Probabilistic Multicompartmental Model for Interpreting DGT Kinetics in Sediments

2011 ◽  
Vol 45 (22) ◽  
pp. 9558-9565 ◽  
Author(s):  
P. Ciffroy ◽  
Y. Nia ◽  
J. M. Garnier

1985 ◽  
Vol 26 (7) ◽  
pp. 806-818 ◽  
Author(s):  
M H Green ◽  
L Uhl ◽  
J B Green


2013 ◽  
Vol 135 (12) ◽  
Author(s):  
Arun V. Kolanjiyil ◽  
Clement Kleinstreuer

This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, “Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part I: Whole-Lung Aerosol Dynamics,” ASME J. Biomech. Eng., 135(12), p. 121003) with a new multicompartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction of temporal nanoparticle accumulation in the blood and lymphatic systems and in organs. The multicompartmental model parameters were determined from experimental retention and clearance data in rat lungs and then the validated model was applied to humans based on pharmacokinetic cross-species extrapolation. This hybrid simulator is a computationally efficient tool to predict the nanoparticle kinetics in the human body. The study provides critical insight into nanomaterial deposition and distribution from the lungs to systemic regions. The quantitative results are useful in diverse fields such as toxicology for exposure-risk analysis of ubiquitous nanomaterial and pharmacology for nanodrug development and targeting.



2007 ◽  
Vol 292 (5) ◽  
pp. F1548-F1559 ◽  
Author(s):  
Vivian S. Lee ◽  
Henry Rusinek ◽  
Louisa Bokacheva ◽  
Ambrose J. Huang ◽  
Niels Oesingmann ◽  
...  

The purpose of this study was to determine the accuracy and sources of error in estimating single-kidney glomerular filtration rate (GFR) derived from low-dose gadolinium-enhanced T1-weighted MR renography. To analyze imaging data, MR signal intensity curves were converted to concentration vs. time curves, and a three-compartment, six-parameter model of the vascular-nephron system was used to analyze measured aortic, cortical, and medullary enhancement curves. Reliability of the parameter estimates was evaluated by sensitivity analysis and by Monte Carlo analyses of model solutions to which random noise had been added. The dominant sensitivity of the medullary enhancement curve to GFR 1–4 min after tracer injection was supported by a low coefficient of variation in model-fit GFR values (4%) when measured data were subjected to 5% noise. These analyses also showed the minimal effects of bolus dispersion in the aorta on parameter reliability. Single-kidney GFR from MR renography analyzed by the three-compartment model (4.0–71.4 ml/min) agreed well with reference measurements from 99mTc-DTPA clearance and scintigraphy ( r = 0.84, P < 0.001). Bland-Altman analysis showed an average difference of 11.9 ml/min (95% confidence interval = 5.8–17.9 ml/min) between model and reference values. We conclude that a nephron-based multicompartmental model can be used to derive clinically useful estimates of single-kidney GFR from low-dose MR renography.



2020 ◽  
Vol 105 (10) ◽  
pp. 3152-3164
Author(s):  
Véronique Ferchaud-Roucher ◽  
Yassine Zair ◽  
Audrey Aguesse ◽  
Michel Krempf ◽  
Khadija Ouguerram

Abstract Context Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids



1986 ◽  
Vol 11 (3) ◽  
pp. 239-243 ◽  
Author(s):  
E. Bodd ◽  
M. H. Green ◽  
Ca. Drevon ◽  
J. Mørland




2019 ◽  
Vol 22 ◽  
pp. 112-121 ◽  
Author(s):  
Esther Oyaga-Iriarte ◽  
Asier Insausti ◽  
Lorea Bueno ◽  
Onintza Sayar ◽  
Azucena Aldaz

Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring. Methods: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion. Results: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug. Conclusions: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases.



SIMULATION ◽  
1992 ◽  
Vol 59 (1) ◽  
pp. 7-12
Author(s):  
N. David Charkes ◽  
Jeffrey A. Siegel ◽  
Alan H. Maurer ◽  
Christopher Hansen ◽  
Alfred A. Bove


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