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  • Articles  (157)
  • 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
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  • Springer  (151)
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  • Articles  (157)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 26 (1987), S. 125-137 
    ISSN: 1436-6215
    Keywords: vitamin C ; functions ; kinetics ; pool ; saturation ; requirements ; RDA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Die Bedeutung von Vitamin C für den menschlichen Organismus wird aus den wichtigen Funktionen ersichtlich, an denen das Vitamin beteiligt ist, wie zum Beispiel Kollagen- und Karnitinsynthesen. In neuerer Zeit entdeckt wurde seine Rolle bei der Noradrenalinsynthese, der Inaktivierung von freien Radikalen sowie der Verhinderung der Nitrosaminbildung. Die Vielfalt dieser Vitamin-C-abhängigen Funktionen läßt erkennen, daß die Bedarfsfestsetzung für Vitamin C nicht nur die Verhütung der Mangelkrankheit Skorbut anvisieren, sondern auch berücksichtigen sollte, daß alle diese Funktionen jederzeit genügend Vitamin C zur Verfügung haben müßten, um optimal reagieren zu können. Das Konzept der Gewebesättigung kommt diesem Ziel am nächsten. Studien mit einem kinetischen Modell haben ergeben, daß eine Sättigung mit täglicher Einnahme von 100 mg Vitamin C bei Nichtrauchern und von 140 mg bei Rauchern eintritt, Mengen, die als optimale Werte gelten können. Bei verschiedenen Krankheiten dürfte der Bedarf höher sein; die genauen Mengen müssen jedoch erst noch ermittelt werden.
    Notes: Summary The importance of vitamin C is reflected in its multifunctional roles which include participation in collagen and carnitine syntheses, promotion of iron absorption and the more recently discovered participation in noradrenaline synthesis, inactivation of free radical chain reactions, prevention of N-nitroso compound formation and more. Given the many extra-antiscorbutic functions of the vitamin, the Recommended Dietary Allowances (RDA) should not just prevent deficiency disease but should aim at providing sufficient amounts for all vitamin C-dependent functions to operate at full capacity. The concept of vitamin C tissue saturation is best able to meet this demand. The use of kinetic models has shown that the body pool is saturated with a daily intake of 100 mg vitamin C in non-smokers and 140 mg in smokers, amounts that may be regarded as optimal RDA values. Certain disease states may be accompanied by still higher vitamin C requirements but the exact amounts are not yet known.
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  • 2
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    Springer
    Colloid & polymer science 261 (1983), S. 188-189 
    ISSN: 1435-1536
    Keywords: Polymerization ; kinetics ; redox polymerization ; acrylamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 3
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    Springer
    Colloid & polymer science 266 (1988), S. 958-964 
    ISSN: 1435-1536
    Keywords: a-Se colloids ; photoadsorption ; kinetics ; activation energy ; compensation effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract In this study, a model is developed to explain in microscopic terms the results obtained from thermally activated photoadsorption experiments in a-Se colloids. The observed compensation effect can be described for two different cases. At low efficiency adsorption, the process is controlled by the potential at the boundary layer. In the high efficiency adsorption case, the process is controlled by diffusion transport.
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  • 4
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    Colloid & polymer science 262 (1984), S. 366-373 
    ISSN: 1435-1536
    Keywords: kinetics ; isothermal crystallization ; polymer ; spherulite ; differential scanning calorimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract In the DSC technique, isothermal crystallization experiments are usually performed on thin flat specimens, but their interpretation generally uses theories developed for an unbounded volume. In this paper, isothermal crystallization of spherical entities in the volume limited by two parallel infinite planes is considered. Our model, derived from Avrami's theory, gives an analytical expression for the transformed volume fraction as a function of time. It is shown that the influence of thickness becomes important when thickness becomes of the order of or smaller than the average spherulite radius. The main effects of a decreasing thickness are a slower crystallization kinetics and a decrease in the Avrami exponent. These results can be used to interpret experimental data obtained in isothermal polymer crystallization.
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  • 5
    ISSN: 1435-1536
    Keywords: Phospholipid bilayer ; kinetics ; laser temperature jump ; phase transition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The iodine-laser temperature-jump technique has been used to investigate the main phase transition in single shell vesicles of dimyristoylphosphatidylcholine. The probe molecules DPH and TMA-DPH were incorporated into the lipid bilayer and laserT-jump experiments with turbidity and flourescence polarization detection were performed. We found three well separated relaxation processes between 5 μs and 10 ms. The relaxation signals showed strong cooperativity in the relaxation times as well as in their corresponding amplituedes. We attributed the relaxation to the formation and dissolution of clusters of different order inside the bilayer.
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  • 6
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    Colloid & polymer science 265 (1987), S. 58-64 
    ISSN: 1435-1536
    Keywords: Polymerisation ; emulsion ; styrene ; methylmethacrylate ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The dependence of emulsion polymerisation rates on a number of important parameters is considered. Attention is paid to the use of seeded emulsion systems for the evaluation of radical desorption coefficients (k o). Experimental conditions are shown to be important. When the average number of radicals per particle is low, large changes in the rate coefficient for chain termination do not have a large effect on the kinetics. With styrene and methylmethacrylate, radical re-absorption by the polymer particles is shown to be important and radical capture efficiences can be high. Consistency is established between the results of a number of workers and values fork o are shown to be lower than those calculated from chain transfer rates.
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  • 7
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    Colloid & polymer science 261 (1983), S. 621-625 
    ISSN: 1435-1536
    Keywords: Polyamide 6 ; crystallisation ; kinetics ; titania
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The kinetics of isothermal and nonisothermal crystallization of polyamide-6 (PA6) containing titania was studied by means of DSC. It was found thatTiO 2 causes an acceleration in the crystallization of polyamide-6 and lowers the value of the Avrami exponent,n. The presence of TiO2 does not affect equilibrium melting pointT m 0 , glass temperatureT g, or surface free energiesσ e andσ of the basal and lateral surfaces.
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  • 8
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    Fire technology 20 (1984), S. 47-63 
    ISSN: 1572-8099
    Keywords: Extinguishment ; fire modeling ; mass loss ; heat release ; char ; reflash ; sprinklers ; radiant flux ; kinetics ; reaction rate ; heat loss ; ash ; latent heat ; spray density ; extinguishing agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying
    Notes: Abstract The Ad Hoc Mathematical Fire Modeling Working Group was organized about seven years ago to facilitate voluntary cooperation and coordination in developing mathematical fire modeling capability. The group has a steering committee of representatives of agencies that support fire modeling and related research. These include the National Bureau of Standards' Center for Fire Research, Factory Mutual Research Corp., the Naval Research Laboratory, NASA, and the Federal Aviation Agency. The Group holds plenary meetings when it seems desirable to do so (about once each 1 1/2 years), and workshops on topical subjects. Three workshops were held in 1983. Normally, Group meetings are held before or after other meetings at which a number of interested personnel would likely be present. Minutes are mailed to those who attended and to others (including European and Japanese personnel) who have indicated interest. This workshop was arranged by Ron Alpert of Factory Mutual Research Corp. and held at their facilities at Norwood, MA, in November 1983.
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  • 9
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    Journal of solution chemistry 11 (1982), S. 339-346 
    ISSN: 1572-8927
    Keywords: Carbon dioxide ; hydrolysis ; aqueous solution ; kinetics ; activation volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pressure dependence of the dehydration reaction of H2CO3 was measured in acidic aqueous solution for pressures up to 1 kbar using a high-pressure stopped-flow instrument. The corresponding volume of activation was found to be 6.4±0.4 cm3-mol−1 at 25°C and 0.5 ionic strength. Volume equation calculations result in a value of −9.9±1.9cm3-mol−1 for the volume of activation for the hydrolysis of CO2 under the same conditions. For the first time, the reaction mechanism can be interpreted in terms of dissociative and associative modes, respectively. These data are used to construct an overall reaction volume profile.
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  • 10
    ISSN: 1572-8927
    Keywords: Temperature jump ; kinetics ; thermodynamics ; TRIS ; iminodiacetic acid ; magnesium ion ; phenol red
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Equations describing the temperature jump amplitudes associated with a system of two coupled reactions (TRIS-phenol red) as well as the ternary system (Mg2+-iminodiacetic acid-phenol red) are presented. The termodynamic parameters calculated from experimentally measured temperature perturbation amplitudes using a multiparametric curve fitting procedure are found to be in good agreement with those determined from pH- and costant rate thermometric titrations. For phenol red, pK I =7.55, ΔH I =3.45 kcal, and for Mg2+ iminodiacetic acid, log K M =2.84, ΔH M =3.25 kcal, were obtained. It is shown that this method can be used to determine accurate thermodynamic enthalpy changes over a narrow temperature interval of less than 1.0°C from a single experiment requiring about 50 μl of sample solution.
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  • 11
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    Journal of solution chemistry 12 (1983), S. 771-781 
    ISSN: 1572-8927
    Keywords: Ultrasonics ; kinetics ; aqueous solution ; iso-butyl cellosolve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Ultrasonic absorption and velocity measurements in aqueous solution of iso-butyl cellosolve (ethylene glycol iso-butyl ether) as a function of the concentration are reported. The two relaxational absorptions have been attributed to the perturbation of the equilibria expressed by AB⇌A+B and Aα(1/n)An where A is the solute, B is the solvent, AB is the complex and A n is the solute aggregate. The rate constants for each step have been determined. From the concentration dependence of the maximum excess absorption per wave length, the enthalpy change and the volume change for the reaction between the solute and the solvent have been determined for aqueous solutions of butyl cellosolve (ethylene glycol n-butyl ether), iso-butyl cellosolve and propyl cellosolve (ethylene glycol n-propyl ether). The results are consistent with a hydrogen bonding reaction. The effect of the ethers on water structure are considered and it is clear that the fraction of water molecules which can hydrogen bond to the solute decreases with the increasing hydrophobicity of the solute.
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  • 12
    ISSN: 1572-8927
    Keywords: Enthalpies of reaction ; heats of reaction ; kinetics ; ester hydrolysis ; microcalorimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The conditions under which the Picker flow microcalorimeter can be used to measure enthalpies and rates of reactions were investigated. For this purpose, systematic studies were made of the enthalpies of neutralization of HCl, HBr, HNO 3 , acetic, proprionic, and butyric acids with NaOH, enthalpies of hydrolysis of methyl and ethyl acetate with NaOH, and the reaction rates of the ester hydrolysis with NaOH. The general procedure and various sources of error are discussed and it is concluded that enthalpies of slow reactions can be measured to about 1% when the calorimeter is operated in the quasi-isothermal mode and the reaction rates to about 3% when operated in the quasi-adiabatic mode.
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  • 13
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    Journal of solution chemistry 15 (1986), S. 221-229 
    ISSN: 1572-8927
    Keywords: Ultrasonics ; kinetics ; aqueous solution ; triethylene glycol monobutyl ether
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The ultrasonic absorption from 6.5 to 220 MHz and velocities at 2.5 MHz have been measured in aqueous solution of triethylene glycol monobutyl ether as a function of concentration at 25°C. A single relaxational excess absorption, observed from 0.60 to 2.5 mol-dm−3, is attributed to a perturbation of an equilibrium associated with solute-solvent interaction. Rate constants for the forward and reverse processes have been determined from the concentration dependence of the relaxation frequency, and the influence on the water structure by an addition of the solute has been considered. Solution densities were also measured in order to obtain the expansivity of the solution. The standard volume and enthalpy changes of the reaction have been estimated from the concentration dependence of the maximum excess absorption per wave length. A linear relationship between the number of oxyethylene groups and the free energy change between bonded water and nonbonded water is established.
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  • 14
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    Microchimica acta 94 (1988), S. 277-278 
    ISSN: 1436-5073
    Keywords: kinetics ; FT-IR ; temporal resolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A system for performing gas-phase rapid scanning Fourier transform infrared time-resolved Spectrometry (FT-IR/TRS) has been evaluated. This technique can be applied to the study of the lifetimes and reactivity of transient species and can provide detailed information regarding reaction rate constants. Temperature-jump experiments have been initiated and preliminary results are presented.
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  • 15
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    Microchimica acta 94 (1988), S. 323-328 
    ISSN: 1436-5073
    Keywords: FTIR spectroscopy ; kinetics ; polymers ; rheo-optics ; variable-temperature measurements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The rapid-scanning capability of FTIR instrumentation has revitalized the field of vibrational spectroscopy in polymer research and will be discussed with reference to the study of polyurethane kinetics, the temperature dependence of hydrogen bonding in polyamide 6 and strain-induced crystallization in a polydimethylsiloxane elastomer.
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  • 16
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    Cellular and molecular life sciences 41 (1985), S. 1563-1564 
    ISSN: 1420-9071
    Keywords: Cytosine deaminase ; kinetics ; pyrophosphate ; orotidine monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The maximal velocity of the reaction (Vmax) and the half-saturation constant (K0.5) values of theS. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.
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  • 17
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    European journal of clinical pharmacology 21 (1981), S. 215-220 
    ISSN: 1432-1041
    Keywords: phenytoin ; cimetidine ; antipyrine test ; drug interaction ; drug metabolism ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a prospective study in nine patients the effects of phenytoin and of cimetidine (1000mg/day) + phenytoin on the antipyrine test and serum phenytoin concentrations were studied. Serum phenytoin increased from the steady state level of 5.7±1.3 mg/l to 9.1±1.4mg/l after three weeks on cimetidine (p〈0.01), and fell to 5.8±1.2 mg/l within two weeks after withdrawal of cimetidine. The protein binding of phenytoin was not changed by cimetidine. After use of phenytoin for 2–4 months, antipyrine clearance increased from 0.67±0.06ml/min/kg to 1.61±0.22 ml/ min/kg, and antipyrine half-live fell from 10.9±1.3h to 4.5±0.6h as compared to the values before phenytoin treatment (p〈0.01). After three weeks combined use of cimetidine and phenytoin, antipyrine clearance was decreased to 1.01±0.07 ml/min/kg and antipyrine half-life was prolonged to 6.1±0.5h, (p〈0.01) compared to the values on phenytoin alone. The distribution volume of antipyrine was not affected by phenytoin nor by cimetidine + phenytoin. The half-life of cimetidine was 2.8±0.3h in the patients on longterm phenytoin treatment. There was a significant positive correlation (p〈0.001) between the increase in serum phenytoin concentration and the prolongation of antipyrine half-life caused by cimetidine. Thus, cimetidine increases serum phenytoin concentration, very probably by inhibiting its metabolism. Care should be taken in the concomitant use of cimetidine and phenytoin, and the dose of phenytoin should be modified according to the clinical symptoms and serum phenytoin concentrations.
