Reproducibility of optical coherence tomography in vein grafts used for coronary revascularization

Background: Optical coherence tomography (OCT) is a high-resolution imaging modality able to provide near-histological images of vessel walls making it possible to distinguish intima and media layers of the vessel wall separately. The use of this imaging technique is increasing while data on the variability and reliability is lacking. The aim of this study was to investigate the reproducibility of frequency-domain OCT in vein grafts used for coronary revascularization.Methods: Five pullbacks were analyzed by the same analyst with a 1-month delay (intraobserver) and by two different analysts (interobserver). Five pairs of pullbacks from the same catheters and vein graft were also analyzed (inter pullback).Results: Optical coherence tomography showed low variability in intra- and interobserver analysis with relative differences of mean media and intima thicknesses and areas of less than 5% for most parameters.Relative differences of the same parameters in the inter pullback analysis were in the 5–15% range. Intra- and interobserver reliability was excellent (intraclass correlation coefficient [ICC] > 0.90) for intima thickness and intima, media and intima-media area measurements. Inter pullback reliability was good (ICC: 0.75–0.90) for intima and intima-media area measurements, and moderate to good for mean intima thickness measurements (ICC: 0.79; 0.7338–0.8284).Conclusions: Optical coherence tomography provides good reproducibility for the measurements of parameters relevant for the development of atherosclerosis in vein grafts.Clinical trial registration: ID NCT01834846

Full inhibition of spinal FAAH leads to TRPV1-mediated analgesic effects in neuropathic rats and possible lipoxygenase-mediated remodeling of anandamide metabolism.

Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI) of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX), and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats

Glucocorticoid receptor signaling in astrocytes is required for aversive memory formation

Abstract Stress elicits the release of glucocorticoids (GCs) that regulate energy metabolism and play a role in emotional memory. Astrocytes express glucocorticoid receptors (GR), but their contribution to cognitive effects of GC’s action in the brain is unknown. To address this question, we studied how astrocyte-specific elimination of GR affects animal behavior known to be regulated by stress. Mice with astrocyte-specific ablation of GR presented impaired aversive memory expression in two different paradigms of Pavlovian learning: contextual fear conditioning and conditioned place aversion. These mice also displayed compromised regulation of genes encoding key elements of the glucose metabolism pathway upon GR stimulation. In particular, we identified that the glial, but not the neuronal isoform of a crucial stress-response molecule, Sgk1, undergoes GR-dependent regulation in vivo and demonstrated the involvement of SGK1 in regulation of glucose uptake in astrocytes. Together, our results reveal astrocytes as a central element in GC-dependent formation of aversive memory and suggest their relevance for stress-induced alteration of brain glucose metabolism. Consequently, astrocytes should be considered as a cellular target of therapies of stress-induced brain diseases

OCT-Derived Plaque Morphology and FFR-Determined Hemodynamic Relevance in Intermediate Coronary Stenoses

Background: optical coherence tomography (OCT) might allow identifying lesion features reportedly associated with plaque vulnerability and increased risk of clinical events. Previous studies on correlation between OCT and functional lesion significance indices reported contradictory results, yet integration of complementary information from both modalities is gaining increased interest. The aim of the study was to compare plaque morphology using OCT in hemodynamically relevant vs. non-relevant lesions by fractional flow reserve (FFR). Methods: consecutive patients with intermediate grade coronary stenoses by angiography were evaluated by both FFR and OCT in this single-center study. Stenoses were labeled hemodynamically relevant in case of the FFR ≤ 0.80. Minimal lumen area (MLA), fibrous cap thickness (FCT), minimal cap thickness over the calcium, angle of the calcium, and necrotic core within the lesions were evaluated. Results: a total of 105 patients (124 vessels) were analyzed. Of them, 65 patients were identified with at least one lesion identified as hemodynamically relevant by FFR (72 vessels, 58.1%). Lesions with FFR ≤0.80 presented with lower mean and minimal lumen area (3.46 ± 1.29 vs. 4.65 ± 2.19, p =0.001 and 1.84 ± 0.97 vs. 2.66 ± 1.40, p = 0.001) compared to patients with FFR > 0.80. No differences were found between groups in the mean and minimal FCT, mean, and maximal necrotic core, calcium angle, as well as the overall rate of calcified and lipid plaques. Conclusion: hemodynamic relevance of intermediate grade lesions correlated moderately with the luminal assessment by OCT. No differences were identified in the plaque morphology between relevant and non-relevant coronary stenoses by FFR

Changes in properties of scandia-stabilised ceria-doped zirconia ceramics caused by silver migration in the electric field

Silver is one of the most promising cathode materials for low temperature (300e500 C) solid oxide fuel cells. The most important disadvantage of silver is its migration in the electric field. For better understanding of this phenomenon, an in situ observation of the migration mechanism was undertaken with the use of high-temperature microscopes. Scandia stabilised ceria doped zirconia CeScSZ electrolyte prepared from commercial powder was examined before and after silver migration experiments using scanning electron microscope. X-ray diffraction, broadband electrochemical impedance spectroscopy, and X-ray photoelectron spectroscopy. The silver electrodes for solid oxide fuel cells were prepared using magnetron sputtering. The described cells under polarisation were examined using a high-temperature low energy electron microscope. Reference cells and post-mortem cells were observed using a scanning electron microscope equipped with high temperature stage. Under polarisation, silver moved inside the electrolyte and along the surface towards the region between electrodes. The structures thus formed were similar to those previously described in the literature; however, direct observation of the deposit growth was unsuccessful. In situ scanning electron microscopy observations of the silver electrode at 650 C revealed neither melting of the smallest silver particles nor movement of silver structures. Silver migration through the electrolyte caused a reduction in grain interior conductivity of the electrolyte, whereas its grain boundary conductivity remained unaffected

Western blot analysis of LOX-15 protein levels measured in the lumbar dorsal horn (L5–L6) of the spinal cord on day 7 of control (sham) and CCI in rats.

<p>The data are presented as means ± SEM, which represent GAPDH (lower line) normalized averages derived from 6 samples per each group Results are presented as a % of control densitometry analysis of all sections. Statistical analyses were performed with one-way ANOVA with Bonferroni as post-hoc test. **p<0.01 ipsilateral versus contralateral of CCI-exposed rats and ## p<0.01 CCI ipsilateral versus control (naïve and sham) rats.</p