The Standardization of Supporting Tools: Advantage Competitive for Collaborative Networks

doi: 10.1016/j.proeng.2013.08.277Traditionally, manufacturing companies, the gateway for information technology (IT) have been implementing business management tools, tools typically enterprise resource planning (ERP) focused exclusively on internal processes manufacturing and remaining largely isolated from the rest of the elements of the value chain (suppliers, customers, etc.). The objective of this paper is to propose action lines to solve the problems inherent in collaborative knowledge management related technological barrier by implementation project business management tools. As mist relevant contribution are both the search for standardization and the application of techniques in Project Management to try to achieve success in the implementation and establishing of collaborative networks.The authors thank the Consejería de Economía, Innovación y Ciencia of the Junta de Andalucía and to the European Union for their incentives for the training of teaching staff and pre-doctoral researchers in deficient areas of knowledge (2009 Edict) co-financed by the Fondo Social Europeo (FSE). Thanks also to the Department of Mechanical Engineering and Industrial Design at the University of Cadiz School of Engineering

The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol

N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC's effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allosteric modulator of mGluR5 (MTEP 0.1 mg/kg). Thereafter, the cFOS IR-cell expression was analyzed. Secondly, we explored the effect of 120 mg/kg of NAC on the neurochemical and behavioral activation induced by intra-VTA ethanol administration (150 nmol). Our results showed that the high NAC dose stimulated cFOS expression in the NAcc, and that this effect was suppressed in the presence of MTEP, thus suggesting the implication of mGluR5. Additionally, high doses could attenuate the ethanol-induced increase in cFOS-expression in the NAcc, probably due to a phenomenon based on the long-term depression of the MSNs. Additional experiments are required to corroborate our hypothesis

Relación entre la presión inspiratoria pico y la activación mecánica de los músculos inspiratorios durante respiración tranquila en pacientes con EPOC

En la enfermedad pulmonar obstructiva crónica (EPOC) la fuerza muscular inspiratoria (FMI) y la eficiencia mecánica de los músculos inspiratorios (EMMI) podrían verse reducidas como consecuencia de la hiperinsuflación. En este trabajo se registraron la presión inspiratoria en boca (PIpico) y la activación mecánica de los músculos inspiratorios en 10 pacientes EPOC severos y muy severos, durante respiración tranquila. Para determinar la activación mecánica de los músculos inspiratorios se empleó la señal mecanomiográfica diafragmática: MMGdi. La amplitud de la señal MMGdi fue estimada a través de índices lineales (ARV: valor rectificado medio) y no lineales (MLZ: Lempel-Ziv multiestado, y fSampEn: entropía muestral con valores de tolerancia fijos). Nuestra hipótesis es que el ratio entre PIpico, que refleja la FMI, y la amplitud de la señal MMGdi constituye una expresión de la EMMI. Los resultados obtenidos muestran ligeras diferencias entre la PIpico registrada en EPOC severos y muy severos, así como una correlación débil a moderada con los parámetros de función pulmonar y los índices estudiados. Sin embargo, mientras mayor es el grado de severidad (que supone un mayor grado de hiperinsuflación) mayor es el nivel de activación mecánica de los músculos inspiratorios. La activación mecánica de los músculos inspiratorios y la EMMI estimadas mediante MLZ estuvieron mejor correlacionadas con la función pulmonar que ARV y fSampEn. Por consiguiente, la estimación de la actividad mecánica del diafragma mediante el MLZ de la señal MMGdi podría mejorar la estimación no invasiva de la FMI y la EMMI, incluso para niveles muy bajos de esfuerzo inspiratorio.Peer ReviewedPostprint (author’s final draft

N-Acetylcysteine normalizes brain oxidative stress and neuroinflammation observed after protracted ethanol abstinence: a preclinical study in long-term ethanol-experienced male rats

