Scavenger Receptor-AI-Targeted Iron Oxide Nanoparticles for in Vivo MRI Detection of Atherosclerotic Lesions.

Scavenger Receptor-AI-Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions.

Arterioscler Thromb Vasc Biol. 2013 Jun 6;
Segers FM, den Adel B, Bot I, van der Graaf LM, van der Veer E, Gonzalez W, Raynal I, de Winther M, Wodzig WK, Poelmann RE, van Berkel TJ, van der Weerd L, Biessen EA

OBJECTIVE: In search of molecular imaging modalities for specific detection of inflammatory atherosclerotic plaques, we explored the potential of targeting scavenger receptor-AI (SR-AI), which is highly expressed by lesional macrophages and linked to effective internalization machinery. APPROACH AND RESULTS: Iron oxide-based ultrasmall superparamagnetic iron oxide (USPIO) was conjugated to a peptidic SR-AI ligand (0.371 mol Fe/L and 0.018 mol PP1/L). In vitro incubation of human or murine macrophages with SR-AI-targeted USPIO led to significantly higher iron uptake in vitro than with nontargeted USPIO, as judged by quantitative atomic absorption spectroscopy and Perl’s staining. Incremental uptake was strictly mediated by SRs. SR-AI-targeted USPIO displayed accelerated plasma decay and a 3.5-fold increase (P=0.01) in atherosclerotic plaque accumulation on intravenous injection into apolipoprotein E-deficient mice compared with nontargeted USPIO. In keeping, atherosclerotic humanized LDLr(-/-) chimeras with leukocyte expression of human SR-AI showed a significant improvement in contrast-to-noise ratio (2.7-fold; P=0.003) in the atherosclerotic aortic arch plaques 24 hours after injection of SR-AI-targeted USPIO compared with chimeras with leukocyte SR-AI deficiency. CONCLUSIONS: Collectively, our data provide several lines of evidence that SR-AI-targeted molecular imaging of USPIO-based contrast agents holds great promise for in situ detection of inflammatory plaques in manifest atherosclerosis. HubMed – drug


Correction: Analysis of mRNA Profiles after MEK1/2 Inhibition in Human Pancreatic Cancer Cell Lines Reveals Pathways Involved in Drug Sensitivity.

Mol Cancer Res. 2013 Jun 6;

HubMed – drug


Drug therapy in undifferentiated arthritis: a systematic literature review.

Ann Rheum Dis. 2013 Jun 6;
Wevers-de Boer KV, Heimans L, Huizinga TW, Allaart CF

Undifferentiated arthritis (UA) is defined as an inflammatory oligoarthritis or polyarthritis in which no definitive diagnosis can be made. We performed a literature review to assess the efficacy of various drug therapies in patients with UA. The literature search was conducted using electronic databases Pubmed, EMBASE and MEDLINE in adults with UA or early arthritis (not fulfilling the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis). Drug therapy consisted of disease modifying antirheumatic drugs (DMARDs), biological agents and oral, intramuscular or intra-articular corticosteroids. Nine publications on eight randomised controlled trials (RCTs), two publications on two uncontrolled open-label trials and seven publications on three cohort studies were included. Temporary treatment with methotrexate (MTX), abatacept and intramuscular corticosteroids were demonstrated in RCTs with 12 months to 5 years follow-up to be more effective than placebo in suppressing disease activity or radiological progression. One study suggests that DMARD combination therapy is, at least after 4 months, superior to MTX monotherapy in patients with UA at high risk of developing persistent arthritis. The open-label uncontrolled trials and cohort studies also suggested that early treatment may provide immediate suppression of inflammation. The long-term benefit of early treatment in UA remains unclear. In conclusion, patients with UA benefit from early treatment with MTX. Combining multiple DMARDs or DMARDs with corticosteroids and biological agents may be even more beneficial. However, which treatment may provide the best results or may alter the disease course has still to be determined. More RCTs with longer follow-up time are needed. HubMed – drug


The Effect of a Bolus Dose of Intravenous Lidocaine on the Minimum Alveolar Concentration of Sevoflurane: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.

Anesth Analg. 2013 Jun 6;
Hamp T, Krammel M, Weber U, Schmid R, Graf A, Plöchl W

BACKGROUND:The anesthetic effect of volatile anesthetics can be quantified by the minimum alveolar concentration (MAC) of the drug that prevents movement in response to a noxious stimulus in 50% of patients. The underlying mechanism regarding how immobilization is achieved by volatile anesthetics is not thoroughly understood, but several drugs affect MAC. In this study, we investigated the effect of a single IV bolus dose of lidocaine on the MAC of sevoflurane in humans.METHODS:We determined the MAC for sevoflurane using the Dixon “up-and-down” method in 3 groups of patients, aged 30 to 65 years, who underwent elective surgery (30 patients per group). Study medication (placebo, 0.75 mg·kg(-1) lidocaine or 1.5 mg·kg(-1) lidocaine) was administered 3 minutes before skin incision after a 15-minute equilibration period and the response to skin incision was recorded (movement versus no movement).RESULTS:MAC was 1.86% ± 0.40% in the placebo and 1.87% ± 0.45% in the 0.75 mg·kg(-1) lidocaine group (P = 1.00). MAC was 1.63% ± 0.24% in the 1.5 mg·kg(-1) lidocaine group, which was significantly lower than that of the placebo group (mean difference of 0.23% sevoflurane [95% adjusted confidence interval {CI}, 0.03-0.43]; P = 0.022). No significant difference was observed between the 0.75 mg·kg(-1) lidocaine and the placebo groups (mean difference of -0.01% sevoflurane [95% adjusted CI, -0.27 to 0.25]; P = 1).CONCLUSIONS:IV 1.5 mg·kg(-1) lidocaine decreased the MAC by at least 0.03% sevoflurane (mean difference 0.23% sevoflurane [95% adjusted CI, 0.03-0.43]). We did not observe a significant reduction in the MAC of sevoflurane with the IV administration of 0.75 mg·kg(-1) lidocaine. HubMed – drug