Time-dependent Concentration Changes Research Articles

Kinetics of anaerobic metabolism in human skeletal muscle: influence of repetitive high-intensity exercise on sedentary dominant and non-dominant forearm. A 31P NMR study

Potential differences were assessed between the dominant (D) and non-dominant (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed voluntary concentric contractions of D and ND forearm muscle during a series of three high-intensity (60% of the maximal voluntary contraction force (MVC)) exercise bouts. The time-dependent changes in intracellular pH (pH i), Pi, and PCr concentrations, and their relation to muscular work were examined using 31P magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm metabolic kinetics in sedentary individuals are improved during repetitive high-intensity exercise compared to their respective ND forearm muscle. We postulate that the more regular and preferential utilization of the D limb leads to a “trained-like” condition.

Fourier transform infrared analysis of gas composition in low-volume light bulbs.

Fourier transform infrared spectroscopy has been used for in situ analysis of HBr, CH3Br, and CO within light bulbs at different stages of burning time. The interference fringes originated in the quartz walls of the bulbs have been eliminated by different methods. The NIPALS procedure yielded higher S/N ratio than the fringe-elimination method applied. The CO and HBr showed time-dependent concentration changes during the burning period. The maximum CO concentration (approximately 6 ppm) was detected after 30-50 s of burning time, and then it practically burned out after 5 h. The HBr concentration increased in the first 3 min of burning, and then its concentration stabilized at a 10-15 ppm level. After 5 s of illumination, the CH3Br concentration became undetectable.

Mast Cell-Derived VEGF Enhances the Passage of IgE FE-3 through the Rat Aortic Endothelial Cell Monolayer

Background: It is well known that the IgE-mediated allergic reaction in various extravascular tissues is induced by the mutual interaction of IgE, target cells (mast cells, MCs) and allergens. However, so far little has been known about the detailed mechanism whereby IgE in the circulating blood is transferred to the extravascular tissue. To examine whether or not MCs are involved in the permeability of IgE across rat aortic endothelial cells (RAECs) in vitro, we determined the permeability constant (PC) of dinitrophenyl-specific rat IgE (IgE FE-3) using a dual chamber system. Methods: Isolated RAECs obtained by a primary explant technique were seeded on a collagen-coated membrane in the upper chamber. MCs were collected from the peritoneal cavity of Wistar rats and suspended in the lower chamber. The time-dependent changes in concentration of IgE FE-3 (IgE) in the upper and lower chambers were measured by IgE capture ELISA after addition of IgE (10 µg/ml) to the upper chamber. Results: The cultured medium of IgE-stimulated MCs significantly increased the PC of IgE (9.86 ± 0.46 × 10^–6 cm/s), as compared to the value to which calcium ionophore A 23187-stimulated MCs increased the PC of IgE (7.97 ± 0.21 × 10^–6 cm/s). The increase of PC by IgE-stimulated MCs was most strongly inhibited by suramin (92.3% ± 1.89), and was weakly inhibited by tranexamic acid, cimetidine and diphenhydramine. In addition, the PC of IgE was increased with the increase in the MC-derived vascular endothelial growth factor/permeability factor (VEGF). Conclusions: After IgE is transferred from the circulating blood to the extravascular tissue, it may bind to FcΕRI of the MC and the other FcΕRI-bearing cells. The MC is then activated through the interaction of IgE and FcΕRI. Release of VEGF from the activated MC increases, and the VEGF enhances the permeability of IgE.

Time-dependent changes in plasma concentrations of 3-methylindole and blood concentrations of 3-methyleneindolenine-adduct in feedlot cattle.

