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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 32 (1993), S. 71-73 
    ISSN: 1436-6215
    Keywords: Rat ; glutamate-induced obesity ; postprandial thermogenesis ; Ratte ; Glutamat-induzierte Adipositas ; postprandiale Thermogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Bei 4 Monate alten Ratten mit Glutamat-induzierter Adipositas wurde die postprandiale Thermogenese über 8 h nach Fütterung von 300, 450 und 600 kJ/kg0,75 einer Pellet-Diät mittels indirekter Kalorimetrie in computergesteuerten Stoffwechselkäfigen mit offenem Kreislauf bestimmt. Bei den adipösen Tieren war die postprandiale Thermogenese nach Aufnahme von 600 kJ/kg0,75 (oberhalb des Energieerhaltungsbedarfs) signifikant auf 40% der Thermogenese der Kontrolltiere reduziert (12,0 gegenüber 31,5 kJ/kg0,75×8 h). Es wird geschlußfolgert, daß die Ratte mit Glutamat-induzierter Adipositas als ein Tiermodell mit beeinträchtigter fakultativer Thermogenese anzusehen ist, die hauptsächlich durch eine Verminderung der sympathischen adrenergen Aktivität verursacht ist.
    Notes: Summary Postprandial thermogenesis was estimated in 4-month-old male rats with glutamate induced obesity after being fed with 300, 450 and 600 kJ/kg0.75 of a pellet diet, respectively by indirect calorimetry in computer-controlled open circuit metabolic cages over 8 h. After an intake of 600 kJ/kg0.75 (above the maintenance energy requirement) postprandial thermogenesis was significantly reduced in the obese animals to about 40% of control rats (12.0 versus 31.5 kJ/kg0.75×8 h). It is concluded that the glutamate obese rat can be accepted as an animal model with impaired facultative thermogenesis, mainly caused by a reduction of sympathetic adrenergic activity.
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  • 2
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    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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    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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  • 4
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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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  • 5
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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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  • 6
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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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  • 7
    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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  • 8
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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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  • 9
    ISSN: 1572-8927
    Keywords: Solvolysis ; kinetics ; aqueous solvent mixtures ; Co(III) complexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of the solvolysis of [Co(CN)5Cl]3− have been investigated in water +2-methoxyethanol and water + diethylene glycol mixtures. Although the addition of these linear hydrophilic cosolvent molecules to water produces curvature in the variation of log(rate constant) with the reciprocal of the dielectric constant, their effect on the enthalpy and entropy of activation is minimal, unlike the effect of hydrophobic cosolvents. The application of a Gibbs energy cycle to the solvolysis in water and in the mixtures using either solvent-sorting or TATB values for the Gibbs energy of transfer of the chloride ion between water and the mixture shows that the relative stability of the emergent solvated Co(III) ion in the transition state compared to that of Co(CN)5Cl3− in the initial state increases with increasing content of cosolvent in the mixture. By comparing the effects of other cosolvents on the solvolysis, this differential increase in the relative stabilities of the two species increases with the degree of hydrophobicity of the cosolvent.
