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Kinetic model for carbon partitioning in Solanum tuberosum tubers stored at 2 degrees C and the mechanism for low temperature stress-induced accumulation of reducing sugars.

Exposure to low but nonfreezing temperatures induces the breakdown of starch and the accumulation of sucrose, glucose and fructose in potato tubers, a complex phenomenon known as low-temperature sweetening (LTS). A kinetic model for the degradation of starch to sucrose, fructose, glucose, hexose phosphates and carbon dioxide in 2 degrees C-stored mature Solanum tuberosum cv. Norchip (LTS-sensitive) and Solanum tuberosum seedlling ND860-2 (LTS-tolerant) tubers is presented in this work. Analysis of sugar accumulation data in tubers grown in 1993 and 1994 showed no significant differences in the rates of conversion of starch to hexose phosphates and hexose phosphates to sucrose for both cultivars (P > 0.05). The rate constant corresponding to invertase activity was 2.3 day(-1) for Norchip tubers and 1.1 day(-1) for ND860-2 tubers grown in 1993 (P < or = 0.05); however, no significant differences were observed in invertase activity for 1994-grown tubers (P > 0.05). The accumulation of the reducing sugars fructose and glucose was found to be dependent on the relative difference in rate constants corresponding to invertase activity and glycolytic/respiratory capacity. This difference was 3-4 fold greater for Norchip in 1993, and 4-6 fold greater for Norchip in 1994, than for ND860-2 (P < or = 0.05). Results from the analysis also suggest that the amount of available starch for degradation was greater in Norchip tubers than ND860-2 tubers (P < or = 0.05). Our analysis suggests that tubers with decreased invertase activity coupled to increased glycolytic/respiratory capacity should be more tolerant to low-temperature stress.

Journal Article↗

Interaction of energized bacteria cells with particles of colloidal gold: peculiarities and kinetic model of the process.

It is found that the cells of Bacillus cereus B-4368 at energized state can concentrate the colloidal gold particles on their surface. It is shown that the process depends on metabolic reactions proceeding on the plasma membrane. The inhibitory analysis permits to suppose that the metal concentration is due to the functioning of ATP-dependent generator of the transmembrane potential, apparently, of proton ATPase. Kinetic characteristics of the process show the presence of an intermediate state in the formation of biomineral aggregates. A kinetic model of the studied process is suggested which describes the experimental data well.

Adenosine Triphosphatases↗

Kinetic model for integrin-mediated adhesion release during cell migration.

Under many circumstances, cell migration speed is limited by the rate of cell-substratum detachment at the cell rear. We have constructed a mathematical model to integrate how the biophysical and biochemical interactions between integrins, the cytoskeleton, and the matrix affect rear retraction and linkage dissociation mechanisms. Our model also examines how applied forces and integrin clustering affect retraction kinetics. The model predicts two distinct detachment phenotypes. In the first, detachment is extremely rapid, dominated by integrin extracellular-matrix dissociation, and it occurs at high forces or low adhesiveness. In the second, detachment is much slower, dominated by integrin-cytoskeleton dissociation, and it occurs at low forces or high adhesiveness. The amount of integrin extracted from the rear of the cell is an assay for the detachment phenotype. During rapid detachment cells leave little integrin on the substratum whereas during slow detachment a large fraction of integrin rips from the membrane. This model delineates parameters which can be exploited to regulate cell speed in each detachment regime. The model also offers an explanation as to why some cell types, such as leukocytes or keratocytes, are able to detach easily and move very quickly while other cell types, such as fibroblasts, tend to migrate more slowly and release many more integrins during detachment.

Binding Sites↗

Kinetic modelling of [123I]CNS 1261--a potential SPET tracer for the NMDA receptor.

N-(1-napthyl)-N'-(3-[(123)I]-iodophenyl)-N-methylguanidine ([(123)I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [(123)I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [(11)C]-ketamine and [(18)F]-memantine PET studies. These data provide a methodological basis for further direct in vivo challenge studies.