To describe time-dependent changes in plasma concentrations of 3-methylindole (3MI) and blood concentrations of 3-methyleneindolenine (3MEIN)-adduct in feedlot cattle. 64 yearling steers. Steers were assigned to 2 groups (32 steers/group). During the first 8 weeks, blood samples were collected from group 1 before the morning ration was fed, whereas samples from group 2 were collected 2 to 3 hours after the ration was fed. Blood samples were collected from all steers approximately 4 times/wk for 3 weeks and 3 times/wk for the subsequent 5 weeks. Samples were collected at the same time for all steers for an additional 10 weeks. Plasma samples were analyzed for 3MI concentrations. Blood samples collected from cattle in group 2 during the first 8 weeks were analyzed for 3MEIN-adduct concentrations. Mean blood concentration of 3MEIN-adduct increased to a maximum value on day 33 (0.80 U/microg of protein) and then decreased to a minimum on day 54 0.40 U/microg of protein). Plasma 3MI concentrations initially decreased and remained low until after day 54. Group-1 cattle had lower plasma 3MI concentrations, compared with concentrations for group-2 cattle. Blood 3MEIN-adduct concentrations and plasma 3MI concentrations were not associated with deleterious effects on weight gains. Blood 3MEIN-adduct concentrations peaked during the period of greatest risk for development of bovine respiratory disease complex. Conversely, plasma 3MI concentrations decreased during the same period. Animal-to-animal variation in metabolic capacity to convert 3MI to 3MEIN may be of more importance than differences in plasma 3MI concentration.

Time-Dependent Changes in Orally Exhaled Nitric Oxide and Pulmonary Functions Induced by Inhaled Cortico-steroids in Childhood Asthma

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92 ± 0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FENO levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25–75% of the vital capacity (FEF25–75%) values, as compared to controls (p < 0.05). In addition, FENO levels were significantly higher in asthmatics with respect to control subjects (30.8 ± 3.0 and 4.0 ± 0.5 ppb, respectively; p < 0.01). All asthmatics had FENO levels higher than 8.8 ppb (i.e., >2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF25–75% (p = 0.0001; each comparison) and a reduction of FENO levels (p = 0.0001). A weak significant correlation was found between percent decrease in FENO levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF25–75% (r = 0.4, p = 0.01) after treatment. When changes in FENO levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FENO levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF25–75% (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FENO levels (p < 0.01) and the significant increase in FEV1 and FEF25–75% values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.

Estimation of Diffusion Coefficients in Biomembranes

In this paper, the determination of diffusion coefficients in plant biomembranes for the nonstationary diffusion state is discussed. It is suggested that any point in the heterogeneous structures may be considered to be in Donnan equilibrium with a given external salt concentration. For this purpose, the non-stationary-state nonlinear differential equation for the salt concentration profile is solved numerically, which could be used to determine the diffusion coefficients of biomembranes from experimental concentration values in the receiver phase as a function of time. Quantitative relations were obtained which describe the time-dependent concentration changes of a membrane system with equilibrium distribution.

Effects of the peripherally selective κ -opioid asimadoline, on substance P and CGRP mRNA expression in chronic arthritis of the rat

We have previously shown that the κ-opioid agonist, asimadoline, produces time-dependent changes in neuropeptide concentrations in the joints of rats with chronic arthritis. We hypothesized that asimadoline acts on peripheral terminals to modulate substance P (SP) release. To address this hypothesis, here we have examined neuropeptide expression in their source cells in dorsal root ganglia (DRG) that innervate the joint, as well as in non-neuronal tissue, after treatment with asimadoline. We found an increased production of SP and CGRP in untreated chronic arthritic animals which supports our previous finding of increased SP content in the joint. More importantly, the κ-opioid asimadoline reduced the expression of both SP and calcitonin gene-related peptide-α (α-CGRP) in DRG cells but had no effect on the very low expression of neuropeptides in non-neuronal tissue. The fact that SP synthesis is attenuated by asimadoline accords with our hypothesis that the increased tissue levels of SP result from κ-mediated pre-synaptic inhibition of release leading to augmented tissue stores. These in vivo data confirm literature findings that opioids inhibit SP release from peripheral endings of primary afferent fibres.

Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas deferens.