Rationale Using a preclinical model based on the Alcohol Deprivation Effect (ADE), we have reported that N-Acetylcysteine (NAC) can prevent the relapse-like drinking behaviour in long-term ethanol-experienced male rats. Objectives To investigate if chronic ethanol intake and protracted abstinence affect several glutamate transporters and whether NAC, administered during the withdrawal period, could restore the ethanol-induced brain potential dysfunctions. Furthermore, the antioxidant and anti-inflammatory effects of NAC during abstinence in rats under the ADE paradigm were also explored. Methods The expression of GLT1, GLAST and xCT in nucleus accumbens (Nacc) and dorsal striatum (DS) of male Wistar was analysed after water and chronic ethanol intake. We used the model based on the ADE within another cohort of male Wistar rats. During the fourth abstinence period, rats were treated for 9 days with vehicle or NAC (60, 100 mg/kg; s.c.). The effects of NAC treatment on (i) glutamate transporters expression in the Nacc and DS, (ii) the oxidative status in the hippocampus (Hip) and amygdala (AMG) and (iii) some neuroinflammatory markers in prefrontal cortex (PFC) were tested. Results NAC chronic administration during protracted abstinence restored oxidative stress markers (GSSG and GGSH/GSH) in the Hip. Furthermore, NAC was able to normalize some neuroinflammation markers in PFC without normalizing the observed downregulation of GLT1 and GLAST in Nacc. Conclusions NAC restores brain oxidative stress and neuroinflammation that we previously observed after protracted ethanol abstinence in long-term ethanol-experienced male rats. This NAC effect could be a plausible mechanism for its anti-relapse effect. Also, brain oxidative stress and neuroinflammation could represent and identify plausible targets for searching new anti-relapse pharmacotherapies

Different brain oxidative and neuroinflammation status in rats during prolonged abstinence depending on their ethanol relapse-like drinking behavior: Effects of ethanol reintroduction

Rationale: Accumulating evidence suggests that chronic alcohol consumption is associated with excessive oxidative damage and neuroinflammatory processes and these events have been associated to early alcohol withdrawal. In the present research we wonder if brain oxidative stress and neuroinflammation remains altered during prolonged withdrawal situations and whether these alterations can be correlated with relapse behavior in alcohol consumption. The effects of alcohol reintroduction were also evaluated. Methods: We have used a model based on the alcohol deprivation effect (ADE) within a cohort of wild-type male Wistar rats. Two subpopulations were identified according to the alcohol relapse-like drinking behavior displayed (ADE and NO-ADE subpopulations). Oxidized and reduced glutathione content was determined within the hippocampus and the amygdala using a mass spectrometry method. The levels of mRNA of seven different inflammatory mediators in the prefrontal cortex of rats were quantified. All the analyses were performed in two different conditions: after 21-day alcohol deprivation (prolonged abstinence) and after 24 h of ethanol reintroduction in both subpopulations. Results: ADE and NO-ADE rats showed different endophenotypes. ADE rats always displayed a significant lower alcohol intake rate and ethanol preference than NO-ADE rats. The results also demonstrated the existence of altered brain redox and neuroinflammation status after prolonged abstinence exclusively in ADE rats. Moreover, when ethanol was reintroduced in the ADE subpopulation, altered oxidative stress and neuroinflammatory markers were restored. Conclusions: Present findings provide new mechanisms underlying the neurobiology of relapse behavior and suggest the development of new pharmacological approaches to treat alcohol-induced relapse

Two-Dimensional Gel Electrophoresis to Study the Activity of Type IIA Topoisomerases on Plasmid Replication Intermediates

DNA topoisomerases are the enzymes that regulate DNA topology in all living cells. Since the discovery and purification of ω (omega), when the first were topoisomerase identified, the function of many topoisomerases has been examined. However, their ability to relax supercoiling and unlink the pre-catenanes of partially replicated molecules has received little attention. Here, we used two-dimensional agarose gel electrophoresis to test the function of three type II DNA topoisomerases in vitro: the prokaryotic DNA gyrase, topoisomerase IV and the human topoisomerase 2α. We examined the proficiency of these topoisomerases on a partially replicated bacterial plasmid: pBR-TerE@AatII, with an unidirectional replicating fork, stalled when approximately half of the plasmid had been replicated in vivo. DNA was isolated from two strains of Escherichia coli: DH5αF’ and parE10. These experiments allowed us to assess, for the first time, the efficiency of the topoisomerases examined to resolve supercoiling and pre-catenanes in partially replicated molecules and fully replicated catenanes formed in vivo. The results obtained revealed the preferential functions and also some redundancy in the abilities of these DNA topoisomerases in vitro

