scholarly journals Isotopic and modeling investigation of long-term protein turnover in rat tissues

2013 ◽  
Vol 304 (3) ◽  
pp. R218-R231 ◽  
Author(s):  
Nathalie Poupin ◽  
Jean-François Huneau ◽  
François Mariotti ◽  
Daniel Tomé ◽  
Cécile Bos ◽  
...  

Fractional synthesis rates (FSR) of tissue proteins (P) are usually measured using labeled amino acid (AA) tracer methods over short periods of time under acute, particular conditions. By combining the long-term and non-steady-state 15N labeling of AA and P tissue fractions with compartmental modeling, we have developed a new isotopic approach to investigate the degree of compartmentation of P turnover in tissues and to estimate long-term FSR values under sustained and averaged nutritional and physiological conditions. We measured the rise-to-plateau kinetics of nitrogen isotopic enrichments (δ15N) in the AA and P fractions of various tissues in rats for 2 mo following a slight increase in diet δ15N. Using these δ15N kinetics and a numerical method based on a two-compartment model, we determined reliable FSR estimates for tissues in which P turnover is adequately represented by such a simple precursor-product model. This was the case for kidney, liver, plasma, and muscle, where FSR estimates were 103, 101, 58, and 11%/day, respectively. Conversely, we identified tissues, namely, skin and small intestine, where P turnover proved to be too complex to be represented by a simple two-compartment model, evidencing the higher level of subcompartmentation of the P and/or AA metabolism in these tissues. The present results support the value of this new approach in gaining cognitive and practical insights into tissue P turnover and propose new and integrated FSR values over all individual precursor AA and all diurnal variations in P kinetics.

1998 ◽  
Vol 80 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Nicola M. Lowe ◽  
Leslie R. Woodhouse ◽  
Janet C. King

The physiological importance and mechanism of the postprandial fall in plasma Zn concentration is not well understood. In order to gain further information on this apparent redistribution of plasma Zn, a stable isotope, 70Zn, was used to study the effect of a breakfast meal on plasma Zn kinetics. Nine women participated in two trials, a fasting trial and a breakfast-meal trial; five of the women participated in a third trial in which the energy content of the breakfast meal was doubled. At each trial, 0.1mg of 70Zn was infused intravenously, and the plasma disappearance of the isotope was analysed using a two-compartment model of Zn kinetics. Plasma Zn concentration fell significantly following the two trials in which the subjects were given meals, reaching low points that were 13 and 19 %, respectively, below concentrations at comparable times during the fasting trial. Kinetic analysis revealed that after the doubled breakfast meal there was a significant fall (P < 0.007) in the size of the most rapidly turning over Zn pool (pool (a)) from 2.90 (se 0.13)mg in the fasting state to 2.47 (se 0.14) mg postprandially. The fractional turnover rate of pool (a) to other extravascular Zn pools, i.e. outside the two-compartment system, was also significantly elevated after the doubled breakfast meal (P < 0.05). These results suggest that the decline in plasma Zn concentration following a meal is due to a redistribution of Zn from the plasma to other more slowly turning over extravascular pools that may be involved in the assimilation and metabolism of fuels following food intake.


1990 ◽  
Vol 329 (1255) ◽  
pp. 361-368 ◽  

Although the decomposition of plant material in soil is an extremely complex process, relatively simple models can give good fits to the decay process. Thus a two-compartment model gives a close representation, over the first few years, of the decay of 14 C-labelled plant material in soil. A model containing a single homogeneous humus compartment decomposing by a first-order process is surprisingly useful for soil organic nitrogen over periods measured in decades. More sophisticated multicompartmental models are now widely used to represent turnover in soil. One of these, the Rothamsted turnover model, is described in detail and shown to give a useful representation of data from the Rothamsted long-term field experiments.


2015 ◽  
Vol 39 (4) ◽  
pp. 288-296 ◽  
Author(s):  
Francisco Maduell ◽  
Juan Sanchez ◽  
Marta Net ◽  
Miquel Gomez ◽  
Jose M. Gonzalez ◽  
...  

