Hepatotoxicidad asociada al consumo de estatinas: análisis de los casos incluidos en el Registro Español de Hepatotoxicidad / Hepatotoxicity associated with statin use: analysis of the cases included in the Spanish Hepatotoxicity Registry

Objetivos: el potencial hepatotóxico de las estatinas es controvertido. Los objetivos de este estudio fueron describir la frecuencia relativa de hepatotoxicidad por estatinas y los fenotipos de presentación en España. Pacientes y métodos: se analizaron las incidencias de hepatotoxicidad atribuidas a estatinas en el Registro Español de Hepatotoxicidad (REH) y se compararon con las atribuidas a otros fármacos. Resultados: entre abril de 1994 y agosto de 2012 se incluyeron en el REH un total 858 casos de los que 47 (5,5 %) se atribuyeron a estatinas. De ellos, 16 fueron por atorvastatina (34 %); 13 por simvastatina (27,7 %); 12 por fluvastatina (25,5 %); 4 por lovastatina (8,5 %) y 2 por pravastatina (4,3 %). Las estatinas representaban aproximadamente la mitad del grupo cardiovascular que ocupaba la 3ª posición (10 %), tras anti-infecciosos (37 %) y fármacos del sistema nervioso central (14 %). El patrón hepatocelular fue predominante, especialmente en el grupo de simvastatina (85 %), el colestático/mixto fue más frecuente con fluvastatina (66 %) y se distribuyó de manera similar con atorvastatina. Los pacientes con toxicidad por estatinas eran de edad más avanzada (62 años vs. 53 años, p < 0,001) y mostraban más frecuentemente un fenotipo de hepatitis autoinmune (8,5 % vs. 1,4 %, p < 0,003). Conclusiones: las estatinas no son una causa frecuente de hepatotoxicidad en España. La atorvastatina es la estatina implicada en un mayor número de incidencias. El patrón de lesión hepática varía entre las distintas estatinas. El fenotipo de hepatitis con rasgos de autoinmunidad parece ser una firma característica de la hepatotoxicidad por estatinas (AU)

Objectives: The hepatotoxic potential of statins is controversial. The objectives of this study were to describe the relative frequency of hepatotoxicity caused by statins and the phenotypes found in Spain. Patients and methods: The incidence of hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH) were studied and compared with those attributed to other drugs. Results: Between April 1994 and August 2012, the REH included a total of 858 cases of which 47 (5.5 %) were attributed to statins. Of these, 16 were due to atorvastatin (34 %); 13 to simvastatin (27.7 %); 12 to fluvastatin (25.5 %); 4 to lovastatin (8.5 %) and 2 to pravastatin (4.3 %). Statins represented approximately half of the cardiovascular group which occupied third place (10 %), after anti-infectious agents (37 %) and central nervous system drugs (14 %). The hepatocellular pattern was predominant, especially in the simvastatin group (85%), the cholestatic/mixed pattern was more frequent with fluvastatin (66 %) and had a similar distribution to atorvastatin. Patients with statin-induced toxicity were older (62 years versus 53 years, p < 0.001) and more often demonstrated an autoimmune hepatitis phenotype (8.5 % versus 1.4 %, p < 0.003). Conclusions: Statins are not a common cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the greatest number of incidents. The liver injury pattern varies among the different statins. The hepatitis phenotype with autoimmune features appears to be a characteristic signature of statin-induced hepatotoxicity (AU)

Enhancing team learning in nursing teams through beliefs about interpersonal context.

AIM: This article is a report of a study that examines the relationship between team-level learning and performance in nursing teams, and the role of beliefs about the interpersonal context in this relationship. BACKGROUND: Over recent years, there has been an increasing interest in the learning processes of work teams. Researchers have investigated the impact of team learning on team performance, and the enabling conditions for this learning. However, team learning in nursing teams has been largely ignored. DESIGN: A cross-sectional field survey design was used. METHODS: The sample comprises a total of 468 healthcare professionals working in 89 nursing teams at different public hospitals throughout Spain. Members of nursing teams participated voluntarily by completing a confidential individual questionnaire. Team supervisors evaluated nursing teams' performance. Data were collected over 2007-2008. RESULTS: The results show a mediating effect of team learning on the relationship between beliefs about interpersonal context (psychological safety, perceived task interdependence, and group potency) and team performance. CONCLUSION: Our findings suggest that beliefs about interpersonal context and team learning are important to effective nursing team performance.

FMRFamide-related peptide expression in the vestibular-afferent neurons.

