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At least 271 records · Page 15Linked to original sources
PubMed1998

Urea reduction ratio and urea kinetic modeling: a mathematical analysis of changing dialysis parameters.

Based mainly on the simplicity of its calculation, the urea reduction ratio (URR) has been suggested as an alternative to urea kinetic modeling (Kt/V) as a measure of hemodialysis adequacy. However, recent studies have raised questions concerning the accuracy of URR, particularly in the presence of residual kidney function (KrU). This study was initiated to evaluate the relationship between URR and Kt/V under a variety of dialysis conditions. Equations based on the variable-volume, single-pool model described by Gotch were used to construct a model incorporating the variables used in the estimation of URR and Kt/V. The model's prediction of URR correlated closely with measured URR in 30 patients (r = 0.9987, p < 0.000001). This analytic approach showed that changes in each of several dialysis parameters caused divergence in the values of URR and Kt/V. The model showed that URR could be less than 0.65, while total Kt/V was greater than 1.2, whether or not KrU was present. In fact, when KrU was greater than 1. 0, URR could be less than 0.65, while Kt/V might be 2.0 or higher. On the other hand, the model showed instances where URR could be greater than 0.65, when Kt/V was less than 1.2. This occurred only when KrU was less than 1.0. To determine the prevalence of these anomalies in clinical practice, 767 kinetic modeling determinations were evaluated in 207 patients. One of the above discrepancies was observed at least once in 30.9% of the patients, representing 12.1% of all determinations. In addition, it was found that omitting KrU from the calculation of Kt/V generally leads to a Kt/V <1.2. This, when associated with a URR <0.65, could erroneously imply inadequate dialysis. The patient data are consistent with the view that URR and Kt/V are the net result of several variables that may act together or even in opposing directions. Based on this mathematical model and the observed clinical data, the use of URR alone to assess dialysis adequacy, or neglecting the contribution of KrU to Kt/V, may lead to changes in the dialysis prescription that are neither correct nor necessary.

Aged↗
PubMed1990

Kinetic modeling of intracellular pH and comparison with 31P NMR experimental values in dialysed uremic patients.

Changes in intra-erythrocytic pH values over time, during and after bicarbonate hemodialysis, were studied with 31P Nuclear Magnetic Resonance. Simultaneously, pH values of whole blood were obtained by a gazometric method. A two-compartment model appeared to be the simplest kinetic model to explain the shifts in proton concentrations in extra- and intra-cellular media. Non-linear regression was used to determine exchange constant values. There was a very good correlation between the experimental and calculated proton concentrations. This model can describe all patients but individual experimental constants must be determined. Under these conditions a single blood pH determination before dialysis will permit determination of the initial intra-erythrocytic pH and monitoring of intra-erythrocytic pH during hemodialysis.

Acid-Base Equilibrium↗
PubMed1988

Kinetic models for association of 2,3,7,8-tetrachlorodibenzo-p-dioxin with the Ah receptor.

Saturation binding studies of the interaction between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the Ah receptor obtained from the hepatic cytosol of Wistar rats have been carried out. The conventional Scatchard analysis for determination of the equilibrium constant for ligand-receptor binding has been shown to be inappropriate due to thermal inactivation of the unoccupied receptor. Simulation models of the receptor-ligand binding kinetics which take into account receptor degradation have been developed and the results are consistent with two alternative kinetic models. In Model 1, reversible 2,3,7,8-TCDD-receptor binding occurs in parallel with inactivation of the unbound receptor; analysis of the observed data using this model suggests that the previously determined equilibrium constants (Kass) for association of the ligand with the receptor are orders of magnitude too low and the total initial receptor concentrations are somewhat underestimated. In Model 2, the unbound receptor is converted unimolecularly to an activated state which then undergoes competitive degradation or entrapment by ligand. Experiments have been carried out over the temperature range 4-37 degrees C, enabling activation parameters to be obtained. According to Scheme 1, the activation enthalpies for association of receptor with ligand and for thermal inactivation of the unoccupied receptor are high, and numerically almost identical (delta H++ ca 125 kJ mol-1). These reactions are strongly entropically driven and this is consistent with association being accompanied by a conformational change in the receptor protein, and the previously postulated binding of the ligand to a hydrophobic pocket. According to Scheme 2, there is only one enthalpy of activation because both inactivation and entrapment by 2,3,7,8-TCDD are fast processes which follow the same slow activation step. On the basis of this latter model, a 10(-9) M concentration of 2,3,7,8-TCDD is sufficient to trap roughly two-thirds of the activated receptors.

