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PubMed2005

Kinetic modeling of liquid-phase adsorption of reactive dyes on activated carbon.

In this paper, adsorption equilibrium and kinetics of three reactive dyes from their single-component aqueous solutions onto activated carbon were studied in a batch reactor. Effects of the initial concentration and adsorbent particle size on adsorption rate were investigated Adsorption equilibrium data were then correlated with several well-known equilibrium isotherm models. The kinetic data were fitted using the pseudo-first-order equation, the pseudo-second-order equation, and the intraparticle diffusion model. The respective characteristic rate constants were presented. A new adsorption rate model based on the pseudo-first-order equation has been proposed to describe the experimental data over the whole adsorption process. The results show that the modified pseudo-first-order kinetic model generates the best agreement with the experimental data for the three single-component adsorption systems.

Journal Article↗
PubMedDate not supplied

Improving of the accuracy of in vitro-in vivo linear correlation using kinetic models for ultra sustained release theophylline tablets.

The objective of the current study was to establish and evaluate a new technique to increase the accuracy of the in vitro/in vivo linear correlation of single and multiple dose ultra-sustained release theophylline (USRT) preparation (Xantium) in hospitalized patients. In vitro dissolution data for theophylline were collected for 24 h using a USP I (basket) and USP II (paddle) methods. In vivo plasma concentration data were obtained from 8 patients after administration of either single or multiple doses of theophylline. Both in vitro and in vivo results were evaluated by zero-order, first-order, RRSBW, Hixson-Crowell, Higuchi, Hopfenberg, Langenbucher, modified Langenbucher and (Bt)a kinetic models. The individual linear correlations between each in vitro and in vivo percent results and their kinetic distributions were established and regression equations were obtained. The determination coefficient results of the linear kinetic correlations were found to be 0.994 and 0.997 for single and multiple doses by basket method and 0.992 and 0.998 for single and multiple doses by paddle method, respectively. Furthermore, the results of the linear correlations were found as 0.953 and 0.950 for single and multiple doses by basket method and 0.963 and 0.962 for single and multiple doses by paddle method respectively. Therefore, this study suggested that the accuracy of the linear correlation could be improved signilicantly by using linear kinetic correlation.

Adult↗
PubMed1993

Limitations of kinetic models as predictors of nutritional and dialysis adequacy in continuous ambulatory peritoneal dialysis patients.

Nutrition has been shown to predict clinical outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. However, despite the positive relationship between KT/V (urea) and the normalised protein catabolic rate, the ability of urea kinetic modelling to predict clinical outcome or nutrition remains inconclusive. We have evaluated the relationship between nutrition and achieved dialysis in a cross-sectional study of 147 stable CAPD patients on dialysis for a mean period of 22 months. Protein-energy malnutrition was present in 22-32% of the study population. 39 and 41% of the population failed to achieve suggested adequacy targets of 50 liters/week for total creatinine clearance and a weekly KT/V (urea) of 1.7, respectively. Severely malnourished patients had significantly greater normalised clearance and adequacy values than well-nourished patients. Intrinsic actual peritoneal clearance bore no relation to patient size. The subsequent normalisation of this value by a component of patient mass results in a mathematical bias against well-nourished or obese patients. This may explain the failure of such adequacy values to reflect outcome and argues against accepting such values as measures of dialysis well-being.

Body Weight↗
PubMedDate not supplied

A kinetic model of the cell culture cytotoxicity of metabolically activated agents: N-methyl-N-(acetoxymethyl)nitrosamine, methylnitrosourethane, and (methylazoxy)methanol acetate.

The activity of three metabolically activated methylating agents, N-methyl-N-(acetoxymethyl)nitrosamine (DMN-OAc), methylnitrosourethane (MNUT), and (methylazoxy)methanol acetate (MAM-Ac), were determined in cell culture by using a P388 cell growth rate inhibition assay. Experiments were conducted with normal P388 cells in Fischer's medium and under conditions in which the esterase-mediated activation was modified by pretreating cells with the irreversible esterase inhibitor paraoxon and by adding acetylcholinesterase to the medium. Inhibition of intracellular esterase had a much greater effect on activity than did addition of enzyme to medium. These experiments provided data that were used to assess the utility of kinetic models as a means to gain a more detailed understanding of the cytotoxicity process in cell culture. Growth rate inhibition was related to the amount of intracellular alkylation resulting from formation of metabolic intermediates and their subsequent chemical reaction to form methyldiazonium ion and methylation products by using kinetic rate laws and measured rate constants. The model is applicable to systems that form unstable metabolites that can, in part, partition between the cell volume and incubation medium. When growth rate inhibition effects were related to cumulative intracellular alkylation [P], the ED50 values were the same for all three agents and for three previously reported chemically activated methylating agents, N-methyl-N-nitrosourea, streptozotocin, and N-methyl-N'-nitro-N-nitrosoguanidine, which are also thought to act through the methyldiazonium ion. This observation is consistent with a growth rate inhibition effect of the methyldiazonium ion that reflects the intrinsic activity of this species that is independent of the precursor molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed2001

