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

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

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

Tumorigenic transformation of human prostatic epithelial cell line RWPE-1 by growth hormone-releasing hormone (GHRH)

Background: Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In this study, we analyzed the carcinogenetic potential of exposure to GHRH of a nontumor human prostate epithelial cell line (RWPE-1) as well as its transforming effect in a xenograft model. Methods: We performed cell viability, cell proliferation, adhesion and migration assays. In addition, metalloprotease (MMP)-2 activity by means gelatin zymography, GHRH-R subcellular location using confocal immunofluorescence microscopy and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunoassay were assessed. Besides, we developed an in vivo model in order vivo model to determine the role of GHRH on tumorigenic transformation of RWPE-1 cells. Results: In cell cultures, we observed development of a migratory phenotype consistent with the gelatinolytic activity of MMP-2, expression of VEGF, as well as E-cadherin-mediated cell-cell adhesion and increased cell motility. Treatment with 0.1 µM GHRH for 24 h significantly increased cell viability and cell proliferation. Similar effects of GHRH were seen in RWPE-1 tumors developed by subcutaneous injection of GHRH-treated cells in athymic nude mice, 49 days after inoculation. Conclusions: Thus, GHRH appears to act as a cytokine in the transformation of RWPE-1 cells by mechanisms that likely involve epithelial-mesenchymal transition, thus reinforcing the role of GHRH in tumorigenesis of prostate.Universidad de Alcal

Growth hormone-releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer

Background: Therapeutic strategies should be designed to transform aggressive prostate cancer phenotypes to a chronic situation. To evaluate the effects of the new growth hormone-releasing hormone receptor (GHRH-R) antagonists: MIA-602, MIA-606, and MIA-690 on processes associated with cancer progression as cell proliferation, adhesion, migration, and angiogenesis. Methods: We used three human prostate cell lines (RWPE-1, LNCaP, and PC3). We analyzed several molecules such as E-cadherin, ?-catenin, Bcl2, Bax, p53, MMP2, MMP9, PCNA, and VEGF and signaling mechanisms that are involved on effects exerted by GHRH-R antagonists. Results: GHRH-R antagonists decreased cell viability and provoked a reduction in proliferation in LNCaP and PC3 cells. Moreover, GHRH-R antagonists caused a time-dependent increase of cell adhesion in all three cell lines and retarded the wound closure with the highest value with MIA-690 in PC3 cells. GHRH-R antagonists also provoked a large number of cells in SubG0 phase revealing an increase in apoptotic cells in PC3 cell line. Conclusions: Taken all together, GHRH-R antagonists of the MIAMI series appear to be inhibitors of tumor progression in prostate cancer and should be considered for use in future therapeutic strategies on this malignancy.Junta de Comunidades de Castilla-La ManchaUniversidad de Alcal