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At least 685 records · Page 38Linked to original sources

Validation of a kinetic model for the reactions in RIA.

The goal of this work was to check the validity of a model previously described for the study of kinetics of the processes taking place during the immuno-analytical measurement of insulin. The antibody was immobilized on the suface wall of the reaction tube. Tracer and insulin concentration, temperature, viscosity and ionic strength in the reaction medium were taken as independent variables. Biexponential kinetics depending on the concentration was observed. The results of the viscosity study show a clear negative influence of this parameter on the direct reaction velocity. Ionic strength had a slight effect, which suggests that the observed variation due to the addition of glycerol is not induced by the influence of the dielectric constant of the solution used. The effect of the temperature shows activation parameters similar to water flow-viscosity energy, which suggests a diffusion control for the reaction. The proposed model correctly interprets the influence of the studied variables.

Antibodies↗

On the undecidability among kinetic models: from model selection to model averaging.

This article deals with the problem of model selection for the mathematical description of tracer kinetics in nuclear medicine. It stems from the consideration of some specific data sets where different models have similar performances. In these situations, it is shown that considerate averaging of a parameter's estimates over the entire model set is better than obtaining the estimates from one model only. Furthermore, it is also shown that the procedure of averaging over a small number of "good" models reduces the "generalization error," the error introduced when the model selected over a particular data set is applied to different conditions, such as subject populations with altered physiologic parameters, modified acquisition protocols, and different signal-to-noise ratios. The method of averaging over the entire model set uses Akaike coefficients as measures of an individual model's likelihood. To facilitate the understanding of these statistical tools, the authors provide an introduction to model selection criteria and a short technical treatment of Akaike's information-theoretic approach. The new method is illustrated and epitomized by a case example on the modeling of [11C]flumazenil kinetics in the brain, containing both real and simulated data.

Carbon Radioisotopes↗

Kinetic modeling of the light-dependent photosynthetic activity of the green microalga Chlorella vulgaris.

Light-dependent photosynthesis of Chlorella vulgaris was investigated by using a novel photosynthesis measurement system that could cover wide ranges of incident light and cell density and reproduce accurate readings. Various photosynthesis models, which have been reported elsewhere, were classified and/or reformulated based upon the underlying hypotheses of the light dependence of the algal photosynthesis. Four types of models were derived, which contained distinct light-related variables such as the average or local photon flux density (APFD or LPFD) and the average or local photon absorption rate (APAR or LPAR). According to our experimental results, the LPFD and LPAR models could predict the experimental data more accurately although the APFD and APAR models have been widely used for the kinetic study of microalgal photosynthesis.

Cell Culture Techniques↗

Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models.

An improve pharmacokinetic model is described for inhalation of volatile xenobiotics from a closed gas phase system. This model is based on steady-state kinetics and covers metabolic elimination processes of either first-order, zero-order, or Michaelis-Menten characteristics. It is emphasized that the distribution of a volatile compound between gas phase and organism under steady-state conditions may be much different from a static equilibrium obtained in absence of metabolism, as it is observed after application of a metabolic inhibitor. A re-analysis or previous experimental data on dose-dependent pharmacokinetics of different haloethylenes reveals that, in general, the metabolic elimination processes of the rapidly equilibrating mono-haloethylenes (and vinylidene fluoride) can be resolved with excellent accuracy into sections of first-order and zero-order kinetics. Other compounds show a more smooth transition from first-order elimination (at lower atmospheric concentrations) into conditions of saturation (dichloroethylenes, trichloroethylene). The analyses are consistent with a recent concept of Andersen (1980) that metabolic elimination of inhaled xenobiotics is limited by either the capacity of metabolic enzymes or factors of transport to the metabolic sites.

Animals↗

A steady-state kinetic model of butyrylcholinesterase from horse plasma.

The steady-state kinetics of the butyrylcholinesterase-catalysed hydrolysis of butyrylthiocholine and thiophenyl acetate were shown to deviate from Michaelis-Menten kinetics. The ;best' empirical rate law was selected by fitting different rate equations to the experimental data by non-linear regression methods. The results were analysed in view of two alternative interpretations: (1) the reaction is catalysed by a mixture of enzymes, or (2) the activity is due to a single enzyme displaying deviations from Michaelis-Menten kinetics. It was concluded that the second alternative applies, and this conclusion was further supported by experiments involving simultaneous hydrolysis of alternative thiol ester substrates (butyrylthiocholine/thiophenyl acetate) as well as alternative thiol ester and oxygen ester substrates (butyrylthiocholine/phenyl acetate; thiophenyl acetate/butyrylcholine; acetylthiocholine/phenyl acetate). On the basis of the conclusion that a single enzyme is responsible for the activity, a molecular model is proposed. This model involves an acylated enzyme, and implies binding to the enzyme of one acyl group and one ester molecule, but not two ester molecules at the same time. Thus butyrylcholinesterase, which is structurally a tetramer, behaves functionally as a co-operative dimer, an interpretation in accordance with available data from active-site titrations.

