The effect of cytokines on intestinal sugar absorption during sepsis in rabbits.

The endotoxin that triggers an immune response to Gram-negative bacterial infection namely lipopolysaccharide (LPS), is also associated with gastrointestinal abnormalities and induces the release of proinflammatory cytokines such as IL-1 and TNF-α. The main aim of this study was to determine the effect of cytokine release on intestinal D-fructose absorption in LPS-treated rabbits in order to provide information that could be used to understand their septic status. The results obtained, using whole tissue and brush border membrane vesicles from rabbit jejunum, showed that LPS, TNF-α and IL-1ß inhibit d-fructose absorption across the jejunum. The effect of LPS is completely reversed by a TNF-α antagonist and partially by a specific IL-1 receptor antagonist (IL-1ra) and disappears completely in the presence of both these cytokine antagonists. Similarly, the effects of TNF-α and LPS were not totally blocked by IL-1ra, whereas the effect of IL-1ß disappeared completely in the presence of a TNF antagonist. In summary, these results show that TNF-α and IL-1ß could act synergistically on sugar absorption in rabbit with LPS-induced sepsis. In addition, the effects of IL-1ß depend on, or are related to TNF-α production since this effect returns to basal (control) levels in the presence of a TNF-α antagonist.

Imbalance of neurotrophin receptor isoforms TrkB-FL/TrkB-T1 induces neuronal death in excitotoxicity.

A better understanding of the mechanisms underlying neuronal death in cerebral ischemia is required for the development of stroke therapies. Here we analyze the contribution of the tropomyosin-related kinase B (TrkB) neurotrophin receptor to excitotoxicity, a primary pathological mechanism in ischemia, which is induced by overstimulation of glutamate receptors of the N-methyl-D-aspartate type. We demonstrate a significant modification of TrkB expression that is strongly associated with neurodegeneration in models of ischemia and in vitro excitotoxicity. Two mechanisms cooperate for TrkB dysregulation: (1) calpain-processing of full-length TrkB (TrkB-FL), high-affinity receptor for brain-derived neurotrophic factor, which produces a truncated protein lacking the tyrosine-kinase domain and strikingly similar to the inactive TrkB-T1 isoform and (2) reverse regulation of the mRNA of these isoforms. Collectively, excitotoxicity results in a decrease of TrkB-FL, the production of truncated TrkB-FL and the upregulation of TrkB-T1. A similar neuro-specific increase of the TrkB-T1 isoform is also observed in stroke patients. A lentivirus designed for both neuro-specific TrkB-T1 interference and increased TrkB-FL expression allows recovery of the TrkB-FL/TrkB-T1 balance and protects neurons from excitotoxic death. These data implicate a combination of TrkB-FL downregulation and TrkB-T1 upregulation as significant causes of neuronal death in excitotoxicity, and reveal novel targets for the design of stroke therapies.

Agresiones a trabajadores sanitarios en España: un estudio multicéntrico / No disponible

En los últimos años parecen haber aumentado los casos de agresiones de pacientes a trabajadores sanitarios. En Españano existen estudios científicos que hayan abordado esta cuestión. Hemos analizado los datos de una encuesta sobre agresionesen el lugar de trabajo en una muestra estratificada de 1826 profesionales de la salud procedentes de 3 hospitales y 22 centrosde Atención Primaria rurales y urbanos localizados en el noreste y este de España. Encontramos que un 11% de los trabajadoressanitarios han sido víctimas de una agresión física, 5% en más de una ocasión, mientras que un 64% se han vistoexpuestos a comportamientos amenazantes, intimidación o insultos. Alrededor de un 34% han sufrido amenazas e intimidaciónen al menos una ocasión, y 23,8% de forma repetida. En torno al 35% han sido insultados en al menos una ocasión,y 24,3% repetidamente. En general la incidencia era mayor en los hospitales grandes, con niveles muy altos en servicios como accidentes, emergencias y psiquiatría(AU)

In recent years instances of aggression by patients towards health workers appear to have become more frequent. InSpain, no scientific studies appears to have been performed so far on this question. We analyzed questionnaires on workplaceaggression from a stratified sample of 1826 health professionals at 3 hospitals and 22 rural and urban Primary Care facilitieslocated in the Northeast and East of Spain. We found 11% of health workers had been a victim of physical aggression,5% on more than one occasion, while 64% had been exposed to threatening behaviour, intimidation or insults. About34% had suffered threats and intimidation on at least one occasion, and 23.8% repeatedly. Over 35% had been subjectedto insults on at least one occasion, and 24.3% repeatedly. In general the incidence was higher in large hospitals, with veryhigh levels in services such as Accident and Emergency and Psychiatry(AU)

e-Learning strategies in occupational legal medicine based on problem solving through "CASUS" system.