Real-time monitoring of the interactions of transforming growth factor-beta (TGF-beta ) isoforms with latency-associated protein and the ectodomains of the TGF-beta type II and III receptors reveals different kinetic models and stoichiometries of binding.

Mature transforming growth factor-beta (TGF-beta) is proteolytically derived from the C terminus of a precursor protein. Latency-associated protein (LAP), the N-terminal remnant of the TGF-beta precursor, is able to bind and neutralize TGF-beta. Mature TGF-beta exerts its activity by binding and complexing members of two subfamilies of receptors, the type I and II receptors. In addition to these signaling receptors, TGF-beta can also interact with an accessory receptor termed the type III receptor. Using a surface plasmon resonance-based biosensor (BIAcore), we determined the mechanisms of interaction of four binding proteins (LAP, the type II and III receptor ectodomains (EDs), and a type II receptor ED/Fc chimera) with three TGF-beta isoforms, and we quantified their related kinetic parameters. Using global fitting based on a numerical integration data analysis method, we demonstrated that LAP and the type II receptor/Fc chimera interacted with the TGF-beta isoforms with a 1:1 stoichiometry. In contrast, the type II ED interactions with TGF-beta were best fit by a kinetic model assuming the presence of two independent binding sites on the ligand molecule. We also showed that the type III ED bound two TGF-beta molecules. Further experiments revealed that LAP was able to block the interactions of TGF-beta with the two EDs, but that the two EDs did not compete or cooperate with each other. Together, these results strongly support the existence of a cell-surface complex consisting of one type III receptor, two TGF-beta molecules, and four type II receptors, prior to the recruitment of the type I receptor for signal transduction. Additionally, our results indicate that the apparent dissociation rate constants are more predictive of the neutralizing potency of these TGF-beta-binding proteins (LAP, the type II and III receptor EDs, and the type II receptor/Fc chimera) than the apparent equilibrium constants.

Animals↗
PubMed2002

The effect of cobalt compounds on uninfected and Ascaridia galli-infected chickens: a kinetic model for Ascaridia galli populations and chicken growth.

The effect of dietary cobalt from three different sources on uninfected and Ascaridia galli-infected Hisex chickens, has been studied. The chicken diet was supplemented with 0.06 Co2+ kg-1 food either in the form of two glycine-cobalt compounds or mixed zinc-cobalt basic salt. An excess of dietary cobalt in small doses increases the gain of body weight and decreases host mortality. A greater bioefficiency of cobalt was established in infected chickens. A mathematical model has been used to provide a quantitative interpretation of the observed results. The model solutions of the kinetics of worm numbers and body weight are in a good agreement with experimental data. The model is valid for different degrees of A. galli infections and for treatment with different trace elements. The value of the kinetic parameter, regarded as a phenomenological constant of the host immune response, depends on the degree of infection.

Animals↗
PubMed2001

Two-lesion kinetic model of double-strand break rejoining and cell killing.