Animals↗

Refinement of the kinetic model of the 2-[14C]deoxyglucose method to incorporate effects of intracellular compartmentation in brain.

A translocase to transport hexose phosphate formed in the cytosol into the cisterns of the endoplasmic reticulum, where the phosphatase resides, is absent in brain (Fishman and Karnovsky, 1986). 2-Deoxyglucose-6-phosphate (DG-6-P) may therefore have limited access to glucose-6-phosphatase (G-6-Pase), and transport of the DG-6-P across the endoplasmic reticular membrane may be rate limiting to its dephosphorylation. To take this compartmentation into account, a five-rate constant (5K) model was developed to describe the kinetic behavior of 2-deoxyglucose (DG) and its phosphorylated product in brain. Loss of DG-6-P was modeled as a two-step process: (a) transfer of DG-6-P from the cytosol into the cisterns of the endoplasmic reticulum; (b) hydrolysis of DG-6-P by G-6-Pase and subsequent return of the free DG to the precursor pool. Local CMRglc (LCMRglc) was calculated in the rat on the basis of this model and compared with values calculated on the basis of the three-rate constant (3K) and the four-rate constant (4K) models of the DG method. The results show that under normal physiological conditions all three models yield values of LCMRglc that are essentially equivalent for experimental periods between 25 and 45 min. Therefore, the simplest model, the 3K model, is sufficient. For experimental periods from 60 to 120 min, the 4K and 5K models do not correct completely for loss of product, but the 5K model does yield estimates of LCMRglc that are closer to the values at 45 min than those obtained with the 3K and 4K models.

Animals↗

A microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET.

The microdosimetric-kinetic (MK) model for cell killing by ionizing radiation is summarized. An equation based on the MK model is presented which gives the dependence of the relative biological effectiveness in the limit of zero dose (RBE1) on the linear energy transfer (LET). The relationship coincides with the linear relationship of RBE1 and LET observed for low LET, which is characteristic of a Poisson distribution of lethal lesions among the irradiated cells. It incorporates the effect of deviation from the Poisson distribution at higher LET. This causes RBE1 to be less than indicated by extrapolation of the linear relationship to higher LET, and to pass through a maximum in the range of LET of 50 to 200 keV per micrometer. The relationship is compared with several experimental studies from the literature. It is shown to approximately fit their results with a reasonable choice for the value of a cross-sectional area related to the morphology and ultrastructure of the cell nucleus. The model and the experiments examined indicate that the more sensitive cells are to radiation at low LET, the lower will be the maximum in RBE they attain as LET increases. An equation that portrays the ratio of the sensitivity of a pair of cell types as a function of LET is presented. Implications for radiotherapy with high-LET radiation are discussed.

Cell Line↗

An assessment of a coupled three-state kinetic model for sodium conductance changes.

The behavior of a coupled three-state kinetic scheme is examined to see if it might be a viable model for the conductance changes of sodium channels. It is found that for simulations of experiments which determine the properties of the Hodgkin-Huxley m and h gates, the three-state scheme performs approximately equivalently to the Hodgkin-Huxley model. In particular, the three-state scheme successfully simulates those experiments which the Hodgkin-Huxley model successfully simulates, but fails to simulate those newer voltage clamp experiments which give results anomalous to the H-H model. It is concluded that the three-state scheme is probably as good as the H-H model, but is not a viable successor to it.

Axons↗

Quantitative in vivo receptor binding III: Tracer kinetic modeling of muscarinic cholinergic receptor binding.

A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term "free receptor density" is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of [3H]scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period. In this instance, specific tracer binding may be accurately determined by measuring tissue ligand concentration at a single time point after bolus intravenous injection, providing that regional cerebral blood flow is known. This derivation has potential clinical application, because it will permit construction of quantitative pictorial maps of regional free receptor densities in the human brain by means of positron emission tomographic imaging.

Animals↗

Kinetic modeling of batch hydrogen production process by mixed anaerobic cultures.

The kinetics of batch anaerobic hydrogen production by mixed anaerobic cultures was systemically investigated in this study. Unstructured models were used to describe the substrate utilization, biomass growth and product formation in the hydrogen production process. The relationship between the substrate, biomass and products were also evaluated. Experimental results show that the Michaelis-Menten equation, Logistic model and modified Gompertz equation all could be adopted to respectively describe the kinetics of substrate utilization, biomass growth and product formation. Furthermore, the relationship between the acidogenic products and biomass was simulated by Luedeking-Piret model very well. The experimental results suggest that the formation of hydrogen and the main aqueous products, i.e., butyrate and acetate, was all growth-associated.

Acetates↗