The use of online teaching tools facilitate the incorporation of self-learning methods. With a view to encouraging convergence in teaching tools and methods in Occupational Legal Medicine, an initiative was set up within the classes of Legal and Forensic Medicine at Saragossa University, as part of the EU funded NetWoRM project, which has been led since 1999 by Ludwig-Maximilians-Universität in Munich (Germany). The interest of medical students in Occupational Legal Medicine has so far been low and in addition different aspects complicate the teaching of Occupational Legal Medicine at medical schools: One reason for the low interest is the limited availability of bedside teaching, one of the students' most favourite and effective way to learn. The reason for that is that most medical schools with occupational departments only have outpatient clinics. "Interesting" patients who be need for educational purposes are therefore only available for a limited part of the day. However, in order to recognize and prevent occupational disorders each medical student and physician needs profound clinical knowledge in Occupational Legal Medicine. This project has proven to be highly efficient in permitting the creation and validation of teaching tools which cover and improve the traditional training of the Occupational Legal Medicine programme imparted in the degree of Medicine.

Aggressions against healthcare workers: an approach to the situation in Spain and the victims psychological effects.

Aggression against healthcare workers is a problem of important consequences which is becoming a focus of research. However, its possible effects on psychological health have not been studied sufficiently in spite of the fact that they may be of importance even in the absence of physical aggression [Winstnaley S, Whittington R. Aggression towards health care staff in a UK general hospital: variation among professions. J Clin Nurs 2004;13:3-10,[1]].

Entrenamiento en relajación como terapia complementaria en pacientes con gastroenterología / No disponible

Aunque la etiología de la enfermedad de Crohn es desconocida, se han descrito factos de carácter genético, infecciosos, inmunológico, y ambiental que aumentan el riesgo de padecerla, entre otros, eventos estresantes que exacerban o agravan la enfermedad. Desde el año 200 6, este mal, englobado dentro del grupo de las enfermedades inflamatorias intestinales (E.II, I.B.D.) clasifica a los pacientes en función de la edad de comienzo, localización de la enfermedad y comportamiento de ésta. Como es bien conocido, actualmente no es curable, pero sí controlarle, y la mayoría de las personas pueden hacer una vida normal, bajo tratamiento y vigilancia. Paralelamente a los tratamientos de tipo farmacológico, dietético, sintomático o quirúrgico, el poder proporcionar técnicas de relajación a los pacientes con trastornos gastrointestinales, que puedan aplicar fácilmente en cualquier momento puede convertirse en una inestimable herramienta que les ayude al control de su propia salud. El estudio muestra los beneficios obtenidos al comparar una muestra de pacientes de Crohn que siguieron un entrenamiento en relajación y lo incorporaron a su vida cotidiana, comparado con otro grupo de pacientes de la misma enfermedad, sin tratamiento(AU)

Aprendizaje, mediante casos prácticos online en Medicina del Trabajo. Experiencia de la Universidad de Zaragoza en el proyecto Europeo NetWorm / No disponible

El uso de métodos de aprendizaje online facilita la incorporación de métodos de auto-aprendizaje que pueden ser un buen instrumento de apoyo para la enseñanza en un contexto internacional. Con esta filosofía y con la vista puesta en el compromiso de convergencia en métodos de aprendizaje en Medicina del Trabajo y en Medicina Legal, se pues en marcha una iniciativa desde la Cátedra de Me3dicina Legal y Forense de la Universidad de Zaragoza, como parte del Proyecto NetWorm de la Unión Europea, liderado desde 1999 por la Universidad Ludwig-Maximilians de Múnich (Alemania) Este proyecto ha resultado ser de una gran eficiencia, permitiendo la creación y validación de casos en Medicina Legal y del Trabajo en el programa de la Licenciatura en Medicina(AU)

The use of online teaching tools facilitate the incorporation of methods in self-learning which could provide a good instrument for teaching support and even help in common training activities in an international context. Based on this philosophy and with a view to encouraging convergence in teaching tools and methods in Occupational and Legal Medicine, an initiative was set up within the Master Classes of Legal and Forensic Medicine at Saragossa University, par of the EU funded NetWorm project, with has been led since 1999 by Lud wigMaximilians-Universität in Munich (Germany). This project has proven to be highly efficient in permitting the creation and validation of casus in Occupational Legal Medicine programme imparted to students in the Medicine degree(AU)

Excitotoxicity and focal cerebral ischemia induce truncation of the NR2A and NR2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95.

