Dataset Information

Measurement of internal body time by blood metabolomics.

ABSTRACT: Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, "molecular-timetable method," which was originally inspired by Linné's flower clock. In Linné's flower clock, one can estimate the time of the day by watching the opening and closing pattern of various flowers. Similarly, in the molecular-timetable method, one can measure the BT of the day by profiling the up and down patterns of substances in the molecular timetable. To make this method clinically feasible, we now performed blood metabolome analysis and here report the successful quantification of hundreds of clock-controlled metabolites in mouse plasma. Based on circadian blood metabolomics, we can detect individual BT under various conditions, demonstrating its robustness against genetic background, sex, age, and feeding differences. The power of this method is also demonstrated by the sensitive and accurate detection of circadian rhythm disorder in jet-lagged mice. These results suggest the potential for metabolomics-based detection of BT ("metabolite-timetable method"), which will lead to the realization of chronotherapy and personalized medicine.

SUBMITTER: Minami Y

PROVIDER: S-EPMC2689311 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Measurement of internal body time by blood metabolomics.

Minami Yoichi Y Kasukawa Takeya T Kakazu Yuji Y Iigo Masayuki M Sugimoto Masahiro M Ikeda Satsuki S Yasui Akira A van der Horst Gijsbertus T J GT Soga Tomoyoshi T Ueda Hiroki R HR

Proceedings of the National Academy of Sciences of the United States of America 20090601 24

Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, "molecular-timetable method," which was originally inspired by Linné's flower clock. In Linné's flower clock, one can estimate the time of the day by watching the ope ...[more]

PMID: 19487679

Similar Datasets

Project description:PurposeA 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed.MethodsOrgan TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms.ResultsA short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume.ConclusionsLong-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.

Project description:IntroductionInternal standards correct for measurement variation due to sample loss. Isotope labeled analytes are ideal internal standards for the measurement of fatty acids in human plasma but are not always readily available. For this reason, quantification of multiple analytes at once is most often done using only a single or few internal standards. The magnitude of the impact this has on method accuracy and precision is not well studied for gas chromatography-mass spectrometry systems.ObjectiveThis study aims to estimate bias and changes in uncertainty associated with using alternative fatty acid isotopologue internal standards for the estimation of similar or dissimilar long chain fatty acids.MethodUsing a previously reported method for the quantification of 27 fatty acids in human plasma using 18 internal standards we obtained estimates of bias and uncertainty at up to three levels of fatty acid concentration.ResultsWith some notable exceptions, method accuracy remained relatively stable when using an alternative internal standard (Median Relative Absolute Percent Bias: 1.76%, Median Spike-Recovery Absolute Percent Bias: 8.82%), with larger changes in method precision (Median Increase in Variance: 141%). Additionally, the degree of difference between analyte and internal standard structure was related to the magnitude of bias and uncertainty of the measurement.ConclusionThe data presented here show that the choice of internal standard used to estimate fatty acid concentration can affect the accuracy and reliability of measurement results and, therefore, needs to be assessed carefully when developing analytical methods for the measurement of fatty acid profiles.Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

Dataset Information

Measurement of internal body time by blood metabolomics.

Publications

Measurement of internal body time by blood metabolomics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets