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.

Emerging environmental and weather challenges in outdoor sports

Given the climatic changes around the world and the growing outdoor sports participation, existing guidelines and recommendations for exercising in naturally challenging environments such as heat, cold or altitude, exhibit potential shortcomings. Continuous efforts from sport sciences and exercise physiology communities aim at minimizing the risks of environmental-related illnesses during outdoor sports practices. Despite this, the use of simple weather indices does not permit an accurate estimation of the likelihood of facing thermal illnesses. This provides a critical foundation to modify available human comfort modeling and to integrate bio-meteorological data in order to improve the current guidelines. Although it requires further refinement, there is no doubt that standardizing the recently developed Universal Thermal Climate Index approach and its application in the field of sport sciences and exercise physiology may help to improve the appropriateness of the current guidelines for outdoor, recreational and competitive sports participation. This review first summarizes the main environmental-related risk factors that are susceptible to increase with recent climate changes when exercising outside and offers recommendations to combat them appropriately. Secondly, we briefly address the recent development of thermal stress models to assess the thermal comfort and physiological responses when practicing outdoor activities in challenging environments.

Maintenance process development for remote administration of network servers

Maintenance is a part of system development and it is possible to develop operation models for accomplishing maintenance tasks. These models can be applied to individual maintenance tasks, maintenance projects and version management. Beneficial operation models makes maintenance more effective and they assist in managing various changes. The purpose of this thesis was to develop a maintenance process which can be used to remote administer network servers. This consisted of defining those operation models and technical specifications which enable to set up, manage changes, maintain and monitor resources of information systems that are located in several different sites. At first in this thesis the needs of the process were determined and requirements were defined based on those needs. The meaning of processes in maintenance of information systems, maintenance workflows and challenges were studied. Then current practical problems and disadvantages of maintenance work were analyzed in order to focus the development to proper issues. Because available operation models did not cover all the recent needs, new maintenance process which fulfilled the requirements was developed.

Is Inefficiency under control in the Justice Administration?

Efficiency in the administration of justice is found to increase over time, while the variation in the efficiency of the courts tended to remain low and fall over time. This would appear to be good news, at least for the case studied here: the civil courts of first instance in Spain between 2005 and 2009. Apart from the simple passing of time, the percentage of temporary judges in the system also determines some of the differences in efficiency between courts over time. Thus, we find that the greater the percentage of temporary judges, the lower is the efficiency of the courts. Overall, the average relative efficiency level for the period 2005 to 2009 was 97.46%, suggesting the matter is under control.

Annales de l'Institut national agronomique : administration, enseignement et recherche

1919 (SER2,T14).

Annales de l'Institut national agronomique : administration, enseignement et recherche

1879 (A4,N5)-1880.

Annales de l'Institut national agronomique : administration, enseignement et recherche

1904 (SER2,T3,FASC1).

Annales de l'Institut national agronomique : administration, enseignement et recherche

1892 (N15,A20)-1896.

Annales de l'Institut national agronomique : administration, enseignement et recherche

Variante(s) de titre : Ecole supérieure de l'agriculture

Annales de l'Institut national agronomique : administration, enseignement et recherche

1929 (SER2,T24)-1931.