Adult↗

Allosteric intermediates in hemoglobin. 2. Kinetic modeling of HbCO photolysis.

Nanosecond absorption spectra are measured in the Soret and near-UV spectral regions of human hemoglobin (Hb) after laser photolysis of the carbonyl adduct in order to study the dynamics of globin tertiary and quaternary conformational changes. Spectra and concentrations of physical intermediates, distinguished by extent of heme ligation and intraprotein relaxation, are obtained from a global analysis using a microscopic kinetic model that explicitly accounts for six observed relaxation and recombination processes. Three observed rate constants for CO rebinding and two intraprotein relaxation constants obtained are similar to constants determined by Hofrichter et al. [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2235], the latter two comprising the 20-30-microseconds R --> T quaternary transition and a previously unassigned 1-microseconds intraprotein relaxation. On the basis of the modeled intermediate spectra, as well as UV circular dichroism results observed on this time scale [Björling, S.C., Goldbeck, R.A., Paquette, S.J., Milder, S.J., & Kliger, D.S. (1996) Biochemistry 35, 8619-8627], the 1-microsecond relaxation is assigned to heme conformational changes concomitant with a relaxation of protein conformation at the alpha 1 beta 2 interface corresponding to an initial step in a compound R --> T reaction path.

Allosteric Regulation↗

Physiologic response to a protein, carbohydrate, fat meal in patients with human immunodeficiency virus who underwent small intestinal enteropathy as characterized by a kinetic model of D-xylose absorption.

PURPOSE: Small intestinal human immunodeficiency virus enteropathy is characterized by profound absorptive dysfunction unrelated to histology or pathogens. Frequently an attempt is made to compensate for this intestinal failure by supplementing nutrient intake with nourishing liquid meals. It is not known how the diminished absorptive function in these patients will respond to this intake. With the use of a D-xylose kinetic model of absorption, we determined the absorptive response of patients with small intestinal enteropathy to an isotonic liquid feeding. METHODS: Seven male patients with acquired immunodeficiency syndrome (AIDS), diarrhea, weight loss, and no detectable pathogens (stool studies and duodenal biopsy) were enrolled. After an overnight fast, the patients were studied on three separate days. On day 1, the patients received 15 g oral D-xylose. On day 2, 10 g i.v. D-xylose was given. On day 3, 15 g oral D-xylose was again given along with 250 mL of a liquid polymeric isotonic diet. Serum and urine collections were obtained to calculate the kinetic rate constants and extent of D-xylose absorption. RESULTS: Mean values for the rate constant for absorption of D-xylose, Ka, (0.26/h; N > 0.65) and the rate constant for nonabsorptive loss, K0' (2.47/h; N < 0.353) were very abnormal before the meal. Mean K0 improved (decreased to 0.66), but Ka and bioavailability, F, did not have a statistically significant change after the meal. The improvement in mean K0 with the meal was much more pronounced in the five subjects with high K0 values before the meal (without meal 3.22: with meal 0.67; p < .05). CONCLUSIONS: (1) An isotonic liquid polymeric diet leads to less nonabsorptive loss of D-xylose, but does not affect the extent of D-xylose absorption in this group as a whole. This is probably due to the meal slowing gastric emptying. (2) Improvement in nonabsorptive loss with a meal is most pronounced when there is excessive nonabsorptive loss, K0, without a meal. (3) Improvement in nonabsorptive losses with a meal might predict which patients will benefit from antimotility agents and continued feedings vs those requiring i.v. hyperalimentation.

Administration, Oral↗

A reaction kinetics model of water sonolysis in the presence of a spin-trap.

The time development of the concentration of a spin-trapped OH radical was studied by electron spin resonance at various sound intensities and various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations in water sonolysis. The lifetime of the spin-trapped OH radical was also studied, and factors governing sonolysis are discussed. We found that the production of spin-trapped OH radical increases with increasing ultrasound intensity. The lifetime of a spin-trapped OH radical decreases linearly with increase in sonication time. This result suggests that an unknown scavenger is produced by ultrasound. Based on the above results, we suggested a model of the reaction kinetics and estimated the production rate of OH radical from this model.

