Carbohydrate effect of novel arene Ru(II) phenanthroline-glycoconjugates on metastatic biological processes

Novel water-soluble half-sandwich ruthenium(II) polypyridyl-glycoconjugates [Ru(p-cymene)Cl{N-(1,10-phenanthroline-5-yl)-& beta;-glycopyranosylamine}][Cl] (glycopyranosyl = D-glucopyranosyl (1), D-mannopyranosyl (2), L-rhamnopyranosyl (3) and L-xylopyranosyl (4)) have been synthesized and fully characterized. Their behaviour in water under physiological conditions has been studied by nuclear magnetic resonance spectroscopy, revealing their hydrolytic stability. Interactions of the novel compounds with duplex-deoxiribonucleic acid (dsDNA) were investigated by different techniques and the results indicate that, under physiological pH and saline conditions, the metal glycoconjugates bind DNA in the minor groove and/or through external, electrostatic interactions, and by a non-classical, partial intercalation mechanism in non-saline phosphate buffered solution. Effects of compounds 1-4 on cell viability have been assessed in vitro against two human cell lines (androgen-independent prostate cancer PC-3 and non-tumorigenic prostate RWPE-1), showing moderate cytotoxicities, with IC50 values higher than those found for free ligands [N-(1,10-phenanthroline-5-yl)-& beta;-glycopyranosylamine] (glycopyranosyl = D-glucopyranosyl (a), D-mannopyranosyl (b), L-rhamnopyranosyl (c) and L-xylopyranosyl (d)) or corresponding metal-aglycone. Cell viability was assayed in the presence and absence of the glucose transporters (GLUTs) inhibitor [N4-{1-(4-cyanobenzyl)-5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl}-7-fluoroquinoline-2,4dicarboxamide] (BAY-876), and the results point to a negligible impact of the inhibition of GLUTs on the cytotoxicity caused by Ru(II) compounds 1-4. Remarkably, glycoconjugates 1-4 potently affect the migration pattern of PC-3 cells, and the wound healing assay evidence that the presence of the carbohydrate and the Ru(II) center is a requisite for the anti-migratory activity observed in these novel derivatives. In addition, derivatives 1-4 strongly affect the matrix metalloproteinase MMP-9 activities of PC-3 cells, while proMMP-2 and especially proMMP-9 were influenced to a much lesser extent

Water soluble, optically active monofunctional Pd(II) and Pt(II) compounds: promising adhesive and antimigratory effects on human prostate PC-3 cancer cells

New water soluble, enantiopure palladium and platinum compounds R-N-[M{(1S, 4R)-kappa NOH,kappa(NH)-N-2(2-pic)} Cl]Cl and S-N-[M{(1R, 4S)-kappa NOH,kappa(NH)-N-2(2-pic)}Cl]Cl (2-pic = 2-picolyl, M = Pd 1 and 1', Pt 2 and 2', respectively), and heterometallic Pd/Ti [(eta(5)-C5H5)(2)Ti{(1S, 4R)-kappa ON,kappa(NH)-N-2(2-pic)}(PdCl)] Cl (3) have been synthesized. These novel compounds were fully characterized by NMR spectroscopy and CHN elemental analysis and 1, 1', 2 and 2' were further evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The aqueous stability of novel compounds was studied by NMR spectroscopy under physiological conditions and the new species detected under such conditions have been characterized by NMR techniques and HR-ESI-MS (High-Resolution Electrospray Ionization Mass Spectrometry). CompoundDNA interactions have been investigated for the palladium and platinum compounds by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) DNA melting assays and viscometric titrations, revealing a better binding affinity and ability to affect duplex DNA of the palladium compounds. Metal derivatives have been tested in vitro against three cancer (prostate PC-3, cervical HeLa and breast MCF-7) and one non-tumorigenic (human prostate RWPE-1) cell lines. The highest anticancer activities were shown by palladium compounds 1 and 1' in all cancer lines, although their toxicity was lower than that found for cisplatin. Most importantly, the effect of the compounds on the cell adhesion and migration of the androgen- independent prostate cancer PC-3 cells has been assessed, and the efficacy of Pd enantiomers to affect the invasive phenotype of PC-3 cells has been demonstrated.Universidad de AlcaláComunidad de Madri

