Pharmacokinetics of Busulfan: gastrointestinal absorption and the influence of DMSO

Se ha estudiado la farmacocinética de la absorción gastrointestinal del busulfán en dos grupos de ratas, tras su administración por vía oral. La dosis influye en el valor de la constante de absorción (Ka) y en la concentración máxima normalizada (Cmax), presentando ambos parámetros una disminución al aumentar la dosis de 0,5 a 5 mg. El empleo de un modelo aparente monocompartimental con absorción de primer orden permite una adecuada descripción del perfil de niveles plasmáticos del antineoplásico. El dimetilsulfóxido, utilizado como disolvente del busulfán, no interfiere en los parámetros farmacocinéticos orales del mismo.We have studied the pharmacokinetics of gastrointestinal absorption of busulfan in two groups of rats, after oral administration. The dose effect on the value of the absorption constant (Ka) and the normalized maximum concentration (Cmax), presenting both parameters decreased with increasing dose from 0.5 to 5 mg. Using a model with monocompartimental apparent first order absorption allows an adequate description of the profile of plasma levels of antineoplastic. The dimethylsulfoxide used as busulfan solvent, does not interfere with oral pharmacokinetic parameters of it

Pharmacokinetics of Busulfan: gastrointestinal absorption and the influence of DMSO

Se ha estudiado la farmacocinética de la absorción gastrointestinal del busulfán en dos grupos deratas, tras su administración por vía oral. La dosis influye en el valor de la constante de absorción(Ka) y en la concentración máxima normalizada (Cmax), presentando ambos parámetros unadisminución al aumentar la dosis de 0,5 a 5 mg. El empleo de un modelo aparentemonocompartimental con absorción de primer orden permite una adecuada descripción del perfil deniveles plasmáticos del antineoplásico. El dimetilsulfóxido, utilizado como disolvente del busulfán, nointerfiere en los parámetros farmacocinéticos orales del mismo.We have studied the pharmacokinetics of gastrointestinal absorption of busulfan in two groups of rats,after oral administration. The dose effect on the value of the absorption constant (Ka) and thenormalized maximum concentration (Cmax), presenting both parameters decreased with increasingdose from 0.5 to 5 mg. Using a model with monocompartimental apparent first order absorptionallows an adequate description of the profile of plasma levels of antineoplastic. The dimethylsulfoxideused as busulfan solvent, does not interfere with oral pharmacokinetic parameters of it

Relevancia del problema de control motor y reconsideración del protocolo NIOSH en las tareas con manipulación manual de cargas

En este trabajo de investigación se ha analizado la manipulación manual de cargas utilizando los sistemas electrónicos y tecnologías desarrolladas en el Laboratorio de Biomecánica del Movimiento Humano y Ergonomía de la Universidad de Extremadura que han permitido medir la geometría del movimiento y el nivel de esfuerzo que suponen estas tareas. Los resultados obtenidos corroboran todas las hipótesis establecidas respecto de la intervención de los músculos analizados y su relación con el problema de control de los movimientos Además los resultados sugieren una discusión científica sobre la fiabilidad del protocolo NIOSH que tendría que tener en cuenta la calidad de control postural en la manipulación manual de cargas y de la técnica en la determinación del nivel de riesgo de padecer problemas músculo – esqueléticos. Concluyendo se puede afirmar que en Extremadura se dispone de una metodología científica altamente fiable que permite analizar y evaluar tareas que incluyen manipulación manual de cargas que puede ser de mucha utilidad tanto para la prevención de riesgos laborales como para la formación de los prevencionistas

Pyrolysis and combustion of electronic wastes

The decreasing costs and increasing availability of electronic products of all kinds, including mobile phones, audio and video equipment, and personal computers and their accessories, coupled with advances in technology that rapidly make these products obsolete, foretell a growing disposal problem. The materials employed in the present work were amobile phone (printed circuit board + casing) and printed circuit boards alone. Pyrolysis and combustion runs at 500 8C in a horizontal laboratory furnace were performed, and the analyses of the gas and semivolatile fractions (including dioxins and furans and ‘‘dioxin-like’’ PCBs) are shown. The mobile phone and printed circuit boards were analysed for PCDD/F and ‘‘dioxin-like’’ PCB content in order to establish the level of pollutant in the samples themselves. Some TG–MS experiments were carried out in order to better know the thermal decomposition of electronicwastes and identify some compounds emitted during the controlled heating of these materials. Furthermore, a kinetic study of the thermal decomposition of the electronic circuit (EC) both in nitrogen and nitrogen:oxygen atmospheres using different heating rates is presented.Support for this work was provided by the Spanish MEC, research project CTQ2005-05262

Measures for the assessment of stressful life events in the Spanish adult population: A systematic review

