RESUMO
In this article, we present a detailed analysis of archival films of 12 different patients with Parkinson's disease (PD). This unique collection of films was made by Arthur Van Gehuchten (1861-1914), the first professor of neurology in Belgium at the turn of the 20th century. These extraordinarily well-preserved century-old documents are a precise iconography of PD before encephalitis lethargica swept the world and with clinical features unaffected by treatments such as levodopa. In view of the universal interest of the International Parkinson and Movement Disorder Society-sponsored revision of the UPDRS (MDS-UPDRS) in evaluating patients with PD, we based our analysis on this scale. Of course, given the lack of detailed clinical files and the impossibility of rating a number of items, rating disease severity in a strict clinimetric sense could not be achieved. However, we did this exercise in order to place these one-century-old cases in a modern perspective. In most patients, we could score numerous items of the motor examination part of the MDS-UPDRS. These archival documents constitute a superb lesson in the semiology of PD, which keeps today its fresh didactical value.
RESUMO
The partial agonist profile of novel antipsychotics such as aripiprazole has hardly been demonstrated in biochemical assays on animal tissues. As it is established that responses induced by dopamine D2 receptor agonists are increased in models of dopaminergic sensitization, this paradigm was used in order to facilitate the detection of the partial agonist properties of aripiprazole. At variance with all other partial and full agonists tested, the partial agonist properties of aripiprazole were not revealed in guanosine 5'-O-(γ-[³5S]thiotriphosphate ([³5S]GTPγS) binding assays on striatal membranes from haloperidol-treated rats. Hence,aripiprazole behaved as an antagonist, efficiently inhibiting the functional response to dopamine. Similarly, in behavioural assays, aripiprazole dose-dependently inhibited the stereotypies elicited by apomorphine. However, at variance with haloperidol, repeated administrations of aripiprazole(3 weeks) at the doses of 10 and 30 mg/kg did not induce any up-regulation or hyperfunctionality of the dopamine D2 receptors in the striatum. These data highlight the putative involvement of other pharmacological targets for aripiprazole that would support in the prevention of secondary effects commonly associated with the blockade of striatal dopamine D2 receptors. Hence, in additional experiments, aripiprazole was found to efficiently promote [³5S]GTPγS binding in hippocampal membranes through the activation of 5-HT(1A) receptors. Further experiments investigating the second messenger cascades should be performed so as to establish the functional properties of aripiprazole and understand the mechanism underlying the prevention of dopamine receptor regulation in spite of the observed antagonism.
