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PubMedDate not supplied

Kinetics of drug decomposition. Part 62. Kinetics of penicillin G potassium salt (PGP) thermal degradation in solid phase.

The kinetics of degradation of penicillin G K salt (PGP) in solid phase in the temperature range 70-140 degrees C were investigated. The obtained sigmoidal curves were interpreted in terms of the Prout-Tompkins kinetics. The appropriate mathematical equations were derived for the induction and acceleration periods which enable to calculate the degradation half-time, t0.1 value and the induction time (t'). The Arrhenius plot shows the isokinetic point where the rates of reaction for both periods are identical.

Drug Stability↗
PubMed1976

Kinetics of drug decomposition. Part 38. Hydrolysis and autoxidation of sodium phenylbutazone and aminophenazone in binary kinetic system.

The kinetics of hydrolysis and autoxidation of sodium phenylbutazone (PhB-Na) and aminophenazone (APh) was studied in ammonia-acetate, Carmody and Welford buffers at different buffer concentration, pH, ionic strengths and temperatures. The reaction in N2 atmosphere and under a constant O2 pressure, carried out in calibrated ampoules, followed the first order reaction kinetics. The assay of PhB-Na and APh in the presence of their degradation produces was carried out spectrophotometrically in the degraded solutions.

Aminopyrine↗
PubMedDate not supplied

[Analysis of stationary kinetics of translation elongation within the framework stereospecific stabilization hypothesis of codon- anticodon complexes in a ribosome. I. Kinetic schemes of factorless elongation].

Dependences of steady-state rates of polypeptide elongation on concentrations of substrate (aminoacyl-tRNA) and product (deacylated tRNA) in the absence of elongation factors and GTP are theoretically analyzed in context of stereospecific stabilization of the codon-anticodon complexes at a ribosome. General kinetic scheme and different ribosome isomerization stages are examined. The effect of isomerization stage allows to identify reaction stage experimentally. Regulation of the direct reaction by product and regulation of the reverse reaction by substrate are possible. Under certain conditions elongation system may show kinetic cooperativity.

Anticodon↗
PubMedDate not supplied

[Analysis of stationary kinetics of translation elongation within the framework of the stereospecific stabilization hypothesis of codon- anticodon complexes in a ribosome. II. Kinetic schemes in the presence of protein elongation factors and GTP].

Kinetics of the factor-dependent polypeptide elongation is theoretically studied in context of stereospecific stabilization of the codon-anticodon complexes at a ribosome. Kinetic schemes for the different ribosome isomerization stages are examined. The dependence of steady-state elongation rate on elongation factor concentration for each of the schemes is unique, allowing to identify isomerization stages experimentally.

Anticodon↗
PubMed1996

Cell cycle kinetics in normal human skin by in vivo administration of iododeoxyuridine and application of a differentiation marker--implications for cell cycle kinetics in psoriatic skin.

Renewal of epidermal cells is a highly coordinated process in which terminal differentiation balances the proliferative rate in the germinative compartment. Exact quantitative data on cell cycle parameters of normal human epidermis are fragmentary, and do not allow firm conclusions on issues such as cell cycle time, duration of the various cell cycle phases, and the pool sizes of the different cellular populations. As part of a study on bone marrow cell cycle kinetics, 14 lymphoma patients were infused with the thymidine analogue iododeoxyuridine (IdUrd). This provided us with the unique opportunity to study the cell cycle kinetics in normal epidermis obtained from these patients. Single epidermal cell suspensions were prepared from skin, stained with propidium iodide (PI) for relative DNA content, and simultaneously labeled with an anti-IdUrd antibody to detect DNA-synthesizing cells. In parallel samples suprabasal cells were analyzed by labeling with an anti-cytokeratin 10 antibody. Analysis was performed using bivariate flow cytometry. The results showed that 3.5% of the total epidermal cell population was in S-phase. An S-phase duration of 9.7 +/- 0.6 h and a cytokeratin 10-positive pool size of 59.6 +/- 4.6% were obtained. The duration of the G1-phase and the G2M-phase were calculated to be 7.6 +/- 2.0 h and 11.1 +/- 2.0 h, respectively. From these data a total cell cycle time can be calculated of 28.4 h. Combining this data with previous findings we were able to determine a similar cell cycle time of 27.8 h, and pool sizes of the epidermal cells: 30% quiescent (resting, G0) and 10% cycling cells. The implications of these findings for the interpretation of deviations in growth control as found in hyperproliferative skin diseases (e.g. psoriasis) are discussed.