The N-methyl-D-aspartate receptor (NMDAR) is central to physiological and pathological functioning of neurons. Although promising results are beginning to be obtained in the treatment of dementias, clinical trials with NMDAR antagonists for stroke, trauma and neurodegenerative disorders, such as Hungtinton's disease, have failed before. In order to design effective therapies to prevent excitotoxic neuronal death, it is critical to characterize the consequences of excessive NMDAR activation on its expression and function. Previous data have reported partial downregulation of the NR1 and NR2B receptor subunits in response to excitotoxicity and cerebral ischemia. However, the effect of NMDAR overactivation on NR2A, a subunit fundamental to synaptic transmission and neuronal survival, is still elusive. In this study, we report the rapid and extensive proteolytic processing of NR2A, together with the scaffolding protein postsynaptic density-95 (PSD-95), induced by excitotoxic stimulation of cortical neurons in vitro and by transient focal cerebral ischemia. Processing of the C terminus of NR2A is irreversibly induced by brief agonist exposure of NR2B-containing receptors, and requires calcium influx and the activity of calpain, also responsible for PSD-95 cleavage. The outcome is a truncated NR2A subunit that is stable and capable to interact with NR1 at the surface of neurons, but lacking the structural domains required for association with scaffolding, downstream signaling and cytoskeletal proteins. Therefore, a rapid and significant uncoupling of synaptic NMDARs from downstream survival pathways is expected to occur during ischemia. This novel mechanism induced by excitotoxicity helps to explain the failure of most therapies based on NMDAR antagonists.

Rehabilitación de profesionales afectados de disfonía / Rehabilitation of professional workers suffering dysphonia

La disfonía funcional es una patología que afecta con frecuencia a los profesionales de la voz (cantantes, periodistas, maestros, médicos…), y representa una importante causa de baja laboral. El tratamiento rehabilitador pretende corregir el mal uso y abuso de los órganos de fonación que suelen realizar los afectados, contribuyendo a mejorar la disfonía y a prevenir nuevos episodios. Con el presente trabajo se pudo observar objetivamente la mejoría producida mediante un programa de rehabilitación foniátrica en profesionales de la voz afectados de disfonía (AU)

Functional dysphonia is a condition frequently affecting “voice professionals” (singers, news reporters, teachers, physicians, etc.), and is an important cause of sick leave among this professional group. Rehabilitation therapy aims at correcting misuse and abuse of the phonation organs that is usually seen among the people affected, thus contributing to the improvement of dysphonia and to the prevention of further episodes. In the course of the here presented study we have been able to objectively observe the improvement achieved through a phoniatric rehabilitation programme among voice professionals suffering dysphonia (AU)

[Pilot study for the inclusion of the portfolio of the family medicine specialist book in training]. / Estudio piloto para la incorporación del portafolio del libro del especialista en medicina de familia en formación.

BACKGROUND: The Spanish Family Medicine National Commission is proposing a new portfolio-type Specialist Training Book (STB). OBJECTIVE: To pilot its contents, structure, and implementation strategies. DESIGN: Cross-sectional, descriptive study. SETTING: A Provincial Family Medicine Teaching Unit. PARTICIPANTS: Twenty-eight tutors and 36 residents. METHODS: For 9 months the participants conducted a training assessment on diverse areas of competence by means of tasks at work. Tutors recorded information on the quality of reflection achieved by residents and the tasks they performed by means of the card model proposed in the STB. Residents filled in an ad hoc survey. A univariate analysis of quantitative data was conducted. RESULTS: Thirty-three surveys were received from residents; 21 tutors handed in 67 evaluation reports (average: 3 per tutor). They dealt with all the areas of competence, particularly those of communication, teaching, and ethics. Tasks most used were clinical sessions, critical incidents and video-recording. Both tutors and residents thought that the new method could be useful for reflecting on clinical practice, understanding their own areas of competence better and for strengthening the tutor-trainee relationship, especially if some suggestions to improve its practical use and reduce time and effort involved were taken into account. CONCLUSIONS: The new STB in its current version or with some modifications is a useful tool for residents' training assessment and is probably accepted well in our ambit.

