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PubMed1995

Analytic solution of the Variable-Volume Double-Pool urea kinetics model applied to parameter estimation in hemodialysis.

An analytic solution of the Variable-Volume Double-Pool urea kinetics model and its application to the estimation of clinically relevant parameters of the patient-machine system, are presented. These include the urea distribution volume and generation rate and the mean dialyzer clearance. The estimation of these parameters is based on the assumption of constant values for the diffusion coefficient between the two pools and the intra-extracellular volume ratio. Results obtained by computer simulations show that the effect of a +/- 50% variation of these parameters influences the estimates less than standard measurement errors. Starting from these results, four methods to in vivo estimate the urea distribution volume and generation rate from blood samples are compared. Two methods are based on the analytic solution of the double-pool model using seven samples (reference method) or three samples (new clinical method). The remaining methods are based on urea mass-balance and are largely used in the clinical practice. These last techniques differ from each other for the blood sample taken at the end of the treatment or 30 min later. The results obtained from hemofiltration sessions show that the urea generation rate is accurately estimated by all methods. The total distribution volume is still accurately estimated by the new clinical method while it is systematically underestimated by the urea mass-balance when the blood sample at the end of dialysis is used. Instead, a high overcompensation results using the blood sample taken 30 min after the end of dialysis. Finally, the new clinical method also provides reliable estimates for the dialyzer clearance starting from only three blood samples all taken during dialysis.

Algorithms↗
PubMed2004

[Assessment of total body water of patients on hemodialysis with urea kinetic model].

OBJECTIVE: To propose a method to evaluate the total body water (TBW) of patients on hemodialysis with urea kinetic model (UKM), and compare it with body surface bio-impedance spectrum (BIS) analysis. METHODS: We enrolled 24 adult patients with end stage renal disease (ESRD) without hyper-catabolism in our dialysis center. All of them had been on hemodialysis for more than 3 months. TBW was measured with BIS analysis immediately before and after dialysis session, and one hour after hemodialysis session. Spent dialysate was collected; blood samples were taken before and one hour after hemodialysis session, TBW before hemodialysis session were calculated by UKM. RESULTS: Patients were 6 men and 18 women, the average age was (51.2+/-13.5) years and the average time on dialysis was (33.2+/-36.7) months. Causes of ESRD included chronic glomerulonephritis (8 patients), diabetic nephropathy (1 patients), hypertensive renal damage (1 patients), interstitial nephritis(two patients), chronic pyelonephritis (two patients). The average ultrafiltration volume was (2.7+/-1.0) L (0.5-4.4 L) . Plasma urea concentrations were (23.06+/-5.76) mmol/L and (8.15+/-2.06) mmol/L before and one hour after hemodialysis session, respectively. There was no significant difference between TBW measured immediately after and one hour after hemodialysis session with BIS analysis [(29.9+/-8.8) L and (29.8+/-8.6) L, respectively; average difference was (0.1+/-0.9)L, P=0.70]. These two measurements correlated very well (Pearson r=0.99, P<0.05). There was no significant difference between UKM and BIS analysis [(31.4+/-7.3) L and (31.3+/-8.6) L, respectively; average difference was (0.2+/-4.5) L, P=0.87]. Results of these two methods correlated very well (Pearson r=0.86, r(2)=0.73,P< 0.05). CONCLUSION: TBW measured with UKM in patients on hemodialysis provides theoretic basis for fluid status evaluation and dry body weight assessment.

Adult↗
PubMed2001

Reaction kinetics of protease with substrate phage. Kinetic model developed using stromelysin.

Peptide libraries generated using phage display have been widely applied to proteolytic enzymes for substrate selection and optimization, but the reaction kinetics between the enzyme and substrate phage are not well understood. Using a quantitative ELISA assay to monitor the disappearance of substrate, we have been able to follow the course of reaction between stromelysin, a metalloprotease, and its substrate phage. We found that under the proteolytic conditions where the enzyme was present in nanomolar concentration or higher, in excess over the substrate, the proteolysis of substrate phage was a single exponential event and the observed rate linear with respect to enzyme concentration. The enzyme concentration dependence could be described by pseudo first-order kinetic equations. Our data suggest that substrate binding is slow relative to the subsequent hydrolysis step, implying that the phage display selection process enriches clones that have high binding affinity to the protease, and the selection may not discriminate those of different chemical reactivity toward the enzyme. Considering that multiple substrate molecules may be present on a single phage particle, we regard the substrate phage reaction kinetic model as empirical. The validity of the model was ascertained when we successfully applied it to determine the binding affinity of a competitive inhibitor of stromelysin.