Antibodies, Monoclonal↗
PubMed1997

The kinetic characteristics of the L-type calcium channels in cardiocytes of hibernators. 1. Development of a kinetic model.

The present paper described the experimental and theoretical investigations of the kinetic characteristics of the L-type Ca2+ channels in ground squirrels Citellus undulatus in two different physiological states (hibernation and spontaneous arousal). The perforated patch-clamp method was used in the experiments. It is shown that the potential-dependent Ca2+ current in isolated cardiocytes from hibernating animals is strongly inhibited during hibernation. An attempt was made to describe the kinetics of Ca2+ currents by the modified Hodgkin-Huxley equations. The experimental current traces are compared to the nonstationary solutions of the modified model, and the model parameters were found by optimization methods. It is shown that the simple dmfn model, where d is activation, f is inactivation, can not be used to describe the experimental characteristics at any power values m and n. Analysis of other models based on the conception of independence of activation and inactivation processes showed that in both physiological states-hibernation and spontaneous arousal-Ca2+ current was described by the model d2f1(2)f2, where d is activation, f1 and f2 are slow (f1-type) and fast (f2-type) inactivations of the channel.

Animals↗
PubMed1995

Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in comparison with single-dose kinetics.

Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine-induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, Cmax,ss = 391.8 ng mL-1 against Cmax,sd = 132.8 ng mL-1; M2, Cmax,ss = 143.2 ng mL-1 against Cmax,sd = 25.8 ng mL-1). However, significant increases of AUC (AUC tau = 261.9 ng h mL-1 against AUC0-infinity,sd = 182.9 ng h mL-1), Cmax (Cmax,ss = 75.9 ng mL-1 against Cmax,sd = 56.9 ng mL-1) and t 1/2 beta (t 1/2 beta,ss = 4.0 h against t 1/2 beta,sd = 2.4 h) of the parent compound indicate non-linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non-renal tiracizine clearance with repeated dosing led to the assumption that non-linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at the tmax of the parent compound, whereas there was no change in any ECG parameter after a single-dose administration of 50 mg tiracizine.

Administration, Oral↗
PubMed2003

Experimental and theoretical multiple kinetic isotope effects for an SN2 reaction. An attempt to determine transition-state structure and the ability of theoretical methods to predict experimental kinetic isotope effects.

The secondary alpha-deuterium, the secondary beta-deuterium, the chlorine leaving-group, the nucleophile secondary nitrogen, the nucleophile (12)C/(13)C carbon, and the (11)C/(14)C alpha-carbon kinetic isotope effects (KIEs) and activation parameters have been measured for the S(N)2 reaction between tetrabutylammonium cyanide and ethyl chloride in DMSO at 30 degrees C. Then, thirty-nine readily available different theoretical methods, both including and excluding solvent, were used to calculate the structure of the transition state, the activation energy, and the kinetic isotope effects for the reaction. A comparison of the experimental and theoretical results by using semiempirical, ab initio, and density functional theory methods has shown that the density functional methods are most successful in calculating the experimental isotope effects. With two exceptions, including solvent in the calculation does not improve the fit with the experimental KIEs. Finally, none of the transition states and force constants obtained from the theoretical methods was able to predict all six of the KIEs found by experiment. Moreover, none of the calculated transition structures, which are all early and loose, agree with the late (product-like) transition-state structure suggested by interpreting the experimental KIEs.

