Anti-NCL (aa 2-17) polyclonal antibody

The carnitine transporter OCTN2 is associated with asthma and other inflammatory diseases. The aims of this work were (i) to determine carnitine uptake into freshly isolated human alveolar type I (ATI)-like epithelial cells in primary culture, (ii) to compare the kinetics of carnitine uptake between respiratory epithelial in vitro cell models, and (iii) to establish whether any cell line was a suitable model for studies of carnitine transport at the air-blood barrier. Levels of time-dependent [H-3]-acetyl-L-carnitine uptake were similar in ATI-like, NCl-H441, and Calu-3 epithelial cells, whereas uptake into A549 cells was -5 times higher. Uptake inhibition was more pronounced by OCTN2 modulators, such as L-Carnitine and verapamil, in ATI-like primary epithelial cells compared to NCl-H441 and Calu-3 epithelial cells. Our findings suggest that OCTN2 is involved in the cellular uptake of acetyl-L-carnitine at the alveolar epithelium and that none of the tested cell lines are optimal surrogates for primary cells.

Background-The nonculprit lesion (NCL) management in ST-segment-elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario. Methods and Results-The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n= 31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n= 45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n= 110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3-4 days later) procedures (r=0.98; 95% confidence interval, 0.96-0.99; mean difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was kappa=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99). Finally, in cohort C, we identified 110 ST-segmentelevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value <= 0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2-4.5; P=0.01). Conclusions-In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment-elevation myocardial infarction patients.