Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics

Brindle, Joanne T.; Antti, Henrik; Holmes, Elaine; Tranter, George E.; Nicholson, Jeremy K.; Bethell, Hwl; Clarke, Sarah; Schofield, Peter M.; McKilligin, Elaine; Mosedale, David E.; Grainger, David J.

doi:10.1038/nm1202-802

Cited by 918 publications

(603 citation statements)

References 15 publications

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“…It has been applied to a variety of diseases such as heart disease [12], diabetes [13], as well as to the study of the effects of diets and drugs [14]. In kidney diseases, metabolomics demonstrated enormous potential in the research on drug-induced nephrotoxicity [15], diabetic nephropathy [16], as well as AKI.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Liu

Yan²,

Ji³

et al. 2012

Kidney Blood Press Res

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Background: Although great progress has been made in the pathogenesis and treatment of acute kidney injury (AKI), it still has high incidence and poor prognosis. The present study was performed in order to further understand the metabolomic changes of ischemia/reperfusion (I/R)-induced AKI and the protective effect of L-carnitine on AKI. Methods: Kidney tissues and serum samples were collected at different time points from three groups of rats including control group, I/R group and L-carnitine-pretreated group. High-performance liquid chromatography coupled with mass spectrometry-based metabolomics approach was applied to investigate the characteristic of I/R-induced AKI and the protective effects of L-carnitine in rat kidney I/R model. Antioxidant enzymatic activity and phospholipase A₂ activity were determined to validate the metabolic outcomes. Results: Changes in the pattern of endogenous metabolites as a result of kidney I/R injury were readily detected as early as 2 h after reperfusion, and earlier than the increase in blood urea nitrogen and serum creatinine. Twenty-eight differential endogenous metabolites were discovered and structurally identified by MSⁿ analysis. After I/R injury, lysophospholipids, free fatty acids and nitrotyrosine significantly increased, while carnitine and acetyl-carnitine significantly decreased compared to control. Phospholipase A₂ activity and malondialdehyde level also increased, while superoxide dismutase activity decreased in kidney I/R injury rats. Treatment of L-carnitine 30 min prior to reperfusion significantly relieved I/R-induced metabolomic changes. Conclusion: I/R-induced AKI could be characterized by oxidative stress and changes in lipid metabolism through metabolomic investigation, and L-carnitine treatment 30 min before reperfusion had protective effects against I/R-induced AKI.

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Section: Introductionmentioning

confidence: 99%

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Liu

Yan²,

Ji³

et al. 2012

Kidney Blood Press Res

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“…High-resolution 1 H nuclear magnetic resonance (HR-NMR) spectroscopy, when applied to metabolomic studies, has provided significant information on a wide range of pathologies, like cancer (17), meningitis (18), and coronary heart disease (19), as well as a variety of gastrointestinal diseases (20). This is because an NMR profile contains qualitative and quantitative information on the hundreds of different small molecules present in a sample at Ͼ1 M concentration (21).…”

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confidence: 99%

Rifaximin Modulates the Vaginal Microbiome and Metabolome in Women Affected by Bacterial Vaginosis

Laghi

Picone

Cruciani

et al. 2014

Antimicrob Agents Chemother

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Bacterial vaginosis (BV) is a common vaginal disorder characterized by the decrease of lactobacilli and overgrowth of Gardnerella vaginalis and resident anaerobic vaginal bacteria. In the present work, the effects of rifaximin vaginal tablets on vaginal microbiota and metabolome of women affected by BV were investigated by combining quantitative PCR and a metabolomic approach based on 1 H nuclear magnetic resonance. To highlight the general trends of the bacterial communities and metabolomic profiles in response to the antibiotic/placebo therapy, a multivariate statistical strategy was set up based on the trajectories traced by vaginal samples in a principal component analysis space. Our data demonstrated the efficacy of rifaximin in restoring a health-like condition in terms of both bacterial communities and metabolomic features. In particular, rifaximin treatment was significantly associated with an increase in the lactobacillus/BV-related bacteria ratio, as well as with an increase in lactic acid concentration and a decrease of a pool of metabolites typically produced by BV-related bacteria (acetic acid, succinate, shortchain fatty acids, and biogenic amines). Among the tested dosages of rifaximin (100 and 25 mg for 5 days and 100 mg for 2 days), 25 mg for 5 days was found to be the most effective. Bacterial vaginosis (BV) is a complex polymicrobial vaginal disorder associated with an increase in the taxonomic richness and diversity of the vaginal microbiota. BV is microbiologically characterized by replacement of the lactobacillus-predominant vaginal microbiota by potential pathogenic anaerobic bacteria (1, 2). The diagnosis of BV is based on Amsel's criteria (1) and Nugent score determinations (3). The current recommended treatment of BV includes metronidazole (oral or vaginal) or clindamycin (vaginal) (4); however, the short-term (30 days) cure rate is often poor, and recurrences are common (5, 6).Rifaximin is a new candidate for the local treatment of BV thanks to its antibacterial activity, which covers Gardnerella vaginalis and other pathogens responsible for urogenital infections (7,8). Rifaximin is a semisynthetic rifamycin derivative characterized by low systemic absorption and good antibacterial activity. In common with the structural analogue rifampin and other members of the rifamycin class, it acts on the ␤ subunit of the bacterial RNA polymerase to inhibit RNA synthesis (9, 10). Recently, the efficacy of rifaximin vaginal tablets in the treatment of BV was demonstrated by evaluating the rate of clinical remission (11) and the restoration of normal vaginal communities (12) and proteome profiles (13).BV, as well as antibiotics used for the treatment of this disturbance, cause perturbations of the vaginal ecosystem, which are reflected in the overall profile of the metabolites produced by the host-bacterium metaorganism. The study of the comprehensive modifications occurring in the metabolic profiles of living systems actually represents the main field of metabolomics. Metabolomics is, by definitio...

