Ultrasonic reporters of calcium for deep tissue imaging of cellular signals.

Calcium imaging has enabled major biological discoveries. However, the scattering of light by tissue limits the use of standard fluorescent calcium indicators in living animals. To address this limitation, we introduce the first genetically encoded ultrasonic reporter of calcium (URoC). Based on a unique class of air-filled protein nanostructures called gas vesicles, we engineered URoC to produce elevated nonlinear ultrasound signal upon binding to calcium ions. With URoC expressed in mammalian cells, we demonstrate noninvasive ultrasound imaging of calcium signaling in vivo during drug-induced receptor activation. URoC brings the depth and resolution advantages of ultrasound to the in vivo imaging of dynamic cellular function and paves the way for acoustic biosensing of a broader variety of biological signals.

Long-term use of felbamate: clinical outcomes and effect of age and concomitant antiepileptic drug use on its clearance.

PURPOSE: To determine the effects of long-term use of felbamate (FBM) on weight, complete blood count, liver function tests, and seizure control, and also to determine the effect of age on FBM clearance. METHODS: A computerized prospective database was used to identify all subjects who had FBM listed as one of their antiepileptic drugs (AEDs) during their most recent clinic visit. Medical records from each patient were then reviewed for inclusion criteria [treatment >2 years, FBM initiated at the study clinic, data for pre-FBM (Time-1; T1), one-year exposure to FBM (Time-2; T2), and the latest visit (Time-3; T3)]. Clinical information was abstracted from clinic charts. RESULTS: Seventy-seven patients (F = 41, M = 36; ages 10-69 years) met entry criteria. Mean treatment time was 7.4 years, with the longest 20.3 years. Significant weight loss (mean 5.1 kg; p < 0.001) occurred from T1 to T2, but weight was regained by T3. No clinically significant changes in laboratory parameters occurred. Older age was associated with a significant decrease in FBM clearance (p = 0.01). Significant reduction in generalized tonic-clonic seizures was seen at both T2 (p < 0.001) and T3 (p < 0.001) compared with seizure frequency at T1. DISCUSSION: Our results suggest that long-term FBM use is associated with persistent decrease of seizures and no clinically significant changes in major laboratory parameters. Older age correlated with reduced apparent clearance of FBM. The patient population described in this study were long-term users of FBM who were continuing to use the drug, and thus this study does not constitute an "intent to treat" study.