Diagnostic Performance of Positron Emission Tomography for the Presurgical Evaluation of Patients with Non-lesional Intractable Partial Epilepsy : Comparison among 18F-FDG, 11C-Flumazenil, and 11C-Flumazenil Binding Potential Imaging Using Statistical Imaging Analysis

To compare the diagnostic performance of 18F-FDG PET, 11C-FMZ PET, and 11C-FMZ BP imaging for the evaluation of patients with intractable partial epilepsy whose MRI findings are normal by using statistical imaging analysis. Ten patients underwent comprehensive presurgical evaluation, including PET studies, to assess the epileptic foci. The extent of cortical resection was based on the results of intracranial video-electroencephalography (IVEEG) monitoring and brain mapping under stimulation. The images of 10 patients and 30 controls were spatially normalized to templates generated in-house by non-rigid registration and the standardized images of the patients and controls were statistically compared. Epileptic focus candidates were visualized on a color map of axial images of each template and the focus site was identified in candidates for lobar location. In patients with Engel I postoperative seizure outcomes we assessed the sensitivity and specificity of the imaging methods for lobar focus localization. We also compared the concordance scores of patients with Engel I and Engel II-IV postoperative seizures. The sensitivity and specificity for lobar focus localization on 18F-FDG PET scans was 90.0% and 84.8%, respectively; it was 30.0% and 81.4% for 11C-FMZ PET, 40.0% and 66.7% for 11C-FMZ BP images, and 100.0% and 51.4% for 18F-FDG PET/11C-FMZ PET/11C-FMZ BP images. In one patient the epileptic focus not detected on 18F-FDG PET scans was shown on 11C-FMZ BP images. In patients with Engel I post-treatment seizures the concordance scores were significantly higher for 18F-FDG PET than 11C-FMZ PET and 11C-FMZ BP images (p < 0.05). With respect to sensitivity and specificity, 18F-FDG PET was superior to 11C-FMZ PET and 11C-FMZ BP imaging. However, in some patients with normal MRI results, 11C-FMZ BP studies may complement 18F-FDG PET findings in efforts to identify the epileptogenic lobar regions

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Ectopic synaptic ribbons in dendrites of mouse retinal ON- and OFF-bipolar cells

The ectopic distribution of synaptic ribbons in dendrites of mouse retinal bipolar cells was examined by using genetic ablation of metabotropic glutamate receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry. Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites increased gradually during early growth and reached a plateau level of about 20% at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon-specific protein, but the associated vesicles were immunonegative for synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic ribbons was correlated with an increase in the roundness of the invaginating dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of OFF-cone bipolar cells (T1–T4), only the T2-type, which had a greater number of synaptic ribbons at the axon terminal and a thicker axon cylinder than the other types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type mice under enhanced-light adaptation (considered similar to the mGluR6-deficient state), the roundness in the invaginating dendrites and axon terminals of rod bipolar cells increased, but no ectopic ribbons were detected. Based on these findings and known mechanisms for neurotransmitter release and protein trafficking, the possible mechanisms underlying the ectopic ribbons are discussed on the basis of intracellular transport for the replenishment of synaptic proteins