The Therapeutic Potential of D-Amino Acid Oxidase (DAAO) Inhibitors

Abstract

BackgroundHealth care professionals worldwide attend courses and workshops to learn evidence-based medicine (EBM), but evidence regarding the impact of these educational interventions is conflicting and of low methodologic quality and lacks generalizability. Furthermore, little is known about determinants of success. We sought to measure the effect of EBM short courses and workshops on knowledge and to identify course and learner characteristics associated with knowledge acquisition.MethodsHealth care professionals with varying expertise in EBM participated in an international, multicentre before–after study. The intervention consisted of short courses and workshops on EBM offered in diverse settings, formats and intensities. The primary outcome measure was the score on the Berlin Questionnaire, a validated instrument measuring EBM knowledge that the participants completed before and after the course.ResultsA total of 15 centres participated in the study and 420 learners from North America and Europe completed the study. The baseline score across courses was 7.49 points (range 3.97–10.42 points) out of a possible 15 points. The average increase in score was 1.40 points (95% confidence interval 0.48–2.31 points), which corresponded with an effect size of 0.44 standard deviation units. Greater improvement in scores was associated (in order of greatest to least magnitude) with active participation required of the learners, a separate statistics session, fewer topics, less teaching time, fewer learners per tutor, larger overall course size and smaller group size. Clinicians and learners involved in medical publishing improved their score more than other types of learners; administrators and public health professionals improved their score less. Learners who perceived themselves to have an advanced knowledge of EBM and had prior experience as an EBM tutor also showed greater improvement than those who did not.InterpretationEBM course organizers who wish to optimize knowledge gain should require learners to actively participate in the course and should consider focusing on a small number of topics, giving particular attention to statistical concepts.

Effects of sodium benzoate on pre-pulse inhibition deficits and hyperlocomotion in mice after administration of phencyclidine

“…Therefore, it is likely that repeated administration of SB increases D-serine levels in the brain, although a further study is needed to confirm this. Although DAAO inhibitors were proposed as new therapeutic drugs for schizophrenia, their clinical use has been largely unsuccessful (54,55). Ferraris et al (43) reported 5-chloro-benzo[d]isoxazol-3-ol (CBIO; IC 50 = 1680 nM) as being a more potent DAAO inhibitor than SB (Ki≈16 μM).…”

The degradation (by distinct pathways) of human d‐amino acid oxidase and its interacting partner pLG72 – two key proteins in d‐serine catabolism in the brain

“…On the other hand, in the forebrain, DAAO is predominantly expressed in neurones and, in rat models, DAAO was demonstrated to interact with (and to be inhibited by) bassoon protein in the presynaptic zone: this interaction would fine‐tune the d ‐serine concentration at the synapse, consequently affecting NMDAR activity . Because alteration of the cellular concentration of the neuromodulator d ‐serine has been related to schizophrenia, and inhibition of hDAAO by specifically designed inhibitors did not yield an increase in the neuromodulator concentration, the modulation of hDAAO inhibition by pLG72 might represent a novel mechanism for promoting therapeutic approaches targeting the molecular pathogenesis rather than the symptoms of this ‘mental’ disease.…”

Exploring the uptake and framing of research evidence on universal screening for intimate partner violence against women: a knowledge translation case study

“…It is well acknowledged in the KT literature that one of the most difficult things to assess is the actual impact of new knowledge on specific policies or practices, or, ultimately, on health-related outcomes [34,75]. We have used a highly focused approach to assess the uptake and representation of a specific new research report in a range of documents, from news reports to national guidelines embedded in legislation.…”