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ABSTRACTBackground: Local anesthetic systemic toxicity (LAST) is a rare but potentially serious adverse event .Methods: Data from the US Food and Drug Administration Adverse Event Reporting System were examined for liposomal bupivacaine (LB), bupivacaine, or other injectable local anesthetics. Possible LAST cases were identified based on MedDRA system organ classes (Approach 1), a recent publication (Approach 2), and a novel approach based on LAST literature (Approach 3). Disproportionality analyses compared possible LAST cases for LB and bupivacaine with other injectable local anesthetics.Results: Approaches 1, 2, and 3 identified 75, 42, and 29 possible LAST cases associated with LB, respectively, compared with 9,595, 3,422, and 549 for other injectable local anesthetics. The proportional reporting ratios (95% CI) for LB versus other injectable local anesthetics for the 3 approaches were 1.9 (1.6–2.3), 2.9 (2.2–3.9), and 1.6 (1.1–2.2), respectively. Based on sales data, the estimated incidence of possible LAST with LB was 0.1 per 10,000 uses; literature estimates for LAST with other injectable local anesthetics were 0 to 18 per 10,000 uses.Conclusions: Our findings suggest the estimated incidence of possible LAST cases with LB is similar to, or less than, the reported incidence with other injectable local anesthetics.

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with associated systemic effects.Objective: To use gene expression microarrays in peripheral blood leukocytes of current and former cigarette smokers to identify differences associated with COPD.Materials and methods: Random forest modelling and a split-sample case–control approach were used to identify candidate predictors.Results: We identified 1013 genes and one smoking exposure variable that differentiated current and former smokers with or without COPD. This predictor set was reduced to a nine-gene classifier (IL6R, CCR2, PPP2CB, RASSF2, WTAP, DNTTIP2, GDAP1, LIPEand RPL14).Conclusion: These gene expression profiles represent potential biomarkers for COPD and may help increase mechanistic understanding of the disease.

Neurotransmitter transporters play an important role in maintaining synaptic homeostasis and in the actions of many drugs. Utilizing a technique for measuring the kinetics (synthesis, degradation, and half-life) of the dopamine transporter (DAT) protein in the rat striatum and nucleus accumbens, we have investigated the effects of systemic administration of dopamine receptor agonists and antagonists upon DAT kinetics in these brain regions. In the striatum, the dopamine D1 receptor agonist SKF38393 and the dopamine D1 receptor antagonist SCH23390 were without effect. However, the dopamine D2 receptor agonists R-(−)-propylnorapomorphine hydrochloride (NPA) and quinpirole decreased the half-life of DAT. This effect was blocked by the dopamine D2 antagonist eticlopride, which, by itself, increased the half-life of DAT. In the nucleus accumbens, the agonist SKF38393 increased the DAT half-life, whereas the antagonist SCH23390 decreased the half-life. In contrast to the striatum, NPA and quinpirole increased the DAT half-life, which was blocked by eticlopride and by itself had no effect on DAT kinetics. Cocaine increased the half-life of DAT in both the striatum and the nucleus accumbens. The results of the present study suggest that, through dopamine receptors, dopamine indirectly influences DAT protein turnover in the striatum and in the nucleus accumbens, but in different ways.