Estudio estructural de poliésteres derivados del 1,8-octanodiol y ácidos dicarboxílicos pares

Se han estudiado las estructuras cristalinas de los poliésteres alifáticos derivados del 1,8-octanodiol y los ácidos subérico y sebácico (PE(8,8) y PE(8,10)) mediante las técnicas de difracción de rayos X y microscopía electrónica. Los citados poliésteres se sintetizaron mediante una policondensación en masa por etapas, utilizando como catalizador tetrabutóxido de titatio IV. Se prepararon cristales lamelares a partir de cristalizaciones isotérmicas de disoluciones diluidas en alcoholes. La morfología básica de los cristales corresponde a rombos truncados, obteniéndose monocristales, crecimientos en terrazas y dislocaciones helicoidales - L y -D. Las técnicas de decoración con polietileno ponen de manifiesto una sectorización de los cristales y un plegamiento molecular regular a lo largo de éstos. Asimismo, se ha llevado a cabo la degradación enzimática con las lipasas de Pseudomonas Cepacia y Rhizopus Arrhizus. La cristalización desde el fundido da lugar a esferulitas de textura fibrilar con una birrefringencia negativa. Destaca la obtención de diagramas de extinción anillados para el PE(8,8). El PE(8,8) cristaliza en una celda rómbica con parámetros a = 5,03Ǻ, b = 14,78Ǻ y c = 21,70Ǻ y simetría P21ab. Mediante los estudios de simulación del diagrama de difracción de electrones y rayos X, se ha podido determinar el ángulo azimutal y la disposición relativa de las cadenas moleculares en la celdilla cristalina. El PE(8,10) cristaliza en una celda monoclínica con parámetros a = 5,56Ǻ, b = 7,50Ǻ, c = 24,63Ǻ y β = 115,1º, con una simetría P121/a1. A semejanza del poliéster anterior, la cadena molecular adopta una conformación prácticamente extendida

Estudio estructural de poliésteres derivados del 1,8-octanodiol y ácidos dicarboxílicos pares

Se han estudiado las estructuras cristalinas de los poliésteres alifáticos derivados del 1,8-octanodiol y los ácidos subérico y sebácico (PE(8,8) y PE(8,10)) mediante las técnicas de difracción de rayos X y microscopía electrónica. Los citados poliésteres se sintetizaron mediante una policondensación en masa por etapas, utilizando como catalizador tetrabutóxido de titatio IV. Se prepararon cristales lamelares a partir de cristalizaciones isotérmicas de disoluciones diluidas en alcoholes. La morfología básica de los cristales corresponde a rombos truncados, obteniéndose monocristales, crecimientos en terrazas y dislocaciones helicoidales - L y -D. Las técnicas de decoración con polietileno ponen de manifiesto una sectorización de los cristales y un plegamiento molecular regular a lo largo de éstos. Asimismo, se ha llevado a cabo la degradación enzimática con las lipasas de Pseudomonas Cepacia y Rhizopus Arrhizus. La cristalización desde el fundido da lugar a esferulitas de textura fibrilar con una birrefringencia negativa. Destaca la obtención de diagramas de extinción anillados para el PE(8,8). El PE(8,8) cristaliza en una celda rómbica con parámetros a = 5,03Ǻ, b = 14,78Ǻ y c = 21,70Ǻ y simetría P21ab. Mediante los estudios de simulación del diagrama de difracción de electrones y rayos X, se ha podido determinar el ángulo azimutal y la disposición relativa de las cadenas moleculares en la celdilla cristalina. El PE(8,10) cristaliza en una celda monoclínica con parámetros a = 5,56Ǻ, b = 7,50Ǻ, c = 24,63Ǻ y β = 115,1º, con una simetría P121/a1. A semejanza del poliéster anterior, la cadena molecular adopta una conformación prácticamente extendida

Contribution to optimization and standardization of antibacterial assays with silver nanoparticles: the culture medium and their aggregation

The antimicrobial activity of silver nanoparticles is determined by their size and specific properties, as well as by the chemical composition of the exposure medium in which the nanoparticles are suspended. When the antibacterial tests are carried out in a culture medium, aggregation of the nanoparticles is produced, decreasing their effectiveness. This study proposes the addition of surfactants to the culture medium to prevent the aggregation of silver nanoparticles and optimizes the concentrations of these surfactants. The aggregation of silver nanoparticles was studied by dynamic light scattering (DLS) after dispersion in three liquid culture media (Mueller-Hinton (MH), Luria-Bertani (LB) and Brain Heart Infusion) in which four different surfactants (SDS, Triton X100, Tween 80 and CTAB) were added at concentrations of 0, 0.1, 0.5, 1, 1.5 and 2%. Results showed that, the optimal culture media to prevent aggregation of silver nanoparticles were MH and LB with higher concentrations of Tween 80 and Triton X100 surfactants; being MH + 2% of Tween 80 and MH + 1% Triton X100 the best combinations obtained because the results obtained were closest to the sizes of nanoparticles in ultrapure water. In addition, it has been verified that the optimal medium + surfactant combinations chosen did not affect the viability of Escherichia coli bacteria. Nanoparticle aggregation was not observed by single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) when nanoparticles were incubated for long incubations periods (24 h) in the optimal medium chosen