Journal Article↗
PubMed1991

Analysis of kinetic data in transport studies: new insights from kinetic studies of Na(+)-D-glucose cotransport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus.

Using the fast sampling, rapid filtration apparatus (FSRFA) recently developed in our laboratory (Berteloot et al., 1991, J. Membrane Biol. 122:111-125), we have studied the kinetic characteristics of Na(+)-D-glucose cotransport in brush-border membrane vesicles isolated from normal adult human jejunum. True initial rates of transport have been determined at both 20 and 35 degrees C using a dynamic approach which involves linear-regression analysis over nine time points equally spaced over 4.5 or 2.7 sec, respectively. When the tracer rate of transport was studied as a function of unlabeled substrate concentrations added to the incubation medium, a displacement curve was generated which can be analyzed by nonlinear regression using equations which take into account the competitive inhibition of tracer flux by unlabeled substrate. This approach was made imperative since at 20 degrees C, in the presence of high substrate concentrations or 1 mM phlorizin, no measurable diffusion was found and the resultant zero slope values cannot be expressed into a classical v versus S plot. All together, our results support the existence of a single Na(+)-D-glucose cotransport system in these membranes for which Na+ is mandatory for uptake. This conclusion is at variance with that of a recent report using the same preparation (Harig et al., 1989. Am J. Physiol. 256:8618-8623). Since the discrepancy seems difficult to resolve on the consideration of experimental conditions alone, we have determined the kinetic parameters of D-glucose transport using one time point measurements and linear transformations of the Michaelis-Menten equation, in order to investigate the potential problems of such a widely used procedure. Comparing these approaches, we conclude that: (i) the dynamic uptake measurements give a better understanding of the different uptake components involved: (ii) it does not matter whether a dynamic or a one time point approach is chosen to generate the uptake data provided that a nonlinear-regression analysis with proper weighting of the data points is performed; (iii) analytical procedures which rely on linearization of Michaelian process(es) are endowed with a number of difficulties which make them unsuitable to resolve multicomponent systems in transport studies. A more general procedure which uses a nonlinear-regression analysis and a displacement curve is proposed since we demonstrate that it is far superior in terms of rapidity, data interpretation, and visual information.

Biological Transport↗
PubMed2000

Closed kinetic chain alone compared to combined open and closed kinetic chain exercises for quadriceps strengthening after anterior cruciate ligament reconstruction with respect to return to sports: a prospective matched follow-up study.

Rehabilitation after anterior cruciate ligament (ACL) reconstruction has focused over the past decade on closed kinetic chain (CKC) exercises due to presumably less strain on the graft than with isokinetic open kinetic chain exercises (OKC); however, recent reports suggest that there are only minor differences in ACL strain values between some CKC and OKC exercises. We studied anterior knee laxity, thigh muscle torque, and return to preinjury sports level in 44 patients with unilateral ACL; group 1 carried out quadriceps strengthening only with CKC while group 2 trained with CKC plus OKC exercises starting from week 6 after surgery. Anterior knee laxity was determined with a KT-1000 arthrometer; isokinetic concentric and eccentric quadriceps and hamstring muscle torque were studied with a Kin-Com dynamometer before and 6 months after surgery. At an average of 31 months after surgery the patients answered a questionnaire regarding their current knee function and physical activity/sports to determine the extent and timing of their recovery. No significant differences in anterior knee laxity were noted between the groups 6 months postsurgery. Patients in group 2 increased their quadriceps torque significantly more than those in group 1, but no differences were found in hamstring torque between the groups. A significantly higher number of patients in group 2 (n = 12) than in group 1 (n = 5) returned to sports at the same level as before the injury (P < 0.05). Patients from group 2 who returned to sports at the same level did so 2 months earlier than those in group 1. Thus the addition of OKC quadriceps training after ACL reconstruction results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months and also leads to a significantly higher number of athletes returning to their previous activity earlier and at the same level as before injury.