Animals↗
PubMed1987

Kinetic models of cell shape changes and other optically-detected responses to stimulation.

Certain cellular responses to stimulation can be described as a continuous series of virtually infinite but real transient states generated by reactions occurring at the molecular level within the cell. While any particular state can in principle be isolated and examined by using appropriate methods to stop or freeze the reaction, adjacent or nearby states will generally be indistinguishable from one another by kinetic means. In favorable cases, however, the progress curves can be fitted to comparatively very simple kinetic models involving a limited number of steps, which accurately describe the real-time response within the limitations of the experimental setup. The simple series models have their origins in the continuous myriad-state or "microscopic" series description, and the observable or "macroscopic" kinetic rate constants are statistically related to the rate constants describing the transitions between the real states of the ongoing response. This indicates that different aspects of stimulus-response coupling, e.g., shape changes, alterations in cytosolic calcium levels and so forth, can be compared in a self-consistent fashion by modeling the individual responses in terms of simple parallel series models.

Blood Platelets↗
PubMed2000

A kinetic model for the early steps of RNA synthesis by human RNA polymerase II.

Eukaryotic mRNA synthesis is a highly regulated process involving numerous proteins acting in concert with RNA polymerase II to set levels of transcription from individual promoters. The transcription reaction consists of multiple steps beginning with preinitiation complex formation and ending in the production of a full-length primary transcript. We used pre-steady-state approaches to study the steps of human mRNA transcription at the adenovirus major late promoter in a minimal in vitro transcription system. These kinetic studies revealed an early transition in RNA polymerase II transcription, termed escape commitment, that occurs after initiation and prior to promoter escape. Escape commitment is rapid and is characterized by sensitivity to competitor DNA. Upon completion of escape commitment, ternary complexes are resistant to challenge by competitor DNA and slowly proceed forward through promoter escape. Escape commitment is stimulated by transcription factors TFIIE and TFIIH. We measured forward and reverse rate constants for discrete steps in transcription and present a kinetic model for the mechanism of RNA polymerase II transcription that describes five distinct steps (preinitiation complex formation, initiation, escape commitment, promoter escape, and transcript elongation) and clearly shows promoter escape is rate-limiting in this system.

Animals↗
PubMed1999

Wet air oxidation of oily wastes generated aboard ships: kinetic modeling.

Ships are floating industrial plants which generate great amounts of toxic and hazardous wastes. Nevertheless, a feasible model for the management of such wastes has not been developed yet. This work studies the feasibility of treating those wastes aboard the ship by means of aqueous oxidation at high pressures and temperatures. Wet air oxidation has proved to be a very efficient technology for the treatment of those residual currents, resulting in destruction efficiencies of greater than 90% of initial COD and 99.9% of oil/greases content. A kinetic model for the oxidation process, based on a series-parallel reaction pathway, is proposed and is shown to fit the experimental results.

Kinetics↗
PubMed2005

A kinetic model of the formation of organic monolayers on hydrogen-terminated silicon by hydrosilation of alkenes.

