RESUMO
Methylphenidate (MPH) is the most common used drug in child and adolescent psychiatry. Despite of this fact, however, little is known about its exact pharmacological mechanisms. Here we investigated the toxic effects of MPH in vitro in human embryonic kidney (HEK-293) cells stably expressing the human dopamine transporter (HEK-hDAT cells) and in cultured rat embryonic (E14.5) mesencephalic cultures. MPH alone (up to 1 mM) affected neither the growth of HEK-hDAT cells nor the survival of dopaminergic (DA) neurons in primary cultures after treatment up to 72 h. No differences in neuronal arborisation or in the density of synapses were detected. 1-methyl-4-phenylpyridinium (MPP(+)) showed no toxic effect in HEK-293 cells, but had significant toxic effects in HEK-hDAT cells and DA neurons. MPH (1 microM - 1 mM) dose-dependently reduced this cytotoxicity in HEK-hDAT cells and primary mesencephalic DA neurons. The presented results show that application of MPH alone does not have any toxic effect on DA cells in vitro. The neurotoxic effects of MPP(+) could be significantly reduced by co-application of MPH, an effect that is most likely explained by MPH blocking the DAT.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/toxicidade , Metilfenidato/farmacologia , Metilfenidato/toxicidade , Fármacos Neuroprotetores , Síndromes Neurotóxicas/patologia , Animais , Linhagem Celular , Dopamina/fisiologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/fisiologia , Humanos , Imuno-Histoquímica , Intoxicação por MPTP/patologia , Mesencéfalo/citologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/patologia , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , RatosRESUMO
The authors of the publication "Population Explosion: the Making of a Vision" state: "During our research in the US our goal was to find out how the problem of 'overpopulation' had become, or better said, been made universal following the Second World War. How was it possible that the view become consensus that population size is determined by state or internationally controlled economic variables and that the future of this planet depended upon an optimal control? Finally, how did contraception or the decision how many children a women bears become a political question? Better said, how did they become part of US foreign policy? Through our research we became acquainted with the development of the contraception of 'overpopulation,' from myth to scientific fact, from the perspective of those who were responsible for this evolution." This publication also includes the authors' conclusions of their study and 32 documents consulted by them. It is an interesting vision on how consensus is created.