Adolescent↗
PubMed1996

Kinetics of Formation and Dissociation of [Cr(3)O(O(2)CCH(3))(6)(urea)(3)](+): An Example of Statistically Controlled Kinetics and Equilibrium.

Kinetics of the overall reaction [Cr(3)O(O(2)CCH(3))(6)(H(2)O)(3)](+) + 3 urea right harpoon over left harpoon [Cr(3)O(O(2)CCH(3))(6)(urea)(3)](+) + 3H(2)O have been studied spectrophotometrically. Monophasic kinetics were observed in both directions. The reverse steps, of urea dissociation, were monitored using an analytical technique which permits direct determination of the concentration of liberated urea and does not require knowledge of extinction coefficients of intermediate species. Results imply that consecutive steps occur with rate constants in close to the statistical ratios of k(1):k(2):k(3) = 3:2:1 and k(-)(1):k(-)(2):k(-)(3) = 1:2:3. Rates indicate strong labilization of urea, compared to the case of mononuclear complex [Cr(urea)(6)](3+).

Journal Article↗
PubMed1998

Anterior chamber fluorescein kinetics compared with vitreous kinetics in normal subjects.

PURPOSE: Describe and compare barrier properties in various parts of the eye. METHODS: Fluorophotometric measurements of the anterior chamber, vitreous and plasma fluorescein concentrations were performed and subjected to a kinetic two-compartment analysis. RESULTS: The overall barrier properties as revealed by a permeability-index was found to be 12.2% (anterior chamber) and 3.5% (vitreous). The apparent rate constant of permeation into the anterior chamber (Kin=1,59 h(-1)) was found to be significantly higher than into the vitreous (Kin=0,66 h(-1)) and into the apparent peripheral body compartment (Kin=0,23 h(-1)). The terminal rate constant of fluorescein disposition from the anterior chamber (Kout=0,21 h(-1)) was in agreement with the terminal disposition rate constant for plasma fluorescein (P=0,23 h(-1)), whereas elimination from the vitreous (Kout=0,072 h(-1)) was significantly slower. CONCLUSION: Compartment analysis of ocular fluorescein kinetics is suitable for the study of anterior and posterior barrier properties in the eye. In this study fluorescein elimination from the anterior chamber was restricted by terminal plasma fluorescein decay rather than by ocular tissue.

Adult↗
PubMed1967

Kinetics and mechanism of catalysis by proteolytic enzymes: The kinetics of hydrolysis of derivatives of l-lysine and S-(beta-aminoethyl)-l-cysteine(thialysine)by bovine trypsin.

1. Several esters of the alpha-N-toluene-p-sulphonyl and N-benzoyl derivatives of l-lysine and S-(beta-aminoethyl)-l-cysteine have been synthesized. 2. The kinetics of hydrolysis of the esters by bovine trypsin have been compared. Values of k(0) are similar for corresponding derivatives of the isosteric amino acids and deacylation of an acyl-enzyme appears to be rate-determining in each case. There are, however, some quantitative kinetic differences between the various series of substrates.

Journal Article↗
PubMed1975

[The pharmaco-kinetics of angiographic contrast media, with special reference to the extra-vascular space. An experimental study on dogs. Paper II. Pharmaco-kinetics of an angiographic contrast medium used for selective angiography (author's transl)].

Basic studies were carried out on experimental animals in order to investigate the pharmaco-kinetics of angiographic contrast media when used in various ways. Injections were carried out through angiographic catheters in a "physiological angiographic" manner. Measurements obtained by using radioactive compounds have shown that the distribution and excretion of the contrast medium are independent of the site of injection. The kinetics of the contrast within an organ do not differ, whether it is injected selectively or not. The results of all the experiments will be discussed at the conclusion of the third paper.