We have analyzed a kinetic model for the formation of organic monolayers based on a previously suggested free radical chain mechanism for the reaction of unsaturated molecules with hydrogen-terminated silicon surfaces (Linford, M. R.; Fenter, P. M.; Chidsey, C. E. D. J. Am. Chem. Soc 1995, 117, 3145). A direct consequence of this mechanism is the nonexponential growth of the monolayer, and this has been observed spectroscopically. In the model, the initiation of silyl radicals on the surface is pseudo first order with rate constant, ki, and the rate of propagation is determined by the concentration of radicals and unreacted Si-H nearest neighbor sites with a rate constant, kp. This propagation step determines the rate at which the monolayer forms by addition of alkene molecules to form a track of molecules that constitute a self-avoiding random walk on the surface. The initiation step describes how frequently new random walks commence. A termination step by which the radicals are destroyed is also included. The solution of the kinetic equations yields the fraction of alkylated surface sites and the mean length of the random walks as a function of time. In mean-field approximation we show that (1) the average length of the random walk is proportional to (kp/ki)1/2, (2) the monolayer surface coverage grows exponentially only after an induction period, (3) the effective first-order rate constant describing the growth of the monolayer and the induction period (kt) is k = (2ki kp)1/2, (4) at long times the effective first-order rate constant drops to ki, and (5) the overall activation energy for the growth kinetics is the mean of the activation energies for the initiation and propagation steps. Monte Carlo simulations of the mechanism produce qualitatively similar kinetic plots, but the mean random walk length (and effective rate constant) is overestimated by the mean field approximation and when kp >> ki, we find k approximately ki0.7kp0.3 and Ea = (0.7Ei+ 0.3Ep). However the most striking prediction of the Monte Carlo simulations is that at long times, t >> 1/k, the effective first-order rate constant decreases to ki even in the absence of a chemical termination step. Experimental kinetic data for the reaction of undec-1-ene with hydrogen-terminated porous silicon under thermal reflux in toluene and ethylbenzene gave a value of k = 0.06 min(-1) and an activation energy of 107 kJ mol(-1). The activation energy is in reasonable agreement with density functional calculations of the transition state energies for the initiation and propagation steps.

Journal Article↗
PubMed1986

Insulin receptor processing as a function of erythrocyte age. A kinetic model for down-regulation.

The effects of cell aging on insulin binding and on insulin receptor processing in human erythrocytes were studied. Erythrocytes were found to exponentially lose equal proportions of both high and low affinity receptors as a function of age. The affinities of remaining surface receptors did not change significantly. The maximum extent of insulin receptor down-regulation that could be induced decreased linearly with age over the range studied. Together with dose-response and time course studies, these age-related changes in insulin binding and receptor down-regulation were used to develop a kinetic model in which receptor internalization is a function of surface receptor concentration. The ability of the model to predict the behavior of a heterogeneous population suggests that changes in receptor processing with age may be attributed to changes in the surface receptor concentration.

Dose-Response Relationship, Drug↗
PubMed1996

Kinetic modelling of the nitric oxide gradient generated in vitro by adherent cells expressing inducible nitric oxide synthase.

Inducible nitric oxide (NO) synthase produces a long-lasting NO flux which can exert cytotoxic effects on target cells. A prerequisite for the understanding of the molecular basis of NO action is quantitative data on the availability of this small neutral radical molecule at both the spatial and temporal levels. The limits of NO availability depend on the respective rates of NO production, diffusion and autoxidation by molecular oxygen. Kinetic modeling of these processes has been performed for a widely used experimental system consisting of a monolayer of adherent cells cultured in vitro for hours in unstirred culture medium. It appears that: (i) the maximal NO concentration in the culture is in the immediate vicinity of the monolayer, where target cells will sediment; (ii) the steady-state NO concentration in this area is lower than 4 to 5 microM; and (iii) measurements of nitrite/nitrate or citrulline accumulation in the bulk cell medium culture during a given time period significantly underestimate (by a factor of up to 3 to 4) the true rate of NO synthesis at the level of the producer cell. This rate can be, nevertheless, easily estimated from the rate of production of the stable NO synthase products.

Cell Adhesion↗
PubMed1984

[Urea kinetics model of patients on programmed hemodialysis].

Fifty three patients with programmed hemodialysis, in a stable state were studied to the method of urea-kinetic modelling. A high correlation relationship was established between the pre-dialysis values of urea nitrogen in blood and the protein import, calculated from the quantity of the endogenously produced urea nitrogen. The best rehabilitated patients (41,5%) proved to introduce 1,0-1,6 g/kg body weight proteins and maintain a concentration of blood urea nitrogen from 65-95 ng% (32,14-33,8 mmol/1). Furthermore, another three patient groups were formed: with reduced protein introduction, with insufficient clearance and with overnormal protein introduction. The optimal group significantly differ from them, according to the state of nourishment, general rehabilitation, phosphatemia, calcium-phosphorus number and dialysis clearance. Both the stage of anemia and arterial hypertension show only a tendency in similar direction.

Blood Proteins↗
PubMed1989

Application of a molecular enzyme kinetic model for aging cells and tissues.