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  • 18
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    European journal of clinical pharmacology 22 (1982), S. 225-228 
    ISSN: 1432-1041
    Keywords: pinazepam ; N-desmethyldiazepam ; kinetics ; metabolism ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma profile of a single oral dose of pinazepam 10 mg was studied in 6 healthy male volunteers, aged 26 to 31 years. The concentrations of the parent compound and of its metabolite in plasma were measured by gas-chromatography. The peak plasma levels of pinazepam was 36.8±5.1 ng/ml and of N-desmethyldiazepam 150±13.3 ng/ml. The plasma concentration of the metabolite become higher than that of the parent compound shortly after administration, suggesting that pinazepam acts as a prodrug.
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  • 19
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    European journal of clinical pharmacology 22 (1982), S. 545-551 
    ISSN: 1432-1041
    Keywords: oxcarbazepine ; kinetics ; disposition ; metabolites ; renal excretion ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oxcarbazepine (oxcarb) 600 and 900 mg (2360 and 3540 µmol) was taken by 3 volunteers (2 ♀, 1 ♂; 45–67 kg; age 22–34 years) after an overnight fast. Blood, saliva and urine were collected for the next 72 h for assay of oxcarb, 10,11-dihydro-10-hydroxy-carbamazepine (OHcarb), and 10,11-dihydrotrans-10,11-dihydroxy-carbamazepine (diol). Oxcarb reached a maximum level of about 1 µg/ml (3.93 µmol/l) within 1 h and dropped below the detection limit (0.1 µg/ml=0.39 µmol/l) within 3 h. The active metabolite OHcarb appeared in the blood before oxcarb and reached the higher maximum level of 7.4 µg/ml (29 µmol/l) after 7 h. Thereafter serum levels decreased with a t1/2 of about 25 h, and after 40 h with a t1/2 of 9 h, the latter agreeing with the renal excretory t1/2 calculated from the urine data (10 h). The ratio of OHcarb concentration in saliva to that in plasma varied considerably (0.3–1.7; median 1; r〉0.9), whereas that of blood to plasma was 1.25 with only small variation (r〉0.98); OHcarb concentrations in erythrocytes were 50% higher than in plasma. Diol was detected in blood (maximum level 0.5 µg/ml=1.84 µmol/l) in 2 volunteers. 45% of the dose could be recovered in urine (Oxcarb 5%, OH-carb 36%, Diol 4%). Whereas Oxcarb was completely conjugated, only 25% of OHcarb was conjugated and diol was unconjugated.
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  • 20
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    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
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  • 21
    ISSN: 1432-1041
    Keywords: prizidilol ; antihypertensive effect ; acute and long-term blood pressure control ; plasma renin activity ; acetylator phenotype ; antinuclear antibodies ; side effects ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP)〈90 mmHg. Supine and standing BP recorded 24–27 h after drug intake decreased from 172±17/106±6 mmHg (mean±SD) and 167±18/111±8 mmHg, respectively, after placebo to 159±16/99±8 and 154±18/101±9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154±16/97±7 and 148±14/97±7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n=9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0–8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12–15 h after dosing) as compared to the once daily regimen at 14 weeks. During treatment for up to 24 months, 16 patients did not achieve satisfactory BP control. Eight of them were withdrawn and eight received additional treatment with bendroflumethiazide (2.5–5 mg/day). In 7 of the latter satisfactory BP control was achieved. Side effects were few. Dizziness and tiredness occurred in four patients 2–5 h after prizidilol 600–800 mg once daily. These symptoms partly subsided when the subjects changed to a twice daily regimen. No ocular side-effects were found. Before treatment 13 out of 24 patients had a low titre of IgM antinuclear antibodies (ANA) and one patient also a low titre of IgG ANA. During treatment the frequency of patients with positive ANA-titres became higher, and after treatment for 12 months (n=17) 15 patients had positive IgM and seven patients positive IgG ANA-titres. However, the titres were low and no patient showed a clinical lupus erythematosus syndrome. There was no relation between acetylator phenotype of the patient and acute or longterm effecton BP, pharmacokinetics of the drug or the development of a raised ANA-titre.
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  • 22
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    European journal of clinical pharmacology 24 (1983), S. 273-276 
    ISSN: 1432-1041
    Keywords: undernourished ; chlorquine ; kinetics ; plasma levels ; red cell uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and whole blood kinetics of chloroquine was studied in 7 normal and 8 undernourished subjects following a single oral dose of 600 mg. The terminal half-lives were similar in both groups. The AUC was also similar in the 2 groups, even though a higher dose per kg body weight was administered to the undernourished. This was probably because of faster clearance in this group. Chloroquine uptake by erythrocytes, its main site of action in malaria, was also comparable in the two groups. The plasma concentration of chloroquine over a period of time was found to be similar in 4 normal and 4 undernourished subjects following administration of 1.5 g of the drug in divided doses. The undernourished appear, therefore, to handle chloroquine in such a way that they do not suffer a greater risk of toxicity than normals.
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  • 23
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    European journal of clinical pharmacology 24 (1983), S. 525-527 
    ISSN: 1432-1041
    Keywords: theophylline ; airway obstruction ; biotransformation ; kinetics ; oral dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oral theophylline was given to 6 adults with airways obstruction. The initial dose was 125 mg daily and this was increased by 125 mg each week. The final total daily dose reached was determined by side effects and ranged from 500 mg to 1125 mg. At the end of each week and before the next dosage increment steady state, trough plasma theophylline concentrations were measured. For each individual and for the group as a whole there was a highly significant linear correlation between theophylline dose and trough plasma concentration. This indicates that for oral theophylline, in adults, dose-dependent kinetics do not play a significant role and dose may be adjusted without fear of a disproportionate rise in plasma concentration.
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  • 24
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    European journal of clinical pharmacology 27 (1984), S. 491-494 
    ISSN: 1432-1041
    Keywords: amiodarone ; kinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied three healthy volunteers after a single i.v. bolus of amiodarone, during 1 month of chronic oral dosing and after the discontinuation of the drug. Blood concentrations of amiodarone declined rapidly in a bi-exponential fashion after i.v. bolus. The terminal half-life ranged from 10 to 17 h; after discontinuation of chronic treatment the terminal half-lives were 8–21 days. The i.v. data, the trough levels during multiple dosing and the washout phase could be simultaneously fitted using a tri-exponential equation. The subjects were carefully monitored for cardiac and thyroid function. One subject had to stop taking amiodarone because of profound bradycardia. A reduction of serum TT3 and FT3 concentrations and an increase of serum rT3 and FT4 was found.
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  • 25
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    European journal of clinical pharmacology 29 (1985), S. 251-253 
    ISSN: 1432-1041
    Keywords: paracetamol ; antacids ; acetaminophen ; bioavailability ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of two antacids on the bioavailability of paracetamol has been investigated in 12 young healthy volunteers. Following a random cross over design, each subject swallowed, on three separate occasions, one weak apart, 500 mg paracetamol alone, or together with two different aluminium hydroxide, magnesium hydroxide preparations (Dimalan and Maalox). Plasma paracetamol levels were measured by HPLC. The bioavailability of paracetamol was not altered by either antacid, but they both delayed the time to peak plasma concentration (0.85 h; 1.43 h; 1.25 h, without antacid, with Dimalan and with Maalox respectively). The peak plasma concentration was not affected by concurrent antacid administration.
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  • 26
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    European biophysics journal 16 (1989), S. 321-325 
    ISSN: 1432-1017
    Keywords: Sodium currents ; inactivation ; kinetics ; channel gating
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    Topics: Biology , Physics
    Notes: Abstract The time constant of the process producing the delay in Na inactivation development as determined by the two pulse method (τdelay) was extracted and compared to that of the slowest Na activation process τ3 for the I Na during the conditioning pulse of that same determination. τdelay and two pulse inactivation τc values were computer generated using a nonlinear least squares algorithm. τh and single pulse inactivation τh values were independently generated for each determination also with the aid of the computer using the same non-linear least squares algorithm. In one determination at 2 mV, τc was 4.68 and τdelay 0.494 ms while τh was 4.70 and τ3 0.491 ms for a τc/τh of 0.996 and a τdelay/τ3 of 1.006. Mean τdelay/τ3 from five determinations in four axons, both Cs and K perfused, and spanning a potential range of-27 to 2mV was 1.068. The precursor process to inactivation is channel opening. Some fraction of channels presumably inactivate via another route where prior channel opening is not required.
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  • 27
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    European journal of clinical pharmacology 28 (1985), S. 163-169 
    ISSN: 1432-1041
    Keywords: indomethacin ; platelet aggregation ; prostanoids ; plasma concentration ; arachidonic acid ; thromboxane B2 ; 6-keto-prostaglandin F1α ; kinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single oral dose of indomethacin 1 mg/kg was given to 6 male and 6 female volunteers. The formation of thromboxane B2 (TXB2) and 6-ketoprostaglandin F1α (6-keto-PGF1α) in clotting whole blood was measured by radioimmunoassay, and platelet aggregation induced by archidonic acid (AA) was measured with a plasma aggregometer. The results were related to the concomitant plasma concentration of indomethacin. The maximum plasma concentration ranged between 3.24 and 8.11 µg/ml and the elimination half-life between 4 and 11 h. Formation of the prostanoids was reversibly inhibited, with maximum suppression when the drug concentration in plasma exceeded 0.5–1.0 µg/ml; the IC50 was approximately 0.1 µg/ml. Platelet aggregation was also reversibly inhibited. The correlation between the formation of prostanoids and the different phases of the aggregatory response to exogenous AA is discussed.
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  • 28
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    European journal of clinical pharmacology 17 (1980), S. 285-293 
    ISSN: 1432-1041
    Keywords: tolbutamide ; chlorpropamide ; kinetics ; food ; age ; blood glucose ; plasma insulin
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake (standardized breakfast) on the oral single-dose kinetics and effects of tolbutamide (0.5 g) and chlorpropamide (250 mg) was investigated in young, healthy volunteers. The single-dose kinetics of the two drugs was also studied in elderly healthy subjects. There was great interindividual variation in the elimination rate of both drugs, but food intake influenced neither their AUCs nor their rates of absorption and elimination. The peak concentration of chlorpropamide, but not that of tolbutamide, was reduced by food intake. The peak concentrations of serum tolbutamide were approximately doubled by an increase in dose from 0.5 to 1.0 g, and from 1.0 to 2.0 g. At no time did tolbutamide 0.5 g affect the plasma insulin level, neither in the fasting nor in the non-fasting state. However, this dose did reduce the blood glucose level during fasting and the increase in blood glucose in response to the meal. The latter effect was recorded within 30 min, when the serum level of tolbutamide still was close to zero. Plasma insulin concentrations did increase within 30 min after a higher dose of tolbutamide (1.0 g), when the serum concentration of tolbutamide was about 50 µmol/l. Between 2.5 and 8 h after administration of chlorpropamide 250 mg, serum drug concentrations were lower than those following tolbutamide 0.5 g. The blood glucose response was smaller and occurred later, being significant at 2 h, when the serum concentration of the drug was about 70 µmol/l. There was no significant change in plasma insulin. There was no significant pharmacokinetic difference between young and elderly subjects, except that the peak concentration of tolbutamide was higher in the latter. It appears that both for tolbutamide and chlorpropamide there is great interindividual variation in drug disposition, but food intake does not influence the bioavailability of either drug. The effect of any particular drug concentration seems dependent upon the blood glucose level and hence upon the elapsed time since the last meal. Both drugs can reduce blood glucose without an alteration in the peripheral blood concentration of insulin. This may reflect an extrapancreatic effect of the drugs, but it could also be an expression of increased insulin secretion, which is not detected because of enhanced hepatic degradation of the hormone released into the portal circulation. The observations made in young individuals are also probably relevant for elderly subjects.
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  • 29
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    European journal of clinical pharmacology 21 (1982), S. 403-408 
    ISSN: 1432-1041
    Keywords: glibenclamide ; diabetes ; insulin ; kinetics ; blood glucose ; relationship to meals ; absorption
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an attempt to assess whether intake of glibenclamide before meals would improve its therapeutic capacity, the present investigation compared the effect of glibenclamide 2.5mg t.i.d. given before and together with meals. In addition, these effects were compared with that of glibenclamide given as a single morning dose of 7.5mg. The subjects studied were six Type 2 diabetics not previously exposed to sulphonylurea drugs. Irrespective of dosage and mode of administration, addition of glibenclamide to a standardized breakfast, lunch and dinner enhanced plasma IRI concentrations and reduced blood glucose concentrations as compared to administration of meals without the drug. The different modes of glibenclamide administration did not differ significantly with respect to IRI responses. However, the blood glucose reduction after breakfast was significantly greater when glibenclaimde 2.5mg had been given before the meal than when 2.5 or 7.5mg were given with the meal; a similar, but non-significant tendency was observed after lunch; no consistent difference was seen after dinner. Food intake did not affect glibenclamide kinetics. It appears that administration of glibenclamide 2.5mg before breakfast improved glucose utilization following the breakfast load, due to earlier attainment of an effective concentration of glibenclamide.