Radiobiological models, such as the lethal and potentially lethal (LPL) model and the repair-misrepair (RMR) model, have been reasonably successful at explaining the cell killing effects of radiation. However, the models have been less successful at relating cell killing to the formation, repair and misrepair of double-strand breaks (DSBs), which are widely accepted as the main type of DNA damage responsible for radiation-induced cell killing. A fully satisfactory model should be capable of predicting cell killing for a wide range of exposure conditions using a single set of model parameters. Moreover, these same parameters should give realistic estimates for the initial DSB yield, the DSB rejoining rate, and the residual number of unrepaired DSBs after all repair is complete. To better link biochemical processing of the DSB to cell killing, a two-lesion kinetic (TLK) model is proposed. In the TLK model, the family of all possible DSBs is subdivided into simple and complex DSBs, and each kind of DSB may have its own repair characteristics. A unique aspect of the TLK model is that break ends associated with both kinds of DSBs are allowed to interact in pairwise fashion to form irreversible lethal and nonlethal damages. To test the performance of the TLK model, nonlinear optimization methods are used to calibrate the model based on data for the survival of CHO cells for an extensive set of single-dose and split-dose exposure conditions. Then some of the postulated mechanisms of action are tested by comparing measured and predicted estimates of the initial DSB yield and the rate of DSB rejoining. The predictions of the TLK model for CHO cell survival and the initial DSB yield and rejoining rate are all shown to be in good agreement with the measured data. Studies suggest a yield of about 25 DSBs Gy(-1) cell(-1). About 20 DSBs Gy(-1) cell(-1) are rejoined quickly (15-min repair half-time), and 4 to 6 DSBs Gy(-1) cell(-1) are rejoined very slowly (10- to 15-h repair half-time). Both the slowly and fast-rejoining DSBs make substantial contributions to the killing of CHO cells by radiation. Although the TLK model provides a much more satisfactory formalism to relate biochemical processing of DSBs to cell killing than did the earlier kinetic models, some small differences among the measured and predicted CHO cell survival and DSB rejoining data suggest that additional factors and processes not considered in the present work may affect biochemical processing of DSBs and hence cell killing.

Animals↗
PubMed1993

A kinetic model for the competitive reactions of ozone with amino acid residues in proteins in reverse micelles.

Lysozyme and 10 other proteins are solubilized in reverse micelles formed by 0.1 M sodium di-2-ethyl-hexylsulfosuccinate and 2.0-2.5 M water (pH 7.4) in isooctane solvent. Exposure of the protein-containing reverse micellar solutions to ozone causes oxidative damage to the proteins, as assessed by the oxidation of tryptophan residues. The oxidation product of the protein-bound tryptophan has a molar absorption coefficient of 3275 +/- 81 M-1 cm-1 (mean +/- S.D., n = 6) at 320 nm. The product is suggested to be a Criegee ozonide or a tautomer of the Criegee ozonide and not N-formylkynurenine. Ozonation of lysozyme in reverse micelles results in the formation of hydrogen peroxide in yields of only approximately 0.07 mol/mol of tryptophan residues oxidized. The recovery of hydrogen peroxide added as an internal standard to the lysozyme-containing reverse micellar solutions ranges from 84 to 88%, whether or not the samples are subjected to ozonation. This suggests that hydrogen peroxide is neither destroyed during the process of ozonation nor consumed by the protein to a significant extent in an adventitious reaction. A kinetic model for the overall reaction of ozone with the proteins is developed, taking into account the concentrations and the reactivities of individual amino acid residues toward ozone. The model predicts the fractional reaction of ozone with tryptophan residues in the proteins, despite differences in amino acid composition, molecular weight, and tertiary structures. The lack of influence of protein structure is confirmed further by the observation that the native lysozyme (with and without external S-carboxymethylcysteine) and S-carboxymethylated lysozyme give identical values of the fractional reaction of ozone with tryptophan residues. The kinetic equations for the competitive reactions of ozone with amino acid residues in proteins, with some minor modification, are applicable to ozonations on complex mixtures of lipids, proteins, and antioxidants.

Amino Acids↗
PubMed1989

Human selenite metabolism: a kinetic model.

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.

Feces↗
PubMed1983

Kinetic model for the interaction of myosin subfragment 1 with regulated actin.

A one-dimensional kinetic Ising model is developed to describe the binding of myosin subfragment 1 (SF-1) to regulated actin. The model allows for cooperative interactions between individual actin sites with bound SF-1 ligands rather than assuming that groups of actin monomer sites change their state in a cooperative fashion. With the triplet closure approximation, the model yields a set of 16 independent differential (master) equations which may be solved numerically to yield the extent of binding as a function of time. The predictions of the model are compared with experiments on the transient binding of SF-1 to regulated actin in the presence of Ca2+ and in the absence of Ca2+ with varying amounts of SF-1 prebound to the actin filament and on the equilibrium binding of SF-1 X ADP to regulated actin in the absence of Ca2+. In all cases, the calculations fit the data to within the experimental errors. In the case of SF-1 X ADP, the results suggest that a repulsive interaction exists between adjacently bound SF-1 at the ends of two neighboring seven-site actin units.

Actins↗
PubMed1998

Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET.

