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At least 127 records · Page 7Linked to original sources
PubMed2006

Multivariate curve resolution-alternating least squares and kinetic modeling applied to near-infrared data from curing reactions of epoxy resins: mechanistic approach and estimation of kinetic rate constants.

This study describes the combination of multivariate curve resolution-alternating least squares with a kinetic modeling strategy for obtaining the kinetic rate constants of a curing reaction of epoxy resins. The reaction between phenyl glycidyl ether and aniline is monitored by near-infrared spectroscopy under isothermal conditions for several initial molar ratios of the reagents. The data for all experiments, arranged in a column-wise augmented data matrix, are analyzed using multivariate curve resolution-alternating least squares. The concentration profiles recovered are fitted to a chemical model proposed for the reaction. The selection of the kinetic model is assisted by the information contained in the recovered concentration profiles. The nonlinear fitting provides the kinetic rate constants. The optimized rate constants are in agreement with values reported in the literature.

Algorithms↗
PubMed2004

Modeling kinetic data from in vitro drug metabolism enzyme experiments.

Modeling of in vitro enzyme kinetic data derived from drug metabolism experiments can greatly facilitate the drug development process because estimation of kinetic parameters can facilitate decision making regarding whether to continue development of a compound. From this information, predictions can be made regarding the "metabolic stability" of a compound and even the in vivo intrinsic clearance of the drug. Many drugs exhibit typical Michaelis-Menten-type kinetics in vitro that result in a hyperbolic kinetic profile from which Km and Vm can be readily estimated. However, it is increasingly being recognized that many drug compounds exhibit "atypical" enzyme kinetics in vitro, requiring use of more complex kinetic models for data fitting and parameter estimation. These atypical kinetic profiles may include sigmoidal kinetics (autoactivation), biphasic kinetics, substrate inhibition kinetics, and heterotropic cooperativity (activation). This article briefly summarizes the types of equations necessary to adequately model both typical and atypical kinetic profiles in order to facilitate correct estimation of the relevant kinetic parameters.

Algorithms↗
PubMed2001

Chemical kinetic modeling of de novo synthesis of PCDD/F in municipal waste incinerators.

A kinetic model is developed for de novo synthesis of PCDD/F from carbon in incinerator fly ash. The main mechanistic steps considered in the model are carbon gasification, PCDD/F formation, desorption and degradation. Rate equations are derived which can relate PCDD/F formation with process variables including carbon concentration of fly ash, partial pressure of oxygen, reaction temperature and time. The kinetic model has been verified using laboratory de novo synthesis data reported in the literature. When the model is applied to industrial incinerator conditions, PCDD/F formation levels of 0.1-0.5 microg/N m3 in the gas phase and 0.1-1.2 microg/g in the solid phase are calculated, and both are in good agreement with incinerator measurements.

Benzofurans↗
PubMed1993

Kinetic modeling of liposome degradation in blood circulation.

The aim of this study is to develop a kinetic model for the quantitative evaluation of, and to examine dose dependency in liposome degradation in blood circulation in vivo. Multilamellar liposomes labeled with 3H-inulin were administered intravenously into rats and the time courses of blood concentration and urinary excretion of 3H-inulin were measured. The dosages of liposomes were fixed at 1, 5, and 100 mumolPCkg-1. Remarkable saturation was found in the time courses of both blood concentration and urinary excretion. Then a kinetic model for the degradation of liposomes in blood was developed, assuming that the degradation follows the first order rate process for each dose. The model fitted the observed time courses of excreted 3H-inulin well, and dose dependency could be observed in the rate constants for liposome degradation, which are more sensitive than urinary excretion of 3H-inulin. The degradation rate constant correlated well with the uptake rate constant, which suggests the same underlying mechanism for both uptake and degradation. These results indicate the usefulness of kinetic modeling in the quantitative evaluation of liposome degradation in blood circulation in vivo.

Animals↗
PubMed2005

Measurement of regional rates of cerebral protein synthesis with L-[1-11C]leucine and PET with correction for recycling of tissue amino acids: I. Kinetic modeling approach.