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  • 10
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    Journal of solution chemistry 6 (1977), S. 203-216 
    ISSN: 1572-8927
    Keywords: Glucose ; kinetics ; mixed solvent ; kinetic isotope effect ; enthalpy of activation ; entropy of activation ; tetrahydrofuran ; tert-butanol ; mutarotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The mutarotation rates of glucose in aqueous mixtures of tetrahydrofuran andtert-butanol in the mole fraction (xi) range 0〈xi〈0.2 have been measured at 5° intervals in the range 5–35°C. The kinetic deuterium isotope effects have been determined for the same solvent compositions at 25 and 35°C. A statistical analysis of the Arrhenius plots indicates that the experimental errors, although small, are too large for the establishment of any compensation behavior between ΔH
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  • 11
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    Journal of solution chemistry 19 (1990), S. 1073-1084 
    ISSN: 1572-8927
    Keywords: Solvolysis ; kinetics ; mixtures of water+cosolvent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Rates of solvolysis of the complex cation [Co(4tBupy)4Cl2]+ have been determined in mixtures of water with the hydrophobic solvent, t-butyl alcohol. The solvent composition at which the extremum is found in the variation of the enthalpy ΔH* and the entropy ΔS* of activation correlates well with the extremum in the variation of the relative partial molar volume of t-butyl alcohol in the mixture and the straight line found for the variation of ΔH* with ΔS* is coincident with the same plot for water + 2-propanol mixtures. A free energy cycle is applied to the process initial state (C n+) going to the transition state [M(n+1)+...Cl−] in water and in the mixture using free energies of transfer of the individual ionic species, ΔG t o (i), from water into the mixture. Values for ΔG t o (i) are derived from the solvent sorting method and from the TATB/TPTB method: using data from either method, changes in solvent structure on going from water into the mixture are found to stabilize the cation in the transition state, M(n+1)+, more than in the initial state, C n+. This is compared with the application of the free energy cycle to the solvolysis of complexes [Co(Rpy)4Cl2]+ and [Coen2LCl]+ in mixtures of water with methanol, 2-propanol or t-butyl alcohol: the above conclusion regarding the relative stabilization of the cations holds for all these complexes in their solvolyses in water+alcohol mixtures using values of ΔG t o (Cl−) from either source.
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  • 12
    ISSN: 1572-8927
    Keywords: Cu(II) ; kinetics ; reduction ; temperature dependence ; H2O2, NaCl, NaBr, NaClO4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The rates of reduction of Cu(II) with H2O2 have been measured in NaCl and NaBr solutions and mixtures with NaClO4 as a function of pH (6 to 9), temperature (5 to 45°C) and ionic composition (0.1 to 6M). The effect of pH on the rates was found to be independent of temperature and ionic composition. The rates increased as a function of [H+] raised to the power of 1.3 to 1.6. Speciation calculations indicate that this pH dependence can be attributed to Cu(OH)2 being the reactive species. The rate constants in NaCl and NaBr and mixtures with NaClO4 were independent of ionic strength, but proportional to the halide concentration raised to the power of 2.0 (0.2 to 2.6M). These results can be attributed to Cu(OH)2Cl 2 2− being the reactive species to reduction with H2O2. The Cu(I) halide complexes formed from the reduction are not easily oxidized with O2 or H2O2. The faster rates in Br− solutions, which form stronger complexes with Cu+, support this contention. Measurements made in NaCl with added NaHCO3, NaB(OH)4 EDTA, NTA and glycine were also made. These measurements indicate that the CuL complexes (L=B(OH) 4 − , CO 3 2− , EDTA, NTA, and glycine) are not very reactive to reduction with H2O2. The addition of Mg2+ or Ca2+ caused the rates to increase due to the formation of MgL or CaL complexes and the resultant release of reactive Cu2+.
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  • 13
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    Journal of solution chemistry 23 (1994), S. 483-500 
    ISSN: 1572-8927
    Keywords: Thermodynamics ; kinetics ; chemical relaxation ; temperature-jump ; amplitudes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Amplitudes of chemical relaxation signals can provide useful information as to the thermodynamics of coupled chemical reactions. The temperature-jump technique has been used to investigate the thermodynamic behavior of the Nickel(II)-3,5-dinitrosalicylate system in buffer solution, where complex formation steps are coupled to proton transfer steps. The analysis of the relaxation curves is based on the transformation of a set of coupled elementary reactions into a set of uncoupled ‘normal reactions.’ By analogy with classical titrations, the experiments have been performed by changing the metal ion concentration at constant ligand concentration and pH. Each measured amplitude is associated in this way to a point of a ‘dynamic titration’ and a procedure is formulated by which the values of the equilibrium constants and enthalpies of the normal reactions are simultaneously obtained by simple linear plots. From the dependence of these parameters on suitable functions of the concentrations of the reactants the values of ΔG° and ΔH° of the individual steps are derived. It is shown that the addition of a buffer (instead of an indicator) influences the stoichiometric coefficients of the normal reaction in such a way that measurable amplitudes are produced in systems that, as the presently investigated, in unbuffered solution would remain insensitive to the external perturbation. The circumstances under which the dynamic method offers advantages over the classical techniques are discussed.