Animals↗
PubMed2004

Dynamic contrast-enhanced CT of intracranial meningioma: comparison of distributed and compartmental tracer kinetic models--initial results.

Dynamic contrast material-enhanced computed tomographic images of intracranial meningioma were analyzed by using both distributed-parameter and conventional compartmental tracer kinetic models. The distributed-parameter models were found to yield consistently better fitting of data sets than were conventional compartmental models. Although linear correlations were found between the kinetic parameters of the two models, some of these parameters (such as perfusion and mean transit time) did not correspond quantitatively. For all models, the kinetic parameters associated with the extravasation of tracer were found to be distinctly higher in meningiomas than in normal white- and gray-matter tissues.

Contrast Media↗
PubMed2004

A new kinetic model of recombinant beta-galactosidase from Kluyveromyces lactis for both hydrolysis and transgalactosylation reactions.

Previous models based on the Michaelis-Menten kinetic equation, that glucose was not used as an acceptor, did not explain our experimental data for lactose conversion by a recombinant beta-galactosidase from Kluyeromyces lactis. In order to create a new kinetic model based on the data, the effects of galactose and glucose on beta-galactosidase activity were investigated. Galactose acted as an inhibitor at low concentrations of galactose and lactose, but did not inhibit the activity of beta-galactosidase at high concentrations of galactose (above 50mM) and lactose (above 100mM). The addition of glucose at concentrations below 50mM resulted in an increased reaction rate. A new model of K. lactis beta-galactosidase for both hydrolysis and transgalactosylation reactions with glucose and lactose as acceptors was proposed. The proposed model was fitted well to the experimental data of the time-course reactions for lactose conversion by K. lactis beta-galactosidase at various concentrations of substrate.

Dose-Response Relationship, Drug↗
PubMed1998

Trace element trophic transfer in aquatic organisms: a critique of the kinetic model approach.

The bioaccumulation of trace elements in aquatic organisms can be described with a kinetic model that includes linear expressions for uptake and elimination from dissolved and dietary sources. Within this model, trace element trophic transfer is described by four parameters: the weight-specific ingestion rate (IR); the assimilation efficiency (AE); the physiological loss rate constant (ke); and the weight-specific growth rate (g). These four parameters define the trace element trophic transfer potential (TTP = IR.AE/[ke + g]) which is equal to the ratio of the steady-state trace element concentration in a consumer due to trophic accumulation to that in its prey. Recent work devoted to the quantification of AE and ke for a variety of trace elements in aquatic invertebrates has provided the data needed for comparative studies of trace element trophic transfer among different species and trophic levels and, in at least one group of aquatic consumers (marine bivalves), sensitivity analyses and field tests of kinetic bioaccumulation models. Analysis of the trophic transfer potentials of trace elements for which data are available in zooplankton, bivalves, and fish, suggests that slight variations in assimilation efficiency or elimination rate constant may determine whether or not some trace elements (Cd, Se, and Zn) are biomagnified. A linear, single-compartment model may not be appropriate for fish which, unlike many aquatic invertebrates, have a large mass of tissue in which the concentrations of most trace elements are subject to feedback regulation.

Animals↗
PubMed2005

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia.

A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.

Cell Hypoxia↗
PubMed1989

[Application of the urea kinetic model to evaluate the adequacy of hemodialysis].

The evaluation of dialysis adequacy still remains an unsolved problem. The mathematical model proposed by Gotch and Sargent is now currently used to quantify the dialysis need in urysiemic patients. In this study we evaluated the reliability of this kinetic model in 9 patients admitted to high efficiency hemodialysis. Only 5 out of the 9 patients showed a Protein Catabolic Rate normalized (PCRn) within 0.8-1.6 gr/kg/die a range considered optimal for hemodialysis patients. The other patients showed a PCRn higher than 1.6 gr/kg/die and were therefore excluded from this study. The volume of urea distribution (V) measurements deduced from urea kinetic model showed a great variability with a very high mean value (more than 78.3 +/- 6.3%). We therefore suggest that for the evaluation of dialysis adequacy in patients submitted to high efficiency hemodialysis an arbitrary value of urea distribution equal to 60% of the body weight should be used. However further clinical and biochemical evaluations are needed to confirm whether this model might be considered as a reliable parameter of dialysis adequacy.

