Tweets about prescription opioid use may reveal insights into the prescription drug epidemic. We qualitatively assessed 2,100 tweets about prescription opioids utilizing a Twitter Archiving Google Spreadsheet® and determined whether the tweet represented: abuse (i.e., use to get high), not abuse (i.e., use as analgesic), or was not characterizable (e.g., "I need a Percocet") and whether the connotation was positive (i.e. promote psychoactive or analgesic use), negative (i.e., adverse event), or not characterizable. Abuse was commonly described and the majority of terms (>66%) represented a positive connotation. Twitter can be a resource to observe trends in perceptions about prescription opioid use.

Lipoproteins are a family of plasma nanoparticles responsible for the transportation of lipids throughout the body. High-density lipoprotein (HDL), the smallest of the lipoprotein family, measures 7–13 nm in diameter and consists of a cholesteryl ester and triglyceride core that is covered with a monolayer of phospholipids and apolipoproteins. We have developed an iron oxide core HDL nanoparticle (FeO-HDL), which has a lipid based fluorophore incorporated in the phospholipid layer. This nanoparticle provides contrast for optical imaging, magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Consequently, FeO-HDL can be visualized on the anatomical, cellular and sub-cellular level. In the current study we show that the biophysical features of FeO-HDL closely resemble those of native HDL and that FeO-HDL possess the ability to mimic HDL characteristics both in vitro as well as in vivo. We demonstrate that FeO-HDL can be applied to image HDL interactions and to investigate disease settings where HDL plays a key function. More generally, we have demonstrated a multimodal approach to study the behavior of biomaterials in vitro as well as in vivo. The approach allowed us to study nanoparticle dynamics in circulation, as well as nanoparticle targeting and uptake by tissues and cells of interest. Moreover, we were able to qualitatively assess nanoparticle excretion, critical for translating nanotechnologies to the clinic.

Objective Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice due to cytotoxicity from free cholesterol accumulation, while we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on pre-established, advanced lesions of apoE-/- mice. Methods & Results ApoE-/- mice on Western diet for 14 weeks developed advanced plaques, and were either sacrificed (“Baseline”), or continued on Western diet without or with F1394 and sacrificed after 14 more weeks. F1394 was not associated with systemic toxicity. Compared to the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression, and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared to the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol, plaque necrosis was not increased, and efferocytosis (phagocytic clearance of apoptotic cells) was not impaired. The effects of F1394 were independent of changes in plasma cholesterol levels. Conclusions Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apoE-/- mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis in spite of recent trial data.

SummaryNeuronal Calcium Sensor-1 (NCS-1) is a high-affinity, low-capacity Ca 2+ -binding protein expressed in many cell types. We previously showed that NCS-1 interacts with inositol 1,4,5-trisphosphate receptor (InsP3R) and modulates Ca 2+ -signaling by enhancing InsP3-dependent InsP3R channel activity and intracellular Ca 2+ transients. Recently we reported that the chemotherapeutic agent, paclitaxel (taxol) triggers μ-calpain dependent proteolysis of NCS-1, leading to reduced Ca 2+ -signaling within the cell. Degradation of NCS-1 may be critical in the induction of peripheral neuropathy associated with taxol treatment for breast and ovarian cancer. To begin to design strategies to protect NCS-1, we treated NCS-1 with μ-calpain in vitro and identified the cleavage site by N-terminal sequencing and MALDI-mass spectroscopy. μ-calpain cleavage of NCS-1 occurs within an N-terminal pseudoEF-hand domain, which by sequence analysis appears to be unable to bind Ca 2+ . Our results suggest a role for this pseudoEF-hand in stabilizing the three functional EFhands within NCS-1. Using isothermal titration calorimetry (ITC) we found that loss of the pseudoEF-hand markedly decreased NCS-1's affinity for Ca 2+ . Physiologically, this significant decrease in Ca 2+ affinity may render NCS-1 incabable of responding to changes in Ca 2+ levels in vivo. The reduced ability of μ-calpain treated NCS-1 to bind Ca 2+ may explain the altered Ca 2+ signaling in the presence of taxol and suggests a strategy for therapeutic intervention of peripheral neuropathy in cancer patients undergoing taxol treatment.

VLDL is produced by the liver. Its major protein is apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA), reduces VLDL levels and is used therapeutically for hypertriglyceridemia. In model systems, DHA lowers VLDL secretion by inducing presecretory apoB100 degradation, a process dependent on PUFA-derived lipid peroxides. We hypothesized that superoxide (SO) was a major participant in DHA-induced apoB100 degradation, given its promotion of lipid peroxidation. SO levels in a model of VLDL metabolism, rat hepatoma McArdle cells, were either decreased by a mimetic of superoxide dismutase 1 (SOD1) or by overexpressing SOD1 or increased by SOD1 siRNA. ApoB100 recovery was assessed by immunoprecipitation, SO by 2-hydroxyethidine, and lipid peroxides by thiobarbituric acid reactive substances. The SOD1 mimetic or SOD1 overexpression reduced SO and inhibited apoB100 degradation in DHA-treated cells by up to 100%. Surprisingly, silencing SOD1 did not increase DHA-induced degradation, although levels of SO were higher (+44%); those of lipid peroxides were similar, and their reduction by α-tocopherol decreased degradation by 50%. SO is required for lipid peroxidation in DHA-induced apoB100 degradation, but it is the peroxide level that has a tighter relationship to the level of degradation and the regulation of VLDL production.