El síndrome del "falso mobbing": dificultades para su diagnóstico en atención primaria / The "false mobbing" syndrome: difficulties of diagnosis in primary care

No disponible

Bactericidal effect of ADP and acetic acid on Bacillus subtilis.

Bacillus subtilis is a ubiquitous soil bacterium used for measuring the beta-lysin activity and in other bioassays. We observed a complete bactericidal effect of ADP on B. subtilis at concentrations of 50-100 microM at pH values <5.5, which disappeared at pH values above 6. The effect was also found for acetic acid at concentrations >17.4 microM and similar pH values. ATP, adenosine, and HCl were not bactericidal. We used BCECF-AM, a pH-sensitive probe, and found that the killing of B. subtilis was due to a change in the intracellular pH caused by the passage across the cell membrane of these weak organic acids when incubated with B. subtilis at pH values near the pK. More experiments are needed to determine the biological meaning of these in vitro findings.

Sustained increase in rat myocardial alpha 1A-adrenoceptors induced by 6-hydroxydopamine treatment involves a decelerated receptor turnover.

The biochemical mechanisms involved in the alpha 1-adrenoceptor up-regulation and possible changes in subtypes of adrenoceptors in the rat heart after chemical denervation were investigated. The effects of acute 6-hydroxydopamine treatment (two increasing doses 24 h apart) on the pseudo-steady state densities and turnover rates of alpha 1-adrenoceptors were studied in ventricular myocardium of the rat. We have assessed the repopulation kinetics of [3H]prazosin binding sites after irreversible inactivation of alpha 1-adrenoceptors induced by a single dose of phenoxybenzamine (1 mg/kg i.p.) in rats acutely treated either with 6-hydroxy-dopamine or with vehicle (control animals). Seven days after the last administration of 6-hydroxydopamine an enhanced density of [3H]prazosin binding sites (Bmax 58.7 +/- 3.6 fmol/mg protein vehicle-treated rats versus 82.6 +/- 5.3 fmol/mg protein 6-hydroxydopamine-treated rats) was observed. This was not accompanied by changes in the dissociation constant value. Furthermore, the proportion of high affinity sites for WB-4101 was altered (21 +/- 2% versus 72 +/- 3% for animals treated with vehicle and 6-hydroxydopamine, respectively). In rat myocardium, alpha 1-adrenoceptor turnover, evaluated during the 6-hydroxydopamine-induced up-regulation (7-19 days after the completion of treatment with 6-hydroxydopamine) revealed an increase in the half-life of the alpha 1-adrenoceptor (t1/2 of 67.2 h versus 38.7 h in control animals). The present study confirms an increase in alpha 1-adrenoceptors in rat myocardium after chemical denervation and reveals that the effect is almost completely confined to the alpha 1A-adrenoceptor subtype. Furthermore, the up-regulation of alpha 1A-adrenoceptors is the result of a decrease in the cellular processes that control the rate of receptor degradation.

Vacuolar carboxypeptidase Y of Saccharomyces cerevisiae is glycosylated, sorted and matured in the fission yeast Schizosaccharomyces pombe.

Vacuolar carboxypeptidase Y of Saccharomyces cerevisiae (CPYsc) has been expressed in a Schizosaccharomyces pombe strain devoid of the endogenous equivalent peptidase, employing a 2 mu derived plasmid. Immunoblot analysis revealed that CPYsc produced in the fission yeast has a higher molecular mass than mature CPYsc produced by the budding yeast. CPYsc is glycosylated when expressed in S. pombe and uses four N-linked glycosylation sites as shown by endoglycosidase H digestion. Carbohydrate removal leads to a protein moiety which is indistinguishable in size from deglycosylated CPYsc produced by S. cerevisiae. CPYsc isolated from S. pombe soluble extracts is enzymatically active and thus is presumed to undergo correct proteolytic maturation. Subcellular fractionation experiments showed a cofractionation of CPYsc with the S. pombe endoproteinases PrA and PrB, suggesting that the protein is correctly sorted to the vacuole and that these peptidases might be responsible for zymogen activation.

In vivo recovery of alpha 1-adrenoceptors in rat myocardial tissue after alkylation with phenoxybenzamine.