Measurements of regional rates of cerebral protein synthesis (rCPS) require correction for the effect of recycling of tissue amino acids back into the precursor pool for protein synthesis. The fraction of the precursor pool derived from arterial plasma, lambda, can be evaluated as the steady-state ratio of the specific activity of leucine in the tissue tRNA-bound fraction to that in arterial plasma. While lambda can be directly measured in terminal experiments in animals, an alternative method is required for use with PET. We report a method to estimate lambda based on a kinetic model of labeled and unlabeled leucine and labeled CO2 in the tissue. The kinetic model is also used to estimate the amount of labeled protein and rCPS. We measured time courses of [14C]leucine, [14C]protein, and 14CO2 in the blood and brain of anesthetized rats and estimated parameters of the kinetic model from these data. Simulation studies based on the kinetic parameters were then performed to examine the feasibility of this approach for use with L-[1-11C]leucine and PET. Lambda and rCPS were estimated with low bias, which suggests that PET can be used for quantitative measurement of rCPS with L-[1-11C]leucine and a kinetic modeling approach for correction for recycling of tissue amino acids.

Amino Acids↗
PubMed1996

Relation between pulmonary clearance and particle burden: a Michaelis-Menten-like kinetic model.

OBJECTIVES: To test the validity of a Michaelis-Menten-like kinetic model of pulmonary clearance of insoluble dusts. METHODS: Data were investigated from studies of pulmonary clearance in F344 rats exposed to antimony trioxide (Sb2O3), photocopy test toner, polyvinyl chloride powder (PVC), and diesel exhaust particles. The Michaelis-Menten-like model was used to develop a relation in which the pulmonary clearance half time was a linear function of lung burden. After combining all data, linear regression techniques were applied to investigate the underlying relations. With the estimated intercepts and slopes, the Michaelis-Menten-like kinetic parameters kmax (maximal clearance rate) and m1/2 (a characteristic lung burden at which kmax is reduced by 50%) were derived for the four dusts. RESULTS: The experimental data fit the linear regression very well (R2 = 0.989), suggesting that pulmonary clearance for the four dusts followed Michaelis-Menten-like kinetics. Values of the intercept terms were not significantly different among the four dusts (P = 0.294), indicating that the intrinsic clearance rates of F344 rats were the same among the four experiments. The intrinsic clearance half time was estimated to be 77.8 days, leading to an estimated kmax of 0.0089 day-1. However, the slopes of the linear relations were significantly different among the four dusts (P < 0.001). Values of m1/2 were ranked in the order of: Sb2O3 (0.69 mg) < photocopy test toner (0.97 mg) < diesel exhaust (2.49 mg) congruent to PVC (2.90 mg). CONCLUSION: This study suggests that the Michaelis-Menten-like kinetic model reasonably describes the kinetic behavior of pulmonary clearance in F344 rats. The parameters m1/2 can be used to differentiate the potency of a particular dust for impairing pulmonary clearance.

Air Pollutants↗
PubMed1990

Alveolar retention and clearance of insoluble particles in rats simulated by a new physiology-oriented compartmental kinetics model.

A physiology-oriented compartmental kinetics model of alveolar retention of inhaled insoluble particulate matter in rat lungs was proposed in a recent paper, (W. Stöber, P.E. Morrow, and M.D. However, 1989, Fundam. App. Toxicol. 13, 823-843), and the retention patterns obtained with the model for a hypothetical set of input data appeared to simulate phenomena which were observed in inhalation studies with Fischer 344 rats. The present paper represents the results of applying the new model for simulations of the actual experimental retention data of five different inhalation studies with Fischer 344 rats exposed to three different materials. The experimental data showed that model adjustments had to be made in order to account for clearance effects that appeared to be influenced by the age of the animals. After these adjustments were made and an appropriate set of values for the model parameters describing the respective exposure conditions was used, the model was constrained to represent the empirical data of all of the studies by one unique set of parameter values. Changes in particular values of this set were considered to be acceptable only if they reflected changes of relevant properties of the inhaled particulate matter. The final simulations did not completely comply with this self-imposed criterion. However, the degree of compliance and the simulation quality achieved with a minimum of parameter variations seem to be unprecedented in retention modeling. The results of the study encourage attempts for further refining the present model.