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“…Metabolic profiling or metabolomics, defined as the analysis of multiple biofluid metabolites in parallel, holds the promise of earlier disease detection and improved understanding of systems biology (1)(2)(3). Early indications of this potential have been reported for the detection of several diseases, including inborn errors of metabolism, cardiovascular diseases, and cancer (4)(5)(6)(7).…”

mentioning

confidence: 99%

Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced ¹³ C NMR

Shanaiah

DeSilva

Gowda

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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We report a chemical derivatization method that selects a class of metabolites from a complex mixture and enhances their detection by 13 C NMR. Acetylation of amines directly in aqueous medium with 1,1 -13 C2 acetic anhydride is a simple method that creates a high sensitivity and quantitative label in complex biofluids with minimal sample pretreatment. Detection using either 1D or 2D 13 C NMR experiments produces highly resolved spectra with improved sensitivity. Experiments to identify and compare amino acids and related metabolites in normal human urine and serum samples as well as in urine from patients with the inborn errors of metabolism tyrosinemia type II, argininosuccinic aciduria, homocystinuria, and phenylketonuria demonstrate the method. The use of metabolite derivatization and 13 C NMR spectroscopy produces data suitable for metabolite profiling analysis of biofluids on a time scale that allows routine use. Extension of this approach to enhance the NMR detection of other classes of metabolites has also been accomplished. The improved detection of low-concentration metabolites shown here creates opportunities to improve the understanding of the biological processes and develop improved disease detection methodologies.carbon-13 ͉ inborn errors of metabolism ͉ metabolite profiling ͉ metabolomics ͉ metabonomics T he metabolic profile in biofluids represents a snapshot of ongoing biological processes in the human body. The presence of a particular metabolite, panel of metabolites, or a certain ratio of metabolites can indicate normal homeostasis, a response to biological stress, or even a specific disease state. Conventional medical diagnostic methods are typically based on the selective detection of a single or a few biochemical parameters that are associated with a given disease. A major challenge in the present practice of clinical medicine is the lack of suitable biomarkers and bioanalytical technologies for earlier detection of numerous diseases. Metabolic profiling or metabolomics, defined as the analysis of multiple biofluid metabolites in parallel, holds the promise of earlier disease detection and improved understanding of systems biology (1-3). Early indications of this potential have been reported for the detection of several diseases, including inborn errors of metabolism, cardiovascular diseases, and cancer (4-7).NMR and mass spectrometry are the two most often used analytical methods for metabolite profiling because of their high resolution and rich data content (8)(9)(10)(11)(12)(13)(14). Although mass spectrometry is the more sensitive technique, NMR provides broad coverage of the metabolome by detecting all of the (hydrogencontaining) metabolites present in the biofluid simultaneously, with excellent reproducibility and only limited sample pretreatment. Thus, for example, many classic inborn errors of metabolism (IEM) can be diagnosed by the use of 1 H NMR spectroscopy of body fluids (15-17). Several of the IEM are associated with the accumulation of amino acids as metabolites in serum an...

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Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics

Cited by 918 publications

References 15 publications

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Rifaximin Modulates the Vaginal Microbiome and Metabolome in Women Affected by Bacterial Vaginosis

Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced ¹³ C NMR

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Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics

Cited by 918 publications

References 15 publications

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Metabolomic Changes and Protective Effect of <i>L</i>-Carnitine in Rat Kidney Ischemia/Reperfusion Injury

Rifaximin Modulates the Vaginal Microbiome and Metabolome in Women Affected by Bacterial Vaginosis

Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced 13 C NMR

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Product

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About

Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced ¹³ C NMR