scholarly journals The nested enzyme-within-enterocyte (NEWE) turnover model for predicting dynamic drug and disease effects on the gut wall

2019 ◽  
Vol 131 ◽  
pp. 195-207 ◽  
Author(s):  
Adam S. Darwich ◽  
Howard J. Burt ◽  
Amin Rostami-Hodjegan
Keyword(s):  
1993 ◽  
Vol 42 (1) ◽  
pp. 29???35 ◽  
Author(s):  
MARY D. LUCAS ◽  
JAN R. ATWOOD ◽  
ROBERTA HAGAMAN

1998 ◽  
Vol 30 (13) ◽  
pp. 1757-1764 ◽  
Author(s):  
S.A. Blagodatsky ◽  
I.V. Yevdokimov ◽  
A.A. Larionova ◽  
J. Richter

2005 ◽  
Vol 102 (5) ◽  
pp. 985-994 ◽  
Author(s):  
Åke Norberg ◽  
Kirk I. Brauer ◽  
Donald S. Prough ◽  
Johan Gabrielsson ◽  
Robert G. Hahn ◽  
...  

Background Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts. Methods Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion. Results The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments. Conclusion Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.


Author(s):  
Julia Larsson ◽  
Edmund Hoppe ◽  
Michael Gautrois ◽  
Marija Cvijovic ◽  
Mats Jirstrand

2018 ◽  
Vol 19 (5) ◽  
pp. 149-171
Author(s):  
Yoon Hwan Sohn ◽  
Eun Young Lee ◽  
Myeong Ju Lee ◽  
Bongsoon Cho
Keyword(s):  

2011 ◽  
Vol 149 (4) ◽  
pp. 415-425 ◽  
Author(s):  
L. GONZÁLEZ-MOLINA ◽  
J. D. ETCHEVERS-BARRA ◽  
F. PAZ-PELLAT ◽  
H. DÍAZ-SOLIS ◽  
M. H. FUENTES-PONCE ◽  
...  

SUMMARYInformation on the performance of the Rothamsted organic carbon turnover model (RothC model) in predicting changes in soil organic carbon (SOC) in short-term experiments is scarce. In Mexico, it was found that these experiments covered not more than 20 years. The purpose of the present study was to evaluate short-term SOC prediction performance of the RothC model in the following systems: (1) farming with residues added (A+R), (2) farming with no added residues (A−R), (3) pure forest stands (F), (4) grasslands (GR) and (5) rangeland (RL). Work was done in five experimental sites: Atécuaro, Michoacán; Santiago Tlalpan, Tlaxcala; El Batán, State of Mexico; Sierra Norte, Oaxaca; and Linares, Nuevo León. Carbon (C) inputs to the soil were plant residues and organic fertilizers, which need to be known to operate the RothC model. The adjustment coefficients for site modelling had R2 values of 0·77–0·95 and model efficiency (EF) was −0·60 to 0·93. When RothC performance was evaluated by a system, R2 values were 0·06–0·92 and EF was −0·24 to 0·90. The low R2 and EF values in rangelands were attributed to the fact that these systems are complex because of heterogeneous vegetation, soil and climate. In general, the evaluation of the RothC model indicates that it can be useful in simulating SOC changes in temperate and warm climate sites and in farming, forest and grassland systems in Mexico.


2012 ◽  
Vol 56 (4) ◽  
pp. 2091-2098 ◽  
Author(s):  
Wynand Smythe ◽  
Akash Khandelwal ◽  
Corinne Merle ◽  
Roxana Rustomjee ◽  
Martin Gninafon ◽  
...  

ABSTRACTThe currently recommended doses of rifampin are believed to be at the lower end of the dose-response curve. Rifampin induces its own metabolism, although the effect of dose on the extent of autoinduction is not known. This study aimed to investigate rifampin autoinduction using a semimechanistic pharmacokinetic-enzyme turnover model. Four different structural basic models were explored to assess whether different scaling methods affected the final covariate selection procedure. Covariates were selected by using a linearized approach. The final model included the allometric scaling of oral clearance and apparent volume of distribution. Although HIV infection was associated with a 30% increase in the apparent volume of distribution, simulations demonstrated that the effect of HIV on rifampin exposure was slight. Model-based simulations showed close-to-maximum induction achieved after 450-mg daily dosing, since negligible increases in oral clearance were observed following the 600-mg/day regimen. Thus, dosing above 600 mg/day is unlikely to result in higher magnitudes of autoinduction. In a typical 55-kg male without HIV infection, the oral clearance, which was 7.76 liters · h−1at the first dose, increased 1.82- and 1.85-fold at steady state after daily dosing with 450 and 600 mg, respectively. Corresponding reductions of 41 and 42%, respectively, in the area under the concentration-versus-time curve from 0 to 24 h were estimated. The turnover of the inducible process was estimated to have a half-life of approximately 8 days in a typical patient. Assuming 5 half-lives to steady state, this corresponds to a duration of approximately 40 days to reach the induced state for rifampin autoinduction.


2001 ◽  
pp. 912-913
Author(s):  
E. Priesack ◽  
S. Gayler ◽  
R. Brumme ◽  
N. Bartsch ◽  
T. Vor

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