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  • 30
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    European journal of clinical pharmacology 22 (1982), S. 309-314 
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; salicylic acid ; dipyridamol ; bioavailability ; kinetics ; rapid- and slow-release formulations
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylsalicylic acid (ASA) is a strong, irreversible inhibitor of platelet aggregation, but loses this activity following first-pass deacetylation to salicylic acid (SA). In order to compare the bioavailability of unchanged ASA from rapid- and slow-release formulations, the single-dose concentration profiles of ASA and SA were studied in healthy volunteers following intake of two different rapid-release (conventional and effervescent tablets) and three different slow-release (microencapsulated ASA in tablets and in capsules, and enteric-coated tablets) formulations of ASA, and of one slow-release formulation of sodium salicylate. Since anti-platelet therapy with ASA is often combined with dipyridamol, the influence of this drug was also examined. The concentrations of ASA and SA were measured by high-pressure liquid chromatography. While the bioavailability of SA from the 5 ASA formulations was essentially equal and similar to that of the salicylate formulation, the bioavailability and peak concentrations of ASA appeared to be the much greater after rapid-release than after slow-release formulations. Indeed, ASA was only rarely detected in systemic blood following intake of slow-release ASA. Co-administered dipyridamol did not significantly influence the kinetics of ASA or SA. It appears that rapid-release formulations of ASA should be prefered in anti-platelet therapy, either alone or in combination with dipyridamol.
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  • 31
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    European journal of clinical pharmacology 24 (1983), S. 41-47 
    ISSN: 1432-1041
    Keywords: quinidine ; digoxin ; interaction ; kinetics ; absorption ; elimination
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate constant of digoxin (ka) increased from 2.72±1.04 to 3.53±1.34 h−1 (p〈0.05), whereas lag time and peak time decreased from 0.16±0.10 to 0.05±0.04 h (p〈0.05) and from 0.92±0.27 to 0.69±0.19 h (p〈0.02), respectively. Predose plasma digoxin increased from 0.41±0.25 to 0.70±0.31 ng/ml (p〈0.02), while peak plasma digoxin increased from 0.93±0.34 to 1.63±0.46 ng/ml (p〈0.02). The systemic availability of digoxin increased from 68.48±13.35 to 79.09±14.89% (p〈0.05) in the presence of quinidine. Quinidine had no effect on the biotransformation pattern of digoxin, as assessed by thin layer chromatography. Quinidine increases the rate and extent of digoxin absorption, and this interaction contributes significantly to the elevation in plasma digoxin during both its distribution and elimination phases.
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  • 32
    ISSN: 1432-1041
    Keywords: lorcainide ; oral antiarrhythmic therapy ; nor-lorcainide ; first-pass metabolism ; kinetics ; alternative dosage ; regimens
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The feasibility of giving a supplementary starting dose of the antiarrhythmic drug lorcainide, in order to minimalize the impact of the extensive, but saturable first-pass metabolism, was evaluated. Twenty-five adult patients were given 100 mg lorcainide tablets according to one of 3 different dosage schedules: Eight patients took one tablet at 0, 12 and 24h, 8 took 1 tablet at 0, 1, 12 and 24h and 9 took 1 tablet at 0, 2, 12 and 24h. Levels of lorcainide and its metabolite, nor-lorcainide, during treatment were determined by gas-liquid chromatography. The results show that giving a second tablet 1 or 2h after the first may produce faster saturation of the pre-systemic metabolism of lorcainide in the liver.
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  • 33
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    European journal of clinical pharmacology 24 (1983), S. 801-806 
    ISSN: 1432-1041
    Keywords: acebutolol ; hydrochlorothiazide ; kinetics ; drug combination ; interaction ; diacetolol ; healthy subjects ; renal clearance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acebutolol and hydrochlorothiazide (HCT) alone or in combination were studied in 12 healthy subjects in a cross over study. Acebutolol and diacetolol (the main metabolite) in plasma and urine were determined by HPLC and hydrochlorothiazide by GLC. The main pharmacokinetic parameters of acebutolol did not differ significantly: AUC 4492±272 µg l−1 h given alone versus 4118±354 µg l−1 h with HCT, half-life (7,69±0,32 h vs 8,10±0,72 h) and renal clearance (13,1±0,5 lh−1 vs 13,8±0,9 lh−1), respectively. There was no difference in diacetolol pharmacokinetics. HCT values were not significantly different: AUC 784±48 µg l−1 h given alone and 720±42 µg l−1 h with acebutolol, t1/2 (4,79±0,37 h vs 4,73±0,43 h). The renal clearance was slightly higher when HCT was given with acebutolol (26,2±2,6 vs 20,3±2,11 h−1,p〈0,05). This increase, observed during the first four hours, was probably due to competition between the drugs for binding to red blood cells.
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  • 34
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    European journal of clinical pharmacology 23 (1982), S. 261-266 
    ISSN: 1432-1041
    Keywords: mexiletine ; rifampicin ; kinetics ; enzyme induction ; excretion ; antipyrine clearance ; dosage adjustment
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the effects of enzyme induction on its pharmacokinetics, a single oral dose of the new antiarrhythmic agent mexiletine hydrochloride 400 mg was administered to 8 healthy volunteers before and after treatment with rifampicin 300 mg b.i.d. for ten days. The absorption and distribution of mexiletine were not changed after rifampicin, but its elimination half-life fell from 8.5±0.8 h (mean±SE) to 5.0±0.4 h (p〈0.01), and its nonrenal clearance increased from 435±68 ml/min to 711±101 ml/min (p〈0.01). The mean renal clearance of mexiletine did not change, but it showed an exponential correlation with urinary pH. The amount of unchanged mexiletine excreted in urine over two days decreased from 32±7 to 18±3 mg (p〈0.01). The half-life of antipyrine fell from 11.8±0.4 to 5.5±0.3 h and its clearance increased from 40±3 ml to 74±3 ml/min (p〈0.01). There was a significant (p〈0.05) positive linear correlation between both the half-lives and the clearances of antipyrine and mexiletine. The clearances were positively correlated with serum γ-glutamyl transpeptidase. The results suggest that the dosage of mexiletine should be adjusted when enzyme inducing drugs are started or stopped during therapy with it.
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  • 35
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    European journal of clinical pharmacology 29 (1986), S. 529-534 
    ISSN: 1432-1041
    Keywords: pethidine ; epidural injections ; pain scores ; kinetics ; spinal cord
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p〈0.05). The area under the curve (AUC) of pain score versus time (0–18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.
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  • 36
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    European biophysics journal 13 (1986), S. 343-353 
    ISSN: 1432-1017
    Keywords: Lipid/cholesterol ; phase transition ; kinetics ; second order transition ; pressure jump relaxation
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    Topics: Biology , Physics
    Notes: Abstract Lipid bilayers and monolayers composed of dimyristoylphosphatidic acid (DMPA) and cholesterol were characterized by differential scanning calorimetry and film balance measurements. Increasing cholesterol content decreases the bilayer phase transition temperature and enthalpy in a manner similar to that observed before for other lipid/cholesterol systems. In monomolecular films at the air-water interface cholesterol exhibits the well known condensing effect in the liquid-expanded phase, while the liquid-condensed phase is less affected. As with the bilayer phase transition, the transition temperature and change in area at the liquid-condensed to liquid-expanded phase transition, as measured from isobars at 25 dynes/cm, decreases with increasing cholesterol content. The kinetics of the phase transition of DMPA/cholesterol bilayers were measured using the pressure jump relaxation technique with optical detection. Three relaxation times were observed. The relaxation times and amplitudes pass through maximum values at the transition midpoint. With increasing cholesterol content the maximum values of the relaxation times decrease but not in a linear fashion. The time constants display an intermediate maximum at ca. 10% to 12 mol% cholesterol. This observation is discussed in terms of a possible change in the nature of the phase transition from first-order with phase separation to a continuous second-order transition. The dependence of the relaxation amplitudes on cholesterol content gave evidence for nucleation being the rate limiting step for the transition in this particular system.
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  • 37
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    European journal of clinical pharmacology 23 (1982), S. 87-92 
    ISSN: 1432-1041
    Keywords: phenobarbital ; epilepsy ; kinetics ; bioavailability ; epileptic patients
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of phenobarbital (PB) were evaluated in six normal subjects and six epileptic patients treated with phenytoin or carbamazepine. Each normal subject received three single doses of PB: PB-sodium 130 mg i.v. (IV), PB sodium 130 mg i.m. (IM), and PB acid 100 mg orally (PO), in random order at least one month apart. After IV PB distributive half-lives varied from 0.13 to 0.70 h, disposition half-lives were 75 to 126 h, steady state volume of distribution (Vss) was 0.54±0.03 l/kg, and clearance (CL) was 3.8±0.77 ml/h/kg. Absolute bioavailability of IM PB was 101±13%, of PO PB (corrected for dose) 100±11%. Peak serum PB concentrations were achieved from 2 to 8 h after IM administration, and from 0.5 to 4 h after PO administration. Epileptic patients exhibited similar PB kinetics: disposition half-lives were 77 to 128 h, Vss 0.61±0.05 l/kg, and Cl 3.9±0.76 ml/h/kg. Phenobarbital appears to represent an exception among antiepileptic drugs, in that pharmacokinetic data obtained in normals can reasonably be extrapolated to the epileptic population.
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  • 38
    ISSN: 1432-1041
    Keywords: metoprolol ; age ; disposition ; elderly subjects ; kinetics ; metabolism ; alpha-OH-metoprolol
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of α-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.
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  • 39
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    European journal of clinical pharmacology 21 (1981), S. 149-153 
    ISSN: 1432-1041
    Keywords: cinromide ; epilepsy ; kinetics ; metabolites
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cinromide is an experimental anticonvulsant currently in phase II testing. A single oral dose (900 mg) of cinromide was administered to 8 epileptic subjects on phenytoin therapy. Plasma samples drawn during the next 36 h were analyzed for cinromide and its amide and acid metabolites. The absorption rate of cinromide varied widely between subjects producing maximum cinromide concentrations between 0.5 and 2.5 h after the dose. The median elimination half lives of cinromide and the amide and acid metabolites were 0.73, 1.65, and 4.85 h respectively. The oral clearance of cinromide (median=135 l/h) suggests that it is subject to first pass metabolism. In all subjects the area under the curve (AUC) of acid metabolite (632 to 1777 µM/l) was greater than the AUC of amide metabolite (77 to 185 µM/l) which was greater than the AUC of cinromide (5 to 89 µM/l). Steady-state concentration ratios of metabolite to parent drug predicted from the AUC data were 3.8 for the amide and 35.8 for the acid metabolite. The amide metabolite is known to have anticonvulsant properties and, until the relative contributions of metabolites and parent drug to the efficacy of cinromide are resolved, the monitoring of metabolites as well as parent drug is imperative.
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  • 40
    ISSN: 1432-1041
    Keywords: hyperthyroidism ; propranolol ; methimazole ; metoprolol ; atenolol ; kinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic profiles of oral methimazole 40mg, propranolol 80mg, metoprolol 100mg and atenolol 100mg were compared in hyperthyroid patients both during the hyper-and euthyroid states. For methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p〈0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.
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  • 41
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    European journal of clinical pharmacology 27 (1984), S. 233-236 
    ISSN: 1432-1041
    Keywords: glibenclamide ; acarbose ; kinetics ; alpha-glucosidase inhibitor ; blood glucose control ; plasma insulin ; Type 2 diabetes
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of glibenclamide 5 mg was administered to six Type 2 diabetics, randomly treated for 7 days either with acarbose (3×100 mg daily) or with placebo. The serum concentration of the drug was measured for 10 h. Peak concentrations, times-to-peak concentration, elimination half-lives and the extent of bioavailability of the drug were not significantly modified by acarbose. The combined administration of glibenclamide and acarbose resulted in a modest improvement in the blood glucose profile after breakfast and lunch, together with a significant diminution in plasma insulin. Thus, acarbose appears a useful additional treatment for Type 2 diabetics already receiving sulphonylurea derivatives.
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  • 42
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    European journal of clinical pharmacology 26 (1984), S. 521-530 
    ISSN: 1432-1041
    Keywords: chloroquine ; malaria ; rheumatoid disease ; kinetics ; major metabolite ; optimal dosage ; therapeutic regime ; monodesethylchloroquine ; bidesethylchloroquine
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics and disposition of chloroquine (CQ) and its metabolite monodesethylchloroquine (CQM) were investigated in 5 healthy volunteers after incremental (150–300–600 mg CQ base) single oral doses of CQ. The analytical method used (HPLC and fluorescence detection) is the most sensitive known method for CQ and CQM. Plasma and whole blood concentrations of CQ, CQM and a third metabolite, bidesethylchloroquine (CQMM), were determined. The kinetics of CQ was found to be unique. The best fit was obtained by a multicompartmental model. The biological half-life appeared to be between 30–60 days; the volume of distribution (Vd) was ∼ 800l/kg, and the clearance ∼ 11/h/kg when calculated from plasma data. The whole blood concentrations were ∼ 8–10 times higher than in plasma, and consequently the Vd and whole blood clearance were ∼ 10 times lower. The kinetics changed as the dose was increased. An indication of capacity-limited steps in CQ disposition was found, as the rate constants decreased even though the clearance remained the same. The intrinsic half-life of CQM was 1/4 of that of CQ, but was prolonged after the highest dose of CQ. The present knowledge of CQ kinetics could provide a basis for revision of current dosage regimens in malaria suppression and rheumatoid disease to ensure efficacious and safe therapy.
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  • 43
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    European journal of clinical pharmacology 27 (1984), S. 367-369 
    ISSN: 1432-1041
    Keywords: flurbiprofen ; syrup ; suppository ; kinetics ; children ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight subjects, aged 6–12 years and weighing 18.8–36.7 kg, received single doses of flurbiprofen 50 or 75 mg (corresponding to 1.4–2.7 mg/kg) as syrup and suppository in a Latin square design. Half-life (2.7–3.2 h), elimination constant (0.22–0.26 h−1), area under the plasma level curve (72.4–77.3 µg·h·ml−1) and time to reach the concentration peak (1–0.75 h) were similar after the syrup and suppository. Flurbiprofen showed equivalent bioavailability after oral and rectal administration and the same pharmacokinetic profile was confirmed in children as observed in adults.
