Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Chistabino (Pyrenean Aragonese)

Chistabino is the variety of Aragonese, a Romance dialect descended from Latin, like Spanish, still spoken in the Valley of Gistau, bordering on France and formed by the River Cinqueta, in the central part of the Spanish Pyrenees (Province of Huesca). Although it is spoken mainly in the village of Gistaín (c. 240 inhabitants; c. 1400 m above sea-level, near latitude 42°35′), and is fairly well preserved by the older generations there, fluent speakers can still be found also in the nearby locality of San Juan. The other inhabited villages in the valley (Plan, Serveto, Sin and Saravillo) have suffered much greater degrees of erosion by Castilian (Standard Spanish), which has increased its influence through much improved communications, leading to the development of tourism in the area and emigration by the young in search of greater prosperity. The remaining village, Señes, has been uninhabited since 1970.

Directional and fluctuating asymmetry in finger and a-b ridge counts in psychosis: a case-control study

Background: Several studies have reported alterations in finger and a-b ridge counts, and theirderived measures of asymmetry, in schizophrenia compared to controls. Because ridges are fully formed by the end of the second trimester, they may provide clues to disturbed early development. The aim of this study was to assess these measures in a sample of patients with psychosis and normal controls.Methods: Individuals with psychosis (n = 240), and normal controls (n = 228) were drawn from a catchment-area case-control study. Differences in finger and a-b ridge count and Fluctuating Asymmetry were assessed in three group comparisons (non-affective psychosis versus controls; affective psychosis versus controls; non-affective psychosis versus affective psychosis). The analyses were performed separately for males and females. Results: There were no significant group differences for finger nor a-b ridge counts. While there were no group difference for Directional Asymmetry, for Fluctuating Asymmetry measures men with non-affective psychosis had significantly higher fluctuating asymmetry of the index finger ridge count (a) when compared to controls (FA-correlation score, p = 0.02), and (b) when compared to affective psychosis (adjusted FA-difference score, p = 0.04). Conclusion: Overall, measures of finger and a-b ridge counts, and their derived measures of directional and fluctuating asymmetry were not prominent features of psychosis in this sample. While directional asymmetry in cerebral morphology is reduced in schizophrenia, this is not reflected in dermatoglyphic variables.

Investigaciones en Teotihuacan: redefiniendo los viejos problemas

Teotihuacan se encuentra en el sector noroeste de la Cuenca de México (19' 34'N, 99VO'W) entre los 2.240 y 3.100 mt s.n.m. Es una de las culturas de la Antigüedad más asombrosas; no tan sólo por el tamaño de sus pirámides y estructura habitacionales sino porque supone el desarrollo de un fenómeno urbano extremadamente complejo que marcará el desarrollo del periodo Clásico en el Altiplano mexicano a lo largo de setecientos años de historia humana. La arqueología teotihuacana es engañosamente poco complicada. Teotihuacan se encuentra en un área accesible y por varias razones en las que se mezclan aspectos culturales, económicos (es una de las zonas arqueológicas más visitadas del mundo) y también políticos ha gozado de proyectos de investigación más o menos continuados desde hace un siglo. Para el investigador foráneo, el primer impacto se deriva del tamaño y volumen de las estructuras y de la cantidad de material arqueológico que puede derivarse de cualquier excavación en esta zona. A nivel de trabajo de campo, y en comparación con otras culturas de la Antigüedad los teotihuacanos tenían una arquitectura muy bien definida con una traza urbana bien reticulada

Estudi estratègic del coblisme com a bé cultural

Aquest treball de final de carrera tracta sobre l’aplicació de les modernes tècniques de reflexió estratègica aplicades al sector de la cultura popular catalana, concretament la cultura popular catalana que engloba les manifestacions on el vincle comú és la formació musical pròpia: la cobla. Aprofitar aquest sector, a priori tant complex i tant allunyat en principi del món d’estratègia d’empresa com aquest, és l’excusa per veure el comportament d’aquestes eines i teories, i comprovar-ne la seva eficàcia i adaptabilitat als diferents casos de la realitat, a més de poder treballar un tema tant nou com la valoració d’intangibles. A la vegada, es produeix una síntesi de treballs orientats a l’organització d’entitats sense ànim de lucre existents en la bibliografia especialitzada, i que han tingut un inexistent ressò pràctic. Això pot ser un contrasentit en un país on l’associacionisme és tan arrelat i un dels pilars socials que ens vertebren i diferencien. En el cas de la música per a cobla, especialment destacable en un moment molt important i crític per estar en un temps de transició social molt fort. També, cal destacar vivament que té una sèrie de valors afegits de qualitat i complexitat que la situen en un interessant camí entre la cultura popular i les propostes de caràcter més comercial, en unes condicions actuals de gran desconeixement social. Les vinculacions entre estratègia, innovació, responsabilitat social i cultura del coneixement, donen a aquest treball un fort caràcter actual i adaptat a la realitat en les consideracions sobre el management en general.