The rate of recovery of rat myocardial alpha 1-adrenoceptor density and responsiveness after in vivo block with phenoxybenzamine (1 mg/kg, i.p.) have been investigated by measuring [3H]prazosin binding, and noradrenaline-stimulated [3H]inositol phosphate production. Repopulation of alpha 1-adrenoceptors was monoexponential, with a t1/2 of 33 h; functional recovery was also monoexponential, with t1/2 of 28 h. Furthermore, our results clearly demonstrate the absence of a receptor reserve for alpha 1-adrenoceptors mediating noradrenaline-stimulated phosphoinositide breakdown in rat myocardial tissue. These observations indicate a close relationship between the density of [3H]prazosin binding sites and the ability of alpha 1-adrenoceptors to respond to noradrenaline. Moreover, based on competition curves for inhibition of specific [3H]prazosin by WB-4101 to rat myocardial membranes 48 h and 7 days after the administration of phenoxybenzamine, the results suggest that rat myocardial membranes contain both alpha 1-adrenoceptors subtypes, i.e., alpha 1A and alpha 1B, in an approximate ratio of 20:80, and this relative ratio does not seem to be altered during the recovery process.

Effects of age on alpha 1-adrenoceptor subtypes in the heart ventricular muscle of the rat.

The effects of ageing on alpha 1-adrenoceptor subtypes have been examined in heart ventricular muscle of young (2-3 months) and middle-aged (18 months) Sprague-Dawley rats. Radioligand binding studies with [3H]prazosin revealed an age-related loss of binding sites (Bmax 56.7 +/- 1.93 fmol (mg protein)-1 age 2 months vs 31.7 +/- 2.45 fmol (mg protein)-1 age 18 months) not followed by changes in the dissociation constant value (Kd 0.16 +/- 0.03 nM age 2 months and 0.10 +/- 0.03 nM age 18 months). Competition curves with WB 4101 showed two distinct sites with different affinities, the proportion of sites with high affinity being similar for both age groups (22.2 +/- 1.89% vs 17.8 +/- 1.96% for animals aged 2 and 18 months, respectively). Agonist displacement curves of [3H]prazosin indicate the existence of two different affinity sites for the agonist, that are maintained regardless of the ageing process (R(high) = 16.2 +/- 1.54% and R(low) = 83.8 +/- 1.89% in rats aged 2 months and R(high) = 16.3 +/- 3.23% and R(low) = 83.7 +/- 3.95% in rats aged 18 months). The fractional inactivation of alpha 1-adrenoceptors by chloroethylclonidine resulted in a loss of [3H]prazosin specific binding, and a percentage of 22.5 +/- 0.95 and 22.6 +/- 4.2 of remaining binding sites for the groups of 2 and 18 months of age, respectively. The percentage of chloroethylclonidine-insensitive [3H]prazosin binding sites was similar to those with high affinity for WB4101. The present study confirms a decline of alpha 1-adrenoceptors with increasing age and reveals that the equilibrium of the expression of the two existing subpopulations of the receptor is maintained during ageing.

Alpha 1-adrenoceptor subtypes and inositol phosphates production in heart ventricles of spontaneously hypertensive rats.

To study potential cardiac alpha 1-adrenoceptor changes in the stage of established hypertension, [3H]prazosin binding characteristics and norepinephrine (NE) stimulated production of inositol phosphates in the ventricular tissue of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto control rats (WKY) were determined. The maximum number of cardiac [3H]prazosin binding sites was significantly reduced in SHR as compared with WKY rats, but the Kd values were similar in both groups of animals. Distribution of the [3H]prazosin-labeled high- and low-affinity binding sites for WB 4101 was similar in SHR and WKY rats. Pretreatment of ventricular heart membranes with the irreversible alpha 1B-adrenoceptor-selective antagonist chloroethylclonidine resulted in the same percentage of loss of specific [3H]prazosin binding in both groups of rats. Together, these results showed a similar ratio of alpha and alpha 1B-adrenoceptor subtypes in SHR and WKY rats. In addition, [3H]inositol phosphate accumulation in response to cardiac alpha 1-adrenoceptor stimulation by NE was significantly reduced in SHR as compared with WKY rats although the EC50 values were not significantly different in the two strains of animals. Thus, we conclude that in an established stage of hypertension there is a specific loss in the number of cardiac alpha 1-adrenoceptors with consequently reduced inositol phosphate turnover. These results are compatible with the reported decrease in the positive inotropic effect mediated through myocardial alpha 1-adrenoceptors in spontaneous hypertension.