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  • 44
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    European journal of clinical pharmacology 22 (1982), S. 39-45 
    ISSN: 1432-1041
    Keywords: furosemide ; neonates ; kinetics ; placental transfer ; intravenous therapy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of furosemide was evaluated in 12 newborns who received the drug transplacentally, and in 21 neonates who received it directly for therapeutic reasons. In the first group, the apparent plasma half-lives ranged from 96 to 6.8 h with a significant inverse relationship (p〈0.01) between the gestational age and the elimination rate. In two cases a clear effect on diuresis was also observed. In the neonates receiving the drug i.v. for therapeutic reasons, the elimination kinetics appeared to follow a two-compartment open model, with a significant difference in the therminal plasma half-life between premature (26.8±12.2 h) and full-term newborns (13.4±8.6 h). In this group no relationship was observed between elimination rate and either gestational or conceptional age. In the case of repeated administration, an increase in plasma clearance and reduction in t1/2 β was noticed.
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  • 45
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    European journal of clinical pharmacology 22 (1982), S. 435-439 
    ISSN: 1432-1041
    Keywords: azlocillin ; kinetics ; biliary excretion ; liver dysfunction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic of azlocillin was followed in five elderly patients after biliary surgery. Total clearance was 138.6±17.7 ml/min when 2.0 g was given as an i.v. bolus injection. The half-life of the β-phase averaged 110 min. The total clearance and the half-life of azlocillin were influenced by slight impairment of renal function (creatinine clearance 59.4±13.6 ml/min). In patients with normal liver function biliary excretion of the drug amounted to 5.3±2.8% of the dose (n=3) and the kinetics of biliary excretion were linear. In contrast, in two patients with impaired liver function biliary excretion was 0.2% and 0.5% of the dose, and kinetic analysis of biliary excretion rates revealed at least one zero order step in the excretion process. Renal excretion of the drug amounted to 45.0±17.7% of the dose, which means that 50% of the total clearance of azlocillin has to be accounted for by metabolic clearance.
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  • 46
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    European journal of clinical pharmacology 23 (1982), S. 529-533 
    ISSN: 1432-1041
    Keywords: beta-blocker ; bufuralol ; enantiomers ; kinetics ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of (+)-, (−)- and (±)-bufuralol were administered to a healthy volunteer to compare the disposition and metabolism of the individual isomers and the racemate. Plasma levels and area under plasma curve (AUC) of the active isomer, (−)-bufuralol, were higher than those of the (+)-isomer; plasma clearance was correspondingly lower. Intermediate values were found for the racemate. The elimination half-life of (−)-bufuralol was shorter than that of (+)-bufuralol, but similar to the racemate. Both isomers were cleared almost entirely by metabolism. The main metabolic pathway for (−)-bufuralol was aromatic hydroxylation, whereas the principal route for (+)-bufuralol was conjugation. Phenol metabolites in the systemic circulation were present mainly as conjugates. Both isomers also underwent aliphatic hydroxylation. This pathway was more favoured by the (+)-isomer, although plasma levels and AUC of the principal product, 2′-hydroxy-bufuralol, were almost identical for the two forms. Major differences in metabolic fate thus had relatively little effect on the disposition of pharmacologically active metabolites.
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    European journal of clinical pharmacology 24 (1983), S. 243-246 
    ISSN: 1432-1041
    Keywords: tolbutamide ; valproate ; intoxication ; activated charcoal ; inhibition of absorption ; sulphonylureas ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The claim that activated charcoal should be ineffective or even contraindicated in intoxication due to tolbutamide is based only on limited in vitro studies. To test the claim, the effect of activated charcoal 50 g on the absorption of tolbutamide and, as a reference, of sodium valproate, was studied in 6 healthy volunteers. Each volunteer swallowed tolbutamide 500 mg and sodium valproate 300 mg with 50 ml water 1 h after a light breakfast, and within 5 min they took in randomized order either a suspension of activated charcoal or water. The absorption of tolbutamide, calculated as the peak concentration and the area under the serum drug concentration-time curve during 0–48 h, was reduced by 90% by charcoal (p〈0.001). The absorption of valproate in these conditions was reduced on average by 65% (p〈0.01). In each subject charcoal had a greater effect on the absorption of tolbutamide than of valproate. According to these findings and preliminary in vitro studies on other sulphonylureas high doses of activated charcoal can be recommended for the preventing the absorption of sulphonylureas in acute intoxications. The poor aqueous solubility of these substances at the gastric pH probably delays their gastrointestinal absorption, so that they may be adsorbed on to charcoal even given several hours later.
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    European journal of clinical pharmacology 22 (1982), S. 27-32 
    ISSN: 1432-1041
    Keywords: sulfonylureas ; diabetes ; chlorpropamide ; glipizide ; C-peptide ; insulin ; blood glucose ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of sulfonylurea on the secretion, disposal and effect of insulin was studied in 9 Type 2 diabetics during 3 one-month courses of treatment with a) chlorpropamide (t1/2〉24 h) once daily, b) glipizide (t1/2=2–4 h) once daily, and c) glipizide in divided doses. Food intake by each patient was identical during each period. Blood concentrations of immunoreactive insulin (IRI) and C-peptide (radioimmunoassays), and of glucose (enzymatic assay), chlorpropamide (gas chromatography) and glipizide (high-pressure liquid chromatography) were determined before and after breakfast and lunch on the 4th day of each examination period. All comparisons were intraindividual. Despite the lunch-time dose of glipizide given during the divided dose treatment, once-daily administration of this drug led to higher drug concentrations not only after breakfast but also for the first few hours after lunch. Divided dosage, on the other hand, led to higher concentrations later. In contrast to once-daily dosage, continuous exposure to glipizide was found in most patients. Chlorpropamide gave the most continuous sulfonylurea exposure. The blood glucose levels were inversely related to the concurrent sulfonylurea concentrations; glucose levels after breakfast and lunch were lowest during once-daily glipizide, whereas the fasting level was lowest during chlorpropamide treatment. The IRI response to breakfast was 60%–70% higher during once-daily glipizide than during the other two treatments, but the C-peptide responses to breakfast were almost identical. Thus, the greater after-breakfast availability of peripheral insulin appeared to be due to an effect of glipizide on the extrapancreatic disposal of the hormone.
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  • 49
    ISSN: 1432-1041
    Keywords: digoxin ; verapamil ; digoxin-verapamil interaction ; kinetics ; plasma level ; renal clearance ; extra-renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single-dose investigations in healthy subjects have demonstrated substantial impairment of renal and extrarenal clearance of digoxin during coadministration of verapamil. A longitudinal study has been performed to assess the changes in digoxin disposition during long-term verapamil therapy. After one week of verapamil 240 mg/d mean plasma digoxin had risen from 0.21±0.01 ng/ml (SE) to 0.34±0.01 ng/ml (p〈0.01), and renal digoxin clearance had fallen from 197.57±17.37 ml/min to 128.20±10.33 ml/min (p〈0.001). These changes gradually subsided, and after six weeks, renal digoxin clearance had normalized and plasma digoxin had declined to 0.27±0.02 ng/ml (NS). The 24-h urinary recovery of digoxin increased from 46.46±3.23% before to 69.78±3.69% (p〈0.001) after six weeks of verapamil co-administration, and this elevation persisted throughout the study. The verapamil-induced suppression of renal digoxin elimination disappears over a few weeks of drug exposure, whereas the inhibition of the extrarenal clearance of digoxin seems to persist.
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    Plasma chemistry and plasma processing 1 (1981), S. 19-35 
    ISSN: 1572-8986
    Keywords: Decomposition of NH3 ; kinetics ; optical spectroscopy ; gas chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The plasma decomposition of NH3 has been studied as a function of the residence time, power input, and pressure. The process follows apparently zero-order kinetics, which can be interpreted on the basis of a kinetic mechanism involving as initial step the rupture of an N-H bond from vibro-rotationally excited modecules. Simultaneous spectroscopic observations of the emission light due to electronically excited NH2, NH, H, and N2 have been used to confirm the suggested mechanism and to show that NH2 and NH are successive intermediate species and that the final step of the decomposition process is the bimolecular recombination NH+NH→N2+H2.
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    Plasma chemistry and plasma processing 1 (1981), S. 233-245 
    ISSN: 1572-8986
    Keywords: Plasma ; kinetics ; polymerization ; propylene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract Flowing microwave plasma of propylene and propylene with argon was studied by mass spectrometry. Plasma composition was investigated as a function of external parameters such as pressure, argon/propylene ratio, and microwave-induced power. It was found that the propylene broke down to C2H2 and CH4, or reacted further with propylene. Two main products, leading to the determination of three main chain reactions for the polymerization of propylene by ion-molecule interactions, were observed, namely, C2H2 and CH4. These were the propylene, acetylene, and ethylene chain reactions. It was also found that the propylene disappeared in a pseudo-first-order reaction. Consequently an overall rate constant for the polymerization was determined (50 sec−1 at 1 torr pressure for propylene plasma). This constant is found to be linearly dependent upon the propylene percent concentration, and nonlinearly dependent upon plasma pressure.
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    Plasma chemistry and plasma processing 5 (1985), S. 293-316 
    ISSN: 1572-8986
    Keywords: Plasma chemistry ; halocarbon decomposition ; kinetics
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    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract For the case of weak feed gas decomposition, where the concentration of CCl4 exceeds those of decomposition and built-up products, the emission of CCl* is shown to originate from dissociative excitation of CCl4. With electron concentration measured independently, the kinetics of CCl4 decomposition has been extracted from the time dependence of the CCl* intensity. Supported by EPR determinations of radical concentrations in rapidly flowing CCl4 and CCl4/O2 afterglows, the primary decomposition reaction is shown to be the electron impact dissociation into CCl3 and Cl. Its rate constant (k 1=4×10−8 cm3s−1) indicates strongly that dissociative electron attachment is the main reaction channel at least at r.f. power densities just above the threshold of a self-maintaining discharge. At extremely low mean electron energies the emission of a continuum is observed, which is tentatively ascribed to the radiative CCl3-Cl recombination.
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    Plasma chemistry and plasma processing 6 (1986), S. 429-436 
    ISSN: 1572-8986
    Keywords: Plasma ; laser ; diagnostics ; free radicals ; kinetics
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    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The plasma of a pulse discharge (0.05 J/cm3) in methane at low pressure (200 Pa) is studied. The dynamics of formation and decay of C2(a3IIu, v″=0) is monitored using a stroboscopic laser absorption method. It was found that substantial amounts of C2, 1015 cm−3, arise with a 1-µs delay after the current pulse.
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    Plasma chemistry and plasma processing 8 (1988), S. 101-110 
    ISSN: 1572-8986
    Keywords: Plasma ; laser ; diagnostics ; hydrocarbons ; free radicals ; kinetics
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    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract The dynamics of the formation and decay of excited hydrogen during a pulse discharge in methane at a pressure of 200 Pa and energy density of 0.05 J/cm3 has been studied. The population of hydrogen in the n=2 state was monitored by the laser absorption method. The time constant of the decay of the excited hydrogen was measured to be 95±15 ns. The concentration of free electrons reached a maximum value of 7×1014 cm−3, and the time constant of their recombination was 220±50 ns. The formation of appreciable amounts of atomic hydrogen in the ground state during the discharge, H(n=1)〉1016 cm−3, was estimated on the basis of a kinetic model.
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  • 55
    ISSN: 1572-8986
    Keywords: Methane ; acetylene ; kinetics ; modeling
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    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Technology
    Notes: Abstract It is shown that it is basically possible to model plasma-chemical methane conversion using a kinetic concept regardless of the kind of plasma, i.e., the kind of activation. While the temporal plasma-chemical decomposition of methane is controlled by a first-order rate equation, the temporal product formation can be described by a set of first-order consecutive reactions. Prolonged portions of constant product concentrations in the temporal product formation curves were explained by the assumption of an equilibrium between forward and reverse reactions. The modeling revealed the special role of the re-formation of dissociated molecules.
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    Molecular and cellular biochemistry 86 (1989), S. 65-70 
    ISSN: 1573-4919
    Keywords: Hex A ; Hex B ; N-acetyl-glucosaminidases ; kinetics ; thermodynamic transitions ; ion-exchangers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic and thermodynamic properties of N-acetyl-β-D-glucosaminidase A (Hex A) and N-acetyl-β-D-D-glucosaminidase β (Hex B) from goat testes were investigated in free and bound (after binding them on ion-exchangers such as DEAE- or CM-cellulose respectively) forms. The optimum pH of free Hex A and Hex B was at 4.2 and 5.4, whereas the bound forms showed the optimum pH at 4.0 and 5.2 respectively. While apparent Km of free and bound Hex A (0.8 and 1.0 mM respectively) did not differ, the Km of Hex B increased when bound on CM-cellulose (Km of free Hex B = 0.96 mM versus bound Hex B = 1.6 mM). Though the free Hex A was more thermo-labile than the free Hex B, both isozymes, on insoluble matrices decayed at faster rates on heating. Activation analysis revealed that the energy of activation (E infa supo ) for transition state of free Hex B (81 Kcal deg−1 mole−1) did not differ from E infa supo of bound Hex B. On the other hand, E infa supo of free Hex A declined from 77.2 to 71.1 Kcal deg−1 mole−1 when heat transitions were carried out in free and bound state respectively. Thermodynamic analysis suggested a change in entropy of activation (ΔS*) of free Hex A and Hex B as 200 and 211 eu respectively. While ΔS* of Hex B did not change after heat transitions, ΔS* of Hex A was 182.5 eu.
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    Biochemical genetics 23 (1985), S. 859-876 
    ISSN: 1573-4927
    Keywords: allozyme ; Cnidaria ; cline ; isozyme ; kinetics ; Metridium senile ; phosphoglucomutase ; polymorphism ; variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The phosphoglucomutase (Pgm) locus from populations of the sea anemone Metridium senile has three alleles in natural populations from the northeastern coast of North America. Two of the alleles exhibit clinal variation north of Cape Cod, suggesting a possible association of allele frequency with environmental temperature. This clinal pattern is reproducible and stable over at least brief periods of time. The allozymes encoded by each of the six Pgm genotypes have been partially purified and characterized. The symmetrical pH optimum for V max is pH 7.5; the apparent K m (K m app ) of glucose-1-phosphate declines monotonically as the pH increases from 6.5 to 8.5. There are no pronounced differences in heat stabilities of PGM produced by various genotypes, nor are there significant differences in specific activities. There are no differences in the sensitivity of V max to temperature. K m app values are very low for all genotypes, ranging from about 2 to 12 µm, depending upon the temperature. K m app of glucose-1-phosphate declines as the temperature is raised for all genotypes, whether the pH is held constant or allowed to vary with the temperature. Under certain conditions, there are small significant differences among genotypes in K m app values, but there is no systematic pattern to these differences. The present data provide no biochemical explanation for the maintenance of the Pgm cline by selection for functional differences under different thermal regimes.