[Carbonyl-11C]WAY-100635 is a promising PET radioligand for the 5-HT1A receptor, having demonstrated more favorable characteristics for in vivo imaging than the previously available [O-methyl-11C]WAY-100635. The current study evaluates different tracer kinetic modelling strategies for the quantification of 5-HT1A receptor binding in human brain. Mathematical modelling of the carbonyl-labeled radiotracer is investigated using compartmental structures, including both plasma input and reference tissue approaches. Furthermore, the application of basis function methods allows for the investigation of parametric imaging, providing functional maps of both delivery and binding of the radioligand. Parameter estimates of binding from normal volunteers indicate a low intra- versus a high intersubject variability. It is concluded that a simplified reference tissue approach may be used to quantify 5-HT1A binding either in terms of ROI data or as parametric images.

Adult↗
PubMed2005

Frequency dependent heat capacity within a kinetic model of glassy dynamics.

There has been renewed interest in the frequency dependent specific heat of supercooled liquids in recent years with computer simulation studies exploring the whole frequency range of relaxation. The simulation studies can thus supplement the existing experimental results to provide an insight into the energy landscape dynamics. We here investigate a kinetic model of cooperative dynamics within the landscape paradigm for the dynamic heat capacity C(omega,T) behavior. In this picture, the beta-process is modeled as a thermally activated event in a two-level system and the alpha-process is described as a beta-relaxation mediated cooperative transition in a double well. The model resembles a landscape picture, apparently first conceived by Stillinger [Science 267, 1935 (1995)], where an alpha-process is assumed to involve a concerted series of beta-processes. The model provides a description of the activated hopping in the energy landscape in close relation with the cooperative nature of the hopping event. For suitable choice of parameters, the model predicts a frequency dependent heat capacity that reflects the two-step relaxation behavior. The separation between the two peaks grows as the temperature drops, indicating the stringent constraint on the alpha-process due to the cooperativity requirement. The temperature dependence of the position of the low-frequency peak, due to the alpha-relaxation, shows a non-Arrhenius behavior as observed experimentally. The shape of the alpha-peak is, however, found to be temperature independent. The high-frequency peak appears with considerably larger amplitude than the alpha-peak. We attempt a plausible reason for this observation that is in contrast with the general feature revealed by the dielectric spectroscopy. The relative amplitudes of the beta- and alpha-peaks in the present framework are found to depend on several characteristic features of the energy landscape, including the extent of cooperativity requirement for the alpha-relaxation and the asymmetry of the double well.

Journal Article↗
PubMed2006

Angiotensin II production and distribution in the kidney: I. A kinetic model.

Information on the levels of angiotensin II (Ang II) and its receptors in the various renal tissue compartments is still incomplete. A model is presented describing the kinetics of Ang II production, distribution, and disposal in the renal cortex. Basic features are: (1) the model is designed to derive, from Ang II measurements in blood and in whole tissue, estimates of the local densities of the Ang II type 1 (AT(1)) and type 2 (AT(2)) receptors, and to calculate the concentrations of endocrine and paracrine Ang II they actually 'see'; (2) glomerular and peritubular tissue are conceived as separate regions (glomerular region (Glom), peritubular region (Pt)); (3) in Glom and in Pt, Ang II is homogeneously distributed in capillary blood and in interstitial fluid; (4) the model allows for local Ang II concentration gradients between interstitium and blood; (5) Ang II from the circulation diffuses into the interstitium of Glom after convective transcapillary transport; (6) Ang II produced in tubules or Pt enters the microcirculation through diffusive overflow from interstitium; (7) the presence of cell-surface-bound Ang II depends on the reaction with AT(1) and AT(2) receptors, and the presence of intracellular Ang II depends on the internalization of Ang II - AT(1) receptor complex; and (8) the model provides for glomerular filtration, vasopeptidase-mediated degradation, and intracellular degradation as mechanisms of elimination. This model can serve as a framework for detailed quantitative studies of the renin-angiotensin system in the kidney.

Angiotensin II↗
PubMed1985

Multicompartment kinetic model for lead. III. Lead in blood plasma and erythrocytes.

Multicompartment models have been fitted to experimental data on plasma lead and blood lead concentrations of subjects studied by P. E. deSilva (Brit. J. Ind. Med. 38, 209-217, 1981) and one subject studied by W.I. Manton and C.R. Malloy (Brit. J. Ind. Med. 40, 51-57, 1983). Nonlinear models for plasma lead vs blood lead in populations provide significantly better descriptions than does a linear model. Short-term kinetic data do not clearly resolve the precise nonlinear mechanism, however, Parameters of plasma and erythrocyte distribution in a single subject were significantly different on two occasions.