Adolescent↗
PubMed1995

Noninvasive measurement of intrarenal blood flow distribution: kinetic model of renal 123I-hippuran handling.

A new technique for noninvasive measurement of intrarenal blood flow distribution over cortex and medulla is proposed. The technique involves analysis of 123I-labeled hippuran renography, according to a kinetic model that describes the flow of 123I-hippuran from the heart (input) through the renal cortex and medulla to the bladder (output). The method is validated and compared with the standard microsphere injection technique in anesthetized dogs. Changes in intrarenal blood flow distribution were induced by infusion of placebo (n = 6), angiotensin I (n = 5), or atrial natriuretic factor (n = 5). Baseline percentage medullary blood flow in the left kidney was 12 +/- 1% of total renal blood flow measured with microspheres and 15 +/- 1% with renography. During infusion of the placebo, medullary blood flow decreased slightly compared with baseline, as measured with both methods, by 2 +/- 6 (microspheres) and 1 +/- 8% (renography). Infusion of angiotensin I caused a marked fall in medullary blood flow by 42 +/- 11 (microspheres) and 57 +/- 8% (renography). In contrast, infusion of atrial natriuretic factor caused a small rise in medullary blood flow as measured with both methods (9 +/- 3 and 12 +/- 11%, respectively). The absolute and percent changes in medullary blood flow measured with renography correlated with those measured with microspheres (left kidney: r = 0.67, P = 0.005; r = 0.71, P = 0.003, respectively; right kidney: r = 0.62, P = 0.01; r = 0.68, P = 0.004, respectively). We conclude that the proposed kinetic model of renal 123I-hippuran handling can be used to measure changes in intrarenal blood flow distribution and, because of its noninvasive character, may be of use in clinical studies.

Angiotensin I↗
PubMed2004

Web-based kinetic modelling using JWS Online.

UNLABELLED: JWS Online is a repository of kinetic models, describing biological systems, which can be interactively run and interrogated over the Internet. It is implemented using a client-server strategy where the clients, in the form of web browser based Java applets, act as a graphical interface to the model servers, which perform the required numerical computations. AVAILABILITY: The JWS Online website is publicly accessible at http://jjj.biochem.sun.ac.za/ with mirrors at http://www.jjj.bio.vu.nl/ and http://jjj.vbi.vt.edu/

Cell Physiological Phenomena↗
PubMed1981

Hydrolysis of rat chylomicron acylglycerols: a kinetic model.

A quantitative model describing the kinetics of hydrolysis of rat chylomicron acylglycerols by bovine milk lipoprotein lipase has been developed using data from studies on rat lymph chylomicrons containing doubly labeled acylglycerols. The detailed analysis indicates that, in addition to hydrolysis from tri- to di-, di- to mono-, and monoacylglycerol to glycerol, and apparently direct hydrolysis pathway of tri- to monoacylglycerol is also present. This accounts for the transient accumulation of monoacylglycerol seen in some of the experiments. For most hydrolysis steps, a Michaelis-Menten mechanism adequately describes the rate of hydrolysis as a function of lipoprotein lipase concentration. A higher order, more complex mechanism, however, is necessary for the apparent tri- to monoacylglycerol hydrolysis pathway. A mathematical function that describes the way free fatty acid released can control the rates of hydrolysis, and how the presence of the binding sites for free fatty acid on albumin in the incubation medium can modulate this, in included. The model simultaneously satisfies the kinetics of hydrolysis for tri-, di-, and monoacylglycerol together with the kinetics of the glycerol and fatty acid moieties for a wide range of albumin and lipoprotein lipase concentrations.

Animals↗
PubMed2004

A kinetic model of aqueous-phase alkali hydrolysis of 2,4,6-trinitrotoluene.