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    Biochemical genetics 19 (1981), S. 881-893 
    ISSN: 1573-4927
    Keywords: chicken kidney ; ornithine transcarbamylase ; Cochin Bantam ; White Leghorn ; genetics ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Comparisons were made of the renal ornithine transcarbamylase (OTC) activities within different groups of chickens including Japanese native breeds. OTC activities varied markedly within these groups. The Cochin Bantam breed and White Leghorn B line had an especially high activity, about 400 units/g of kidney, in contrast to two Japanese native breeds, Japanese Game (white variety) and Banshuu Gashiwa, and the California Gray breed, which showed a very low activity, the values being almost undetectable. In crossing experiments using the California Gray breed as a tester strain, Cochin Bantam OTC represents a simple autosomal incompletely dominant trait similar to the White Leghorn B line OTC. Kinetic studies using partially purified OTC preparations from the White Leghorn B line and Cochin Bantam breed revealed that both enzymes were identical for a variety of enzymic characteristics. In light of these results, the physiological significance of chick kidney OTC is discussed.
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    Oxidation of metals 17 (1982), S. 359-369 
    ISSN: 1573-4889
    Keywords: Oxidation ; microhardness ; oxide thickness ; kinetics ; oxygen partition
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Oxidation kinetics of Ti-1 wt. % Si and Ti-5 wt. % Si alloys in either pure oxygen or air under a pressure of 0.93 bar and in the temperature range of 1171–1473 K are reported. For the exposure period investigated (up to 12 h) both alloys oxidized slower than pure Ti. The amount of oxygen dissolved in the Ti-1 wt. % Si alloy has been calculated. X-ray diffraction analyses indicate that the oxide scale is mainly TiO 2 ,except for the Ti-5 wt. % Si alloy oxidized at 1473 K where some evidence of SiO 2 was obtained. Hardness profiles were taken across the Ti-1 wt. % Si alloy matrix.
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    Oxidation of metals 20 (1983), S. 37-65 
    ISSN: 1573-4889
    Keywords: Alloy oxidation ; cobalt-chromium-tungsten ; scale formation ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Oxidation rates in air at 1000–1250°C are reported for a series of Co-Cr-W alloys with 34–40 wt. % Cr and up to 10 wt. % W. Alloys with larger W contents exhibited slower oxidation rates and their parabolic rate constants agreed well with those for binary and ternary, Cr2O3 protected, Ni-base and Co-base alloys in the Co-Cr and Ni-Cr-W systems. The resulting scales were characterized by optical and scanning electron metallography, and electron microprobe analysis. The favorable effect of W additions to a Cr2O3-forming Co-Cr base alloy was the opposite of that reported for Ni-Cr-W alloys. The resupply of Cr to a Cr-depleted matrix beneath a protective CrO3 scale is achieved by the dissolution (denuding) of Cr-rich second phases in the Co-Cr-W alloys. Thus, the internal oxidation of Cr beneath the Cr2O3 scale is avoided for high W alloys. No catastrophic failure by liquid phase formation was observed for high-W alloys oxidized 20 hr at 1250°C.
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    Oxidation of metals 26 (1986), S. 139-155 
    ISSN: 1573-4889
    Keywords: oxidation ; Co-Cr-Ti alloys ; kinetics ; scale morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Cobalt-based alloys containing 3,5,10,15, and 20% Cr with 1 and 3% Ti were oxidized at 1000°C in slowly flowing oxygen gas. In general, titanium additions decreased the oxidation rate with the most pronounced effect being observed at the 10% Cr level. Titanium accelerated the formation of Cr2O3 layers at the metal-oxide interface. Faceted CrxTiyOz spinel particles were found at the metal-oxide interface which varied in composition according to microprobe results. There was no evidence of spalling on the Co-Cr-Ti alloys studied in contrast to the severe spalling normally encountered in Ni-Cr-Ti alloys. Distinct morphological differences existed on the outer CoO layer of the 1% Ti alloys in comparison to the O and 3% Ti alloys.
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    Oxidation of metals 26 (1986), S. 417-430 
    ISSN: 1573-4889
    Keywords: cyclic carburization-oxidation ; carbides ; austenite ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Several austenitic heat-resistant steels were exposed to alternating periods of carburization at 1273 K [a c= 1,po2〈10−28 atm] and oxidation at 973°K [a c≈ O,po2 = 0.2 atm]. In all cases the depth of internal carbide precipitation increased with cumulative carburization time. It was found that the carburization rates of high nickel content alloys were unaffected by intermittent oxidation cycles, whereas the low nickel, high iron content alloys experienced a reduction in carburization rate subsequent to oxidation treatment. The latter group of alloys formed external scales of chromium-rich M7C3 which were shown by sulfur tracing experiments to be gas permeable. It was concluded, therefore, that oxidation of these materials led to blockage of cracks and holes in the scales, thereby decreasing the surface carbon activity and hence the carburization rate. High nickel, low iron alloys formed external scales of chromium-rich M7C3 covered by Cr3C2. These scales were shown to have very low gas permeabilities. It was concluded that the carbon activity at the surface of these alloys was controlled by scale-alloy equilibration, and was therefore not affected by brief periods of oxidation. The pattern of carbide scale formation is qualitatively consistent with the thermodynamics of the Fe-Cr-C system.
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    Molecular and cellular biochemistry 64 (1984), S. 45-50 
    ISSN: 1573-4919
    Keywords: cardiac muscle ; kinetics ; pyruvate kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The mechanism of activation by inorganic phosphate and ATP of cardiac muscle pyruvate kinase was studied with the aid of steady-state kinetics. The enzyme was purified to homogeneity to a final specific activity of 400 units/ mg (phosphate buffer, pH 7.6, 25 °C). At pH 7.6 the enzyme displays Michaelis-Menten kinetics with respect to both its substrates, phosphoenolpyruvate and ADP. Substrate kinetic constants are: app.Km(phosphoenolpyruvate) −0.04 mM, app.Km(ADP) =0.22 mM. Under the conditions used in the standard assay the specific activity is greatly enhanced by inorganic phosphate (50 mM) or ATP (2.5 mM). Each of these modifiers, acting separately, increases the Vmax without seriously affecting Michaelis constants and Hill coefficients. In the presence of both Pi and ATP, only a decrease in Vmax was observed. The kinetics of activation by inorganic phosphate of pyruvate kinase was examined. Studying the effect of varying concentrations of Pi on the initial rate we obtained a hyperbolic saturation curve with the app. Km(Pi) = 20 mM and Vmax = 167 units/ mg. The evidence is presented that inorganic phosphate is a substrate for a side reaction catalyzed by cardiac pyruvate kinase. It is shown that in the presence of pyruvate, inorganic phosphate and ATP in the assay system, Pi is incorporated into acid-labile products of this reaction, inorganic pyrophosphate being one of them. These findings indicate the existence of an alternative reaction catalyzed by pyruvate kinase by which energy may be stored in the form of inorganic pyrophosphate.
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    Molecular and cellular biochemistry 86 (1989), S. 171-179 
    ISSN: 1573-4919
    Keywords: porcine glucokinase ; purification ; kinetics ; sulfhydryl-related states
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Porcine hepatic glucokinase (ATP: D-hexose 6-phosphotransferase EC 2.7.1.1) has been purified by a modification of the procedure for its purification from rats. However, difficulties were encountered with endogenous proteases and the reliability of a source for porcine livers. The molecular weight has been determined to be 60 400 ± 1400 by sodium dodecyl sulfate, polyacrylamide gel electrophoresis. The enzyme has been characterized kinetically. The parameter values, S 0.5 (glucose) and Hill coefficient (nH) are 2.4 mM and 1.9 respectively under sulfhydryl-reducing conditions. The enzyme undergoes the two sulfhydryl-related decays of its activity previously observed in the enzyme isolated from rat (Tippett PS, Neet KE: Arch Biochem Biophys 222:285–298, 1983). The enzyme is inhibited by palmitoyl-CoA, K i (apparent) = 1.0 µM, nH = 1.8; this concentration of inhibitor is significantly below its critical micelle concentration. Physically and kinetically glucokinase isolated from pig is similar to the enzyme isolated from rat. The porcine system provides a second source for isolation and further characterization of this important and unusual enzyme.
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    Oxidation of metals 14 (1980), S. 85-108 
    ISSN: 1573-4889
    Keywords: alloy oxidation ; nickel-chromium-tungsten ; scale formation ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The oxidation behavior in air at 1000–1250°C of four Ni-Cr-W alloys containing sufficient chromium content (∼22 at. % Cr) for protective Cr2O3 formation in a binary Ni-Cr alloy is reported. Generally for alloys high in W (10 and 16 at.% W), the rejection of tungsten into the alloy beneath the scale introduced a steep Cr concentration gradient and slower Cr diffusion such that continuous precipitation of Cr2O3 internal oxides prevented the formation of a Cr2O3 protective scale. The alloy most dilute in W (1.6 at. % W) formed a protective scale at short times with little outer NiO scale, but scale fractures led to internal oxidation and rapid nonprotective kinetics. After an initially rapid oxidation increment to form NiO, the 3 at.% Walloy formed a protective Cr2O3 scale with about the same steady-state parabolic kinetics as a binary Ni-30Cr alloy. The effect of ternary Wadditions on the development of Cr2O3 scales on Ni-Cr-W alloys is considered as a ternary analog to Wagner's description of the oxidation of Cu-Pt or Cu-Pd alloys.
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    ISSN: 1573-4889
    Keywords: titanium ; oxidation ; oxide scale ; solid state diffusion ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The oxidation behavior of titanium was studied over the temperature range of 600 to 800°C in a pure oxygen atmosphere. A parabolic kinetics period is made up of a succession of short parts whose weight gain is nearly constant and whose beginning is characterized by an alteration of the oxidation rate. The kinetics curve is closely correlated with the morphology of the oxide scale which contains several layers separated by short cracks. These cracks decrease the diffusional flows of oxygen and titanium and alter the oxidation rate. A parabolic-linear kinetics transition is attributed to the formation of a continuous crack between the oxide scale and the matrix. The oxide scale then forms a porous barrier of constant thickness which induces a linear rate law due to the steady-state oxygen diffusion. Titanium cannot diffuse across the continuous crack. During the linear kinetics period several layers of constant thickness, separated by a continuous crack, spread out.
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    Oxidation of metals 15 (1981), S. 437-445 
    ISSN: 1573-4889
    Keywords: chromium nitriding ; kinetics ; parabolic rate constant ; diffusivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Parabolic rate constants of the reaction of chromium with nitrogen gas under oxygen-free conditions have been determined over a range of temperature (1000–1250°C) and nitrogen pressure (0.265–101.33 kPa). The growth rate of the subnitride was measured by a thermogravimetric technique using a single specimen. Wagner's oxidation theory is used to calculate the self-diffusivity and intrinsic diffusivity of nitrogen in the subnitride from a theoretical analysis of the parabolic rate constant. The calculated diffusivities varied with the composition of the subnitride, having minimum values at intermediate compositions of the nonstoichiometric chromium nitride “Cr2N.”
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    Oxidation of metals 16 (1981), S. 175-191 
    ISSN: 1573-4889
    Keywords: Sulfidation ; Fe-Cr alloy ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The scaling of an Fe-20Cr alloy has been studied in H2-H2O-H2S mixtures between 973 and 1223 K. According to a simplified phase diagram, Cr2O3 and FeS should be the thermodynamically stable compounds in the gas mixtures chosen. The reaction followed a mixed rate law between linear and parabolic, indicating that the reaction rate at the scale-gas interface was comparable with the diffusion rate in the scale. At a constant H2/H2S ratio the scaling rate initially decreased slightly with increasing water-vapor pressure. A further increase of the water-vapor pressure resulted in localized sulfide formation, while the other parts of the surface were covered with a Cr2O3 film. Only Cr2O3 formed above a critical water-vapor content. Three zones could be distinguished when a sulfide scale is formed. The outer zone consisted of practically pure FeS; the intermediate zone was a solid solution of (Fe,Cr)S, partially decomposed to FeCr2S4 and metal during cooling; and the inner zone contained small Cr2O3 inclusions in an (Fe,Cr)S matrix.
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    Oxidation of metals 21 (1984), S. 21-37 
    ISSN: 1573-4889
    Keywords: internal oxidation ; kinetics ; alloy ; silver ; precipitation ; coalescence ; ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The internal oxidation mechanism in silver alloys was studied by residual resistivity, gravimetric, and calorimetric measurements, and by transmission electron microscopy. If the flux, of oxygen atoms is very large with respect to the oxide formation, the mechanism of internal oxidation includes two stages. The first one is the fixation of oxygen in the form of oxidized elementary species, including only one solute atom. These species are stable and keep a certain mobility. The second one is the coalescence process of these elementary species with the formation of the first clusters. When the flux of oxygen atoms is slowed down, the oxide formation mechanisms are more complicated. The initially formed species can include more than one solute atom because of their diffusion. The two stages are not separate.
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  • 70
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    Oxidation of metals 21 (1984), S. 103-118 
    ISSN: 1573-4889
    Keywords: duplex steels ; sulfidation ; kinetics ; transport processes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Two austeno-ferritic stainless steels were sulfidized at temperatures of 783, 873, and 963 K under sulfur pressures in the range 4×10−12 to 3×10−5 atm. In all cases a triplex scale developed, consisting of an outermost layer of (Fe, Cr)1−xS, an intermediate layer of FeCr2S4, and an innermost layer of porous (Cr, Fe)1−xS containing particles of Mo2S3. Parabolic kinetics were observed except at the lowest temperature where one of the steels reacted according to irregular kinetics. The Mo2S3 particles in the innermost layer acted as inert markers, imaging the former positions of the steels' ferrite phase in which Mo is enriched. The lamellar microstructure of the steel was thus reproduced in the innermost sulfide layer. The positions of the Mo2S3 particles together with the porosity of the inner layer are taken to imply inward sulfur transport through this layer and outward metal transport through all three layers.
