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Metabolite Patterns (metabolite + pattern)
Selected AbstractsQuantitative multivoxel proton spectroscopy of the brain in developmental delayJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2009Krijn T. Verbruggen MD Abstract Purpose To assess whether proton MR spectroscopy of the brain in children with developmental delay reveals a consistent pattern of abnormalities. Materials and Methods Eighty-eight patients (median age, 4.6 years; interquartile range, 3.1,8.1 years) with unexplained developmental delay, were compared with 48 normally developing age-matched controls. Patients and controls were assigned to five age-groups. Multivoxel MR spectroscopy was performed on a volume of interest superior to the lateral ventricles. The relative levels of choline, creatine, N-acetyl aspartate, and glutamate/glutamine in 24 voxels containing white matter and 12 voxels containing gray matter were quantified in an operator-independent manner and expressed in proportion to the total metabolite peak area in the volume of interest. Results White matter choline in DD showed less decrease with age. Mean choline levels, compared with mean control levels, increased from 99 to 111% with increasing age. This was statistically significant in the highest age groups (P = 0.015 [7 < yr , 12.8] and P = 0.039 [12.8 < yr]). Other metabolites did not show clear alterations. Conclusion Proton MR spectroscopy in a group of patients with unexplained DD shows small differences in the metabolite pattern, compared with normally developing controls, that is, higher choline in the white matter. The pathophysiological origin and significance may relate to myelination and maturation of the white matter. J. Magn. Reson. Imaging 2009;30:716,721. © 2009 Wiley-Liss, Inc. [source] Differentiation of hydatid cyst from cysticercus cyst by proton MR spectroscopyNMR IN BIOMEDICINE, Issue 5 2002Monika Garg Abstract The metabolite patterns obtained by ex vivo proton MR spectroscopy of fluid from different locations of hydatid cysts of sheep and humans (n,=,16) and cysticercus cysts of swine and humans (n,=,25) were compared with an objective of differentiating the two parasites on the basis of their metabolite pattern. The spectra from hydatid fluid differed from cysticercus cyst by the absence of creatine in the former. When the hydatid cyst was fertile, malate and/or fumarate was also observed, which was absent in cysticercus cyst. The most likely explanation for the presence of creatine only in the cysticercus fluid is its active diffusion from the surrounding host tissue along with a contribution from the musculature present in the bladder wall of the cyst. Copyright © 2002 John Wiley & Sons, Ltd. [source] Characterization of sirolimus metabolites in pediatric solid organ transplant recipientsPEDIATRIC TRANSPLANTATION, Issue 1 2009Guido Filler Abstract:, Potential age-dependent changes of sirolimus metabolite patterns in pediatric renal transplant recipients remain elusive. Thirteen pediatric solid organ transplant recipients (10 kidney, one combined liver,kidney, two liver, mean age 8.0 ± 5.0 yr) underwent a sirolimus pharmacokinetic profile in steady-state with 10 samples drawn over 12 h post-intake to calculate the AUC0,12 h. Concentrations of sirolimus and metabolite were quantified using a validated LC-MS/MS assay and metabolite structures were identified directly in blood extracts using LC-MS/iontrap. Average sirolimus AUC0,12 h was 64.9 ± 29.7 ng h/mL. Median (range) AUC0,12 h for each metabolite (ng h/mL) was: 12-hydroxy-sirolimus 7.6 (0.2,18.8), 46-hydroxy sirolimus 3.1 (0.0,12.4), 24-hydroxy sirolimus 4.3 (0.0,12.6), piperidine-hydroxy sirolimus 3.5 (0.0,8.3), 39- O -desmethyl sirolimus 3.6 (0.0,11.3), 16- O -desmethyl sirolimus 5.0 (0.1,9.9), and di-hydroxy sirolimus 4.3 (0.0,32.5). The metabolites reached a median total AUC0,12 h of 60% of that of sirolimus. The range was 2.6,136%, indicating significant variability. In all, 77.5% of the metabolites were hydroxylated, while 39- O -desmethyl sirolimus accounted for only 8.4% of the AUC0,12 h. This is clinically relevant as 39- O -desmethyl sirolimus shows 86,127% cross-reactivity with the antibody of the widely used Abbott sirolimus immunoassay. The metabolism of sirolimus in the children included in our study differed from that reported in adults, which should be considered when monitoring sirolimus exposure immunologically. [source] Metabolite identification of small interfering RNA duplex by high-resolution accurate mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2008Yan Zou On-line liquid chromatography/electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS) using an LTQ-Orbitrap mass spectrometer was employed to investigate the metabolite profiles of a model siRNA duplex designated HBV263. The HBV263 duplex was incubated in rat and human serum and liver microsomes in vitro. The siRNA drug and its metabolites were then extracted using a liquid-liquid extraction followed by solid-phase extraction (LLE-SPE), and analyzed by LC/ESI-MS. High-resolution accurate mass data enabled differentiation between two possible metabolite sequences with a monoisotopic molecular mass difference of less than 1,Da. ProMass deconvolution software was used to provide semi-automated data processing. In vitro serum and liver microsome incubation samples afforded different metabolite patterns: the antisense strand of the duplex was degraded preferentially in rat and human serum, while the sense strand of the duplex was less stable in rat and human liver microsomes. Copyright © 2008 John Wiley & Sons, Ltd. [source] Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy studyARTHRITIS & RHEUMATISM, Issue 6 2010Manuel Valdés Objective Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques. Methods A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women. Results In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean ± SD 11.9 ± 1.6 arbitrary units [AU] versus 13.4 ± 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean ± SD 2.1 ± 0.4 versus 2.4 ± 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher. Conclusion The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM. [source] Comparative in vitro degradation of the human hemorphin LVV-H7 in mammalian plasma analysed by capillary zone electrophoresis and mass spectrometryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2007Harald John Abstract The human hemorphin LVV-H7 (L32VVYPWTQRF41) is a hemoglobin-,, -,, -, or -, chain derived cationic decapeptide of the µ-opioid receptor binding family. It exhibits potential pharmacological value relevant, for example, for blood pressure regulation, learning performance and Alzheimer's disease. The regulatory potency is strictly dependent on the length of the amino acid sequence which is sensitive towards proteinases from tissues and plasma. To analyse LVV-H7 in vitro degradation in mammalian plasma, a novel multi-component quantitative capillary zone electrophoretic (CZE) procedure was applied, combined with qualitative metabolite profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In all types of plasma, LVV-H7 was N -terminally truncated generating four metabolites (M1,M4) with an intact C -terminus: M1 (V33VYPWTQRF41), M2 (V34YPWTQRF41), M3 (Y35PWTQRF41) and M4 (W37TQRF41). In EDTA plasma these degradation products were detected exclusively, whereas in citrate and heparin plasma four further metabolites appeared resulting from additional C -terminal cleavage of the dipeptide R40F41: M5 (L32VVYPWTQ39), M6 (V33VYPWTQ39), M7 (V34YPWTQ39) and M8 (Y35PWTQ39). In the presence of selective proteinase inhibitors aminopeptidase M and angiotensin-converting enzyme (for N - and C -terminal truncation, respectively) were identified as plasma enzymes responsible for hemorphin degradation. Furthermore, striking inter-mammalian species distinctions were detected revealing strongly differing degradation velocities but similar metabolite patterns. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||