migrants in can coatings. The migration and exposure to chemicals migrating from can coatings are also reviewed and discussed so far, which is essential for risk assessment. Moreover, a brief section on the current status of the legislation on varnishes and coatings for food contact in Europe is also presented. Liquid chromatography coupled to diode array and fluorescence detectors and particularly to mass spectrometry and gas chromatography–tandem mass spectrometry seem to be the techniques of choice for the identification of potential migrants in can coatings. Some studies have reported migration levels of BPA (bisphenol A) and BADGE (bisphenol A diglycidyl ether) and derivatives exceeding the specific migration limits set in the European legislation. On the whole, low dietary exposure to migrants from can coatings has been reported. However, it is interesting to highlight that in these studies the combined exposure to multiple chemicals has not been consideredThis study was funded by the Ministerio de Ciencia, Innovación y Universidades, Fondo Europeo de Desarrollo Regional (FEDER), and Agencia Estatal de Investigación (Ref. no. PGC2018-094518-B-I00 “MIGRACOATING” [MICIU/FEDER, UE])S

A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency

Producción CientíficaOcular stem cell transplantation derived from either autologous or allogeneic donor corneoscleral junction is a functional cell therapy to manage extensive and/or severe limbal stem cell deficiencies that lead to corneal epithelial failure. Mesenchymal stem cells have been properly tested in animal models of this ophthalmic pathology, but never in human eyes despite their potential advantages. We conducted a 6- to 12-month proof-of-concept, randomized, and double-masked pilot trial to test whether allogeneic bone marrow-derived mesenchymal stem cell transplantation (MSCT], n = 17) was as safe and as equally efficient as allogeneic cultivated limbal epithelial transplantation (CLET), (n = 11) to improve corneal epithelial damage due to limbal stem cell deficiency. Primary endpoints demanded combination of symptoms, signs, and the objective improvement of the epithelial phenotype in central cornea by in vivo confocal microscopy. This proof-of-concept trial showed that MSCT was as safe and efficacious as CLET. Global success at 6–12 months was 72.7%–77.8% for CLET cases and 76.5%–85.7% for MSCT cases (not significant differences). Central corneal epithelial phenotype improved in 71.4% and 66.7% of MSCT and CLET cases, respectively at 12 months (P = 1.000). There were no adverse events related to cell products. This trial suggests first evidence that MSCT facilitated improvement of a diseased corneal epithelium due to lack of its stem cells as efficiently as CLET. Consequently, not only CLET but also MSCT deserves more preclinical investigational resources before the favorable results of this proof-of-concept trial could be transformed into the larger numbers of the multicenter trials that would provide stronger evidence. (ClinicalTrials.gov number, NCT01562002.)Ministerio de Sanidad, Consumo y Bienestar Social (project SAS/2481/2009)Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León (grant SAN 1178/200)Red de Terapia Celular TerCel (project RD12/0019/0036