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  • 71
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    Oxidation of metals 25 (1986), S. 1-28 
    ISSN: 1573-4889
    Keywords: sulfidation ; yttrium ; duplex-sulfide scales ; lamellar sulfides ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The sulfidation of Ni-10Cr-5Al, Ni-20Cr-5Al, and Ni-50Cr-5Al, and of the same alloys containing 1% Y, was studied in 0.1 atm sulfur vapor at 700°C. The sulfidation process followed linear kinetics for all the alloys except Ni-50Cr-5Al-1Y, and possibly Ni-50Cr-5Al, which followed the parabolic law. The reaction rates decreased with increasing chromium content in alloys without yttrium, and the addition of yttrium reduced the rates by at least a factor of two for the alloys containing 10 and 20% Cr and by an order of magnitude for Ni-50Cr-5Al. Alloys containing 10 and 20% Cr (with and without yttrium) formed duplex scales consisting of an outer layer of NiS1.03 and an inner lamellar layer of a very fine mixture of Cr2S3 and A12O3 in a matrix of NiS1.03. The two alloys containing 50% Cr formed only a compact layer of Cr2S3, which was brittle and spalled during cooling. The lamellae in the duplex scales were parallel to the specimen surface and bent around corners. The lamellae were thicker than those on Ni-Al binary alloys. The lamellae were also thicker in scales on the 20% Cr alloy than on the 10% Cr alloy. The presence of yttrium refined the lamellae and increased the lamellae density near the scale/metal interface in the 10% alloy, but in the 20% Cr alloy the lammellae were thicker and more closely spaced. Platinum markers were found in the inner portion of the exterior NiS1.03 layer close to the lamellar zone. A counter-current diffusion mechanism is proposed involving outward cation diffusion and inward sulfur diffusion, although diffusion was not rate controlling for alloys containing 10 and 20% Cr. Auger analysis of scales formed on Ni-50Cr-1Y showed an even distribution of yttrium throughout the layer of Cr2S3, suggesting that some yttrium dissolved in the sulfide. The reduced sulfidation rate of samples containing yttrium is explained by the possible dissolution of yttrium as a donor. The presence of Y4+ would then decrease the concentration of interstitial chromium ions in the N-type layer of Cr2S3, which would decrease the reaction rate.
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  • 72
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    Oxidation of metals 23 (1985), S. 207-235 
    ISSN: 1573-4889
    Keywords: stainless steel ; duplex oxide ; kinetics ; growth rates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The nature of the first-formed oxide on 20% Cr/25% Ni/Nb stabilized steel during exposure to CO2 at high and low temperatures has been determined by surface analytical techniques. These results together with a consideration of gas/solid interactions show that the oxide produced may be determined by kinetics or thermodynamic factors, and a diagram is presented to show that rhombohedral Cr2O3 or spinel may be the oxide first formed. Under most standard conditions, a mixed spinel oxide is formed initially, and the subsequent growth of a duplex oxide is analyzed in terms of a solid-state reaction in which the spinel oxide is reduced to Cr2O3 at the metal/oxide interface. Diffusion control of growth by either spinel or Cr2O3 is incorporated in new equations describing the kinetics of oxidation, and weight-gain predictions are tested against experimental observations.
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  • 73
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    Oxidation of metals 32 (1989), S. 225-240 
    ISSN: 1573-4889
    Keywords: Hot corrosion ; nickel ; TGA ; kinetics ; mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The accelerated oxidation of pure nickel in the presence of a molten carbonate mixture has been studied in O2 and CO2-containing atmospheres. The oxidation rate of nickel with carbonate coatings was at least four orders of magnitude faster than that without salt coatings. The extent of oxidation, in terms of unit area weight gain, depended on both the amount of carbonate mixture coatings and the gas atmosphere. The unit area weight gain due to oxidation increased with increasing amounts of salt coatings up to a certain value. These observations suggest that the termination of nickel oxidation results from the exhaustion of either the salt coatings or metallic nickel. Porous and particulate oxide products were observed from scanning electron microscopic (SEM) examinations. The energy-dispersive analysis of x-rays (EDAX) shows that no salt remains on the specimen surface after the oxidation experiment.
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  • 74
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    Molecular and cellular biochemistry 76 (1987), S. 45-54 
    ISSN: 1573-4919
    Keywords: DNA methyltransferase ; hemimethylated DNA ; kinetics ; affinity chromatography ; (rat liver)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract DNA substrate analogs were constructed from poly(dC-dG), M13, and XP12 DNA which do not contain a mixture of types of methylation sites. These were used to distinguish different kinetic mechanisms for maintenance and de novo methylation using a highly purified rat liver DNA (cytosine-5)-methyltransferase (DMase−) preparation. De novo methylation on single (ss) and double-stranded (ds) DNA was found to obey Michaelis-Menten kinetics while methylation of hemimethylated sites showed differences depending on size of the hemimethylated region. On long stretches analogous to maintenance methylation of newly replicated DNA, saturation could not be achieved and the kinetics showed non-ideal positive cooperative kinetics, while short stretches showed non-Michaelis-Menten kinetics and rapid saturation. Two types of DMase-DNA complexes could be distinguished by means of affinity chromatography on DNA-agarose matrices and in preincubation assays. The later complex, which is engaged in methyl group turnover, exhibited enhanced stability. The competitiveness of variously configured DNAs was found to parallel the stability of complex formation, e.g., ss, hemi- and ds DNA, respectively. In studies utilizing 5-bromodeoxyuridine, the thymine analog left the basic reaction mechanisms unchanged but increased the km and S0.5 while reducing the velocity of these reactions.
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  • 75
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    Oxidation of metals 28 (1987), S. 237-258 
    ISSN: 1573-4889
    Keywords: Steel oxidation ; duplex scale ; steam ; activation energy ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The kinetics of the oxidation of ferrous alloys in steam (10–60 kPa) at 450–550°C have been studied by measuring both the rate of hydrogen emission and the amount of metal oxidized. Excellent agreement has been found between the amount of metal oxidized calculated from both the total mass of hydrogen produced in the reaction and the thickness of the oxide layer formed; rate constants calculated from the rate of hydrogen emission, the mass of hydrogen produced as the reaction proceeds, and the oxide formed agree within experimental error. The rate of oxidation of a 9%Cr-1%Mo alloy at 501°C was found to be independent of the partial pressure of the steam. For this alloy, the activation energy agreed with literature values obtained at higher temperatures and pressures. The effect of the chromium and silicon content on the oxidation rates is compared. The rate constants are compared with theoretical calculations, assuming that the rate is determined by diffusion of iron in the magnetite lattice. For the 9%Cr-1%Mo alloy, the parabolic rate constant and activation energy are in excellent agreement with values calculated using Wagner's theory. The experimental rate constants are greater for the alloys containing smaller amounts of chromium; diffusion of iron along magnetite grain boundaries may be the dominant mechanism.
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  • 76
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    Oxidation of metals 14 (1980), S. 147-165 
    ISSN: 1573-4889
    Keywords: oxidation in air or oxygen ; kinetics ; oxide identification ; oxygen diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The oxidation kinetics of Ti-4.32 wt.% Nb (2.27 at.%) alloy in either air or oxygen under 1 bar pressure have been investigated in the temperature range of 1255–1471 K. For oxidation in oxygen the kinetics follow consecutively decreasing parabolic rate laws. The kinetics become nonparabolic after prolonged oxidation in air. X-ray data reveal the presence of TiO2 (rutile) as the main oxide. The presence of Ti2O, δ-TiN, and ɛ-TiN is found on the metal surface after oxidation in air. Microhardness and electron microprobe measurements are used to determine Ti, Nb, O, and N profiles across the oxidized alloy. The oxygen diffusion coefficient in the alloy can be expressed byD=65.6 exp(−234.3/RT) with the activation energy in kilojoules per mole. The oxidation behavior of the alloy is explained.
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  • 77
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    Keywords: oxidation ; titanium ; Ti-Ni alloy ; Ti-Cu alloy ; kinetics ; oxide scale ; solid-state diffusion
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The kinetics and morphologic oxidation properties of titanium, Ti-1.5Ni and Ti-2.5Cu were compared. Titanium and Ti-1.5Ni have a similar behavior, concerning the kinetics and the oxide micro structure. Copper additions decrease the oxidation rate of titanium. The oxide scales formed on Ti-Cu are thinner and less cracked than those obtained on Ti or Ti-1.5Ni. Copper is found in the oxide scale of Ti-Cu, whereas nickel is not found in the oxide scale of Ti-Ni. The oxidation of titanium and its alloys is controlled chiefly by diffusional phenomena in the oxide scale. Thus the alterations of the oxide scale structure and the slower oxidation rate of Ti-2.5Cu can be attributed to the copper which diffuses towards the gas-oxide interface.
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    Oxidation of metals 16 (1981), S. 107-131 
    ISSN: 1573-4889
    Keywords: Oxidation ; iron ; kinetics ; sulfur ; surface analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The growth of thin (0–200 Å) oxide films on iron at 200 and 300 °C has been studied as a function of time and oxygen partial pressure using proton-induced X-ray emission (PIXE) and Auger electron spectroscopy (AES). Oxidation was found to be initially retarded by sulfur which had segregated onto the iron surfaces during preoxidation annealing, but only if the iron surface contained the maximum or near-maximum sulfur coverage (ca. one-half monolayer). During and immediately following the oxygen-sulfur interaction, oxide buildup appeared to be limited by a surface reaction (adsorption, ionization, or dissociation). For most of the oxidation period, pressure-dependent logarithmic oxide growth was observed at 200°C, and pressure-independent parabolic oxide growth at 300°C. Interpretation of the data indicated that oxide growth at 200°C may be limited by quantum mechanical tunneling of electronic species through the previously formed oxide film, and oxide growth at 300°C may be limited by ionic diffusion through the previously formed oxide film. Comparison of AES and PIXE data indicated that the oxide films formed at 200°C were uniform in thickness over the surface of the metal, whereas films formed at 300°C had relatively thin areas where sulfur had remained.
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    Oxidation of metals 17 (1982), S. 43-54 
    ISSN: 1573-4889
    Keywords: Coatings ; oxidation ; titanium silicide ; kinetics
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Coatings of Ti 5Si3 on titanium have been prepared by means of decomposition of silane SiH4 on heated titanium ribbons. Oxidation of the coated titanium specimens was much slower than that of the noncoated ones. Gravimetric and morphological experiments allowed to propose a mechanism describing the oxidation process.
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  • 80
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    Oxidation of metals 22 (1984), S. 45-57 
    ISSN: 1573-4889
    Keywords: Ni-Cr-Mo alloys ; sulfidation ; scale structures ; kinetics
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The effect of molybdenum additions 5, 10, 15, and 20 wt. %, on the sulfidation behavior of Ni-20Cr, and the effect of chromium additions, 5, 10, 15, and 20 wt.%, on the sulfidation of Ni-20Mo were studied in pure sulfur vapor at 700°C. In general, the alloys followed a linear or near-linear rate law, the sulfidation rate of Ni-20Mo being slightly less than that of Ni-20Cr. The alloys having the lowest ternary addition, e.g., Ni-Cr-5Mo and Ni-20Mo-5Cr. exhibited the most rapid reaction rates. The highest alloying additions of 20 wt.% had no appreciable benefit on reaction rates. Scale structures were complex but generally consisted of several layers. The outer layer was always NiS1.03, although both binaries formed Ni3S2 within the NiS1.03. An inner layer of Cr3S4 existed in which there was considerable dissolved molybdenum. A thin, intermediate layer of Cr2S3 generally formed between the Cr3S4 and the outer nickel sulfide. An innermost layer of MoS2 formed on all alloys containing more than 10 wt. % Mo, and a second phase of Mo2S3 formed within the MoS2 on Ni-20Mo. Although the scales changed with alloy composition, no significant changes in reaction rate were observed. Notable differences in both scale structure and reaction kinetics between this study and previous studies were apparent. The differences and possible reaction mechanisms are discussed.
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  • 81
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    Keywords: Ni-base alloy IN 617 ; reactor helium ; oxidation ; carburization ; decarburization ; kinetics ; mechanisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Application of the technical nickel-base alloy IN 617 in the primary circuit of the high-temperature gas-cooled reactor is limited essentially by the chemical reactions with the impurities (CO, CO2, H2, CH4, H2O) in the helium coolant. The interactions of the alloy with the reactive impurities in different helium-base gases were investigated by thermogravimetry in a gas-tight microbalance and by simultaneous measurement of the changes in gas composition by a continuous sensitive mass spectrometric analysis. The results demonstrate that the set of six reaction equations deduced in part 1 can be applied to describe the corrosion of the alloy. The occurrence of the various reactions is determined essentially by temperature. For the case of a standardized helium gas (HHT-He), three temperature regions can be distinguished. Below a critical temperature (about 1105 K), the presence of CO can cause simultaneous oxidation and carburization. Above this temperature, this reaction does not reverse itself. Rather, oxidation by CO2 and H2O takes place that shows, after a transient period, the same kinetics observed in undiluted oxygen-containing gases. At temperatures above about 1205 K, decarburization of the alloy accompanied by the production of CO takes place, leading to severe destruction of the carbide microstructure and, therefore, limiting the applicability of the material.
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    Oxidation of metals 30 (1988), S. 185-200 
    ISSN: 1573-4889
    Keywords: austenitic steels ; oxidation resistance ; protective αA12O3 film ; kinetics
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The cyclical oxidation behavior of an austenitic stainless steel (24% Ni, 10% Cr, 5% Al, and balance Fe) has been evaluated in the temperature range 800–1300°C. The effects of trace elements such as S, Y, Zr, and Ti on the oxidation of the austenitic stainless steel have also been evaluated. The results indicate that Fe-Ni-Cr-Al stainless steels exhibit superior oxidation resistance up to 1300°C due to the formation of a very adherent and thin film of α-Al2O3.
