Monitorización farmacocinética de anticuerpos monoclonales

Los fármacos se utilizan habitualmente en base a la experiencia clínica (estrategia de ”acierto-error”), sin embargo, este empirismo no es posible generalizarlo en todos los casos, ya que el principio activo no se comporta con un patrón idéntico en la totalidad de los organismos vivos, es por esto que nace la farmacocinética clínica a finales de la década de los sesenta cumpliendo el reto de adaptarse a la situación individual de cada paciente. Recientemente la farmacocinética clínica se aplica a la monitorización de medicamentos biotecnológicos como los anticuerpos monoclonales utilizados en el tratamiento de las enfermedades inflamatorias crónicas, sin embargo actualmente no es fácil su incorporación a la práctica clínica. El objetivo primario de esta revisión bibliográfica es poner de manifiesto la metodología a seguir desde el área de farmacocinética clínica para llevar a cabo la monitorización de las concentraciones plasmáticas de los anticuerpos monoclonales. Para elaborar esta revisión bibliográfica se procedió a la búsqueda de información en distintas bases de datos científicas para obtener una idea general del tema y extraer todo tipo de datos que me permitieran desarrollar el trabajo. También se ha hecho uso de un gestor de referencias bibliográficas que facilitara la elaboración de la bibliografía en el formato Vancouver. La farmacocinética clínica como servicio de colaboración aumentaría la productividad del clínico, simplificando y añadiendo efectividad al proceso de decisión terapéutica, asegurando la utilización eficiente del medicamento biológico. Los anticuerpos monoclonales se podrían monitorizar mediante el test ELISA u otros métodos como el HPLC, sin embargo, aún hay mucho por hacer para integrar estos fármacos a los programas de monitorización farmacocinética.Universidad de Sevilla. Grado en Farmaci

Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during pronuclear development in equine zygotes produced by ICSI

Background: Global epigenetic reprogramming is considered to be essential during embryo development to establish totipotency. In the classic model first described in the mouse, the genome-wide DNA demethylation is asymmetric between the paternal and the maternal genome. The paternal genome undergoes ten-eleven translocation (TET)-mediated active DNA demethylation, which is completed before the end of the first cell cycle. Since TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, the latter is postulated to be an intermediate stage toward DNA demethylation. The maternal genome, on the other hand, is protected from active demethylation and undergoes replication-dependent DNA demethylation. However, several species do not show the asymmetric DNA demethylation process described in this classic model, since 5-methylcytosine and 5-hydroxymethylcytosine are present during the first cell cycle in both parental genomes. In this study, global changes in the levels of 5-methylcytosine and 5-hydroxymethylcytosine throughout pronuclear development in equine zygotes produced in vitro were assessed using immunofluorescent staining. Results: We were able to show that 5-methylcytosine and 5-hydroxymethylcytosine both were explicitly present throughout pronuclear development, with similar intensity levels in both parental genomes, in equine zygotes produced by ICSI. The localization patterns of 5-methylcytosine and 5-hydroxymethylcytosine, however, were different, with 5-hydroxymethylcytosine homogeneously distributed in the DNA, while 5-methylcytosine tended to be clustered in certain regions. Fluorescence quantification showed increased 5-methylcytosine levels in the maternal genome from PN1 to PN2, while no differences were found in PN3 and PN4. No differences were observed in the paternal genome. Normalized levels of 5-hydroxymethylcytosine were preserved throughout all pronuclear stages in both parental genomes. Conclusions: In conclusion, the horse does not seem to follow the classic model of asymmetric demethylation as no evidence of global DNA demethylation of the paternal pronucleus during the first cell cycle was demonstrated. Instead, both parental genomes displayed sustained and similar levels of methylation and hydroxymethylation throughout pronuclear development

Coeducación en Educación Infantil

Tradicionalmente se atribuyen cualidades y capacidades con diferenciación de sexo, de ésta forma se considera a las niñas más afectivas y a los niños más intrépidos y curiosos. Desde la educación con frecuencia consideramos algunas áreas más representativas del sexo femenino y otras en las que consideramos que los niños tienen más capacidades para obtener mejores resultados, es el caso del desarrollo lingüístico, en las niñas o de las matemáticas y la visión espacial en los niños. Nuestra investigación se ha centrado en analizar las evaluaciones iniciales de 45 niños y niñas dentro de la etapa infantil y comparar la consecución de objetivos dentro de las áreas curriculares legisladasTraditionally are attributed different qualities and capacities by gender based, so girls are considered more affectives and boys more brave and curious. Education often considerer some areas more representative of female gender and others where boys are considered more able to obtain better results, in case of lingual research for girls, or maths and spatial perception for boys. Our investigation had been focus on analyze the initial evaluations from 45 boys and girls comprised into childhood phase and compare the different achievement of objectives into the legislated curricular areas

Diseño interior aplicado al espacio comercial Burguerlink

El proyecto Diseño interior Aplicado en el espacio comercial BURGUERLINK presenta las diferentes etapas lógicas involucradas en el diseño interior de un espacio comercial, y las directrices que se deben seguir en la planificación, muestra los diversos puntos a tomar en cuenta para la planificación, elaboración, aplicación de un proyectos de diseño interior comercial. El desarrollo del proyecto de tesis comprende cuatro etapas aplicables a proyectos de diseño de espacios comerciales. A continuación un resumen de estas etapas: 1.1 Fundamentación teórica. En esta etapa se recopila los conceptos fundamentales tanto de la teoría del diseño, así como documentación referida a los elementos que podrían formar parte del proyecto de diseño comercial. 1.2 Diagnóstico del espacio. El diagnóstico del espacio permite conocer, cada una de las cualidades del espacio, como el estado de los materiales, distribución espacial, tipologías, y otras cualidades de carácter histórico y social. 1.3 Propuesta de diseño del espacio comercial. Esta tercera etapa comprende la realización de un anteproyecto, el mismo permite el acuerdo entre el cliente y diseñador, permitiendo resolver la problemática de diseño propuesta por el cliente. 1.4 Implementación de la propuesta. En esta etapa final de la panificación del proyecto de diseño comercial, se resuelve de manera casi definitiva el proyecto, se presentan maquetas planos y gráficos y toda la documentación requerida para la ejecución de la obra, se prevé es su mayor parte la situaciones que se puedan suscitar en el proceso constructivo.Diseñador de InterioresCuenc

Update on mammalian sperm capacitation : how much does the horse differ from other species?