Aging↗
PubMed2002

Kinetic modeling of fenton oxidation of phenol and monochlorophenols.

A kinetic model, consisting of 28 reactions, was proposed to understand the key mechanism of the Fenton oxidation of phenol and o-, m-, and p-chlorophenols. Particular attention is paid to the interactions of the organic intermediates with the Fe species. The proposed model reasonably predicts the decomposition kinetics and by-product formation for the different phenols at widely varying levels of Fe2+, H2O2, and the phenols. For the phenols and intermediates, change in concentrations with time was predicted within 20-30% deviation from the measured data. The single model predicts the overall kinetics of Fenton oxidation of all the tested phenols by adjusting the rate constant of hydroxyl radical for each phenol. Sensitivity analysis indicates that the key reactions are those that directly govern the levels of OH radical and Fe2+. Both the model prediction and the experimental results show that the decomposition rate could be complicated particularly by the availability of Fe2+. Understanding the interactions of the organic intermediates with Fe2+ is thus of critical importance to improve the decomposition performance.

Chlorophenols↗
PubMed2006

Software tools that facilitate kinetic modelling with large data sets: an example using growth modelling in sugarcane.

A solution to manage cumbersome data sets associated with large modelling projects is described. A kinetic model of sucrose accumulation in sugarcane is used to predict changes in sucrose metabolism with sugarcane internode maturity. This results in large amounts of output data to be analysed. Growth is simulated by reassigning maximal activity values, specific to each internode of the sugarcane plant, to parameter attributes of a model object. From a programming perspective, only one model definition file is required for the simulation software used; however, the amount of input data increases with each extra interrnode that is modelled, and likewise the amount of output data that is generated also increases. To store, manipulate and analyse these data, the modelling was performed from within a spreadsheet. This was made possible by the scripting language Python and the modelling software PySCeS through an embedded Python interpreter available in the Gnumeric spreadsheet program.

Algorithms↗
PubMed2000

Kinetic modeling of ATP synthesis by ATP synthase and its mechanistic implications.

Based on the torsional mechanism of ATP synthesis by ATP synthase, a kinetic scheme has been developed in this work. The scheme considers adenine nucleotide transport, binding of substrates ADP and P(i), unbinding of product ATP, and ATP synthesis. This kinetic scheme has been analyzed mathematically, and a kinetic model has been obtained to explain the experimentally observed hyperbolic Michaellian dependence of the rate of ATP synthesis on the ADP concentration by ATP synthase under physiological steady-state operating conditions. The principal results of the kinetic model have been compared with the experimental data and an estimate of the enzymological kinetic parameters V(max), K(M), and K(I) has been determined. Mechanistic implications arising from further analysis of the kinetic model have been discussed. These biological implications provide deep insight into the sequence of events leading to ATP synthesis.

Adenosine Diphosphate↗
PubMed1999

A kinetic model of mitochondrial aspartate aminotransferase transmigration in hepatobiliary disorders.

A hypothetical kinetic model of transmigration of mitochondrial aspartate aminotransferase (m-AST) from liver to blood and its elimination from blood was constructed and assessed for prediction by computer simulation. The elimination of m-AST from plasma in healthy rats followed first-order kinetics. Depletion of m-AST from the liver after induction of hepatobiliary disorders in rats with alpha-naphthylisothiocyanate (ANIT) also followed first-order kinetics. In contrast, the changes in metabolic rate in the liver after ANIT administration, as estimated from the plasma indocyanine green clearance, approximated to a second-order time function. Based on these data, the time-dependent change in plasma m-AST activity after ANIT administration was simulated by computer according to a hypothetical kinetic model. The result of computer simulation of the change in plasma m-AST coincided well with that obtained experimentally, suggesting that continuous measurements of m-AST may be helpful to the clinical diagnosis of liver injury.

1-Naphthylisothiocyanate↗
PubMed2001

A microdosimetric-kinetic model for the sensitization of v79 cells to radiation by incorporation of bromodeoxyuridine.