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  • 83
    ISSN: 1573-4927
    Keywords: alcohol dehydrogenase ; inbred mouse strains ; enzyme structure ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Alcohol dehydrogenase activity in mouse liver homogenate-supernatants is 1.7 times greater in the C57BL/10 strain than in the BALB/c strain, regardless of whether activity is expressed in units per gram liver, total liver, or milligram DNA. The K m values for ethanol and NAD+, approximately 0.4 and 0.03mm, respectively, of enzyme purified from both strains are similar. Moreover, the K i for NADH, 1 µm, the pH optimum for ethanol oxidation, 10.5, and the V max for ethanol oxidation, 160 min−1, for ADH from the C57BL/10 and BALB/c strains are similar. Therefore, the difference in ADH activity in the two strains cannot be due to differences in the catalytic properties of the enzyme. The electrophoretic and isoelectric focusing patterns and two-dimensional tryptic peptide maps of the purified enzyme from both strains are identical. Thus the amino acid sequences of enzyme from C57BL/10 and BALB/c mice must also be identical or very similar. The difference in ADH activity in the two strains is most likely the result of genetic differences in the content of ADH protein in liver.
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    The protein journal 8 (1989), S. 529-548 
    ISSN: 1573-4943
    Keywords: carmin ; association-dissociation ; denaturation ; reaggregation ; kinetics ; reversibility ; hydrophobic interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of a decrease inpH on the structural integrity of carmin has been monitored by a variety of biophysical techniques. The protein undergoes initial dissociation up topH 3.5–4.0 without any significant denaturation. Below thispH the process of dissociation and denaturation appears to be simultaneous. Further, in thepH range of 2.5–1.6 the protein reassociates to probably a different polymer resulting from possibly, an entropically driven hydrophobic interaction. The process of dissociation appears to be reversible to a large extent. The process of denaturation appears to be governed by the kinetic path that the denatured protein molecule follows either by a sudden decrease inpH or through a gradual decrease inpH. These results are interpreted while keeping in view the oligomeric and globular structure of carmin at neutralpH. The results would help in understanding of structure-function relationship of the protein and its role in hydrogen ion bindingin vivo.
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  • 85
    ISSN: 1573-4943
    Keywords: lactate dehydrogenase isoenzymes ; lactate-to-pyruvate reaction ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In order to evaluate the functional differences that may exist in human lactate dehydrogenase (LDH) isoenzymes widely used for clinical examination the kinetic and thermodynamic properties of the lactate to pyruvate reaction that they catalize were examined. Small but significant differences in the kinetic properties of the three isoenzymes were observed. The difference in the rate constants might affect the activity measurement of the individual isoenzyme as the initial velocity for the L-P reaction catalyzed will not be the same for an equal amount of enzyme. Equilibrium constants for the overall reaction in the presence and absence of pyruvate have been determined. On the basis of transition-state theory, the standard enthalpy and free-energy changes for formation of ternary activated complex were positive, while the standard entropy change was negative. Although the standard free-energy change was the same for activation by the three isoenzymes, the enthalpy and entropy changes for the LDH-3-catalyzed reaction were different from the respective values for others. A large positive value for the free-energy change and a negative value for the entropy change indicated unfavorable production of the activated complex (K infeq. sup╪ =1.89×10-16). The enzyme appears to stabilize and retain the activated complex until it dissociates into the products.
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    The journal of membrane biology 69 (1982), S. 35-40 
    ISSN: 1432-1424
    Keywords: axon ; hydrostatic pressure ; K currents ; kinetics ; activation volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The effect of pressure upon the delayed, K, voltage-clamp currents of giant axons from the squidLoligo vulgaris was studied in axons treated with 300nm TTX to block the early, Na, currents. The effect of TTX remained unaltered by pressure. The major change produced by pressures up to 62 MPa is a slowing down of the rising phase of the K currents by a time scaling factor which depends on pressure according to an apparent activation volume, ΔV∓, of 31 cm3/mole at 15°C; ΔV∓ increased to about 42 cm3/mole at 5°C. Pressure slightly increased the magnitude, but did not produce any obvious major change in the voltage dependence, of the steady-state K conductance estimated from the current jump at the end of step depolarizations of small amplitude (to membrane potentials,E, ≦20 mV) and relatively short duration. At higher depolarizations, pressure produced a more substantial increase of the late membrane conductance, associated with an apparent enhancement of a slow component of the K conductance which could not be described within the framework of the Hodgkin-Huxley (HH)n 4 kinetic scheme. The apparent ΔV∓ values that characterize the pressure dependence of the early component of the K conductance are very close to those that describe the effect of pressure on Na activation kinetics, and it is conceivable that they are related to activation volumes involved in the isomerization of the normal K channels. The enhancement of the slow component of membrane conductance by pressure implies either a large increase in the conductance of the ionic channels that are responsible for it or a strong relative hastening of their turn-on kinetics.
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    The journal of membrane biology 69 (1982), S. 23-34 
    ISSN: 1432-1424
    Keywords: axon ; hydrostatic pressure ; Na currents ; kinetics ; temperature ; activation volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The effects of hydrostatic pressures up to 62 MPa upon the voltage-clamp currents of intact squid giant axons were measured using mineral oil as the pressure transmitting medium. The membrane resistance and capacitance were not appreciably affected over the whole range of pressures explored. The predominant effect of pressure is to slow the overall kinetics of the voltage-clamp currents. Both the early (Na) currents and the delayed (K) ones were slowed down by approximately the same time scale factor, which was in the range of 2 to 3 when pressure was increased from atmospheric to 62 MPa. Finer details of the effects, most evident at moderate depolarizations, are: the apparent initial delay in the turn-on of Na currents is increased by pressureless than is the phase of steepest time variation, and the later decay is slowedmore than is the rising phase. The initial time course of the currents at high pressures can be made to overlap with that at normal pressure by a constant time compression factor, Θm, together with a small, voltage-dependent delay. In a given axon, Θm was fairly independent of voltage, and it increased exponentially with pressure according to an apparent activation volume, ΔV∓, ranging between 32 and 40 cm3/mole. ΔV∓ tended to decrease with increasing temperature. Contrary to what is observed for moderate or large depolarizations, the kinetics of Na inactivation produced by conditioning prepulses of −50 or −60 mV was little affected over the whole range of pressures explored. Inferences about the pressure dependence of the steady-state Na activation were made from the comparison of the plots of early peak currents,I p, versus membrane potential,E. The Na reversal potential,E Na, and the slope of the plots nearE Na did not change significantly with pressure, but the peak Na conductancevs. E relationship was shifted by about +9 mV upon increasing pressure to 62 MPa. Steady-state Na inactivation,h ∞, was slightly affected by pressure. At 62 MPa the midpoint potential of theh ∞ (E) curve,E h, was shifted negatively by about 4 mV, while the slope atE h decreased by about 38%. Under the tentative assumption that pressure directly affects the gating of Na channels, the Na activation data follows a simple Hodgkin-Huxley scheme if the opening of anm gate involves an activation volume of about 58 Å3 and a net volume increase of about 26 Å3. However, a self-consistent description of the totality of the effects of pressure on Na inactivation cannot be obtained within a similar simple context.
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    The journal of membrane biology 74 (1983), S. 85-94 
    ISSN: 1432-1424
    Keywords: sodium ; lithium ; chloride ; pH ; transport ; kinetics ; ion permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Na+, Li+, K+, Rb+, Br−, Cl− and SO 4 2− transport were studied in brush border membrane vesicles isolated from rabbit jejunum., Li+ uptakes were measured by flameless atomic absorption spectroscopy, and all others were measured using isotopic flux and liquid scintillation counting. All uptakes were performed with a rapid filtration procedure. A method is presented for separating various components of ion uptake: 1) passive diffusion, 2) mediated transport and 3) binding. It was concluded that a Na+/H+ exchange mechanism exists in the jejunal brush border. The exchanger was inhibited with 300 μm amiloride or harmaline. The kinetic parameters for sodium transport by this mechanism depend on the pH of the intravesicular solution. The application of a pH gradient (pHin=5.5, pHout=7.5) causes an increase inJ max (50 to 125 pmol/mg protein·sec) with no change inK t (≈4.5mm). Competition experiments show that other monovalent cations, e.g. Li+ and NH 4 + , share the Na+/H+ exchanger. This was confirmed with direct measurements of Li+ uptakes. Saturable uptake mechanisms were also observed for K+, Rb+ and SO 4 2− , but not for Br−. TheJ max for K+ and Rb+ are similar to theJ max for Na+, suggesting that they may share a transporter. The SO 4 2− system appears to be a Na+/SO 4 2− cotransport system. There does not appear to be either a Cl−/OH− transport mechanism of the type observed in ileum or a specific Na+/Cl− symporter.
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    The journal of membrane biology 74 (1983), S. 175-182 
    ISSN: 1432-1424
    Keywords: kinetics ; transport inhibition ; noncompetitive ; competitive ; inhibition mechanism ; carrier model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A new analysis of the conventional carrier model shows that noncompetitive inhibitors can give rise to either competitive, noncompetitive or uncompetitive kinetics; the true mechanism and also the relative affinity of the inhibitor on each surface of the membrane can be decided from the patterns of inhibition observed in different transport experiments. The priciples governing the kinetics of inhibition apply to both reversible and irreversible inhibitors, for in either case the substrate may increase or decrease inhibition or be without effect. Ambiguity arises if the noncompetitive inhibitor acts on only one side of the membrane and if the substrate, in the course of being transported, alters the steady-state distribution of the carrier between inner and outer forms. In facilitated transport systems only equilibrium exchange should give rise to noncompetitive kinetics, whatever the location of the inhibitor. In active systems even the interpretation of exchange in the final steadystate is complicated if the energy-coupling mechanism produces a large displacement in the distribution of the free carrier or the substrate complex: the inhibition could be competitive or uncompetitive, depending on the location of the inhibitor. The actual mechanism is revealed in the uncoupled system.
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    The journal of membrane biology 90 (1986), S. 67-87 
    ISSN: 1432-1424
    Keywords: cotransport ; kinetics ; reaction kinetic model ; dual isotherm ; random binding ; slip
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Solute uptake in many cells is characterized by a series of additive Michaelis-Menten functions. Several explanations for these kinetics have been advanced: unstirred layers, transport across more than one membrane, effects of solute concentration on membrane potential, numerous carrier systems. Although each of these explanations might suffice for individual cases, none provides a comprehensive basis for interpretation of the kinetics. The most common mechanism of solute absorption involves cotransport of solute with a driver ion. A model is developed in which solute and driver ion bind randomly to a membrane-bound carrier which provides a single transmembrane pathway for transport. The kinetic properties of the model are explored with particular reference to its capacity to generate additive Michaelian functions for initial rate measurements of isotopic solute influx. In accord with previous analysis of ordered binding models (Sanders, D., Hansen, U.-P., Gradmann, D., Slayman, C.L. (1984)J. Membrane Biol. 77:123), the conventional assumption that transmembrane transit rate-limits transport has not been applied. Random binding carriers can exhibit single or multiple Michaelian kinetics in response to changing substrate concentration. These kinetics include high affinity/low velocity and low affinity/high velocity phases (so-called “dual isotherms”) which are commonly observed in plant cells. Other combinations of the Michaelis parameters can result incis-(substrate) inhibition. Despite the generality of the random binding scheme and the complexity of the underlying rate equation, a number of predictive and testable features emerge. If external driver ion concentration is saturating, single Michaelian functions always result and increasing internal substrate concentration causes uncompetitive inhibition of transport. Numerical analysis of the model in conditions thought to resemble those in many experiments demonstrates that small relative differences in a few key component rate constants of the carrier reaction cycle are instrumental in generation of dual isotherms. The random binding model makes the important prediction that the contributions of the two isotherms show opposing dependence on external concentration of driver ion as this approaches saturation. In the one case in which this dependence has been examined experimentally, the model provides a good description of the data. Charge translocation characteristics of the carrier can be determined from steady-state kinetic data on the basis of the response of substrate flux to modulation of internal driver ion concentration. The application of the model to dual isotherm kinetics is discussed in relation to “slip” models of cotransport, in which the carrier is assumed to have the capability to transport substrate alone or with the driver ion. A method for distinguishing between the two models is suggested on the basis of measurement of charge/solute transport stoichiometry as a function of external driver ion concentration.
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  • 91
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    The journal of membrane biology 79 (1984), S. 41-51 
    ISSN: 1432-1424
    Keywords: glucose ; brush borders ; sodium cotransport ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Brush border membrane vesicles (BBMV) purified from steer jejunum were used to study the kinetics of sodiumd-glucose cotransport under voltage clamped, zero-trans conditions. When the initial rate of glucose transport (J gluc) was measured over a wide range of glucose concentrations ([S]=0.01–20mm), curvature of the Woolf-Augustinsson-Hofstee plots was seen, compatible with a diffusional and one major, high capacity (maximal transport rateJ max=5.8–8.8 nmol/mg·min) saturable system. Further studies indicated that changes incis [Na] altered theK t , but not theJ max, suggesting the presence of a rapid-equilibrium, ordered bireactant system with sodium adding first.Trans sodium inhibitedJ gluc hyperbolically. KCl-valinomycin diffusion potentials, inner membrane face positive, loweredJ gluc, while potentials of the opposite polarity raiseJ gluc. At low glucose concentrations ([S]〈0.05mm), a second, minor, high affinity transport system was indicated. Further evidence for this second saturable system was provided by sodium activation curves, which were hyperbolic when [S]=0.5mm, but were sigmoidal when [S]=.0.01mm. Simultaneous fluxes of22Na and [3H]glucose at 1mm glucose and 30mm NaCl yielded a cotransport-dependent flux ratio of 2∶1 sodium/glucose, suggestive of 1∶1 (Na/glucose) high capacity, low affinity system and a ∼3∶1 (Na/glucose) high affinity, low capacity system. Kinetic experiments with rabbit jejunal brush borders revealed two major Na-dependent saturable systems. Extravesicular (cis) Na changed theK t , but not theJ max of the major system.