In contrast to various other mammalian species, conventional in vitro fertilization (IVF) with horse gametes is not reliably successful. In particular, stallion spermatozoa fails to penetrate the zona pellucida, most likely due to incomplete activation of stallion spermatozoa (capacitation) under in vitro conditions. In other mammalian species, specific capacitation triggers have been described; unfortunately, none of these is able to induce full capacitation in stallion spermatozoa. Nevertheless, knowledge of capacitation pathways and their molecular triggers might improve our understanding of capacitation-related events observed in stallion sperm. When sperm cells are exposed to appropriate capacitation triggers, several molecular and biochemical changes should be induced in the sperm plasma membrane and cytoplasm. At the level of the sperm plasma membrane, (1) an increase in membrane fluidity, (2) cholesterol depletion and (3) lipid raft aggregation should occur consecutively; the cytoplasmic changes consist of protein tyrosine phosphorylation and elevated pH, cAMP and Ca2+ concentrations. These capacitation-related events enable the switch from progressive to hyperactivated motility of the sperm cells, and the induction of the acrosome reaction. These final capacitation triggers are indispensable for sperm cells to migrate through the viscous oviductal environment, penetrate the cumulus cells and zona pellucida and, finally, fuse with the oolemma. This review will focus on molecular aspects of sperm capacitation and known triggers in various mammalian species. Similarities and differences with the horse will be highlighted to improve our understanding of equine sperm capacitation/fertilizing events

Atmospheric attenuation measurement system for commercial solar plants based on optical spectrum analysis

The measurement of the solar radiation attenuation is one of the main challenges in concentrating solar power technologies. This work presents a new strategy for this measurement, based on the analysis of the VIS and IR spectra, and its related system. The optical design of the system and its implementation in a central receiver solar power plant is described, and the experimental results are detailed. We present, to the best of our knowledge, the first measurements of the atmospheric attenuation spectrum in a solar power plant. This system provides direct measurements of real atmospheric attenuation values, which opens the way to analyze the impact of aerosols and meteorological conditions at surface level in this attenuation

Suboptimal culture conditions induce more deviations in gene expression in male than female bovine blastocysts

BACKGROUND: Since the development of in vitro embryo production in cattle, different supplements have been added to culture media to support embryo development, with serum being the most popular. However, the addition of serum during embryo culture can induce high birthweights and low viability in calves (Large Offspring Syndrome). Analysis of global gene expression in bovine embryos produced under different conditions can provide valuable information to optimize culture media for in vitro embryo production. RESULTS: We used RNA sequencing to examine the effect of in vitro embryo production, in either serum-containing or serum-free media, on the global gene expression pattern of individual bovine blastocysts. Compared to in vivo derived embryos, embryos produced in serum-containing medium had five times more differentially expressed genes than embryos produced in serum-free conditions (1109 vs. 207). Importantly, in vitro production in the presence of serum appeared to have a different impact on the embryos according to their sex, with male embryos having three times more genes differentially expressed than their female counterparts (1283 vs. 456). On the contrary, male and female embryos produced in serum-free conditions showed the same number (191 vs. 192) of genes expressed differentially; however, only 44 of those genes were common in both comparisons. The pathways affected by in vitro production differed depending on the type of supplementation. For example, embryos produced in serum-containing conditions had a lower expression of genes related to metabolism while embryos produced in serum-free conditions showed aberrations in genes involved in lipid metabolism. CONCLUSIONS: Serum supplementation had a major impact on the gene expression pattern of embryos, with male embryos being the most affected. The transcriptome of embryos produced in serum-free conditions showed a greater resemblance to that of in vivo derived embryos, although genes involved in lipid metabolism were altered. Male embryos appeared to be most affected by suboptimal in vitro culture, i.e. in the presence of serum

Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen.

Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2 μM, chemically classified into 57 clusters and 33 singletons. Up to 68% of the hits are chemotypes described for the first time as late-stage gametocyte-targeting molecules. In addition, the biological profile of 90 compounds representing the chemical diversity is assessed. We confirm in vitro transmission-blocking activity of four of the six selected molecules belonging to three distinct scaffold clusters. Overall, this TCAMS gametocyte screen provides 276 promising antimalarial molecules with dual asexual/sexual activity, representing starting points for target identification and candidate selection

Prevalence of Lynch Syndrome among Patients with Newly Diagnosed Endometrial Cancers

Background: Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population. Methods: Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed. Results: One hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques. Conclusion: The prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.This study was supported by Conselleria Sanidad Comunidad Valenciana, Spain (AP/177/10) (http://www.san.gva.es/); Biomedical Research Foundations of the Alicante University Hospital (PI14/2006 and NI02/2011) (http://www.dep19.san.gva.es/); and the Elche University Hospital, Spain (FIBElx-CO11/03) (http://www.dep20.san.gva.es/)