Background: In a previous study on a nocturnal, every-other-day online haemodiafiltration scheme, different removal patterns were observed for urea, creatinine, β2-​microglobulin, myoglobin and prolactin. The aim of this study was to evaluate the influence of dialysis duration and infusion flow (Qi) on the removal of different molecular weight (MW) solutes, and to quantify the effect of the different treatments on the kinetics of the solutes by using a classical two-compartment model. Methods: This prospective, in-center study was carried out in 10 patients on a nocturnal, every-other-day online post-dilution haemodiafiltration program. Each patient received four dialysis sessions with different conditions, two 4-h sessions (with infusion flows of 50 or 100 ml/min) and two 8-h sessions (with infusion flows of 50 or 100 ml/min). To analyze the solute kinetics, blood samples were obtained hourly during the dialysis treatments and in the first 3 h post-dialysis. Results: Removal patterns differed in the molecules studied, which were quantified by means of the two-compartment mathematical model. The main results show the impact of dialysis duration on the removal of low molecular weight molecules (urea and creatinine), while the impact of Qi is clearly shown for high molecular weight molecules (myoglobin and prolactin). For middle molecular weight solutes, such as β2-microglobulin, both factors (duration and Qi) enhance the removal efficiency of the dialyzer. Conclusions: Our study evaluates experimentally and mathematically how treatment time and infusion flow affect the filtration of solutes of different MW during post-dilution haemodiafiltration. The results provided by the present study should help physicians to select and individualise the most appropriate schedules to deliver an optimum diffusive and convective dialysis dose for each patient.


1982 ◽  
Vol 28 (1) ◽  
pp. 204-206 ◽  
Author(s):  
R Jagenburg ◽  
C G Regårdh ◽  
S Rödjer

Abstract We studied the kinetics of intravenously administered L-phenylalanine with respect to the effect of age and sex, using a two-compartment model. We found that the volume of the peripheral compartment and total body clearance decrease with age. The sex-related influence was less obvious when distribution volumes and total body clearance were corrected for differences in body size. We emphasize the necessity of having age-matched control subjects in kinetic studies.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4528-4528
Author(s):  
Hink Boer ◽  
Johannes H Proost ◽  
Janine Nuver ◽  
Sophie Bunskoek ◽  
Joyce Q. Gietema ◽  
...  

4528 Background: Successful platinum(Pt)-based chemotherapy for testicular cancer (TC) comes at the price of late cardiovascular morbidity and neurotoxicity. Damage induced by circulating Pt could be an etiological mechanism. We investigated the relation between circulating Pt and late effects. Methods: In 96 consecutive TC patients (med age 29 [17-53] at chemotherapy), 3 serum samples and a 24h-urine sample were collected on several time-points med 5 yrs (1-13) after treatment. Pt concentrations ([Pt]) were measured with a sensitive voltammetric method (Lancet 2000, 355:1075). Measured [Pt] combined with cisplatin dose, age, weight and height were analyzed simultaneously to construct a population pharmacokinetic (PK) model using NONMEM. Based on the PK parameters of each patient, individual [Pt] at 1, 3, 5, 10 yrs after start and AUC were calculated. Cardiovascular status, paresthesia and markers of vascular damage were assessed after a med follow-up (FU) of 9 yrs (3-15). Results: Decay of [Pt] was best described by a two compartment model. Mean terminal T1/2 was 3.7 (±0.3) yrs. At all time-points [Pt] correlated with cisplatin dose and renal function during treatment. [Pt] at 3 yrs correlated with systolic blood pressure (BP) (r=.32, p<0.01) and creatinine clearance (CRCL) (r=-.25, p=0.02) at FU. Patients with increased BP had higher Pt AUCs than patients with normal BP (table). Pt AUCs were higher in patients with paresthesia (table). Conclusions: Known late effects of cisplatin-based chemotherapy such as hypertension and paresthesia are related to higher circulating [Pt]. Long-term exposure to Pt is involved in healthy tissue damage in TC survivors. [Table: see text]