Hawkins, R. B. A Microdosimetric-Kinetic Model for the Sensitization of V79 Cells to Radiation by Incorporation of Bromodeoxyuridine. Radiat. Res. 155, 698-702 (2001). The sensitization of G(1)-phase V79 cells to killing by ionizing radiation through incorporation of bromodeoxyuridine (BrdU) in their DNA has been reported to occur exclusively through an increase in the value of the quadratic parameter of the linear-quadratic survival relationship (beta) with no change in the linear parameter (alpha). The consequence of this, as understood through the microdosimetric-kinetic model of cell survival, is discussed. It is shown that the invariance of alpha implies that sensitization is due solely to a decrease in the rate of repair of the initial (potentially lethal) lesions in DNA containing BrdU. Further, for alpha to be unchanged, the average size of the compartments into which the nucleus is partitioned (domains), as postulated in the microdosimetric-kinetic model, must vary in proportion to the reciprocal of the square root of the rate constant for repair of the DNA lesions. This implies that the domain is not a structural subunit of the nucleus. It is a surrogate representation of the consequence of lesions in DNA being restricted to a region in the vicinity of the location in the nucleus at which they are created. A lesion is confined because the distance it can diffuse by random flight to react with another lesion to form a lethal lesion is restricted because a lesion's lifetime is limited by the repair process.

Animals↗
PubMed1981

gamma-Glutamyltransferase in human serum: an analysis of kinetic models.

The purpose of the study was to elucidate details of the kinetic model for gamma-glutamyltransferase when assayed with gamma-glutamyl-3-carboxy-4-nitroanilide and glycylglycine as substrates. Data from several sets of initial velocity measurements were fitted by nonlinear regression to a set of different kinetic models. gamma-Glutamyltransferase acts by a "ping-pong bi-bi" mechanism. A model encompassing transfer and autotransfer, competitive inhibition by the acceptor substrate, and no inhibition by the donor substrate gives the best fit to the experimental data. Effects of spectrophotometric nonlinearity may simulate noncompetitive inhibition by the donor substrate. The nonlinearity is dependent on the absorption of the incubation mixture and therefore is related to the concentration of the donor substrate and the wavelength (405-412 nm) used to monitor the reaction. With decreasing pH the autotransfer fraction decreases and the binding of the donor substrate to the acceptor site increases, simulating an increased competitive inhibition by the donor substrate. These results are of importance when elaborating optimum assay conditions for gamma-glutamyltransferase in serum.

Humans↗
PubMedDate not supplied

Increased urea kinetic modeling volume. Possible mechanisms and its significance.

The presence of access recirculation reduces delivered urea clearance and produces an increased volume/weight (V/M) ratio in three-point kinetic modeling. We measured R in 20 patients receiving conventional hemodialysis and correlated results with normalized intra-access venous pressure (PIA) and with angiographic or color-flow Doppler studies. Twenty patients were equally divided into those with and without persistently elevated modeled V/W ratios (0.64 vs 0.53), and subdivided into those with native and synthetic bridge graft accesses. Kinetic modeling parameters (Kt/V) and P1A did not differ between the two V/W groups. Modeled volume was quite accurately predicted by the equations in the normal group but deviated by 7.3 +/- 2.1 L in the high V/W ratio group. Three of 10 native and 4 of 10 graft accesses had trivial and hemodynamically insignificant abnormalities by color-flow Doppler or angiography. Recirculation was independent of V/W group and when measured by the slow flow/clamp technique was negligible (< 2.0%). Access flow always exceeded prescribed dialyzer blood flow by more than 300 ml/ min. Therefore, access recirculation was unlikely. In many of the high V/W patients, alternative explanations for falsely high modeled volume were found on follow-up modeling. Only one patient appeared to have a true high volume. The authors conclude that high urea volumes during kinetic modeling are unlikely to occur from access recirculation, but arise from other factors affecting the delivered urea clearance.

Adult↗
PubMed1988

Choice in transition: A comparison of melioration and the kinetic model.