Journal Article↗

Kinetic modeling of virus transport at the field scale.

Bacteriophage removal by soil passage in two field studies was re-analyzed with the goal to investigate differences between one- and two-dimensional modeling approaches, differences between one- and two-site kinetic sorption models, and the role of heterogeneities in the soil properties. The first study involved removal of bacteriophages MS2 and PRDI by dune recharge, while the second study represented removal of MS2 by deep well injection. In both studies, removal was higher during the first meters of soil passage than thereafter. The software packages HYDRUS-ID and HYDRUS-2D, which simulate water flow and solute transport in one- and two-dimensional variably saturated porous media, respectively, were used. The two codes were modified by incorporating reversible adsorption to two types of kinetic sites. Tracer concentrations were used first to calibrate flow and transport parameters of both models before analyzing transport of bacteriophages. The one-dimensional one-site model did not fully describe the tails of the measured breakthrough curves of MS2 and PRD1 from the dune recharge study. While the one-dimensional one-site model predicted a sudden decrease in virus concentrations immediately after the peaks, measured data displayed much smoother decline and tailing. The one-dimensional two-site model simulated the overall behavior of the breakthrough curves very well. The two-dimensional one-site model predicted a more gradual decrease in virus concentrations after the peaks than the one-dimensional one-site model, but not as good as the one-dimensional two-site model. The dimensionality of the problem hence can partly explain the smooth decrease in concentration after peak breakthrough. The two-dimensional two-site model provided the best results. Values for k(att2) and k(det2) could not be determined at the last two of four monitoring wells, thus suggesting that either a second type of kinetic sites is present in the first few meters of dune passage and not beyond the second monitoring well, or that effects of soil heterogeneity and dimensionality of the problem overshadowed this process. Variations between single collector efficiencies were relatively small, whereas collision efficiencies varied greatly. This implies that the nonlinear removal of MS2 and PRD1 is mainly caused by variations in interactions between grain and virus surfaces rather than by physical heterogeneity of the porous medium. Similarly, a two-site model performed better than the one-site model in describing MS2 concentrations for the deep well injection study. However, the concentration data were too sparse in this study to have much confidence in the fitted parameters.

Adsorption↗

Kinetic modelling of chloroquine uptake by malaria-infected erythrocytes. Assessment of the factors that may determine drug resistance.

The antimalarial chloroquine, by virtue of its weak base properties, concentrates in the acidic compartment(s) of the intraerythrocytic parasite. Drug accumulation is essential for it to exert its pharmacological activity. Drug resistance has been thought to result from insufficient acidification of drug-accumulating organelle(s), (due to weakened proton pump activity and/or proton leak) or to result from the action of the recently suggested active efflux drug pump. In this work we have devised a kinetic model which takes into account the various processes that have been postulated to account for acidification and drug fluxes. Using this model to analyse the time-course of chloroquine uptake and the steady-state levels of drug accumulation, in strains of Plasmodium falciparum which display variable drug resistance, we demonstrate that drug resistance is compatible with the existence of a weakened proton pump in the resistant parasite strains. Consistent with recent molecular studies that show no correlation between the presence of the multidrug efflux pump gene and the phenotypic expression of chloroquine resistance, our analysis fails to detect any such pump activity. We also show that analysis of drug efflux kinetics cannot distinguish between the possible modes of drug resistance.

Animals↗

Evaluation of the effect of glucose ingestion and kinetic model configurations of FDG in the normal liver.

UNLABELLED: The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. METHODS: Twenty studies were performed on 10 normal volunteers (ages 24 +/- 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph. RESULTS: A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K1, increased significantly (p < 0.05) from 0.864 +/- 0.136 ml/min/g in fasting studies to 1.058 +/- 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k3, from 0.005 +/- 0.003 min-1 in fasting studies to 0.013 +/- 0.007 min-1 in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k3/(k2 + k3)) and the influx constant (K1k3/(k2 + k3)). No significant differences in the liver-to-plasma transport rate constant, k2, dephosphorylation constant, k4, or distribution volume of FDG (K1/(k2 + k3)) were observed. CONCLUSION: Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast.