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  • 14
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    Journal of solution chemistry 5 (1976), S. 163-169 
    ISSN: 1572-8927
    Keywords: Solvent effects ; tetramethylurea ; hydrolysis ; hydrogen bonding ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Tetramethylurea was hydrolyzed in aqueous hydrochloric acid at temperatures of 80, 90, and 100°C. All reactions were carried out in an excess of both tetramethylurea and water, with first-order dependence on acid concentration being observed. As the concentration of water was increased, the rate of hydrolysis decreased until equimolar amounts of water and tetramethylurea were present. Subsequent addition of water had no effect on the observed rate.
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  • 15
    ISSN: 1572-879X
    Keywords: Fischer-Tropsch synthesis ; reaction activation barrier ; carbon chain growth and termination ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A method is established, by which the difference of the reaction activation barriers of carbon chain growth and termination in Fischer-Tropsch (FT) synthesis can be determined from experiments. A FT synthesis is carried out on Fe/Zn catalyst. We apply the method to analyze the experimental result and obtain the difference of reaction activation barriers of carbon chain growth and termination of α-olefins on the catalyst.
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  • 16
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    Cellulose 1 (1994), S. 26-56 
    ISSN: 1572-882X
    Keywords: low-temperature degradation ; kinetics ; mechanisms ; electrical insulation ; transformers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A critical review is given of the degradation of cellulose in the low-temperature region (below about 300°C) of power transformer operation. The large number of kinetic studies, under a variety of environmental conditions from Kraft paper in insulating oil, to cotton and paper in oxygen, are considered in terms of a first-order polymer chain scission model. In many cases, the data are replotted to suit the model. A common activation energy of 111±6 kjmol−1 is calculated and it is shown that the pre-exponential factor, rather than the activation energy, is sensitive to the oxidizing nature of the environment and the susceptibility to degradation of the material. The chemical mechanisms of degradation are reviewed, and conclusions and recommendations are made regarding chemical condition monitoring and life prediction of electrical insulation.
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  • 17
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    Catalysis letters 27 (1994), S. 79-90 
    ISSN: 1572-879X
    Keywords: kinetics ; carbon ; oxygen ; recombination ; rhodium ; surface characterisation ; XPS ; AES
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Different mechanisms of atomic carbon and oxygen recombination on a rhodium surface are studied with Auger electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS). The kinetics of adsorbed carbidic carbon oxidation (carbon coverageθ c ≈ 0.1–0.3 ML) by gas-phase oxygen that proceeds by a Langmuir-Hinshelwood reaction mechanism, provides the value of the activation energy for recombination (E rec ⇂t ≈ 170±20 kJ/mol).E rec ⇂t depends slightly on the carbon coverage. An Eley-Rideal type of reaction was observed for adsorbed oxygen and atomic gas-phase carbon recombination which occurs in a dynamic regime. The low value found for the activation energy (near zero) is consistent with the mechanism that this exothermic reaction is too fast for energy dissipation into the substrate; the energy is mainly transferred into translational, vibrational and rotational energy of CO.
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  • 18
    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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  • 19
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    Topics in catalysis 1 (1994), S. 305-314 
    ISSN: 1572-9028
    Keywords: non-Langmuir ; kinetics ; non-linear dynamics ; oscillations ; chaos ; self-organization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of a catalytic reaction is frequently formulated in terms of simple concepts of the Langmuir type. Apart from limitations arising from the non-uniformity of the catalyst's surface and from the coverage dependence of the rate “constants”, several other complications may come into play. These may arise on the “quantum level” where energy flow between the various degrees of freedom may cause failure of simple transition state theory, as well as on the “continuum level” where formulation of rate equations in terms of coupled non-linear differential equations may give rise to a rich scenario of spatio-temporal self-organization, including kinetic oscillations, chaos, and formation of concentration patterns. Several of these phenomena are illustrated by selected examples.
