ABSTRACT
Methodology for quantitative evaluation of electron radiation damage and calculation of tolerable electron dose was developed to achieve damage-less scanning electron microscope (SEM) observation of beam-sensitive polymer film. The radiation damage is typically evaluated with visual impressions of SEM images; however, this method may be unreliable because observer's subjectivity may affect the results. Evaluation with quantitative value is crucial to improve reliability. In this study, the radiation damage was evaluated by using normalized correlative coefficient (RNCC) between an initial frame and latter frames of the multiple SEM images that were taken consecutively. Tolerable dose was obtained by defining a threshold point of RNCC where rapid reduction of RNCC started. A SEM image with less damage and acceptable signal-to-noise ratio was obtained by integrating the images from the initial frame to the tolerable frame.
ABSTRACT
We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.
Subject(s)
Nutritional Sciences , Quinones/chemistry , Vitamin E/chemistry , Animals , CHO Cells , Cricetinae , Dogs , Dose-Response Relationship, Drug , Drug Design , Fibroblasts/metabolism , Friedreich Ataxia/metabolism , Humans , Hydrolases/chemistry , Mice , Micronucleus Tests , Models, Chemical , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oxidation-Reduction , Oxidative Stress , Rats , Vitamin E/analogs & derivatives , Vitamin E/metabolism , Vitamin E/pharmacology , alpha-Tocopherol/metabolismABSTRACT
We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.
