Safe storage of methadone in the home. An Irish audit of the effectiveness of information provision in pharmacies.

Background: Safe storage of oral methadone at home is an important issue given the risk of accidental paediatric consumption. Pharmacy protocols centre on provision of information to patients relating to general and paediatric dangers of methadone and safe storage of methadone in the home. Aim: The study aimed to audit the effectiveness of pharmacy provision of information on safety of methadone consumption and storage in the home. Methods: The study involved an audit of five criteria relating to patient awareness of general dangers of methadone use and paediatric risks, patient information recall on safe storage of methadone in the home; take home methadone dispensing in child resistant containers and safe and secured storage of methadone. Audit information was collected using a survey with consecutive adult patients attending a specialist methadone clinic over the course of four weeks (n=94), and telephone interviews with dispensing pharmacists recorded in the specialist clinic register (n=43). Results: None of the criteria reached a 100% standard. 51% reported never being provided with safety information. 97% of patients were aware of the dangers of methadone use, with females significantly more aware of dangers of methadone to users. 86% did not place their take-home methadone in a locked place. 90% reported they would seek medical help if a child had accidentally consumed methadone. 58% of pharmacists never questioned patients around storage, but 58% reported counselling patients on safe storage. Conclusions: Safe storage of methadone warrants regular and proactive pharmacy provision of information around harms associated with methadone

Purchasing Over The Counter (OTC) Medicinal Products Containing Codeine - Easy Access, Advertising, Misuse and Perceptions of Medicinal Risk.

PURPOSE: Codeine containing medicines can carry a number of health risks associated with the increase in reported misuse and dependence, however they are still readily available over the counter (OTC) in many countries. The aim of this novel study was to report on the results of a survey of customers purchasing OTC codeine containing medicinal products at pharmacies in Ireland, South Africa and England; exploring use, sources of knowledge and perception of risks. METHODS: The study design was an exploratory cross sectional survey. It involved a customer self-administered questionnaire at the point of purchase (n=1230).  Relationships between categorical variables were analysed using Pearson chi-square for bivariate analysis. Continuous scale variables were analysed using one way analysis of variance. RESULTS: In Ireland 6% stated they purchased codeine containing products weekly, in South Africa 13% and in England 16%. In Ireland and England women are more likely to view codeine containing products as harmful. In England older adults are more likely to perceive codeine containing products as harmful. A higher proportion of customers in South Africa opposed restricting codeine containing products to prescription only when compared with people in Ireland and England. CONCLUSIONS: Codeine containing products are widely purchased and used in all three jurisdictions. Whilst the majority of customers appear to have some awareness and knowledge of risks, it does not materially impact on their purchasing behaviour with a substantial minority purchasing/using such products on a weekly basis. This regularity of purchase whilst indicative of the popularity of such products, may also be a potential indicator of misuse. Future research is needed in relation to cultural and gendered differences and targeted information giving and harm reduction initiatives for safe usage of these medicinal products

Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor.

Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods

Cholesterol Loss Enhances TrkB Signaling in Hippocampal Neurons Aging in Vitro

Binding of the neurotrophin brain-derived neurotrophic factor (BDNF) to the TrkB receptor is a major survival mechanism during embryonic development. In the aged brain, however, BDNF levels are low, suggesting that if TrkB is to play a role in survival at this stage additional mechanisms must have developed. We here show that TrkB activity is most robust in the hippocampus of 21-d-old BDNF-knockout mice as well as in old, wild-type, and BDNF heterozygous animals. Moreover, robust TrkB activity is evident in old but not young hippocampal neurons differentiating in vitro in the absence of any exogenous neurotrophin and also in neurons from BDNF −/− embryos. Age-associated increase in TrkB activity correlated with a mild yet progressive loss of cholesterol. This, in turn, correlated with increased expression of the cholesterol catabolic enzyme cholesterol 24-hydroxylase. Direct cause–effect, cholesterol loss–high TrkB activity was demonstrated by pharmacological means and by manipulating the levels of cholesterol 24-hydroxylase. Because reduced levels of cholesterol and increased expression of choleseterol-24-hydroxylase were also observed in the hippocampus of aged mice, changes in cellular cholesterol content may be used to modulate receptor activity strength in vivo, autonomously or as a way to complement the natural decay of neurotrophin production

Enhancement of LTP in aged rats is dependent on endogenous BDNF

© 2011 American College of Neuropsychopharmacology.Long-term potentiation (LTP), considered the neurophysiological basis for learning and memory, is facilitated by brain-derived neurotrophic factor (BDNF), an action more evident when LTP is evoked by weak θ-burst stimuli and dependent on co-activation of adenosine A2A receptors (A2AR), which are more expressed in aged rats. As θ-burst stimuli also favor LTP in aged animals, we hypothesized that enhanced LTP in aging could be related to changes in neuromodulation by BDNF. The magnitude of CA1 LTP induced by a weak θ-burst stimuli delivered to the Schaffer collaterals was significantly higher in hippocampal slices taken from 36 to 38 and from 70 to 80-week-old rats, when compared with LTP magnitude in slices from 4 or 10 to 15-week-old rats; this enhancement does not impact in cognitive improvement as aged rats revealed an impairment on hippocampal-dependent learning and memory performance, as assessed by the Morris water maze tests. The scavenger for BDNF, TrkB-Fc, and the inhibitor of Trk phosphorylation, K252a, attenuated LTP in slices from 70 to 80-week-old rats, but not from 10 to 15-week-old rats. When exogenously added, BDNF significantly increased LTP in slices from 4 and 10 to 15-week-old rats, but did not further increased LTP in 36 to 38 or 70 to 80-week-old rats. The effects of exogenous BDNF on LTP were prevented by the A2AR antagonist, SCH58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine). These results indicate that the higher LTP magnitude observed upon aging, which does not translate into improved spatial memory performance, is a consequence of an increase in the tonic action of endogenous BDNF.Fundação para a Ciência e Tecnologia, Fundação Calouste Gulbenkian and EU (COST B-30 concerted action