Summary of Study ST000604

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000328. The data can be accessed directly via it's Project DOI: 10.21228/M8MK6M This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000604
Study TitleImpact Of High Sugar Diet On L-Arginine Metabolism In The Lung (part II)
Study SummaryAsthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. We need novel therapeutic agents that are affordable, can decrease the reliance on steroids, and can improve quality of life. This clinical and mechanistic study has the potential to impact treatment of a subset of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and NO biology in the airways of asthmatics. We will pursue a clinical trial in subjects not well controlled on standard drug therapy; this strategy will address whether L-arginine is efficacious in patients receiving standard of care medications. In studies using animal models, we and others have shown that interventions that augment NO levels, through either supplementation of L-arginine or inhibition of arginase, decrease allergic airway inflammation and hyperresponsiveness-the two hallmarks of asthma. Overall, we hypothesize that a responder subset of adult severe asthma patients will derive clinical benefit from supplemental L-arginine therapy and that these patients will have a lower exhaled NO concentrations (<20 ppb) and a higher NOS2/Arg1 mRNA and protein ratio in their airway epithelial cells than non-responders. We aim to: 1) test the hypothesis that uncontrolled, adult severe asthma patients with exhaled breath NO concentrations <20 ppb will have fewer asthma exacerbations over 3 months when treated with L-arginine compared to patients with FeNO > 25, 2) determine the mechanisms by which L-arginine affects the regulation of NOS and arginase enzymes in primary airway epithelial cell cultures from severe asthmatic subjects, and 3) test the hypothesis that inhaled nanoparticle carrier formulations of L-arginine will decrease airway inflammation, airway hyperresponsiveness, and airway fibrosis at lower doses than systemically administered L-arginine. The major impact of our study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy. Our ultimate goal is to develop novel therapeutic agents to treat adult severe asthma patients better. PUBLIC HEALTH RELEVANCE: Asthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. This clinical study has the potential to improve the care of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and nitric oxide biology in the lung. If we demonstrate that L-arginine supplementation can decrease asthma attacks in a subset of severe asthmatics, it will have great implications for future research as well as for the daily lives of patients with asthma.
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Phone(530) 754-8258
Submit Date2017-04-27
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2017-07-10
Release Version1
Oliver Fiehn Oliver Fiehn application/zip

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Sample Preparation:

Sampleprep ID:SP000634
Sampleprep Summary:1. Weigh 50 mg tissue sample in to a 25 ml conical polypropylene centrifuge tube. 2. Add 2.5mL extraction solvent to the tissue sample and homogenize for 45 seconds ensuring that sample resembles a powder. In between samples, clean the homogenizer in solutions of methanol, acetone, water, and the extraction solvent. 3. Centrifuge the samples at 2500 rpm. for 5 minutes. Aliquot 2 X 500μl supernatant, one for analysis and one for a backup sample. Store backup aliquot in the -20°C freezer. 4. Evaporate one 500μl aliquot of the sample in the Labconco Centrivap cold trap concentrator to complete dryness 5. The dried aliquot is then re-suspended with 500l 50% acetonitrile (degassed as given) 6. Centrifuge for 2 min at 14000 rcf using the centrifuge Eppendorf 5415. 7. Remove supernatant to a new Eppendorff tube. 8. Evaporate the supernatant to dryness in the the Labconco Centrivap cold trap concentrator. 9. Submit to derivatization.
Sampleprep Protocol Filename:SOP_Extraction_of_Mammalian_Tissue_Samples.pdf
Sampleprep Protocol Comments:This study combined 2 different injection volumes for certain samples when processing positive mode data. The reason for this was because in certain samples the TG's were overloaded with the 1uL injections, but everything else was at a normal peak height. Therefore samples were run at a 0.1uL injection volume and took the data from 9-12.5 minutes because that's when TG's elute. The samples that were injected at 0.1uL were used for times 9 min-12.5 min and the 1uL samples were used for times 0-8.99min.