Administration, Oral↗

A kinetic model of the system: tyrosyl radical-nitrogen oxide-superoxide ion.

It is generally recognized that the initial step in the formation of atherosclerotic plaque in humans involves the peroxidation of low density lipoproteins (LDL). However, there is no agreement on the mechanism that initiates peroxidation. Among the candidates are several that involve tyrosyl radical, nitrogen oxide, and superoxide ion or their mutual reaction products. In this paper a kinetic model of this system is constructed that examines the nature of these reactions, and places some constraints on their possible overall contribution to the initiation of peroxidation. The reversible reaction of nitric oxide and tyrosyl radical acts to "buffer" tyrosyl radical concentrations while the reaction of tyrosyl radical with superoxide ion scavenges tyrosyl radical. Quantitatively, the reaction of nitric oxide with superoxide to form peroxynitrite is a more important process, but the physiological significance would appear to be related to details of the decay of peroxynitrite that are still in dispute.

Arteriosclerosis↗

In vitro-in vivo extrapolation of quantitative hepatic biotransformation data for fish. I. A review of methods, and strategies for incorporating intrinsic clearance estimates into chemical kinetic models.

Scientists studying mammals have developed a stepwise approach to predict in vivo hepatic clearance from measurements of in vitro hepatic biotransformation. The resulting clearance estimates have been used to screen drug candidates, investigate idiosyncratic drug responses, and support chemical risk assessments. In this report, we review these methods, discuss their potential application to studies with fish, and describe how extrapolated values could be incorporated into well-known compartmental kinetic models. Empirical equations that relate extrapolation factors to chemical log K(ow) are given to facilitate the incorporation of metabolism data into bioconcentration and bioaccumulation models. Because they explicitly incorporate the concept of clearance, compartmental clearance-volume models are particularly well suited for incorporating hepatic clearance estimates. The manner in which these clearance values are incorporated into a given model depends, however, on the measurement frame of reference. Procedures for the incorporation of in vitro biotransformation data into physiologically based toxicokinetic (PBTK) models are also described. Unlike most compartmental models, PBTK models are developed to describe the effects of metabolism in the tissue where it occurs. In addition, PBTK models are well suited to modeling metabolism in more than one tissue.

Animals↗

Kinetic modeling of [(18)F]FDG in skeletal muscle by PET: a four-compartment five-rate-constant model.

Various modeling strategies have been developed to convert regional [(18)F]fluorodeoxyglucose ([(18)F]FDG) concentration measured by positron emission tomography (PET) to a measurement of physiological parameters. However, all the proposed models have been developed and tested mostly for brain studies. The purpose of the present study is to select the most accurate model for describing [(18)F]FDG kinetics in human skeletal muscle. The database consists of basal and hyperinsulinemic-euglycemic studies performed in normal subjects. PET data were first analyzed by an input-output modeling technique (often called spectral analysis). These results provided guidelines for developing a compartmental model. A new model with four compartments and five rate constants (5K model) emerged as the best. By accounting for plasma and extracellular and intracellular kinetics, this model allows, for the first time, PET assessment of the individual steps of [(18)F]FDG kinetics in human skeletal muscle, from plasma to extracellular space to transmembrane transport into the cell to intracellular phosphorylation. Insulin is shown to affect transport and phosphorylation but not extracellular kinetics, with the transport step becoming the main site of control. The 5K model also allows definition of the domain of validity of the classic three-compartment three- or four-rate-constant models. These models are candidates for an investigative tool to quantitatively assess insulin control on individual metabolic steps in human muscle in normal and physiopathological states.

Adult↗

Kinetic model for membrane transport. 1. Effects of membrane volume and partitioning kinetics.