Angiography↗
PubMed1997

Recovery and kinetic characteristics of desflurane and sevoflurane in volunteers after 8-h exposure, including kinetics of degradation products.

BACKGROUND: Desflurane and sevoflurane permit speedier changes in anesthetic partial pressures than do older halogenated anesthetics. The authors determined the kinetic characteristics of desflurane and sevoflurane and those of compound A [CH2F-O-C(=CF2)(CF3)], a nephrotoxic degradation product of sevoflurane. METHODS: Volunteers received 1.25 minimum alveolar concentration of desflurane or sevoflurane, each administered for 8 h in a fresh gas inflow of 2 l/min. Inspired (F(I)) and end-tidal (F(A)) concentrations of anesthetic and compound A were measured during administration, and F(A) relative to F(A0) (the last end-tidal concentration during administration) during elimination. The indices of recovery were also measured. RESULTS: The ratio F(I)/F(A) rapidly approached 1.0, with values greater for sevoflurane (desflurane 1.06 +/- 0.01 vs. sevoflurane 1.11 +/- 0.02, mean +/- SD). The ratio F(A)/F(I) for compound A was approximately 0.8. The F(A)/F(A0) ratio decreased slightly more rapidly with desflurane than with sevoflurane, and objective measures indicated faster recovery with desflurane: The initial response to command (14 +/- 4 min vs. 28 +/- 8 min [means +/- SD]) and orientation (19 +/- 4 vs. 33 +/- 9 min) was quicker, and recovery was faster as defined by results of the Digit Symbol Substitution, P-deletion, and Trieger tests. Desflurane produced less vomiting (1 [0.5, 3]; median [quartiles] episodes) than did sevoflurane (5 [2.5, 7.5] episodes). The F(A)/F(A0) ratio for compound A decreased within 5 min to a constant value of 0.1. CONCLUSIONS: These anesthetics have kinetics consistent with their solubilities. Sevoflurane's greater biodegradation probably increases F(I)/F(A) differences during anesthetic administration and decreases F(A)/F(A0) differences during elimination. The F(A) for compound A differs from F(I) by 20% (F(A)/F(I) = 0.8) because of substantial degradation. Recovery from anesthesia proceeds nearly twice as fast with desflurane than with sevoflurane. Differences in ventilation, or alveolar or tissue elimination, do not completely explain the slower recovery with sevoflurane.

Anesthetics, Inhalation↗
PubMed1998

Effects of Hypoxia on 13NH4+ Fluxes in Rice Roots. Kinetics and compartmental analysis Kinetics and Compartmental Analysis

Techniques of compartmental (efflux) and kinetic influx analyses with the radiotracer 13NH4+ were used to examine the adaptation to hypoxia (15, 35, and 50% O2 saturation) of root N uptake and metabolism in 3-week-old hydroponically grown rice (Oryza sativa L., cv IR72) seedlings. A time-dependence study of NH4+ influx into rice roots after onset of hypoxia (15% O2) revealed an initial increase in the first 1 to 2.5 h after treatment imposition, followed by a decline to less than 50% of influx in control plants by 4 d. Efflux analyses conducted 0, 1, 3, and 5 d after the treatment confirmed this adaptation pattern of NH4+ uptake. Half-lives for NH4+ exchange with subcellular compartments, cytoplasmic NH4+ concentrations, and efflux (as percentage of influx) were unaffected by hypoxia. However, significant differences were observed in the relative amounts of N allocated to NH4+ assimilation and the vacuole versus translocation to the shoot. Kinetic experiments conducted at 100, 50, 35, and 15% O2 saturation showed no significant change in the Km value for NH4+ uptake with varying O2 supply. However, Vmax was 42% higher than controls at 50% O2 saturation, unchanged at 35%, and 10% lower than controls at 15% O2. The significance of these flux adaptations is discussed.

Journal Article↗