Role of Glucocorticoid Receptor in the Relation between Stress and Opiate Addiction

Stressful situations can result in relapse in dependent or abstinent causing reinstatement of drug-seeking. In fact, it has been suggested that activation of the brain stress system results in glucocorticoid release that affects the dopaminergic pathways. Also, the noradrenergic system innervates the extrahypothalamic BSS from the nucleus of tractus solitarius (NTS), resulting in a feedforward loop between the corticotropin-releasing factor (CRF) and noradrenaline (NA) crucial in drug addiction and relapses. Glucocorticoids interact with two receptors: mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) which bind to a GRE site located in tyrosine hydroxylase (TH), resulting in the upregulation of TH synthesis and, finally, increasing dopamine (DA) release in the nucleus accumbens. TH upregulation depends on the phosphorylation of serine 31 and/or serine 40. Previous research has shown that protein kinase C (PKC) activates extracellular signal-regulated kinase (ERK) pathway and in turn phosphorylates serine 31 in the NTS. Besides, cAMP response element binding protein (CREB) is regulated by PKA and PKC. The results shown after pretreating morphine-withdrawn rats with mifepristone and spironolactone (GR and MR antagonists, respectively) suggest that glucocorticoids have a prominent role in addiction because GR would activate ERK and CREB in the NTS, phosphorylating serine 31 and activating TH and indeed noradrenergic release in the paraventricular nucleus (PVN)

Adaptación de la docencia en el cálculo de estructuras a las nuevas tecnologías

La implantación de las nuevas metodologías de enseñanza a partir de las directrices establecidas en el Espacio Europeo de Educación Superior, ha supuesto una renovación necesaria en los materiales docentes utilizados. En este sentido, el presente artículo muestra los avances en el uso de programas informáticos para la resolución de estructuras desarrollado a lo largo de las diferentes asignaturas que conforman las titulaciones de Ingeniería Civil, el Máster de Caminos, Canales, y Puertos, así como el Máster de Ingeniería de los Materiales, Agua y Terreno de la Universidad de Alicante. De esta forma el alumno es capaz de aproximarse a la realidad laboral, pudiendo comparar los resultados analíticos resueltos de forma tradicional, con los obtenidos con software comerciales ampliamente extendidos en el campo profesional. El uso de dichas herramientas se ha introducido de forma progresiva a lo largo de todos los cursos de las titulaciones anteriormente comentadas. Inicialmente, el alumno se familiariza con la resolución de estructuras a través de elementos barra, combinando diferentes materiales y acciones. Finalmente, el alumno desarrolla elementos placa, así como modelos reológicos y análisis dinámicos de estructuras. Por este motivo, y con el fin de completar la educación de los alumnos, en el presente trabajo se ha tratado de aproximar al alumno a las estructuras reales y a su posterior modelización numérica

Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization

The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.This work was supported by the Fondo de Investigación Sanitaria (Grant FI14CIII/00025 to OR-M and research projects PI13/02145 and PI16CIII/00035 to AA-I), and also supported by the Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16CIII/0004/0003) – co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020.S

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p &lt; 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. –19.7% variation, p &lt; 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed

A cost-effective robotic solution for the cleaning of ships' hulls

Hull cleaning before repainting is a key operation in the maintenance of ships. For more than a decade, a means to improve this operation has been sought through robotization and the use of different techniques such as grit blasting and ultra high pressure water jetting. Despite this, it continues to be standard practice in shipyards that this process is carried out manually. This paper presents a family of robots that aims to offer important improvements to the process as well as satisfying, to a great extent, all the operative requirements of efficiency, security, and respect for the environment that shipyards nowadays demand. It is described the family of devices with emphasis on the mechanical design. This set consists of two vertical robotic towers and a robot climber. In addition, it is shown the control architecture of the global system. Finally, operative results are presented together with a comparison between the performance achieved in shipyards through the use of these robots and those obtained with a manual process.The work submitted here has been developed within the framework of the “EFTCoR: Environmentally Friendly and Cost-Effective Technology for Coating Removal (EFTCoR)” project, Fifth Frame Programme of the European Community (ref. GRD2-2001-50004). It has also received financing from the Spanish government (national plan of I + D + I, PET 2008-0131 and MEDWSA-TIN2006-5175-CO5-O2) and from the Government of the Region of Murcia (Séneca Foundation)