Protein C inhibitor (PCI), a plasma serine protease inhibitor of activated protein C, is present at high concentrations in the seminal plasma of normal subjects and is decreased in some infertile patients. We measured the concentrations of PCI, prostate-specific antigen, and fructose in the seminal plasma of infertile patients (n = 125) and of normal subjects (n = 13). We also measured time-dependent changes in the concentrations of PCI and fructose in seminal plasma after ejaculation. A weak correlation was found between the levels of PCI and fructose (r = 0.268, P = 0.016). The PCI level in seminal plasma of patients with seminal vesicle and/or vasal agenesis was significantly lower (P < .01) than in normal subjects. The level of fructose in seminal plasma decreased in vitro in a time-dependent manner after ejaculation, whereas the concentration of PCI was stable at 48 hours after ejaculation. These data suggest that PCI in seminal plasma, as well as fructose, may become one of the markers for agenesis of seminal vesicles and/or the vas deferens.

Optimal control of active transport across a biological membrane

We propose an optimal control principle for active transport across a biological membrane. The modeling of the membrane is based on Hill and Kedem's thermodynamic model. The performance function used to evaluate the optimality of the transport involved the rate of time-dependent changes in the concentration of particles in all the membrane layers as the state variables, and the number of receptor sites on the membrane as the control input. We decided that the optimal transport state is achieved when this cost function has been minimized under the constraints of the system equations characterizing the membrane modeling. The changes in the number of particles in the membrane layer evoked by changes in the kinetic parameters can be explained by the compensatory action of the optimal control strategy in order to prevent excessive decrease or increase of the molecular particles in all the membrane layers. The changes in the number of receptors in the paths of some physiological states can be explained by the optimal control modeling of the membrane transport. This model will be made available to create and evaluate an artificial membrane.

Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles.

An assay was developed to study the spontaneous transfer and transbilayer movement (flip-flop) of lipid analogs labeled with the fluorescent fatty acid, 5-(5,7-dimethyl BODIPY)-1-pentanoic acid (C5-DMB-) in large unilamellar lipid vesicles comprised of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). The assay is based on the concentration-dependent changes in fluorescence intensity that occur when donor vesicles containing a C5-DMB-lipid are mixed with nonfluorescent acceptor vesicles. A kinetic model was developed to describe the time-dependent changes in concentration of a lipid undergoing both spontaneous transfer between unilamellar vesicles and transbilayer movement within the vesicle membranes, and a mathematical solution was obtained. Data were obtained using C5-DMB-labeled analogs of sphingomyelin (C5-DMB-SM), ceramide (C5-DMB-Cer), phosphatidylcholine (C5-DMB-PC), and diacylglycerol (C5-DMB-DAG), and kinetic parameters for each lipid were determined using a nonlinear least-squares fitting program. The half-times for interbilayer transfer of the lipids were C5-DMB-SM (21 s) < C5-DMB-PC (350 s) approximately C5-DMB-Cer (400 s) << C5-DMB-DAG (100 h). C5-DMB-Cer (t1/2 approximately 22 min) and C5-DMB-DAG (t1/2 approximately 70 ms) exhibited rapid spontaneous transbilayer movement, while C5-DMB-SM (t1/2 approximately 3.3 h) and C5-DMB-PC (t1/2 approximately 7.5 h) moved across the bilayer very slowly. These results provide a basis for interpreting the behavior of these lipid analogs in cells.

GABA and epileptogenesis.

GABA and epileptogenesis.

Radiation effects on lead silicate glass surfaces

Radiation-induced changes in the microstructure of lead silicate glass were investigated in situ under Mg Kα irradiation in an ultra-high vacuum (UHV) environment by X-ray photoelectron spectroscopy (XPS). Lead-oxygen bond breaking resulting in the formation of pure lead was observed. The segregation, growth kinetics and the structural relaxation of the lead, with corresponding changes in the oxygen and silicon on the glass surfaces were studied by measuring the time-dependent changes in concentration, binding energy shifts, and the full width at half maximum. A bimodal distribution of the oxygen XPS signal, caused by bridging and non-bridging oxygens, was found during the relaxation process. All experimental data indicate a reduction of the oxygen concentration, a phase separation of the lead from the glass matrix, and the metallization of the lead occurred during and after the X-ray irradiation.