Erythrocytes↗
PubMed1985

Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid.

The antipurine 6-mercaptopurine (6-MP) is effective in the induction and maintenance of remission in patients with acute lymphocytic leukemia. This report presents a compartmental model that describes the kinetics of 6-MP in the plasma and cerebrospinal fluid (CSF) of the monkey. Analysis is based on simultaneously measured plasma and CSF 6-MP concentrations after intravenous and intraventricular bolus administration. Results indicate that 6-MP administered intraventricularly remains largely in the CSF. Disappearance of 6-MP from CSF is principally due to convective losses at a rate equivalent to CSF turnover. Diffusion of 6-MP across the ependymal surface accounts for only 7% of the 6-MP appearing in the plasma. Conversely the dominant route for entry of 6-MP into the CSF from the plasma is entrainment in choroidally formed CSF. Only 12% of 6-MP in the CSF after intravenous administration can be accounted for by permeation of cerebral capillaries and diffusion through brain parenchyma and across the ependymal surface into CSF. These results indicate that the choroid plexus is not a significant barrier for the transfer of molecules like 6-MP from plasma to CSF.

Animals↗
PubMed2004

Cluster analysis in kinetic modelling of the brain: a noninvasive alternative to arterial sampling.

In emission tomography, quantification of brain tracer uptake, metabolism or binding requires knowledge of the cerebral input function. Traditionally, this is achieved with arterial blood sampling. We propose a noninvasive alternative via the use of a blood vessel time-activity curve (TAC) extracted directly from dynamic positron emission tomography (PET) scans by cluster analysis. Five healthy subjects were injected with the 5HT(2A)-receptor ligand [(18)F]-altanserin and blood samples were subsequently taken from the radial artery and cubital vein. Eight regions-of-interest (ROI) TACs were extracted from the PET data set. Hierarchical K-means cluster analysis was performed on the PET time series to extract a cerebral vasculature ROI. The number of clusters was varied from K = 1 to 10 for the second of the two-stage method. Determination of the correct number of clusters was performed by the 'within-variance' measure and by 3D visual inspection of the homogeneity of the determined clusters. The cluster-determined input curve was then used in Logan plot analysis and compared with the arterial and venous blood samples, and additionally with one of the currently used alternatives to arterial blood sampling, the Simplified Reference Tissue Model (SRTM) and Logan analysis with cerebellar TAC as an input. There was a good agreement (P < 0.05) between the values of Distribution Volume (DV) obtained from the K-means-clustered input function and those from the arterial blood samples. This work acts as a proof-of-principle that the use of cluster analysis on a PET data set could obviate the requirement for arterial cannulation when determining the input function for kinetic modelling of ligand binding, and that this may be a superior approach as compared to the other noninvasive alternatives.

Adult↗
PubMed1994

Kinetic modelling of liposome degradation in serum: effect of size and concentration of liposomes in vitro.

The purpose of this study is to propose a new method for quantitative evaluation of liposome degradation in serum. The time course of liposome degradation in rat serum was monitored continuously, using 6(5)-carboxyfluorescein as an aqueous phase marker. The degradation curves exhibited three characteristic phases: lag time, degradation, and plateau. This curve was described by a kinetic model with three parameters: lag time (tau), first-order degradation rate constant (k), and maximum degradation (alpha). The rate and extent of the degradation of liposomes were evaluated separately in terms of k and alpha, respectively. The effects of size and concentration of liposomes on their degradation kinetics were examined using this method. Both k and alpha increased with increasing liposomal size. The increased affinity of larger liposomes for complement was suggested to increase both k and alpha. On the other hand, alpha decreased with increasing liposomal concentration without altering k. The decreased extent of degradation was considered to result from the depletion of complement components. There was no significant effect of size and concentration of liposomes on tau. Quantitative evaluation of the rate and extent of degradation of liposomes will provide deeper insights into the interaction between liposomes and serum components, and basic information on liposomes as potential drug carriers.

Animals↗
PubMed2003

Modeling kinetics of infused 13NN-saline in acute lung injury.

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 +/- 18%) than for LP (5 +/- 4%) and NP (1 +/- 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 +/- 0.09) than for LP (0.96 +/- 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 +/- 0.26) than for LP (0.05 +/- 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.

Algorithms↗