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. – 19.7% variation, p < 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.pre-print2533 K

Uso de Redes Neuronales para el Análisis de Formas Naturales

Este artículo describe una solución basada en redes neuronales para el proceso de inspección visual automatizada de frutas en conserva, en la que se usa el concepto de firma como elemento generador del espacio de características. La solución presentada se ha particularizado para un proceso de clasificación de gajos de mandarinas, que en la actualidad se lleva a cabo mediante el uso de inspectores humanos. Los resultados muestran que esta forma de automatización es adecuada para una inspección en-línea, proporcionando una mejora sustancial de la calidad ofertada con un sistema rápido y de bajo coste.Los autores desean expresar su gratitud al gobierno español por el apoyo CICYT (TIC-200-1765-C03-02) que están prestando al proyecto COSIVA, en el que está incluido el trabajo desarrollado en el presente artículo

Sistema reconfigurable para el prototipado rápido de aplicaciones basadas en Bus PCI

Uno de los principales objetivos en la implantación de un sistema de control consiste en garantizar que cumplirá determinadas restricciones temporales, las cuales dependen en gran medida del hardware usado para implementar el sistema. Actualmente, frente a los costes tanto económicos como temporales en el desarrollo de sistemas mediante ASICs, las arquitecturas reconfigurables y las técnicas de codiseño constituyen unas herramientas muy valiosas en la búsqueda del sistema óptimo. Este artículo propone una arquitectura reconfigurable basada en dispositivos FPGAs, que permite aprovechar la potencia que ofrece el bus PCI; resultando idónea para afrontar el diseño de sistemas de inspección visual automatizados desde el punto de vista de codiseño. La arquitectura que se presenta se basa en las tarjetas de desarrollo PCI Proto-Lab/PLX, de HK Meßsysteme GMBH, y en la XS40 de la empresa Xess.Los autores desean expresar su gratitud al gobierno español por el apoyo CICYT (TIC-200-1765-C03-02) que están prestando al proyecto COSIVA, en el que está incluido el trabajo desarrollado en el presente artículo

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

Background: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD

Implicación del sistema cerebral del estrés en la dependencia de morfina: papel de los receptores de CRF y glucocorticoides

El síndrome de abstinencia a sustancias de abuso activa el sistema cerebral del estrés, que está formado por el eje hipotálamo-hipófisis-adrenal (HHA) y por la amígdala extendida. Ambas estructuras tienen como neurotransmisor principal el factor liberador de corticotropina (CRF). El CRF se une a los receptores CRF1 y CRF2 en la adenohipófisis y provoca la liberación de ACTH que produce liberación de glucocorticoides desde las adrenales. Es conocido que durante el síndrome de abstinencia a morfina se produce una hiperactivación de las vías noradrenérgicas que inervan el núcleo paraventricular del hipotálamo, produciéndose un aumento del turnover de noradrenalina y también de los niveles de corticosterona, así como una serie de signos somáticos. Los resultados obtenidos tras la administración de antagonistas de CRF1R, CRF2R, receptor glucocorticoide y mineralocorticoide, cuya expresión es conocida en el NTS, permite concluir que CRF2R y GR deben mediar probablemente dicha activación del sistema cerebral del estrés. It is known that morphine withdrawal activates brain stress system which is composed of hypothalamus-pituitary-adrenal axis (HPA) and the extended amygdala. Both systems have the same main neurotransmitter Corticotropin-Releasing Factor (CRF). CRF produces its effects by binding to CRF1 and CRF2 receptors. Binding of CRF to the CRF receptors on pituitary induces the release of ACTH which in turn stimulates GC synthesis and secretion from the adrenal cortex. During morphine withdrawal, noradrenergic pathways that innervate paraventricular nucleus of hypothalamus are hyperactivated resulting in an increase of noradrenaline turnover but also enhanced corticosterone levels and some characteristic morphine withdrawal somatic signs. CRF1R, CRF2R, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are expressed in the NTS (noradrenergic nuclei), so the results after administration of their antagonists led us to conclude that probably CRF2R and GR could mediate brain stress system activation during morphine withdrawal