Equations for the transport of solutes through a membrane are derived, taking into account both the membrane volume and the partitioning kinetics, and have been found to involve two rate constants for solute transport, namely, those corresponding to solute transport from the solution to the membrane (k1) and from the membrane to the solution (k2). The time course followed before partitioning equilibrium has been attained, which is usually ignored, is shown to depend strongly on the relative magnitudes of k1 and k2.

Biological Transport↗

Reliability of the Application of a Kinetic Model of Hormone Release: Prolactin and Oestrogen-Stimulated Neurophysin After Electroconvulsive Therapy.

Pituitary hormone release after electroconvulsive therapy (ECT) may provide important information about certain of the effects of ECT on neurotransmitter function. Previously we quantified pituitary hormone release by the increase in the area under the hormone concentration/time curve. Swartz has rightly pointed out that this method ignores the rate of elimination of hormone and cannot be a measure of total hormone released. Swartz has proposed a kinetic model of hormone release, and in this paper we assess the reliability of parameters derived from it when applied to our own data on the effects of ECT on the release of prolactin and oestrogen-stimulated neurophysin. The deviations between observed and predicted values were small when only five post-ECT samples were used. Contrary to expectations, the goodness of fit did not improve when the number of sampling points was increased to nine after ECT. It was possible to fit a unique curve to the observed data in only 28 of 54 data sets. The reasons for these findings are discussed.

Journal Article↗

Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: in vitro kinetic model.

Optimizing pharmacokinetic/pharmacodynamic indices of antibiotics to obtain clinical and microbiological efficacy is essential, but dosing regimens must also be tailored to minimize the risk for emergence of resistance. The aim of the present study was to investigate whether certain concentrations of benzylpenicillin are critical for the selection of resistant subpopulations. A mixed culture of Streptococcus pneumoniae containing ca. 90% susceptible (MIC = 0.031 mg/liter), 9% intermediate (MIC = 0.25 mg/liter), and 1% resistant (MIC = 8 mg/liter) was studied in an in vitro kinetic model. The time that concentrations exceeded the MIC (T>MIC) for the three strains in the culture was varied by different initial concentrations of benzylpenicillin. Samples for viable counts were withdrawn at different times during 24 h and seeded on blood agar plates and on selective antibiotic-containing plates. The T>MIC varied from 46 to 100% for the susceptible strain, from 6 to 100% for the intermediate strain, and from 0 to 48% for the resistant strain. Our study, which may mimic the clinical situation with carriage of a mixed population of S. pneumoniae with different antibiotic susceptibilities, has shown that selection of resistant bacteria may easily occur if dosing regimens are only targeted toward fully susceptible strains.

Area Under Curve↗

A kinetic model describing Shewanella oneidensis MR-1 growth, substrate consumption, and product secretion.

Aerobic growth of Shewanella oneidensis MR-1 in minimal lactate medium was studied in batch cultivation. Acetate production was observed in the middle of the exponential growth phase and was enhanced when the dissolved oxygen (DO) concentration was low. Once the lactate was nearly exhausted, S. oneidensis MR-1 used the acetate produced during growth on lactate with a similar biomass yield as lactate. A two-substrate Monod model, with competitive and uncompetitive substrate inhibition, was devised to describe the dependence of biomass growth on lactate, acetate, and oxygen and the acetate growth inhibition across a broad range of concentrations. The parameters estimated for this model indicate interesting growth kinetics: lactate is converted to acetate stoichiometrically regardless of the DO concentration; cells grow well even at low DO levels, presumably due to a very low K(m) for oxygen; cells metabolize acetate (maximum specific growth rate, micro(max,A) of 0.28 h(-1)) as a single carbon source slower than they metabolize lactate (micro(max,L) of 0.47 h(-1)); and growth on acetate is self-inhibiting at a concentration greater than 10 mM. After estimating model parameters to describe growth and metabolism under six different nutrient conditions, the model was able to successfully estimate growth, oxygen and lactate consumption, and acetate production and consumption under entirely different growth conditions.

Acetates↗