Alkali hydrolysis of 2,4,6-trinitrotoluene (TNT) was studied using batch experiments with starting pH values 11 and 12 in glass conical flasks covered with aluminum foil. Isothermal (25 and 40 degrees C) as well as non-isothermal experiments were conducted. Experiments starting at pH 12 resulted in >95% reduction in the concentration of TNT; those starting at pH 11 had a maximum reduction of 20-25% in TNT concentration. In all the experiments, one major stable intermediate was produced but it could not be identified. The experimental data were used to determine the overall stoichiometry of TNT and hydroxyl ions. Approximately 100 M (standard deviation 11.4) of hydroxyl ions were consistently consumed per mole of TNT. However, control experiments showed that all but 13 M (standard deviation 2) of hydroxyl ions were consumed in reactions not related to TNT. A simple kinetic model involving formation of the intermediate was proposed to account for changes in concentrations of TNT and hydroxyl ions. The rate constants and activation energies of the reactions were identified using isothermal data and the kinetic model was then used to predict the experimental data in the non-isothermal experiments reasonably well.

Alkalies↗
PubMed1989

Transient response of rod outer segment cGMP phosphodiesterase to actinic light pulses. II. Detailed quantitative kinetic model.

In the accompanying article (Schmidt, J.A., and Yguerabide, J. (1989) J. Biol. Chem. 264, 19790-19803), we presented a minimal quantitative kinetic model with one rate-limiting step for the transient response of rod outer segment (ROS) phosphodiesterase (PDE) to stimulating light pulses of low fractional bleach (linear response range) and showed that the model was in excellent quantitative agreement with experimental results. The model characterizes the PDE response in terms of the specific rate constant of the rate-limiting step, kL, the lifetime of photoactivated rhodopsin, tau R, and the lifetime of activated PDE, tau P, but makes no predictions on how these kinetic parameters should depend on the concentrations of the various reactive species involved in the PDE response to light and does not reveal the nature of the rate-limiting step. However, we established by curve fitting experimental data to theoretical expressions from the model that kL increases hyperbolically with [GTP], tau R decreases with [GTP], and tau P is independent of GTP. In this report we present three detailed kinetic models which make specific quantitative predictions on how the kinetic parameters of the minimal model should depend on nucleotide and G protein concentrations and test the models against experimental data. Each model consists of one rate-limiting step. The first detailed model postulates that the rate-limiting step is the dissociation of R*GT into R* and GT (T stands for GTP). The second model postulates that the rate-limiting step is the binding of GTP to R*G, and the third model postulates that the rate-limiting step is the encounter rate of R* and G on the ROS disc membrane. We find that only the first detailed model is consistent with the experimental results as characterized by the minimal model. Using this detailed model we (a) define kL and tau R in terms of more fundamental equilibrium and rate parameters, (b) develop a theory for the systematic evaluation of amplification or gain of the PDE light response from light-stimulated GTP-binding data as well as v(t) versus t graphs, and (c) clarify methods which have been used in the past to evaluate gain experimentally.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

A note on kinetic modeling of stability data and implications on pooling.

In this note we discuss the relationship between the underlying kinetic model and the statistical (or analytic) model used to study degradation. For small degradation rates, the zeroth, first, and second order statistical models give approximately the same fits and predictions on either the original assay scale or the percent of label claim scale. However, It is shown that the zeroth and second order statistical models artificially induce differential degradation rates across strengths when the percent of label claim response data are analyzed and poolability is not allowed across strengths. The first order model is free of this problem when the true degradation kinetics are first order. We make some recommendations in pooling stability data across strengths.

Drug Stability↗
PubMed1997

Kinetic model for batch cellulase production by Trichoderma reesei RUT c30.

A kinetic model for batch cellulase enzyme production by T. reesei from cellulose substrate is constructed from literature concepts and laboratory data. The key concepts included were four: (i) existence of primary and secondary mycelia; (ii) cellulase production by secondary mycelia only; (iii) the adsorption of cellulase (catalyst) on the particulate cellulose (substrate), and (iv) the decline of cellulose reactivity with extent of conversion. The laboratory batch data were biomass (particulate), substrate (particulate cellulose), and product (cellulase enzyme and reducing sugar) concentration vs. time. The kinetic parameters were evaluated simultaneously through a nonlinear fitting routine, and the resultant model is shown to fit the data well. The model's success validates the presumed need to include all four concepts in reactor analysis for cellulase production.

Adsorption↗
PubMed1985

Kinetic models for plasma disappearance of insulin in normal subjects.

