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Transporting protons is essential in several biological processes as well as in renewable energy devices, such as fuel cells. Although biological systems exhibit precise supramolecular organization of chemical functionalities on the nanoscale to effect highly efficient proton conduction, to achieve similar organization in artificial systems remains a daunting challenge. Here, we are concerned with transporting protons on a micron scale under anhydrous conditions, that is proton transfer unassisted by any solvent, especially water. We report that proton-conducting systems derived from facially amphiphilic polymers that exhibit organized supramolecular assemblies show a dramatic enhancement in anhydrous conductivity relative to analogous materials that lack the capacity for self-organization. We describe the design, synthesis and characterization of these macromolecules, and suggest that nanoscale organization of proton-conducting functionalities is a key consideration in obtaining efficient anhydrous proton transport.

The risk of seizure recurrence during drug tapering and after the discontinuation of antiepileptic drug therapy in children with epilepsy is not different whether the medications are tapered over a six-week or a nine-month period.

Proton transport (PT) plays an important role in many biological processes as well as in materials for renewable energy devices. Gaining insights into functional group requirements for PT would aid the design of new materials that provide enhanced proton conduction. In this report, we outline our efforts to understand the most probable proton conduction pathway in 1H-1,2,3-triazole systems. In triazole-based systems, both imidazole-and pyrazole-like pathways are possible. By systematically comparing structurally analogous polymers based on Nheterocycles and benz-N-heterocycles, we find that the imida-zole-like pathway makes a significant contribution to the proton transfer in 1H-1,2,3-triazole systems, while the contribution from pyrazole-like pathway is negligible.

Polyacrylates containing a different number of 1H‐1,2,3‐triazole groups per repeat unit have been synthesized via conventional free radical polymerization. These polymers were characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Proton conductivity measurements were made using impedance spectroscopy. Introduction of more than one triazole per repeat unit did not result in an increase in conductivity as there was an accompanying increase in glass transition temperature (Tg). A maximum conductivity of 17.5 μS/cm was obtained at 200 °C under anhydrous condition. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 188–196, 2009

No abstract

PurposePreventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.MethodsPatient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0–24 h), delayed (>24–120 h), and overall (0–120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.ResultsCR rates were significantly higher for palonosetron (n = 1,787) versus older 5HT3 RAs (n = 1,175) in the delayed (57 vs 45 %, P < 0.0001) and overall periods (51 vs 40 %, P < 0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98–1.34), 1.62 (1.40–1.88), and 1.56 (1.34–1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT3 RAs (27.5 %).ConclusionsPalonosetron is more effective than older 5HT3 RAs for controlling CINV in the delayed and overall postchemotherapy periods.

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (⌬⌬QTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ⌬⌬QTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ⌬⌬QTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug. Delafloxacin (RX-3341, ABT-492, and WQ-3034) is an anionic investigational fluoroquinolone antibiotic, currently in phase III development for the treatment of acute bacterial skin and skin structure infections (ABSSSI) based on its activity against Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus, Gram-negative microorganisms, and anaerobes (1). Pharmacokinetic (PK) studies have shown that the increases in the maximum plasma concentration (C max ) and total exposure (area under the concentration-time curve [AUC]) are dose proportional and greater than dose proportional, respectively, with a single intravenous (i.v.) dose of 300 to 1,200 mg in healthy volunteers (2). Both i.v. and oral formulations are expected to be available, allowing i.v.-to-oral "step-down" therapy in the appropriate patient populations. The proposed dose for the treatment of ABSSSI is 300 mg administered i.v. or 450 mg administered orally (p.o.) twice daily (BID).QT interval prolongation caused by the inhibition of potassium channels encoded by the HERG gene has been described for a variety of drug classes, including the fluoroquinolone antibiotics (3, 4). QT prolongation is associated with an increased risk of life-threatening cardiac arrhythmias, most typically torsades de pointes (TdP). The degree to which the fluoroquinolones block the cardiac potassium channels, thereby prolonging the QT interval, varies by agent (5, 6). In ...