Transition-state choice behavior of pigeons was examined in two experiments designed to test predictions of melioration and the kinetic model. Both experiments began with an initial training condition during which subjects were maintained on concurrent variable-interval schedules. In Experiment 1, subjects were then exposed to concurrent variable-ratio schedules, whereas in Experiment 2, subjects were then exposed to concurrent extinction. Contrary to the predictions of melioration, but consistent with the kinetic model, acquisition of preference on concurrent variable-ratio schedules followed a negatively accelerated logistic trajectory, and preference remained stable in concurrent extinction. Predictions made by the kinetic model concerning rates of switching between alternatives were also supported.

Journal Article↗
PubMed1995

Two-sample hemodialysis urea kinetic modeling: validation of the method.

Urea kinetic modeling (UKM) by a two-sample method (UKM2) was compared with the classical three-sample method (UKM3) and direct quantification. Assuming the patient to be in a weekly steady state and using an approximate treatment schedule, UKM2 can compute urea generation rate (G), distribution volume (V), Kt/V, and normalized protein catabolic rate (NPCR). Twenty-three stable patients were examined. The results obtained by UKM2 and UKM3 differed little (G -4.2%, V -1.0%, Kt/V 0.9%, NPCR -2.7%), and the correlations between them were high (r > or = 0.96). The differences between UKM2 and direct quantification were greater, but also highly correlated. G determined midweekly by UKM2 was highly correlated with G found directly from 1-week collection of dialysate and urine (r = 0.96). Repeating analysis over a 5-week period, the results obtained by UKM2 varied no more than those obtained by UKM3 (around 8% for all four kinetic variables). In conclusion, UKM2 produces reliable results requiring less data to be entered than using UKM3.

Adult↗
PubMed1990

Kinetic modeling of intradialytic and interdialytic pH shifts during and after acetate and bicarbonate hemodialysis.

A kinetic model involving intraerythrocytic and whole blood H+ concentrations during and after bicarbonate and acetate hemodialysis is proposed to account for experimental data. A two-compartment model appeared to be the simplest kinetic model to explain the decrease in proton concentration during bicarbonate hemodialysis and its increase between two dialysis sessions, whether acetate or bicarbonate. This model takes into account the hemoglobin buffer power and the cellular metabolic acidosis. During acetate hemodialysis, one must introduce a new compartment to explain the initial increase in H+ concentration in erythrocytes. This compartment, which generates protons, seems to correspond to the carbonic anhydrase cycle. The various parameters obtained show no significant variations between patients receiving bicarbonate hemodialysis. For acetate hemodialysis, the model describes equally well patients with a great initial increase in H+ concentration and those with a slight initial increase. The variations observed in the parameters are due mainly to the carbonic anhydrase compartment. It is suggested the magnitude of this initial increase and the degree of acetate intolerance are correlated.

Acetates↗
PubMed1994

Urea kinetic modeling at high urea clearances: implications for clinical practice.

The original description of urea kinetic modeling in hemodialysis was based on a single pool of fluid equal to total body water. This assumption is valid only if the rate of transport between compartments is sufficiently rapid compared with the rate of urea removed by hemodialysis. We have reexamined the issue of urea compartmentation using 10 patients with initial BUN values ranging from 28 to 101 mg/dL who were studied while on high flux hemodiafiltration. Sampling was carried out at times as short as 1 minute after the beginning of the treatment. In 4 patients, samples were also drawn after the dialysis ended. The measured BUN values were used to fit a two-compartment, variable-volume kinetic model. The mean urea diffusive clearance of the dialyzer during the treatment was 503 mL/minute, and the bidirectional urea clearance between compartments was 1,282 mL/minute. The percentage of total body water in the rapidly exchangeable compartment was 35.4%. Comparison with a one-compartment, variable-volume model showed a statistically better fit for all patients with the more complex model. In the 4 patients studied in the postdialysis period, the rebound in BUN ranged from 22% to 24%. These studies show that, at high urea clearances, the urea distribution space and, therefore, dialysis modeling requires two compartments. These results explain the majority of the rebound in urea concentration observed 30 to 60 minutes following the discontinuation of the dialysis treatment and point out an improved strategy for monitoring the efficiency of the treatment delivered to the patient.

Blood Urea Nitrogen↗