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  • 92
    ISSN: 1432-1424
    Keywords: sodium ; pyruvate ; transport ; proximal tubule ; kinetics ; kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The experiments reported in this paper aim at characterizing the carboxylic acid transport, the interactions of pyruvate and citrate with their transport sites and specificity. The study of these carriers was performed using isotopic solutes for the influx measurements in brush-border membrane vesicles under zerotrans conditions where the membrane potential was abolished with KCl preloading with valinomycin or equilibrium exchange conditions and Δψ=0. Under zerotrans condition and Δψ=0, the influence of pyruvate concentrations on its initial rates of transport revealed the existence of two families of pyruvate transport sites, one with a high affinity for pyruvate (K t =88 μm) and a low affinity for sodium (K t =57.7mm) (site I), the second one with a low affinity for pyruvate (K t =6.1mm) and a high affinity for sodium (K t =23.9mm) (site II). The coupling factor [Na]/[pyruvate] stoichiometry were determined at 0.25mm and 8mm pyruvate and estimated at 1.8 for site I, and 3 when the first and the second sites transport simultaneously. Under chemical equilibrium (Δψ≅0) single isotopic labeling, transport kinetics of pyruvate carrier systems have shown a double interaction of pyruvate with the transporter; the sodium/pyruvate stoichiometry also expressed according to a Hill plot representation wasn=1.7. The direct method of measuring Na+/pyruvate stoichiometry from double labeling kinetics and isotopic exchange, for a time course, gives an=1.67. Studies of transport specificity, indicate that the absence of inhibition of lactate transport by citrate and the existence of competitive inhibition of lactate and citrate transports by pyruvate leads to the conclusion that the low pyruvate affinity site can be attributed to the citrate carrier (tricarboxylate) and the high pyruvate affinity site to the lactate carrier (monocarboxylate).
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  • 93
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    The journal of membrane biology 108 (1989), S. 253-261 
    ISSN: 1432-1424
    Keywords: Chara ; Cl− ; cotransport ; reaction kinetic model ; pH ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary H+-coupled transport in plant and fungal cells is relatively insensitive to external pH (pH o ). H+-coupled Cl− transport at the plasma membrane ofChara corallina was studied to explore the phenomena responsible for this insensitivity. Raising pH o from a control value of 7.5 to 9.0 results in a modest (2.5-fold) decline inJ max and increase inK m . Further increase in pH o results in a selective increase inJ max, in accordance with predictions from a reaction kinetic model of the transport system (Sanders, D., Hansen, U.-P., 1981.J. Membrane Biol. 58:139–153). Increase in cytosolic Cl− concentration ([Cl−] c ) also results in a selective decrease inJ max at pH o =7.5. Quantitative kinetic modeling of the results is not possible if it is assumed that the sole effect of pH o isvia mass action on the binding of external H+ to a transport site. If, instead, the dependence of cytosolic pH (pH c ) on pH o (Smith, F.A., 1984,J. Exp. Bot. 35:1525–1536) is taken into account along with the dependence of Cl− influx on pH c (Sanders, D., 1980,J. Membrane Biol. 53:129–141), then the observed modest changes in Michaelis parameters can be accommodated by a reaction kinetic model. The quantitative parameters of the model yield respective pK a s of the internal and external H+-binding sites=7.85 and 7.2, respective dissociation constants of the internal and external Cl−-binding sites=160 and 40 μm, and an additional, kinetically transparent, H+-binding site with a pK a 〉8.0. The quantitative model independently predicts the response ofJ max andK m to acidic conditions. The results are discussed in terms of the general physiological requirement that fluxes through H+-coupled transport systems are relatively insensitive to environmental variation in pH o . It is proposed that (i) the weak (but finite) dependence of pH c on pH o , coupled with (ii) the strong dependence of H+-coupled transport on pH c are instrumental in endowing H+-coupled transport systems with a relative insensitivity to variation in pH o . This hypothesis might also explain why pH c in plants and fungi is not acutely controlled with respect to variation of pH o .
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  • 94
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    The journal of membrane biology 110 (1989), S. 57-65 
    ISSN: 1432-1424
    Keywords: fluorescence ; water transport ; vasopressin ; kidney collecting tubule ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Water transport across the mammalian collecting tubule is regulated by vasopressin-dependent water channel insertion into and retrieval from the cell apical membrane. The time course of osmotic water permeability (P f ) following addition and removal of vasopressin (VP) and 8-Br-cAMP was measured continuously by quantitative fluorescence microscopy using an impermeant fluorophore perfused in the lumen. Cortical collecting tubules were subjected to a 120 mOsm bath-to-lumen osmotic gradient at 37°C with 10–15 nl/min lumen perfusion and 10–20 ml/min bath exchange rate. With addition of VP (250 μU/ml), there was a 23±3 sec (sem,n=16) lag in whichP f did not change, followed by a rise inP f (initial rate 1.4±0.2×10−4 cm/sec2) to a maximum of 265±10×10−4 cm/sec. With addition of 8-Br-cAMP (0.01–1mm) there was an 11±2 sec lag. For [8-Br-cAMP]=0.01, 0.1 and 1mm, the initial rate ofP f increase following the lag was (units 10−4 cm/sec2): 1.1±0.1, 1.2±0.1 and 1.7±0.3. MaximumP f was (units 10−4 cm/sec): 64±4, 199±9 and 285±11. With removal of VP,P f decreased to baseline (12×10−4 cm/sec) with aT 1/2 of 18 min; removal of 0.1 and 1mm 8-Br-cAMP gaveT 1/2 of 4 and 8.5 min. These results demonstrate (i) a brief lag in theP f response, longer for stimulation by VP than by 8-Br-cAMP, representing the transient build-up of biochemical intermediates proximal to the water channel insertion step, (ii) similar initialdP f /dt (water channel insertion) over a wide range of [8-Br-cAMP] and steady-stateP f values, and (iii) more rapidP f decrease with removal of 8-Br-cAMP than with VP. These pre-steady-state results define the detailed kinetics of the turn-on and turn-off of tubuleP f and provide kinetic evidence that the rate-limiting step for turn-on ofP f is not the step at which VP regulates steady-stateP f . If water channel insertion is assumed to be the rate-limiting step in the turn-on ofP f , these results raise the possibility that water channels must be activated following insertion into the apical membrane.
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  • 95
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    The journal of membrane biology 76 (1983), S. 289-297 
    ISSN: 1432-1424
    Keywords: neuron ; internal perfusion ; Mn current ; kinetics ; Ca blocker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Characteristics of currents carried by Mn2+ and other divalent cations were studied in the isolated identified neuron in the circumesophageal ganglia ofHelix aspersa using a suction pipette technique which allows internal perfusion of the cell body and voltage clamp. Increases in [Mn2+] 0 induced not only saturation of the peak ofI Mn but also shifts theI–V relationships along the voltage axis to the more positive potentials. Internal perfusion with F−, which blocks Ca channels, depressedI Mn. Diltiazem, an organic Ca blocker, inhibitedI Mn over the entire range of theI–V relation without shifting the threshold and peak voltage of theI–V relation. Co2+, Ni2+, Cd2+ and La3+ also suppressedI Mn. Relative maximum peak currents of the divalent cations wereI Ba=I Sr〉I Ca〉I Mn=I Zn. Time constants for activation (τ m ) and inactivation (τ h ) of these cations were voltage dependent, and both time constants were greater in the sequence ofI Mn=I Zn〉I Ba=I Sr〉I Ca over the whole voltage range.
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  • 96
    ISSN: 1432-1424
    Keywords: charybdotoxin ; erythrocytes ; iodination ; kinetics ; peptides ; potassium channels ; scorpions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Two charybdotoxin peptides were purified from venom of the Israeli scorpion,Leiurus quinquestriatus hebraeus. Microsequencing of the most abundant toxin, ChTX-Lq1, revealed identity with the 37-residue peptide previously sequenced by Gimenez-Gallego et al. [Gimenez-Gallego, G., et al.,Proc. Natl. Acad. Sci. USA 85:3329–3333 (1988)]. Sequence data on the minor peptide, ChTX-Lq2, showed substantial homology to ChTX-Lq1 with differences observed at eight positions. These two charybdotoxin sequences, along with that of noxiustoxin, define a distinct family of scorpion peptide toxins with activity against K+ channels. Both charybdotoxin homologs inhibited Ca2+-dependent K+ efflux from human erythrocytes with similar potency,K 0.5∼-40nm. In planar bilayer assays of single K(Ca) channels from rat muscle, ChTX-Lq1 and ChTX-Lq2 blocked with intrinsicK d's of 1.3 and 43nm, respectively, in the presence of 50mm external KCl. A new application of dwell-time histogram analysis of single-channel blocking events was used to characterize the kinetic homogeneity of toxin samples and the blocking kinetics of ChTX derivatives. The lower blocking affinity of ChTX-Lq2 was the combined result of a faster dissociation rate and a slower association rate as compared to ChTX-Lq1. The blocking activity of two mono-iodinated derivatives of ChTX-Lq1 was also analyzed. Blocked dwell-time histograms of the iodinated peptides were characterized by predominately brief (0.2–2 sec) blocking events in comparison to the native toxin (20 sec). Histogram analysis revealed that mono-iodination of ChTX-Lq1 impairs blocking activity by adverse effects on both dissociation and association rate constants. Frequency density histograms of single channel blocking events provide a sensitive assay of toxin purity suitable for quantitating structure-activity relationships of charybdotoxin derivatives.
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  • 97
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    The journal of membrane biology 102 (1988), S. 225-234 
    ISSN: 1432-1424
    Keywords: erythrocytes ; valinomycin ; protonophore ; CCCP ; permeability ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A transport model for translocation of the protonophore CCCP across the red cell membrane has been established and cellular CCCP binding parameters have been determined. The time course of the CCCP redistribution across the red cell membrane, following a jump in membrane potential induced by valinomycin addition, has been characterized by fitting values of preequilibrium extracellular pHvs. time to the transport model. It is demonstrated, that even in the presence of valinomycin, the CCCP-anion is “well behaved,” in that the translocation can be described by simple electrodiffusion. The translocation kinetics conform to an Eyring transport model, with a single activation energy barrier, contrary to translocation across lipid bilayers, that is reported to follow a transport model with a plateau in the activation energy barrier. The CCCP anion permeability across the red cell membrane has been calculated to be close to 2.0×10−4 cm/sec at 37°C with small variations between donors. Thus the permeability of CCCP in the human red cell membrane deviates from that found in black lipid membranes, in which the permeability is found to be a factor of 10 higher.
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  • 98
    ISSN: 1432-1424
    Keywords: ion transport ; carriers ; lipid bilayers ; kinetics ; nonactin ; methylation ; macrotetralides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The effects of methylation on the rate constants of carrier-mediated ion transport have been studied on monooleindecane bilayers with K+, Rb+, NH 4 + , and TI+ ions, using the series of homologue carriers, nonactin, monactin, dinactin, trinactin, and tetranactin, each member of the series differing from the previous one by only one methyl group. Measurements of the amplitude and time constant of the current relaxation after a voltage jump over a large domain of voltage and permeant ion concentration, together with a computer curve-fitting procedure, have allowed us, without the help of steady-state current-voltage data, to deduce and compare the values of the various rate constants for ion transport: formation (k Ri) and dissociation (k Di) of the ion-carrier complex at the interface, translocation across the membrane interior of the carrier (k s) and the complex (k is). With the additional information from steady-state low-voltage conductance measurements, we have obtained the value of the aqueous phase-membrane and torus-membrane partition coefficient of the carrier ({ie191-1} and {ie191-2}). From nonactin to tetranactin with the NH 4 + ion,k is, and {ie191-3} are found to increase by factors of 5 and 3, respectively,k Di and {ie191-4} to decrease respectively by factors 8 and 2, whilek Ri andk s are practically invariant. Nearly identical results are found for K+, Rb+, and Tl+ ions.k Ri,k s andk is are quite invariant from one ion to the other except for Tl+ wherek Ri is about five times larger. On the other hand,k Di depends strongly on the ion, indicating that dissociation is the determining step of the ionic selectivity of a given carrier. The systematic variations in the values of the rate constants with increasing methylation are interpreted in terms of modifications of energy barriers induced by the carrier increasing size. Within this framework, we have been able to establish and verify a fundamental relationship between the variations ofk is andk Di with methylation.
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  • 99
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    Investigational new drugs 7 (1989), S. 27-36 
    ISSN: 1573-0646
    Keywords: kinetics ; fluorouracil ; bolics ; administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thymidylate synthase (TS) is the enzyme target of 5-fluorouracil (FUra) that recent laboratory and clinical studies with folinic acid (calcium leucovorin) suggest may mediate important antitumor cytotoxicity. Measurement in carcinoma tissue of parameters related to TS inhibition by 5-fluorodeoxyuridylate (FdUMP), by analogy to hormone receptor analysis, should be useful to determine which patients should receive fluoropyrimidine drug therapy and to evaluate folinic acid requirements. Folinic acid is metabolized to 5,10-methylenetetrahydropteroylglutamine (CH2FH4), which must be present in large excess to effect desired levels of maximal inhibition of TS, by promoting formation and stabilization of TS-FdUMP-CH2FH4 ternary complexes. In patients with metastatic disease, serial biopsies of tumor and normal tissues for studies of pharmacodynamic responses to test-dose FUra or folinic acid are shown to be easily added to routine intraoperative management. A suitable methodologic approach is described and examples given of assays of free TS, FdUMP, dUMP, and CH2FH4 levels after FUra or folinic acid, that may be useful in future studies aimed at improving the cost-effectiveness of FUra-folinic acid combinations.
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  • 100
    ISSN: 1573-0646
    Keywords: heterogeneity ; polyamines ; cell killing ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of α-difluoromethylornithine (DFMO) on survival, cell kinetics and polyamine levels were studied on two clones of human astrocytoma in vitro. The survival responses were dose and time dependent; and treatments with DFMO which lasted for 72 h resulted in heterogeneous responses with one clone being up to 6 times more sensitive than the other. Shorter treatments produced more uniform killing in the clones. A continuous exposure of the cells to 5 mM DFMO resulted in a rapid decrease in putrescine values in both clones, followed by decreases in the spermidine levels. These effects were closely followed by 148% to 170% increases in cell population doubling times, and a lowering of saturation densities. No clear correlations could be established among baseline polyamine levels and cell kinetics or survival responses to DFMO treatments.
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