Characteristics of atrial re-entry and meander computed from a model of a rabbit single atrial cell

A two-dimensional excitable medium model of atrial tissue has been constructed by incorporating the Earm-Hilgemann-Noble excitation equations for membrane voltage-dependent ionic currents and pump exchanger currents, time-dependent changes in intracellular and extracellular ionic concentrations, and storage and release of Ca 2+, for an atrial cell in an homogeneous partial differential equation. A diffusion coefficient of 1.25 cm 2sec −1gives the conduction velocity of a solitary planar wave as 0.6 m sec −1. A spiral wave with a period of 78 msec develops from a broken wavefront, and initially rotates around a circular core of 2 mm diameter. After 1.5 sec of rotation, a biperiodic meander, with 6 epicycles/cycle, develops. This simple meander pattern is reflected in a period-6 modulation of the intervals between successive wavefronts.

Surface modification of lead silicate glass under X-ray irradiation

Radiation-induced changes in the microstructure of lead silicate glass were investigated in-situ under MgKα irradiation in an ultra-high vacuum (UHV) environment by X-ray Photoelectron Spectroscopy (XPS). Lead-oxygen bond breaking to result in pure lead formation was observed. The segregation, growth kinetics and the structure relaxation of lead, plus the corresponding changes of oxygen and silicon on the glass surfaces were all studied by measuring the time-dependent changes in concentration, binding energy, and the full-width at half-maximum. A bimodal distribution of the oxygen XPS signal, caused by bridging and non-bridging oxygens, was found during the relaxation process. All experimental data indicate a reduction of the oxygen, a phase separation of lead from the glass matrix, and the metallization of lead during and after X-ray irradiation.

A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts.

Afovirsen sodium is a 20-mer phosphorothioate oligonucleotide designed to be complementary to the messenger ribonucleic acid sequence for the translation initiation codon of the E2 protein vital to replication of human papillomaviruses types 6 and 11. 14C-Labeled afovirsen was given as a single-dose intradermal injection in each of four warts of five patients to determine the time-dependent changes in concentration of intact afovirsen in genital warts and to determine the systemic absorption and elimination of radiolabeled compound. Intact afovirsen in genital warts was determined by high pressure liquid chromatography analysis of protease K digested extracts. Intact afovirsen was present in wart tissue for at least 72 hours at concentrations several times in excess of the estimated minimal inhibitory concentration of 1 mumol/L. Absorption of radiolabeled afovirsen from the injection site was rapid, with a peak plasma concentration achieved within 1 hour. Clearance of afovirsen was primarily attributable to slow metabolism, with about 30% of the radiolabel eliminated as 14C-CO2 in expired air over a 6-day period after dosing. Radioactivity eliminated in urine represented metabolites of afovirsen. From the clinical pharmacokinetic data presented here and from previously published pharmacokinetic data in rats, the disposition of afovirsen in humans appears to be relatively similar to that in rats. These data suggest that once or twice weekly dosing regimen in the clinic may be appropriate.

Concentration-Effect Analysis of Antihypertensive Drug Response

Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic areas. With antihypertensive drugs this approach has clearly identified direct relationships between pharmacokinetic and pharmacodynamic profiles within individual patients. Thus, either a linear or nonlinear model can be used to quantify the antihypertensive drug response in terms of parameters that incorporate pharmacokinetic and pharmacodynamic information. Furthermore, these models take account of placebo effects and time-dependent changes in blood pressure and drug concentrations during a dosage interval. Concentration-effect analysis has been used to characterise the responses to a range of calcium antagonist drugs. These studies have demonstrated that these analyses are useful for optimising dosage schedules, identifying determinants of blood pressure response, and predicting steady-state profiles of blood pressure (including peak/trough effects) after administration of a single ('test') dose. This mode of analysis warrants early inclusion in the clinical development of any new antihypertensive agent, so that the familiar difficulties in identifying the optimum dosage range are avoided.