1987 ◽  
Vol 58 (1) ◽  
pp. 113-125 ◽  
Author(s):  
M. Hidiroglou ◽  
K. Karpinski

1. Kinetics of physiological doses of D-α-[5-Me-3H]tocopherol(200 μCi) administered to twenty-four sheep were studied using one of four routes: intravenous, oral (capsules), intraruminal and intramuscular.2. Blood samples were withdrawn from the jugular vein periodically for 96 h after the intravenous and oral administrations, for 168 h after the intraruminal administration and for 216 h after the intramuscular administration.3. The study indicated that the biological availability of α-tocopherol followed the order intravenous > intramuscular > oral > intraruminal.4. The rate of elimination was in the order intravenous > oral > intraruminal ˜ intramuscular.5. The intravenous route was fitted with a three-compartment model, whereas the other routes exhibited a good fit for either a one- or two-compartment model.


1983 ◽  
Vol 244 (3) ◽  
pp. G314-G320 ◽  
Author(s):  
R. F. Bonewitz ◽  
E. C. Foulkes ◽  
E. J. O'Flaherty ◽  
V. S. Hertzberg

Effects of dexamethasone and adrenalectomy on the kinetics of jejunal 65Zn uptake and absorption were studied in the anesthetized adult rat. The jejunal lumen was perfused in situ with 5 mM glucose in 150 mM saline containing 65Zn and [14C]polyethylene glycol as volume marker. Over the 30-min perfusion period, the rate of net 65Zn removal from the perfusate was biexponential due to the establishment of a return flux to the lumen. An open two-compartment model satisfactorily describes these observations: (formula; see text) Dexamethasone (2 mg/kg ip 7 h before perfusion) increased k12 by 75% (P less than 0.0002) and decreased k20 by 45% (P less than 0.04). Both effects were independent of adrenalectomy. Mathematical simulations using the compartmental model and experimentally determined kinetic constants predicted that transfer of 65Zn into the body should be enhanced by adrenalectomy and retarded by dexamethasone administered to adrenalectomized rats. Dexamethasone and adrenalectomy thus differentially affect Zn uptake and absorption in this system, suggesting a possible adrenocortical hormone involvement in the regulation of Zn absorption. These changes are apparently not mediated via metallothionein.


1989 ◽  
Vol 9 (6) ◽  
pp. 840-849 ◽  
Author(s):  
Mark M. Bahn ◽  
Sung-Cheng Huang ◽  
Randall A. Hawkins ◽  
Nagichettiar Satyamurthy ◽  
John M. Hoffman ◽  
...  

The in vivo tracer kinetics of 3-(2apos;-[18F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics ( n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 ± 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well; this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma–tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.


Author(s):  
Wenjun Long ◽  
Liangqiong Peng ◽  
Xiaofeng Jiang ◽  
Faming He ◽  
Wenhua Zhang

The release of chromium from leather inevitably results in potential risks and this study is conducted to investigate the long-term releasing behavior. The leaching tests proceed using water at solid to liquid ratio of 1:20 and rotational speed 60 r/min for 240 hours to simulate the release of chrome leather under natural conditions. The experimental data successfully fit with the Pseudo-second-order equation, Elovich equation, and Weber-Morris model, indicating the long-term leaching behavior of chromium in heterogeneous leather is controlled by liquid-solid film, while the interparticle and intraparticle diffusion also play important roles. The leachable chromium accounts for 2.8-4.5% total chromium in leather and increases with temperature. The Three-compartment model depicts the releasing process as rapid, slow, and very slow stages, and temperature mainly affected the very slow stage. The amount of released chromium in rapid and slow stages slightly increases with temperature, which could be used to assess the hazard of chrome leather.


Sign in / Sign up

Export Citation Format

Share Document