According to the membrane hypothesis of aging (MHA), cellular senescence is attributable to a life-long, cross-linking action of oxygen-free radicals in the cell plasma membrane, resulting in a continuous decrease of the passive ion permeabilities. The consequent increase in the intracellular potassium content is accompanied by a considerable condensation of the intracellular mass (i.e., by loss of water). MHA suggested that an age-dependent increase in the physical density of the intracellular mass can underly the well-known age-dependent decreases of the macromolecular synthetic processes, the enzymic turnover rates, etc. MHA was partly based on a molecular enzyme kinetic model (MEKM) suggesting that environmental factors can substantially influence the enzyme catalysis and regulation through collisional coupling. However, the possible quantitative ranges of alterations in enzyme activities have not been estimated. This paper concludes, using principal features of the two models, that known age-dependent changes in the membrane lipid fluidity and intracellular density may result in even a 10-fold overall decrease in the enzyme activities (characterized by kcat and k-1) during the life.

Aging↗
PubMed2003

A simple kinetic model describes the processivity of myosin-v.

Myosin-V is a motor protein responsible for organelle and vesicle transport in cells. Recent single-molecule experiments have shown that it is an efficient processive motor that walks along actin filaments taking steps of mean size close to 36 nm. A theoretical study of myosin-V motility is presented following an approach used successfully to analyze the dynamics of conventional kinesin but also taking some account of step-size variations. Much of the present experimental data for myosin-V can be well described by a two-state chemical kinetic model with three load-dependent rates. In addition, the analysis predicts the variation of the mean velocity and of the randomness-a quantitative measure of the stochastic deviations from uniform, constant-speed motion-with ATP concentration under both resisting and assisting loads, and indicates a substep of size d(0) approximately 13-14 nm (from the ATP-binding state) that appears to accord with independent observations.

Adenosine Diphosphate↗
PubMed2002

Fate and kinetic modeling of reactivity of alkanesulfenic acids and thiosulfinates in model systems and onion homogenates.

The dynamic changes in thiosulfinate profiles were studied in reaction systems containing a crude onion alliinase, S-alk(en)yl-L-cysteine sulfoxide substrates (1) and preformed thiosulfinates (4). Regioisomeric excesses of one of two possible heterologous 4 species (RS(O)SR', where R does not equal R') could be manipulated under conditions where alliinase, 1, and 4 levels were varied. Regioisomeric excesses could be explained by a thiosulfinate (4)/alkanesulfenic acid (2) trapping mechanism, with the greatest control over product profile governed by the rate of 2 generation in the system. The series of reactions existing in this dynamic reaction system was kinetically modeled with reasonable fits to the experimental data. The application of the 4/2 trapping strategy to manipulate thiosulfinate and related organosulfur product profiles in diluted onion homogenates was demonstrated using exogenous MeS(O)SMe (4a), PrS(O)SPr (4c), and AllS(O)SAll (4d) as the preformed thiosulfinate.

Alkanes↗
PubMed2004

UV photolysis of trichloroethylene: product study and kinetic modeling.

Direct UV photolysis of trichloroethylene (TCE) in dilute aqueous solution generated chloride ions as a major end product and several reaction intermediates, such as formic acid, di- and monochloroacetic acids, glyoxylic acid, and, to a lesser extent, mono- and dichloroacetylene, formaldehyde, dichloroacetaldehyde, and oxalic acid. Under prolonged irradiation, these byproducts underwent photolysis, and a high degree of mineralization (approximately 95%) was achieved. TCE decays through the following major pathways: (1) TCE + h nu --> ClCH=C*Cl + Cl*; (2) TCE (H2O) + h nu --> ClCH(OH)-CHCl2; (3) TCE + h nu --> HC[triple bond]CCl + Cl2; (4) TCE + h nu --> ClC[triple bond]CCl + HCl; (5) TCE + Cl* --> Cl2HC-C*Cl2. A kinetic model was developed to simulate the destruction of TCE and the formation and fate of byproducts in aqueous solution under irradiation with polychromatic light. By fitting the experimental data, the quantum yields for the four photolysis steps were predicted as phi(1) = 0.13, phi(2) = 0.1, phi(3) = 0.032, and phi(4) = 0.092, respectively. The reaction mechanism proposed for the photodegradation of TCE accounts for all intermediates that were detected. The agreement between the computed and experimental patterns of TCE and reaction products is satisfactory given the complexity of the reaction mechanism and the lack of photolytic kinetic parameters that are provided in the literature.