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

New water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.Ministerio de Economía y CompetitividadComunidad Autónoma de MadridUniversidad de Alcal

Estudio comparativo y análisis de la situación actual de las obras huérfanas en Europa: informe científico-técnico

En un primer nivel de análisis, se realiza una radiografía del estado de la cuestión de los 28 estados miembros de la UE en lo que se refiere a aspectos relacionados con la transposición de la Directiva Europea de obras huérfanas (Directiva 2012/28/UE del Parlamento Europeo y del Consejo, de 25 de octubre de 2012, sobre ciertos usos autorizados de las obras huérfanas). En un segundo nivel de análisis, se caracterizan e identifican (como foco principal de la investigación) los elementos relacionados con las obras huérfanas directamente vinculados con el ámbito de la Documentación, es decir, aquellos relacionados con la existencia de pautas y procedimientos vinculados al planteamiento, realización y registro de expedientes de búsquedas diligentes en bases de datos y que hayan sido definidos por parte de los 28 estados miembros analizados en el estudio

Buenas Prácticas en los Programas Universitarios para Mayores en España

Ana Isabel Muñoz Alcón y Francisco Trullén Galve (Universidad Catolica de Ávila); María P. García de la Torre y Francisco Ascón Belver (Universidad de A Coruña); M. Isabel Luis Rico, Ángel Gañán Adánez, Tamara de la Torre Cruz, Vanesa Baños Martínez (Universidad de Burgos); Yolanda Lázaro Fernández y Jaime Cuenca Amigo (Universidad de Deusto); Camino Caballero Posado (Universidad de Extremadura); Mª Adoración Holgado Sánchez y Mª Teresa Ramos Bernal (Universidad Pontificia de Salamanca); Sara Serrate González, Javier Alba Barrios y José Manuel Muñoz Rodríguez; Miguel Ángel Nombela Castaño (Universidad de Vigo

GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000–2016)

[Objective] To study the prevalence and distribution of HBV genotypes in Spain for the period 2000–2016.[Methods] Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded.[Results] 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41–62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found.[Conclusions] We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.This study has been funded in part by the funds of the research project GEHEP-2018-010, granted by the Hepatitis Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (Grupo de Hepatitis de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, GEHEP/SEIMC)

Multicenter evaluation of the Panbio™ COVID-19 rapid antigen-detection test for the diagnosis of SARS-CoV-2 infection

Objetives: The standard RT-PCR assay for coronavirus disease 2019 (COVID-19) is laborious and time-consuming, limiting testing availability. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Panbio™ COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swab specimens. Methods: This prospective multicentre study was carried out in ten Spanish university hospitals and included individuals with clinical symptoms or epidemiological criteria of COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the PanbioRT as a point-of-care test and a diagnostic RT-PCR test. Results: Among the 958 patients studied, 325 (90.5%) had true-positive results. The overall sensitivity and specificity for the PanbioRT were 90.5% (95%CI 87.5-93.6) and 98.8% (95%CI 98-99.7), respectively. Sensitivity in participants who had a threshold cycle (CT) < 25 for the RT-PCR test was 99.5% (95%CI 98.4-100), and in participants with ≤5 days of the clinical course it was 91.8% (95%CI 88.8-94.8). Agreement between techniques was 95.7% (κ score 0.90; 95%CI 0.88-0.93). Conclusions: The PanbioRT performs well clinically, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. The results must be interpreted based on the local epidemiological context.S

Un modelo de formación flexible y polivalente : la cooperación, autonomía y autorregulación del aprendizaje en la enseñanza superior

Contribució inclosa al CD-ROM que acompanya al llibre 'Nuevas estrategias formativas para las organizaciones'. Dins l'Índex del CD-ROM, correspon a l'Apartat F: 'Evaluación y Formación', Capítol XI: 'Fomación Superior y Profesional', Núm 1.El aprendizaje cooperativo debe ir orientado a la consecución de unos resultados con entidad educativa. Debe perseguir que el alumno ponga en juego procedimientos intelectuales de identidad y unas destrezas interpersonales basadas en el aprendizaje académico y social

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms)