J. Neurochem. (2010) 114, 51–61.
Abstract
Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio‐behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2‐receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D2‐receptor were higher in knockout mice compared with wild‐type. However, the binding of dopamine D2‐receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D2‐receptors to G‐proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre‐synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D2‐receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild‐type mice. Involvement of specific methionine residue oxidation in the dopamine D2‐receptor third intracellular loop is suggested by in vitro studies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D2‐receptor physiology and may be related to symptoms associated with neurological disorders and diseases.
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Purpose
To describe the development, implementation, and evaluation of a pharmacy clinical decision support tool designed to increase naloxone coprescription among people at risk for opioid overdose in a large healthcare system.
Summary
The Military Health System Opioid Registry and underlying presentation layer were used to develop a clinical decision support capability to improve naloxone coprescription at the pharmacy point of care. Pharmacy personnel use a patient identification card barcode scanner or manually enter a patient’s identification number to quickly visualize information on a patient’s risk for opioid overdose and medical history related to pain and, when appropriate, receive a recommendation to coprescribe naloxone. The tool was made available to military treatment facility pharmacy locations. An interactive dashboard was developed to support monitoring, utilization, and impact on naloxone coprescription to patients at risk for opioid overdose.
Conclusion
Initial implementation of the naloxone tool was slow from a lack of end-user awareness. Efforts to increase utilization were, in part, successful owing to a number of enterprise-wide educational initiatives. In early 2020, the naloxone tool was used in 15% of all opioid prescriptions dispensed at a military pharmacy. Data indicate that the frequency of naloxone coprescription to patients at risk for opioid overdose was significantly higher when the naloxone tool was used than when the tool was not used.
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