Kinetics↗
PubMedDate not supplied

A kinetic model of benzoylecgonine disposition after cocaine administration in humans.

Cocaine (C) and benzoylecgonine (BZ) plasma levels and urinary excretion rate data from a series of intravenous cocaine studies were used to develop a kinetic model for C and BZ, with the main objective of characterizing BZ disposition. Kinetic analyses were made with the CONSAM 30 computer program. Under assumptions of the model, calculated parameters indicated a BZ distribution volume of 50 L, a half-time for BZ formation of 1.9 h and a BZ excretion half-time of 4.7 h. The model may eventually provide a basis for interpretation of analytical data on isolated samples of plasma or urine.

Adult↗
PubMed2006

Determining RuBisCO activation kinetics and other rate and equilibrium constants by simultaneous multiple non-linear regression of a kinetic model.

The forward and reverse rate constants involved in carbamylation, activation, carboxylation, and inhibition of D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) have been estimated by a new technique of simultaneous non-linear regression of a differential equation kinetic model to multiple experimental data. Parameters predicted by the model fitted to data from purified spinach enzyme in vitro included binding affinity constants for non-substrate CO2 and Mg2+ of 200+/-80 microM and 700+/-200 microM, respectively, as well as a turnover number (k(cat)) of 3.3+/-0.5 s(-1), a Michaelis half-saturation constant for carboxylation (K(M,C)) of 10+/-4 microM and a Michaelis constant for RuBP binding (K(M,RuBP)) of 1.5+/-0.5 microM. These and other constants agree well with previously measured values where they exist. The model is then used to show that slow inactivation of RuBisCO (fallover) in oxygen-free conditions at low concentrations of CO2 and Mg2+ is due to decarbamylation and binding of RuBP to uncarbamylated enzyme. In spite of RuBP binding more tightly to uncarbamylated enzyme than to the activated form, RuBisCO is activated at high concentrations of CO2 and Mg2+. This apparent paradox is resolved by considering activation kinetics and the fact that while RuBP binds tightly but slowly to uncarbamylated enzyme, it binds fast and loosely to activated enzyme. This modelling technique is presented as a new method for determining multiple kinetic data simultaneously from a limited experimental data set. The method can be used to compare the properties of RuBisCO from different species quickly and easily.

Carbon Dioxide↗
PubMed1988

A chemical kinetic model for ligand binding to identical and independent binding sites in vivo.

In living systems, hormones bind to receptor proteins that are continuously synthesized and degraded. Since these systems cannot be described by equilibrium binding equations, we present a chemical kinetic model for the binding of a hormone to a receptor with identical and independent binding sites in which synthesis and degradation occur. We have derived, from the model, equations that can be used to calculate the bound ligand concentration and the total protein concentration as a function of the free ligand concentration and time. These results show that the methods for experimental measurements, parameter estimation, interpretation of the parameters, and error analysis that are commonly used for equilibrium binding to identical and independent binding sites can be adapted for the analysis of steady-state binding data. The equations we derived for the steady-state ligand binding permit determination of the total receptor protein concentration and the binding affinity from experimental data. In contrast, if an equilibrium model were used, the values of these parameters would not necessarily approximate the true values. A useful approximation to the total receptor concentration as a function of time was found that requires only three of the five rate constants required for exact description by the model. This approximation is shown to be accurate in the biologically relevant range by using previously published parameters estimated from steroid binding data, and adding perturbations to include experimental error and variations among biological systems. When complexities exist, such that the model does not describe the data, these analyses aid in assessing the types of additional components and interactions that may exist.

Binding Sites↗
PubMed2002

[Kinetic model and simulation of the adsorption-biofilm theory for the process of biopurifying VOC waste gases].

For the process of biopurifying waste gas containing VOC in low concentration by using a biological trickling filter, the related kinetic model and simulation of the new Adsorption-Biofilm theory were investigated in this study. By using the lab test data and the industrial test data, the results of contrast and validation indicated that the model had a good applicability for describing the practical bio-purification process of VOC waste gas. In the simulation study for the affection of main factor, such as the concentration of toluene in inlet gas, the gas flow and the height of biofilm-packing, a good pertinence was showed between calculated data and test dada, the interrelation coefficients were in 0.80-0.97.

Adsorption↗