Biomedical subjects

Jeremy K Nicholson

Publications and source records attributed to Jeremy K Nicholson.

96 records · Page 6Linked to original sources

PubMed2002

Multi-component metabolic classification of commercial feverfew preparations via high-field 1H-NMR spectroscopy and chemometrics.

There is increasing interest in evaluating the clinical efficacy of herbal medicines. However, there are significant analytical problems associated with quality control and the measurement of the overall composition of such complex, multi-component mixtures as normally required in the pharmaceutical industry. Here we describe a novel NMR spectroscopic and pattern recognition analytical approach to investigate composition and variability of a commonly used herbal medicine. 600 MHz (1)H-NMR spectroscopy and principal components analysis (PCA) was used to discriminate between batches of 14 commercially available feverfew samples based on multi-component metabolite profiles. Two of the batches were significantly different from the other twelve. The twelve remaining classes could be classified into discrete groups by PCA on the basis of minor differences in overall chemical composition. NMR based pattern recognition (PR) analysis of extracts proved to be superior to PR analysis of HPLC traces of the same mixtures. This work indicates the potential value of NMR combined with PCA for the characterisation of complex natural product mixtures, and the discrimination of samples containing allegedly identical ingredients.

Chemistry, Pharmaceutical↗

PubMed2002

Application of directly coupled high performance liquid chromatography-NMR-mass spectometry and 1H NMR spectroscopic studies to the investigation of 2,3-benzofuran metabolism in Sprague-Dawley rats.

The urinary excretion of metabolites of 2,3-benzofuran was studied in Sprague-Dawley rats (n = 5) given a single dose of 150 mg/kg i.p. Urine samples were collected at defined intervals up to 7 days postdose and analyzed using (1). H NMR and directly coupled high performance liquid chromatography (HPLC)-NMR, HPLC-(mass spectrometry) MS and HPLC-MS-NMR methods. The principal metabolites were determined to be 2-hydroxyphenylacetic acid and 2-(2-hydroxyethyl)phenyl hydrogen sulfate, representing 24.3 +/- 6.0% and 19.6 +/- 6.4% of the dose, respectively. This indicates that metabolism of benzofuran to the polar species excreted in urine involves cleavage of the furan ring.

Animals↗

PubMed2002

Metabonomic assessment of toxicity of 4-fluoroaniline, 3,5-difluoroaniline and 2-fluoro-4-methylaniline to the earthworm Eisenia veneta (Rosa): identification of new endogenous biomarkers.

High-resolution 1H nuclear magnetic resonance (NMR) spectroscopy can be used to produce a biochemical fingerprint of low-molecular-weight metabolites from complex biological mixtures such as tissue extracts and biofluids. Changes in such fingerprint profiles can be used to characterize the effects of toxic insult in in vivo systems. The technique is nonselective and requires little sample preparation or derivatization. In the present study, earthworms (Eisenia veneta) were exposed to three different model xenobiotics by a standard filter paper contact test, and toxicant-induced biochemical changes were then investigated by characterizing the changes in endogenous metabolites visible in 600-MHz 1H NMR spectra of tissue extracts. The NMR spectral intensities were converted to discrete numerical values and tabulated in order to provide data matrices suitable for multivariate analysis. Principal component analysis showed that changes had occurred in the biochemical profiles relative to the undosed controls. The 2-fluoro-4-methylaniline-treated worms showed a decrease in a resonance from a compound identified as 2-hexyl-5-ethyl-3-furansulfonate using a combination of high-performance liquid chromatography (HPLC)-Fourier transform mass spectrometry (IonSpec, Lake Forest, CA, USA) and 1H and 13C NMR spectroscopy. An increase in inosine monophosphate was also observed. The 4-fluoroaniline-treated worms showed a decrease in maltose concentrations, and 3,5-difluoroaniline exerted the same effect as 2-fluoro-4-methylaniline but to a lesser extent. These changes could potentially be used as novel biomarkers of xenobiotic toxicity and could be used to determine the mechanism of action of other toxic chemicals.

Aniline Compounds↗

PubMedDate not supplied

High resolution "ultra performance" liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies.

The combination of a new 1.7 mum reversed-phase packing material, and a chromatographic system, operating at ca. 12,000 psi, (so-called ultra performance liquid chromatography, UPLC) has enabled dramatic increases in chromatographic performance to be obtained for complex mixture separation. This increase in performance is manifested in improved peak resolution, together with increased speed and sensitivity. Here, we show that UPLC offers significant advantages over conventional reversed-phase HPLC amounting to a more than doubling of peak capacity, an almost 10-fold increase in speed and a 3- to 5-fold increase in sensitivity compared to that generated with a conventional 3.5 microm stationary phase. The first functional genomic application of UPLC-MS technology is illustrated here with respect to multivariate metabolic profiling of urines from males and females of two groups of phenotypically normal mouse strains (C57BL19J and Alpk:ApfCD) and a "nude mouse" strain. We have also compared this technology to conventional HPLC-MS under similar analytical conditions and show improved phenotypic classification capability of UPLC-MS analysis together with increased ability to probe differential pathway activities between strains as a result of improved analytical sensitivity and resolution.

Animals↗

PubMedDate not supplied

Biochemical characterization of rat intestine development using high-resolution magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis.

We report details of metabolic profiles for small intestinal samples obtained using high-resolution magic-angle-spinning (HRMAS) (1)H NMR spectroscopy. Intact samples of jejunum and ileum from male Long Evans rats were analyzed on a 600 MHz spectrometer using standard one and two-dimensional (1)H NMR spectroscopic pulse sequences. The metabolic profiles of ileum and jejunum predominantly comprised a number of amino acids, lipids, glycerophosphocholine (GPC), choline, creatine, and ethanol, a number of carboxylic acids including acetate and lactate, and nucleoside bases including cytosine, isocytosine, and uracil. Principal component analysis (PCA) was applied to these NMR data to characterize the biochemical differences between jejunum and ileum tissues. Compared with ileum, jejunum contained higher levels of lipids, GPC, choline, lactate and creatinine, but lower levels of amino acids and acetate. In addition, the age dependence of the biochemical composition of intestinal tissues from young rats (15, 36 days and 3-4 months old) was studied. In general, levels of lipids, lactate, taurine and creatinine were positively correlated with age while amino acids and GPC decreased in the older age group. This study will provide a metabolic reference for further studies assessing the metabolic consequences of nutrition, stress and gut microbiota on intestinal composition.

Age Factors↗

PubMedDate not supplied

Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis.

In this review, metabonomics, a combination of data-rich analytical chemical measurements and chemometrics for profiling metabolism in complex systems, is described and its applications are reviewed. Metabonomics is typically carried out using biofluids or tissue samples. The relevance of the technique is reviewed in relation to other '-omics', and it is shown how the methods can be applied to physiological evaluation, drug safety assessment, characterization of genetically modified animal models of disease, diagnosis of human disease, and drug therapy monitoring. The different types of analytical data, mainly from nuclear magnetic resonance spectroscopy and mass spectrometry, are summarized. The outputs from a metabonomics study allow sample classification, for example according to phenotype, drug safety or disease diagnosis, and interpretation of the reasons for classification yields information on combination biomarkers of effect. Transcriptomic and metabonomic data is currently being further integrated into a holistic understanding of systems biology. An assessment of the possible future role and impact of metabonomics is presented.

Age Factors↗