Vestibular-afferent neurons innervate hair cells from the sensory epithelia of vestibular end-organs and their action-potential discharge dynamics are driven by linear and angular accelerations of the head. The electrical activity of the vestibular-afferent neurons depends on their intrinsic properties and on the synaptic input from hair cells and from the terminals of the efferent system. Here we report that vestibular-afferent neurons of the rat are immunoreactive to RFamide-related peptides, and that the stronger signal comes from calyx-shaped neuron dendrites, with no signal detected in hair cells or supporting cells. The whole-cell voltage clamp recording of isolated afferent neurons showed that they express robust acid-sensing ionic currents (ASICs). Extracellular multiunit recordings of the vestibular nerve in a preparation in vitro of the rat inner ear showed that the perfusion of FMRFamide (a snail ortholog of this family of neuropeptides) exerts an excitatory effect on the afferent-neurons spike-discharge rate. Because the FMRFamide cannot activate the ASIC but reduces its desensitization generating a more robust current, its effect indicates that the ASIC are tonically active in the vestibular-afferent neurons and modulated by RFamide-like peptides.

Facilitadores y consecuentes del aprendizaje de equipo: apuntes para futuras investigaciones

El aprendizaje ha sido destacado como uno de los pilares fundamentales de la organización (Senge, 1990) y especialmente en los momentos actuales, de incertidumbre y cambio. Como señalan Alcover y Gil (2002) ‘La capacidad para aprender más, y de hacerlo más deprisa que las demás organizaciones, se convierte en la principal, y quizás la única ventaja competitiva sostenible, y por tanto la razón de subsistencia’. El aprendizaje tiene lugar en distintos niveles; además del aprendizaje individual, resulta fundamental el aprendizaje colectivo, tanto organizacional, como de equipo. En relación al aprendizaje de equipo, los investigadores se han centrado en analizar, partiendo de los trabajos pioneros de Edmondson (1999), por una parte los principales factores que influyen en dicho aprendizaje y en segundo lugar la influencia del mismo en los resultados de los equipos. Este artículo tiene un doble objetivo. Primero, sintetizar e integrar las definiciones de aprendizaje de equipo, entendido éste tanto como proceso y como resultado. Segundo, analizar las principales variables antecedentes y de resultado de la investigación actual sobre aprendizaje de equipo.(AU)

Facilitadores y consecuentes del aprendizaje de equipo: apuentes para futuras investigaciones / Facilitators and consequences of team learning: Notes for future investigations

El aprendizaje ha sido destacado como uno de los pilares fundamentales de la organización (Senge, 1990) y especialmente en los momentos actuales, de incertidumbre y cambio. Como señalan Alcover y Gil (2002) 'La capacidad para aprender más, y de hacerlo más deprisa que las demás organizaciones, se convierte en la principal, y quizás la única ventaja competitiva sostenible, y por tanto la razón de subsistencia'. El aprendizaje tiene lugar en distintos niveles; además del aprendizaje individual, resulta fundamental el aprendizaje colectivo, tanto organizacional, como de equipo. En relación al aprendizaje de equipo, los investigadores se han centrado en analizar, partiendo de los trabajos pioneros de Edmondson (1999), por una parte los principales factores que influyen en dicho aprendizaje y en segundo lugar la influencia del mismo en los resultados de los equipos. Este artículo tiene un doble objetivo. Primero, sintetizar e integrar las definiciones de aprendizaje de equipo, entendido éste tanto como proceso y como resultado. Segundo, analizar las principales variables antecedentes y de resultado de la investigación actual sobre aprendizaje de equipo.

The learning has been highlighted as one of the main pillars of the organization (Senge, 1990) and especially in the present time of uncertainty and change. As Alcover and Gil (2002) affirm, the 'capacity to learn more, and make it more quickly than the other organizations becomes the main, and perhaps only sustainable competitive advantage, and therefore the reason for subsistence'. The learning takes place at various levels; in addition to the individual learning, it is essential the collective learning, both organizational, and team. In relation to the learning of teams, researchers have focused on analyze, on the basis of the pioneering work of Edmondson (1999), first in what concerns the main factors that influence such learning and secondly the influence of the same in the results of the teams. This article has a dual purpose. First, to synthesize and integrate the definitions of team learning, understood that as a process and as a result. Second, to analyze the main background and outcoming variables of the current research on team learning.

Team learning and effectiveness in virtual project teams: the role of beliefs about interpersonal context.

There has been increasing interest in team learning processes in recent years. Researchers have investigated the impact of team learning on team effectiveness and analyzed the enabling conditions for the process, but team learning in virtual teams has been largely ignored. This study examined the relationship between team learning and effectiveness in virtual teams, as well as the role of team beliefs about interpersonal context. Data from 48 teams performing a virtual consulting project over 4 weeks indicate a mediating effect of team learning on the relationship between beliefs about the interpersonal context (psychological safety, task interdependence) and team effectiveness (satisfaction, viability). These findings suggest the importance of team learning for developing effective virtual teams.

