ABSTRACT
ABSTRACT: Ketamine is a dissociative anesthetic commonly used for procedural sedation owing to its perceived favorable safety profile. Despite its frequent use, overdoses of ketamine are rarely reported, and no cases with serum levels of ketamine or its metabolite have previously been reported. We report a case of an iatrogenic pediatric ketamine 20 mg/kg intramuscular overdose with serial ketamine and norketamine levels that resulted in minimal toxicity.
Subject(s)
Drug Overdose , Ketamine , Anesthetics, Dissociative , Child , Humans , Iatrogenic Disease , Ketamine/adverse effects , MorbidityABSTRACT
Accumulation of oxidized proteins, and especially ß-amyloid (Aß), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aß through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aß in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aß. Indeed, the novel MsrA-deficient APP mice (APP(+)/MsrAKO) exhibited higher levels of soluble Aß in brain compared with APP(+) mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP(+)/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aß solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.