Three theoretical kinetic models for plasma disappearance of insulin were examined in six normal men. The models allowed for the existence of non-saturable and/or saturable mechanisms. Constant infusion of porcine insulin at different rates was used to achieve different levels of steady state plasma insulin concentrations, while normoglycaemia was secured by a glucose clamp technique. Appropriate validation procedures demonstrated that one of the three models was superior to the others in describing the relationship between the exogenous insulin infusion rate Iex and the steady state plasma insulin concentration C: Iex = -Iend + k2 X C/(k3 + C), where Iend is the endogenous post-hepatic insulin delivery rate. Thus, only saturable mechanism(s) could be demonstrated. The median value of k2 (the maximal insulin disappearance rate) and k3 (the plasma insulin concentration at which the insulin disappearance rate is half maximal) were 7.31 nmol X min.-1 and 3.89 nmol X 1-1. The median value of k2/k3 (the clearance rate of insulin for infinitesimal plasma insulin concentrations) was 25.0 ml X kg-1 X min.-1. Thus, at physiological levels of plasma insulin concentrations the metabolic clearance rate of insulin is higher than insulin clearance estimates previously reported in studies based on the assumption of first order kinetics.

Adolescent↗
PubMed1991

Evaluation of parameters for adequate dialysis therapy: (1). Monitoring of parameters by urea kinetic modeling.

In an attempt to evaluate the adequacy of regular dialysis therapy, calculations of Kt/V-urea and protein catabolic rate (pcr) from the data of routine laboratory examinations by means of urea kinetic modeling were performed in 59 regular dialysis patients (28 males and 31 females; mean age, 59 +/- 2 years old; mean dialysis duration, 83 +/- 10 months). The mean values of Kt/V-urea and pcr were 1.10 +/- 0.04 and 0.98 +/- 0.03 g/kgBW.day, respectively. The number of patients who were within the optimal range (0.9-1.4 for Kt/V urea and 0.9-1.5 for pcr) was 37 (62.7%) for Kt/V-urea and 38 (64.4%) for pcr. Furthermore, we inferred that, based on an appropriate dietary protein intake, removal of urea by intermittent dialysis should be adjusted to maintain the patient in equilibrium for a defined pre-dialysis plasma urea concentration. From the data obtained, we concluded that: (1) it is possible to apply urea kinetic modeling on the basis of routine laboratory examinations, (2) it is important to maintain the pre-dialysis plasma urea concentration at more than a certain level, and (3) it is also important to control the post-dialysis plasma urea concentration at a low level.

Creatinine↗
PubMed2003

Kinetic modelling of Amadori N-(1-deoxy-D-fructos-1-yl)-glycine degradation pathways. Part I--reaction mechanism.

The fate of the Amadori compound N-(1-deoxy-D-fructos-1-yl)-glycine (DFG) was studied in aqueous model systems as a function of pH and temperature. The samples were heated at 100 and 120 degrees C with initial reaction pH of 5.5 and 6.8. Special attention was paid to the formation of the free amino acid, glycine; parent sugars, glucose and mannose; organic acids, formic and acetic acid and alpha-dicarbonyls, 1- and 3-deoxyosone together with methylglyoxal. For the studied conditions decreasing the initial reaction pH with 1.3 units or increasing the temperature with 20 degrees C has the same effect on the DFG degradation as well as on glycine formation. An increase in pH seems to favour the formation of 1-deoxyosone. The lower amount found comparatively to 3-deoxyosone, in all studied systems, seems to be related with the higher reactivity of 1-deoxyosone. Independently of the taken pathway, enolization or retro-aldolization, DFG degradation is accompanied by amino acid release. Together with glycine, acetic acid was the main end product formed. Values of 83 and 55 mol% were obtained, respectively. The rate of parent sugars formation increased with pH, but the type of sugar formed also changed with pH. Mannose was preferably formed at pH 5.5 whereas at pH 6.8 the opposite was observed, that is, glucose was formed in higher amounts than mannose. Also, independently of the temperature, at higher pH fructose was also detected. pH, more than temperature, had an influence on the reaction products formed. The initial steps for a complete multiresponse kinetic analysis have been discussed. Based on the established reaction network a kinetic model will be proposed and evaluated by multiresponse kinetic modelling in a subsequent paper.

Acetic Acid↗