Consensus statement on the use of intramuscular aripiprazole for the rapid control of agitation in bipolar mania and schizophrenia.

As much as the ideal treatment goal for severe mental illnesses such as bipolar disorder and schizophrenia is to prevent or delay the recurrence or relapse of acute episodes, when the patient presents with an acute episode, the goal should be to manage behavioural symptoms, and return to prior levels of symptomatic control. In a serious mental illness, the management of the acutely agitated state may require rapid tranquillisation (RT) to control violent and/or disturbed behaviour when all other methods of de-escalation have failed. Current clinical practice guidelines for emergency interventions in the case of acutely disturbed behaviours favour calming the patient by reducing agitation with mild sedation, but not sleep, to allow continued interaction with the patient, to ensure an accurate diagnosis, and to enable patients to be actively engaged in treatment decisions.

Effect of aripiprazole on verbal memory and fluency in schizophrenic patients : results from the ESCAPE study.

Background: Second-generation antipsychotics have gradually replaced first-generation antipsychotics as first-line treatment for patients with schizophrenia. Some positive effects on verbal cognition have been shown for the second-generation antipsychotics, but most studies are based on relatively small numbers of patients.

Objective: In the frame of the prospective, multi-centre, open-label study ESCAPE (A Prospective, Multicenter, Open-Label Study to Evaluate the Effectiveness and the Effect on Cognitive Function of a Treatment With Aripiprazole in a Broad Range of Schizophrenic Patients; clinicaltrials.

Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells.

To contribute to the question of the putative role of cystatins in Alzheimer disease and in neuroprotection in general, we studied the interaction between human stefin B (cystatin B) and amyloid-beta-(1-40) peptide (Abeta). Using surface plasmon resonance and electrospray mass spectrometry we were able to show a direct interaction between the two proteins. As an interesting new fact, we show that stefin B binding to Abeta is oligomer specific.

Loss of neuronal cell cycle control as a mechanism of neurodegeneration in the presenilin-1 Alzheimer's disease brain.

Presenilin-1 (PS1) is a component of the beta-catenin degradation machinery, and PS1 mutations linked to familial Alzheimer's disease (FAD) represent a loss of this function, leading, in non-neuronal cells, to accumulation of cyclin D1, aberrant cell cycle activation and hyperproliferation. In post-mitotic neurons, cell cycle activation is thought to be abortive and initiate apoptosis, thus contributing to AD pathogenesis. Consequently, we tested here the hypothesis that, in the PS1 FAD brain, cyclin D1 accumulation may occur and lead to neuronal apoptosis secondary to an abortive entry into the cell cycle.

Presenilin 1 stabilizes the C-terminal fragment of the amyloid precursor protein independently of gamma-secretase activity.

The cleavage of the transmembrane amyloid precursor protein (APP) by beta-secretase leaves the C-terminal fragment of APP, C99, anchored in the plasma membrane. C99 is subsequently processed by gamma-secretase, an unusual aspartyl protease activity largely dependent on presenilin (PS), generating the amyloid beta-peptide (Abeta) that accumulates in the brain of patients with Alzheimer's disease. It has been suggested that PS proteins are the catalytic core of this proteolytic activity, but a number of other proteins mandatory for gamma-secretase cleavage have also been discovered.

Failure of the interaction between presenilin 1 and the substrate of gamma-secretase to produce Abeta in insect cells.

Aggregates of beta-amyloid peptide (Abeta) are the major component of the amyloid core of the senile plaques observed in Alzheimer's disease (AD). Abeta results from the amyloidogenic processing of its precursor, the amyloid precursor protein (APP), by beta- and gamma-secretase activities. If beta-secretase has recently been identified and termed BACE, the identity of gamma-secretase is still obscure.