No abstract

Recent evidence indicates that systemic glucose treatment enhances memory while producing a corresponding increase in hippocampal acetylcholine (ACh) output. The present experiments examined whether unilateral intrahippocampal infusions of glucose would enhance spontaneous alternation performance and whether there would be a corresponding increase in ACh output in the ipsilateral and contralateral hippocampus. Extracellular ACh was assessed in samples collected at 12 min intervals using in vivo microdialysis with HPLC with electrochemical detection. Twelve minutes after a unilateral infusion of artificial cerebrospinal fluid (CSF) or glucose (6.6 mM), rats were tested in a cross maze for spontaneous alternation behavior with concurrent microdialysis collection. In two experiments, glucose infusions significantly increased alternation scores (67.5 and 59%) compared with CSF controls (42.4 and 39.5%, respectively). In both experiments, behavioral testing resulted in increased ACh output in the hippocampus. Glucose administration at the time of alternation tests enhanced ACh output beyond that of behavioral testing alone both ipsilateral (+93.8%) and contralateral (+85%) to the infusion site, as compared with ACh output (+36.1% and +55.5%) of CSF controls. Glucose infusions did not affect hippocampal ACh output in rats kept in a holding chamber. These results suggest that glucose may enhance alternation scores by modulating ACh release. The findings also indicate that unilateral glucose infusions increase hippocampal ACh output both ipsilateral and contralateral to the site of injection. Furthermore, glucose increased ACh output only during maze testing, suggesting that specific behavioral demands, perhaps requiring activation of cholinergic neurons, determine the efficacy of glucose in modulating ACh release.

Globally, national pharmacovigilance systems rely on spontaneous reporting in which suspected adverse drug reactions (ADRs) are reported to a national coordinating centre by health professionals, manufacturers or patients. Spontaneous reporting systems are the easiest to establish and the cheapest to run but suffer from poor-quality reports and underreporting. It is difficult to estimate rates and frequencies of ADRs through spontaneous reporting. Public health programmes need to quantify and characterize risks to individuals and communities from their medicines, to minimize harm and improve use, to sustain public confidence in the programmes, and to track problems due to medication errors and poor quality medicines. Additional methods are therefore needed to monitor the quantitative aspects of medicine safety, to better identify specific risk factors and high-risk groups, and to characterize ADRs associated with specific medicines and in specific populations. The present paper introduces two methods, cohort event monitoring and targeted spontaneous reporting, that are being implemented by the WHO, in its public health programmes, to complement spontaneous reporting. The advantages and disadvantages of these methods and how each can be applied in clinical practice are discussed.

This study has helped identify some of the special challenges and barriers to promoting pharmacovigilance in low- and middle-income countries. A pharmacovigilance strategy in these settings needs to help build health systems that can serve the purpose of multiple health conditions. It needs to identify and implement feasible systems, governance, infrastructures, human resource, training and capacity building, sustainable methodologies and innovations in pharmacovigilance; a key component will be the dissemination of medicines safety information to policy makers and regulators and knowledge sharing with healthcare professionals through high quality informatics and learning tools, with rational use of medicines and patient safety as the ultimate goal of pharmacovigilance.

This study provides a comprehensive review on the methods used in patient reporting of ADRs. Although there are some differences in the way various countries handle patient reports of ADRs, the importance of giving the public the opportunity to report and the additional scientific value of the collected data is widely recognized by the countries who participated in this survey.