Team learning and effectiveness in virtual project teams: the role of beliefs about interpersonal context

There has been increasing interest in team learning processes in recent years. Researchers have investigated the impact of team learning on team effectiveness and analyzed the enabling conditions for the process, but team learning in virtual teams has been largely ignored. This study examined the relationship between team learning and effectiveness in virtual teams, as well as the role of team beliefs about interpersonal context. Data from 48 teams performing a virtual consulting project over 4 weeks indicate a mediating effect of team learning on the relationship between beliefs about the interpersonal context (psychological safety, task interdependence) and team effectiveness (satisfaction, viability). These findings suggest the importance of team learning for developing effective virtual teams (AU)

En los últimos años, se ha producido un creciente interés por los procesos de aprendizaje grupal en equipos de trabajo. Se ha investigado la influencia del aprendizaje de equipo en la efectividad grupal, así como las condiciones que facilitan dicho aprendizaje. Sin embargo, pocos trabajos han analizado los procesos de aprendizaje en equipos virtuales. Este estudio examina la relación entre aprendizaje de equipo y efectividad en equipos virtuales, así como el papel de las creencias compartidas sobre el contexto interpersonal en esta relación. 48 equipos desarrollaron un proyecto de consultoría de manera virtual durante cuatro semanas. Los resultados mostraron un efecto de mediación del aprendizaje de equipo en la relación entre las creencias sobre el contexto interpersonal (seguridad psicológica, interdependencia de tarea) y la efectividad grupal (satisfacción, viabilidad). Estos hallazgos sugieren la importancia del aprendizaje de equipo para desarrollar equipos virtuales efectivos (AU)

Nitric oxide in the amphibian (Ambystoma tigrinum) lateral line.

Nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d) histochemistry was investigated in the axolotl (Ambystoma tigrinum) lateral line. Hair cells of neuromast organs of the head skin and neurons of the postotic ganglia showed a significant NADPH-d reaction. Multiunit recording of neuromast afferent activity was also performed. Nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) produced an initial slight excitation followed by a significant inhibition of the resting discharge of neuromast afferent neurons. In contrast N(G)-nitro-L-arginine (L-NOARG) produced non-significant actions on the afferent neurons discharge. These findings suggest that afferent neurons and hair cells of the lateral line produce nitric oxide that plays an active role in the mechanisms sustaining basal spike discharge in afferent neurons.

pH modulates the vestibular afferent discharge and its response to excitatory amino acids.

In the isolated inner ear of the axolotl (Ambystoma tigrinum) acid pH decreased and basic pH increased the resting and mechanically evoked spike discharge of semicircular canal afferent neurons. Variations in pH also modified the afferent neuron response to N-methyl-D-aspartic acid (NMDA) acid and to (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Responses to both excitatory amino acid agonists increased at pH 7.8 (41% and 22%, respectively) and decreased by perfusion of the preparation with a saline solution, of pH 7.0 (28% in both cases). These results indicate that vestibular endorgans have a significant sensitivity to pH that could play a significant role in various pathological states, and may also contribute to the post-transductional processing of sensory information.

[Morphologic and electrophysiologic characteristics of cultured vestibular ganglia neurons]. / Características morfológicas y electrofisiológicas de las neuronas del ganglio vestibular en cultivo.

Vestibular afferent neurons have been classified on the basis of their spontaneous activity as regular and irregular; this has been attributed to their synaptic input, but it remains to be defined the participation of some intrinsical properties of the afferent neurons in the determination of their discharge pattern. In this work, we have developed tissue cultures of the rat vestibular ganglia. Isolated cells were plated using poly-D-lysine or collagen as substrates and L-15 or Neurobasal as culture media. After 48 hrs cells in the four experimental conditions give forth neurites of variable longitude. By using antibodies against the neurofilaments 160 kDa the cell structure was studied. Monopolar (30.6%), bipolar (63.9%) and multipolar (5.5%) cells were found. By using the voltage and current clamp procedures the voltage dependence and kinetics of the tetrodotoxin sensitive Na+ current was fully characterized. Cultured cells were shown to generate action potentials under electrical stimulation, and they were capable of repetitive spike discharge under the influence of 4-aminopyridine. These results demonstrate that tissue cultures constitute an excellent system to study the intrinsical properties of vestibular afferent neurons.

Características morfológicas y electrofisiológicas de las neuronas del ganglio vestibular en cultivo / Morphologic and electrophysiologic characteristics of cultured vestibular ganglia neurons

Vestibular afferent neurons have been classified on the basis of their spontaneous activity as regular and irregular; this has been attributed to their synaptic input, but it remains to be defined the participation of some intrinsical properties of the afferent neurons in the determination of their discharge pattern. In this work, we have developed tissue cultures of the rat vestibular ganglia. Isolated cells were plated using poly-D-lysine or collagen as substrates and L-15 or Neurobasal as culture media. After 48 hrs cells in the four experimental conditions give forth neurites of variable longitude. By using antibodies against the neurofilaments 160 kDa the cell structure was studied. Monopolar (30.6), bipolar (63.9) and multipolar (5.5) cells were found. By using the voltage and current clamp procedures the voltage dependence and kinetics of the tetrodotoxin sensitive Na+ current was fully characterized. Cultured cells were shown to generate action potentials under electrical stimulation, and they were capable of repetitive spike discharge under the influence of 4-aminopyridine. These results demonstrate that tissue cultures constitute an excellent system to study the intrinsical properties of vestibular afferent neurons.