Electrophoretic mobility of supercoiled, catenated and knotted DNA molecules

We systematically varied conditions of two-dimensional (2D) agarose gel electrophoresis to optimize separation of DNA topoisomers that differ either by the extent of knotting, the extent of catenation or the extent of supercoiling. To this aim we compared electrophoretic behavior of three different families of DNA topoisomers: (i) supercoiled DNA molecules, where supercoiling covered the range extending from covalently closed relaxed up to naturally supercoiled DNA molecules; (ii) postreplicative catenanes with catenation number increasing from 1 to ∼15, where both catenated rings were nicked; (iii) knotted but nicked DNA molecules with a naturally arising spectrum of knots. For better comparison, we studied topoisomer families where each member had the same total molecular mass. For knotted and supercoiled molecules, we analyzed dimeric plasmids whereas catenanes were composed of monomeric forms of the same plasmid. We observed that catenated, knotted and supercoiled families of topoisomers showed different reactions to changes of agarose concentration and voltage during electrophoresis. These differences permitted us to optimize conditions for their separation and shed light on physical characteristics of these different types of DNA topoisomers during electrophoresi

Efficacy of N-acetylcysteine in the prevention of alcohol relapse-like drinking: Study in long-term ethanol-experienced male rats

Alcohol use disorders are chronic and highly relapsing disorders, thus alcoholic patients have a high rate of recidivism for drug use even after long periods of abstinence. The literature points to the potential usefulness of N-acetylcysteine (NAC) in the management of several substance use disorders probably due to its capacity to restore brain homeostasis of the glutamate system disrupted in addiction. However, there is little evidence in the case of alcohol. The aim of this study was to explore the potential anti-relapse efficacy of NAC using the alcohol deprivation effect (ADE) model in long-term experienced rats. Two experiments were performed in male Wistar rats to: (a) test the efficacy of NAC to prevent relapse and (b) discriminate the best administration schedule (intermittent vs. continuous) for NAC. In the first experiment, animals were implanted with mini-osmotic pumps delivering 0 or 1 mg/hr NAC during 14 days. In a second experiment, rats received 0, 60, or 100 mg/kg once daily by subcutaneous injection. The efficacy to prevent ADE was evaluated in both experiments. NAC subcutaneously administered, either by continuous infusion or by intermittent injections regimen, is able to block the ADE. The best results were obtained after using 60 mg/kg NAC dose. Our findings support the hypothesis that NAC may represent a valuable therapy in the management of alcohol relapse.GVA2016-09

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: a multicenter prospective study

[Abstract] BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.Instituto de Salud Carlos III; FIS081430Instituto de Salud Carlos III; FIS1101323Instituto de Salud Carlos III; FIS150147

Evaluación de la actividad de los músculos inspiratorios mediante señales mecanomiográficas en pacientes con EPOC durante un protocolo de carga incremental

El estudio de señales mecanomiográficas (MMG) de músculos respiratorios es una técnica prometedora para evaluar el esfuerzo muscular respiratorio. En este trabajo se han analizado las señales MMG del músculo diafragma derecho e izquierdo registradas en pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) durante un protocolo de carga incremental. La población de estudio está compuesta por un grupo de 6 pacientes con EPOC severa (FEV1>50% ref and DLCO<50% ref). Se ha obtenido una alta correlación positiva entre la presión inspiratoria máxima (PImax) desarrollada y diferentes parámetros de amplitud de las señales MMG izquierda y derecha (RMS, izquierda: 0.68±0.11 – derecha: 0.69±0.12; entropía de Rényi, izquierda: 0.73±0.10 – derecha: 0.77±0.08; Lempel-Ziv Multiestado, izquierda: 0.73±0.17 – derecha: 0.74±0.08), y una correlación negativa entre la PImax y la frecuencia máxima de la señal MMG (izquierda: -0.39±0.19 – derecha: -0.65±0.09). Además hemos encontrado que la pendiente de la evolución con el incremento de carga de los parámetros de amplitud de la señal MMG, tiene una correlación positiva con el parámetro funcional respiratorio %FEV1/FVC de los 6 pacientes EPOC analizados (RMS, izquierda: 0.38 – derecha: 0.41; entropía de Rényi, izquierda: 0.45 – derecha: 0.63; Lempel-Ziv Multiestado, izquierda: 0.39 – derecha: 0.64). Estos resultados sugieren que la información proporcionada por las señales MMG podría ser utilizada para evaluar el esfuerzo respiratorio y la eficiencia muscular en pacientes EPOC.Postprint (published version