Objetivo: Este estudio pretende identificar y analizar los instrumentos de evaluación de los eventos vitales estresantes creados/adaptados para su uso con población española adulta, publicados en la literatura nacional e internacional, con especial atención en sus propiedades psicométricas y en su asociación con medidas de problemas de salud. Métodos: Se llevó a cabo una revisión sistemática de la literatura de todos los instrumentos publicados a través de los buscadores MEDLINE; ProQuest Health y Medical Complete ProQuest Psychology Journals PsycARTICLES PsycINFO Psicodoc OpenSIGLE desde la fecha de inicio hasta el 31 de enero de 2016. Dos investigadores independientes evaluaron la elegibilidad de todos los artículos, extrajeron los datos y evaluaron sus propiedades psicométricas. Resultados: Se seleccionaron 12 instrumentos que cumplían los criterios de inclusión en el estudio. Las medidas presentaron una gran heterogeneidad. La mayoría no incluían información sobre sus propiedades psicométricas o necesitaban aportar más datos, ya que eran pocas los que evaluaban su estabilidad test-retest y/o su estructura interna. Los cuestionarios creados o adaptados por González de Rivera y Morena (1983), Sandín y Chorot (1987), Fernández y Mielgo (1992), Gracia y Herrero (2004) y Motrico et al. (2013) mostraron asociaciones significativas con variables de problemas de salud. Discusión: Se requieren más estudios sobre la asociación de los instrumentos con variables de problemas de salud mental y física, lo que facilitaría su aplicación clínica. Estos resultados tienen una gran utilidad a la hora de seleccionar un instrumento de evaluación de eventos vitales estresantes en el ámbito clínico y de investigación en España

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5) in pituitary and pancreatic neuroendocrine tumors

Somatostatin receptor subtype 5 (SST5) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response.Junta de AndalucíaMinisterio de EconomíaMinisterio de Ciencia e Innovació

Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions. © 2013 Martín-Rodríguez et al.Funding for this project was provided by an R&D grant from Novartis Oncology and the Plan Andaluz de Investigación (CTS-444). DAC was supported by the “Ramón y Cajal” program (RYC-2006-001071) of the Spanish Ministry of Science and Innovation.Peer Reviewe

Unwrap Them First: Operando Potential- induced Activation Is Required when Using PVP-Capped Ag Nanocubes as Catalysts of CO2 Electroreduction

Metallic nanoparticles of different shape can be used as efficient electrocatalysts for many technologically and environmentally relevant processes, like the electroreduction of CO2. Intense research is thus targeted at finding the morphology of nanosized features that best suits catalytic needs. In order to control the shape and size distribution of the designed nanoobjects, and to prevent their aggregation, synthesis routes often rely on the use of organic capping agents (surfactants). It is known, however, that these agents tend to remain adsorbed on the surface of the synthesized nanoparticles and may significantly impair their catalytic performance, both in terms of overall yield and of product selectivity. It thus became a standard procedure to apply certain methods (e.g. involving UV-ozone or plasma treatments) for the removal of capping agents from the surface of nanoparticles, before they are used as catalysts. Proper design of the operating procedure of the electrocatalysis process may, however, render such cleaning steps unnecessary. In this paper we use poly-vinylpyrrolidone (PVP) capped Ag nanocubes to demonstrate a mere electrochemical, operando activation method. The proposed method is based on an observed hysteresis of the catalytic yield of CO (the desired product of CO2 electroreduction) as a function of the applied potential. When as-synthesized nanocubes were directly used for CO2 electroreduction, the CO yield was rather low at moderate overpotentials. However, following a potential excursion to more negative potentials, most of the (blocking) PVP was irreversibly removed from the catalyst surface, allowing a significantly higher catalytic yield even under less harsh operating conditions. The described hysteresis of the product distribution is shown to be of transient nature, and following operando activation by a single 'break-in' cycle, a truly efficient catalyst was obtained that retained its stability during long hours of operation

The implication of sucrose metabolism in the rootstock- mediated contrasting growth and yield responses of pepper plants subjected to salinity stress

[ESP] La tecnología del injerto modifica el balance reproductivo de plantas, que está controlado por el flujo de fotoasimilados hacia los frutos. El objetivo de este trabajo fue estudiar el efecto del injerto sobre la tasa de hidrólisis de sacarosa en frutos de plantas de pimiento sometidas a estrés salino. En condiciones salinas, las concentraciones de glucosa y fructosa disminuyeron significativamente en plantas injertadas sobre Terrano, que indica una mayor utilización en los órganos sumidero por su alta tasa reproductiva. Sin embargo, en plantas injertadas sobre Atlante, con una menor tasa reproductiva, se produjo una acumulación de sacarosa en condiciones salinas, que podría ser debida a una ralentización de su actividad sacarolítica. Por tanto, existen respuestas diferenciales en el metabolismo de la sacarosa de frutos de plantas de pimiento sometidas a estrés salino, que podrían explicar las diferencias de desarrollo asociadas al tipo de portainjerto utilizado. [ENG] Grafting technology modifies the reproductive balance of plants, which is controlled by the flow of photoassimilates to the fruits. The objective of this work was to study the effect of grafting on the rate of sucrose hydrolysis in fruits of pepper plants subjected to salt stress. Under saline conditions, glucose and fructose concentrations decreased significantly in plants grafted on Terrano, which indicates a higher utilization in the sink organs due to its high reproductive rate. However, in plants grafted onto Atlante, with a lower reproductive rate, there was an accumulation of sucrose in saline conditions, which could be due to a slowdown in its saccharolytic activity. Therefore, there are differential responses in the metabolism of sucrose in the fruits of pepper plants subjected to salt stress, which could explain the differences in development associated with the type of rootstock used

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

Somatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response