ABSTRACT
Curcumin and related compounds have been validated to remove even well-developed human ß-amyloid plaques from the brain of transgenic mice, in vivo. However, their molecular mechanism of the plaque buster activity is rather unknown. Computational chemistry was employed here to better understand the ß-amyloid protein elimination. According to our docking studies, a tautomeric "keto-enol" flip-flop mechanism is proposed that may chop up ß-amyloid plaques in Alzheimer's due to removing each hairpin-foldamers one by one from both ends of aggregated fibrils. According to the experimented models, other bi-stable "keto-enol" pharmacophores might be identified to break up amyloid plaques and enhance rapid clearance of toxic aggregates in Alzheimer's disease.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Curcumin/pharmacology , Plaque, Amyloid/drug therapy , Plaque, Amyloid/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/drug effects , Animals , Brain/drug effects , Brain/metabolism , Curcumin/chemistry , Dietary Supplements , Humans , In Vitro Techniques , Mice , Mice, Transgenic , Molecular Docking Simulation , Phytotherapy , Plaque, Amyloid/chemistry , Protein Aggregates/drug effects , Protein Aggregation, Pathological , Protein Binding/drug effectsABSTRACT
OBJECTIVES: Our aim was to investigate the feasibility of digital variance angiography (DVA) in lower extremity CO2 angiography and to compare the quantitative and qualitative performance of the new image processing technique with that of the current reference standard digital subtraction angiography (DSA). MATERIALS AND METHODS: This prospective study enrolled 24 patients (mean age ± SD, 65.5 ± 9.2 years; 14 males, 65.1 ± 7.5 years; 10 females, 66.1 ± 11.6 years) undergoing lower-limb CO2 angiography between December 2017 and April 2018 at 2 clinical centers: The Heart and Vascular Center (HVC) of Semmelweis University, Budapest (7 patients), and the Bács-Kiskun County Hospital (BKCH) in Kecskemét (17 patients). The interventional protocol was similar at both sites, but the image acquisition instruments and protocols were different, which allowed us to investigate DVA in different settings. For comparison, the signal-to-noise ratio (SNR) of DSA and DVA images were calculated. The visual quality of DSA and DVA images were compared by independent clinical specialists using an online questionnaire. Interrater agreement was characterized by percent agreement and Fleiss kappa. The specialists also evaluated in a random and blinded manner the individual DSA and DVA images on a 5-grade scale ranging from poor (1) to outstanding (5) image quality, and the mean ± standard error of mean (SEM) was calculated. RESULTS: A total of 4912 regions of interest were carefully selected in 110 image pairs to determine the SNRs. The ratio of SNRDVA/SNRDSA was calculated. At HVC, it ranged between 2.58 and 4.16 in the anatomical regions (abdominal, iliac, femoral, popliteal, crural, talar), and the overall median value was 3.53, whereas at BKCH the range was 2.71 to 4.92 and the overall median value was 4.52. During the visual evaluation, 120 DSA and DVA image pairs were compared. At HVC in 78%, although at BKCH in 90% of comparisons, it was judged that DVA provided higher quality images. The interrater agreement was 88% (P < 0.001) and 90% (P < 0.01), respectively. DVA images received consistently higher individual rating than DSA images, regardless of the research site and anatomical region. At HVC, the overall DSA and DVA scores (mean ± SEM) were 2.75 ± 0.12 and 3.23 ± 0.16, respectively (P < 0.05), whereas at BKCH these values were 2.49 ± 0.10 and 3.03 ± 0.09, respectively (P < 0.001). CONCLUSIONS: These data show that lower-limb CO2 angiography DVA, regardless of the image acquisition instruments and protocols, produces higher SNR and significantly better image quality than DSA; therefore this new image processing technique might help the widespread use of CO2 as a safer contrast agent in clinical practice.