Growth hormone-releasing hormone (GHRH) promotes metastatic phenotypes through EGFR/HER2 transactivation in prostate cancer cells

The involvement of growth hormone-releasing hormone (GHRH) in several relevant processes that contribute to prostate cancer progression was analyzed. Firstly, we evaluated GHRH effects on cell proliferation and adhesion in human cancer prostate cell lines, LNCaP and PC3, by using specific assays (BrdU incorporation and collagen adhesion). The expression levels of the main marker molecules of these processes were measured by RT-PCR, Western blotting and zymography assays. GHRH increased both cell proliferation and proliferating cell nuclear antigen (PCNA) levels in LNCaP cells and in PC3 cells; however, such a rise was faster in the PC3 cells that represent the most aggressive stage of prostate cancer. Furthermore, GHRH significantly reduced cell adhesion and E-cadherin levels in LNCaP and PC3 cells and up-regulated the total and nuclear expression of ?-catenin in PC3 cells. In addition, we assessed cell cycle, cell migration and VEGF secretion in PC3 cells. GHRH augmented the number of cells in G2/M-phase but diminished that corresponding to G1-phase. Cell-cycle specific markers were evaluated since GHRH effects may be related to their differential expression; we observed a decrease of p53, p21, and Bax/Bcl2 ratio. Furthermore, GHRH increased the expression of CD44, c-myc and cyclin D1, MMP-2 and MMP-9 activity, and VEGF secretion. We also observed that EGFR and/or HER2 transactivation is involved in cell adhesion, cell migration and VEGF secretion produced by GHRH. Consequently, present results define GHRH as a proliferative, anti-apoptotic and migratory agent in prostate cancer.Junta de Comunidadesde Castilla-La Manch

The Conformational Stability and Biophysical Properties of the Eukaryotic Thioredoxins of Pisum Sativum Are Not Family-Conserved

Thioredoxins (TRXs) are ubiquitous proteins involved in redox processes. About forty genes encode TRX or TRX-related proteins in plants, grouped in different families according to their subcellular localization. For instance, the h-type TRXs are located in cytoplasm or mitochondria, whereas f-type TRXs have a plastidial origin, although both types of proteins have an eukaryotic origin as opposed to other TRXs. Herein, we study the conformational and the biophysical features of TRXh1, TRXh2 and TRXf from Pisum sativum. The modelled structures of the three proteins show the well-known TRX fold. While sharing similar pH-denaturations features, the chemical and thermal stabilities are different, being PsTRXh1 (Pisum sativum thioredoxin h1) the most stable isoform; moreover, the three proteins follow a three-state denaturation model, during the chemical-denaturations. These differences in the thermal- and chemical-denaturations result from changes, in a broad sense, of the several ASAs (accessible surface areas) of the proteins. Thus, although a strong relationship can be found between the primary amino acid sequence and the structure among TRXs, that between the residue sequence and the conformational stability and biophysical properties is not. We discuss how these differences in the biophysical properties of TRXs determine their unique functions in pea, and we show how residues involved in the biophysical features described (pH-titrations, dimerizations and chemical-denaturations) belong to regions involved in interaction with other proteins. Our results suggest that the sequence demands of protein-protein function are relatively rigid, with different protein-binding pockets (some in common) for each of the three proteins, but the demands of structure and conformational stability per se (as long as there is a maintained core), are less so

VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells

The nuclear factor kappa B (NF-kappa B) is a powerful activator of angiogenesis, invasion and metastasis. Transactivation and nuclear localisation of NF-kappa B is an index of recurrence in prostate cancer. Vasoactive intestinal peptide (VIP) exerts similar effects in prostate cancer models involving increased expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) which are related to NF-kappa B transactivation. Here we studied differential mechanisms of VIP-induced NF-kappa B transactivation in non-tumour RWPE-1 and tumour LNCaP and PC3 human prostate epithelial cells. Immunofluorescence studies showed that VIP increases translocation of the p50 subunit of NF-kappa B1 to the nucleus, an effect that was inhibited by curcumin. The signalling transduction pathways involved are different depending on cell transformation degree. In control cells (RWPE1), the effect is mediated by protein kinase A (PKA) activation and does not implicate extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3-K) pathways whereas the opposite is true in tumour LNCaP and PC3 cells. Exchange protein directly activated by CAMP (EPAC) pathway is involved in transformed cells but not in control cells. Curcumin blocks the activating effect of VIP on COX-2 promoter/prostaglandin E-2 (PGE(2)) production and VEGF expression and secretion. The study incorporates direct observation on COX-2 promoter and suggests that VIP effect on VEGF may be indirectly mediated by PGE(2) after being synthesised by COX-2, thus amplifying the initial signal. We show that the signalling involved in VIP effects on VEGF is CAMP/PKA in non-tumour cells and cAMP/EPAC/ERK/PI3K in tumour cells which coincides with pathways mediating p50 nuclear translocation. Thus, VIP appears to use different pathways for NF-kappa B1 (p50) transactivation in prostate epithelial cells depending on whether they are transformed or not. Transformed cells depend on pro-survival and pro-proliferative signalling pathways involving ERK, PI3-K and cAMP/EPAC which supports the potential therapeutic value of these targets in prostate cancer

Galleria mellonella como modelo animal de la infección por Helicobacter pylori y para estudios de eficacia preclínica de nuevos antimicrobianos frente a este patógeno.