SYNTAX: A Rule-Based Stochastic Simulation of the Time-Varying Concentrations of Positional Isotopomers of Metabolic Intermediates

We present a new approach to simulation of metabolic pathways. The syntactic approach combines a rule-based description of biochemical reactions with a stochastic model of chemical kinetics. Each syntactic rule describes the location in a product molecule to which a particular carbon of a reactant molecule will be transferred. Using specifically labeled substrates and known rates of chemical reactions, our simulation predicts the time-dependent changes in concentration of positional isotopomers of metabolic intermediates. (A positional isotopomer of a compound is an isomer that is determined by the positions of isotopes within the molecule, e.g., [1, 2- 13C]glucose and [1, 3, 5- 13C]glucose.) For the simulation of the 13 C-positional isotopomers of the citric acid cycle in heart cells we require only 39 syntactic rules, compared to the 176 ordinary differential equations required by the traditional approach. Addition of chemical reactions to the simulation does not require changing the program code for the existing reactions. In comparison, addition of a reaction to a system described by differential equations requires altering the equations for all isotopomers of all reactants and products of the new chemical reaction.

Inhibition of nitric oxide synthase increases extracellular cerebral glutamate concentration after global ischemia

The effects of nitric oxide synthase (NOS) inhibition on extracellular glutamate release were investigated in rats during global brain ischemia and reperfusion (IR) using cerebral microdialysis. A dialysis probe was inserted into the hippocampus of anesthetized rats. Forebrain ischemia was produced by hypotension and occlusion of both carotid arteries. After 15 min, brain flow was restored for 60 min. Time-dependent changes in the dialysate glutamate concentration were analyzed with HPLC in both control rats and those treated with N ω- nitro- l-arginine methyl ester 30 min prior to ischemia. The data show that the NOS inhibitor did not prevent glutamate release from hippocampus during ischemia. Inhibition of NOS also enhanced glutamate release during reperfusion resulting in dialysate concentrations up to 10 times higher than control values.

An analysis of the time-dependent changes in intracellular calcium concentration in endothelial cells in culture induced by mechanical stimulation.

When bovine pulmonary artery endothelial cells in culture are subjected to mechanical strain, their physiology is altered. Experimentally, this mechanical strain is generated by increased tension in the substrate to which the cells are attached and results in altered levels of fibronectin. Studies of the structural response of the endothelial cell suggest that this stimulus is transmitted to the cell membrane, organelles, and cytoskeleton by natural cell attachments in a quantifiable and predictable manner. This report examines altered intracellular calcium homeostasis as a possible messenger for the observed strain-induced physiologic response. In particular, using the intracellular trapped calcium indicator dyes, Quin2 and Fura2, we observed changes in cytosolic free calcium ion concentration in response to biaxial strain of bovine pulmonary artery endothelial cells in culture. The magnitude and time course of this calcium transient resemble that produced by treatment with the calcium ionophore, Ionomycin, indicating that mechanical stimulation may alter cell membrane permeability to calcium. Additional experiments in the presence of EDTA indicated that calcium was also released from intracellular stores in response to strain. In order to explain the stretch-induced calcium transients, a first-order species conservation model is presented that takes into account both the cell's structural response and the calcium homeostatic mechanisms of the cell. It is hypothesized that the cell's calcium sequestering and pumping capabilities balanced with its mechanically induced changes in calcium ion permeability will determine the level and time course of calcium accumulation in the cytosol.

In situ measurements on surfactant–mineral interactions by polarographic adsorption kinetics

Adsorption of surfactants at the mercury/electrolyte interface causes changes in electrode capacity. This phenomenon can be used for surfactant analysis in low and ultra-low concentration ranges. Tensammetry is carried out by alternating current or potential pulse techniques. Time-dependent concentration changes can be determined by adsorption kinetics at the mercury/electrolyte interface. As the interaction of surfactants with the mercury/electrolyte interface strongly depends on the potential of the electrode, repeated potential jumps can be used to generate adsorption–desorption cycles. This permits rapid determination of constant or time-dependent concentration. The adsorption kinetics of cationic and non-ionic surfactants on clay minerals were determined by Kalousek polarography. These two types of surfactant exhibit different behaviour. Many other adsorption phenomena might also be investigated by using the method described here.