H. pylori es una bacteria Gram-negativa que coloniza el estómago de los humanos. La prevalencia de la infección por H. pylori en el mundo varía en función de numerosos factores como la edad, el origen étnico, el estado geográfico y socioeconómico. Más del 50 % de la población mundial está infectada con H. pylori y se considera un agente etiológico importante en el desarrollo de enfermedades como gastritis, úlcera péptica, linfoma gástrico asociado a mucosa (MALT) y cáncer gástrico. El dinamismo genético del organismo, unido a diversos factores ambientales y del propio huésped determina el daño epitelial y la capacidad colonizadora de H. pylori, lo que explica la diversidad de enfermedades causadas por la bacteria. Existen varios factores de virulencia que se han relacionado con la agresividad de la bacteria y por tanto, están implicados en la colonización y daño en la mucosa. Los regímenes farmacológicos más utilizados para tratar la infección por H. pylori han variado durante los últimos años y no existe un tratamiento único. La creciente prevalencia de cepas de H. pylori resistentes a antibióticos es una de las principales causas de la dificultad actual de erradicar la infección. Además, la Organización Mundial de la Salud en 2017 catalogó a H. pylori como una de las infecciones con resistencia a antibióticos alta. Por ello, hoy en día en necesario encontrar una nueva terapia efectiva contra H. pylori. Como modelo animal para el estudio de la eficacia de tratamientos en la infección por H. pylori se han utilizado modelos animales como ratones y jerbos, pero debido al gran coste que suponen y a los impedimentos éticos que supone el uso de animales actualmente se están buscando alternativas que permitan reducir el número de los mismos. Por ello, se están reemplazando con modelos de animales invertebrados como es el caso de G. mellonella. Se ha demostrado que este modelo es susceptible a la infección por H. pylori y se puede utilizar para estudiar mecanismos patogénicos y factores de virulencia de la bacteria. <br /

La prostitución en los siglos XVI y XVII.

La prostitución ha sido un empleo al que han tenido que recurrir muchas mujeres para poder sobrevivir a lo largo de la historia, por ello en este trabajo se va a tratar la relación de las prostitutas con la sociedad que les rodea pero también cómo eran ellas y qué vida les esperaba dedicándose a tan polémico oficio. Lo siglos XVI y XVII suponen un cambio fundamental ya que al principio de la Edad Moderna y como herencia de la Edad Media, va a ser tolerada y los poderes comenzarán a crear toda una legislación para tenerla controlada, hasta llegar a finales del siglo XVI y principios del XVII que debido a diferentes cambios en las sociedades deja de ser vista como “mal necesario” y empiezan los cierres de los burdeles públicos y la prohibición del ejercicio de la prostitución.<br /

Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?

lntroduction: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. Materials and Methods: A total 172 men with total prostate-specific antigen of 2-10 ng/ml underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health lndex (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Results: Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. AII the models that incorporated PHI worked better in terms of calibration close to 45º on the slope. In the decision curve analysis, a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. Conclusions: PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient

UV-A activation of peroxymonosulfate for the removal of micropollutants from secondary treated wastewater

The occurrence of micropollutants (MPs) in the aquatic environment poses a threat to the environment and to the human health. The application of sulfate radical-based advanced oxidation processes (SR-AOPs) to eliminate these contaminants has attracted attention in recent years. In this work, the simultaneous degradation of 20 multi-class MPs (classified into 5 main categories, namely antibiotics, beta-blockers, other pharmaceuticals, pesticides, and herbicides) was evaluated for the first time in secondary treated wastewater, by activating peroxymonosulfate (PMS) with UV-A radiation, without any pH adjustment or iron addition. The optimal PMS concentration to remove the spiked target MPs (100 mu g L-1) from wastewater was 0.1 mM, leading to an average degradation of 80% after 60 min, with most of the elimination occurring during the first 5 min. Synergies between radiation and the oxidant were demonstrated and quantified, with an average extent of synergy of 69.1%. The optimized treatment was then tested using non-spiked wastewater, in which 12 out of the 20 target contaminants were detected. Among these, 7 were degraded at some extent, varying from 10.7% (acetamiprid) to 94.4% (ofloxacin), the lower removals being attributed to the quite inferior ratio of MPs to natural organic matter. Phytotoxicity tests carried out with the wastewater before and after photo-activated PMS oxidation revealed a decrease in the toxicity and that the plants were able to grow in the presence of the treated water. Therefore, despite the low degradation rates obtained for some MPs, the treatment effectively reduces the toxicity of the matrix, making the water safer for reuse