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  • 20
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    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    ISSN: 1420-9071
    Keywords: Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
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  • 21
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    Cellular and molecular life sciences 46 (1990), S. 457-458 
    ISSN: 1420-9071
    Keywords: Rat ; carnitine ; lipolysis ; exercise ; glycogen ; triglycerides ; muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary To test the effect of L-carnitine on glycogen sparing when fat oxidation is increased, 100 mg/kg/d were given to rats orally for 3 days, resulting in 1.8-fold higher muscle carnitine levels. Even when FFA were raised by heparin-stimulated lipolysis, the rate of glycogen degradation was not reduced during exercise.
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  • 22
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    Cellular and molecular life sciences 40 (1984), S. 974-975 
    ISSN: 1420-9071
    Keywords: Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
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  • 23
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    Cellular and molecular life sciences 49 (1993), S. 110-117 
    ISSN: 1420-9071
    Keywords: Polymerization ; sickle hemoglobin ; sickle cell disease ; kinetics ; thermodynamics ; polymer domains ; nucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The polymerization of sickle hemoglobin occurs by the same mechanisms in solutions and in cells, and involves the formation of 14 stranded fibers from hemoglobin molecules which have assumed a deoxy quaternary structure. The fibers form via two types of highly concentration-dependent nucleation processes: homogeneous nucleation in solutions with hemoglobin activity above a critical activity, and heterogeneous nucleation in similarly supersaturated solutions which also contain hemoglobin polymers. The latter pathway is dominant, and creates polymer arrays called domains. The individual polymers bend, but also cross-link, and the resulting mass behaves as a solid. The concentration of polymerized hemoglobin increases exponentially unless clamped by rate limiting effects such as oxygen delivery.
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  • 24
    ISSN: 1572-879X
    Keywords: propane ; oxidation ; platinum ; palladium ; sulfur dioxide ; alumina ; zirconia ; activity ; acidity ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Earlier studies have shown that sulfur dioxide and metal-support interaction can strongly influence propane oxidation over platinum. In particular, oxidation activity is enhanced when platinum is supported on sulfated γ-alumina or zirconia compared to γ-alumina. Therefore, it is of interest to compare the performance of palladium under the same experimental conditions. Four model catalysts were examined: Pt/γ-alumina, Pt/zirconia, Pd/γ-alumina and Pd/zirconia. The metal loading was kept at or below 0.05 wt% to emphasize changes in activity attributable to metal-support interaction. Reaction rates were measured with and without sulfur dioxide. Surface sulfation was analyzed by measuring acid strength and evaluating spectra obtained by Fourier-transform infrared spectroscopy. In contrast to platinum, sulfation does not promote propane oxidation on Pd/γ-alumina, and Pd/zirconia is less active than Pd/γ-alumina.
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  • 25
    ISSN: 1572-879X
    Keywords: Ultraviolet heterogeneous photocatalysis ; oxidation ; trichloroethylene ; titania ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Kinetics of the gas/solid heterogeneous photocatalytic oxidation of dilute trichloroethylene (TCE) vapors by ultraviolet-illuminated titanium dioxide have been determined using a fixed-bed dynamic photoreactor. Reaction rate dependences on inlet TCE, oxygen and water vapor concentrations were found to consist of both reactant sensitive and insensitive regions. In the reactant sensitive regions, measured limiting apparent reaction rate orders for TCE, oxygen and water vapor are 0.8, 1.7 and — 3, respectively. Water vapor in the reactant stream lowersinitial reaction rates relative to corresponding water free conditions, but is required to sustain photocatalytic activity for extended periods of time.
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  • 26
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    Calcified tissue international 23 (1977), S. 161-170 
    ISSN: 1432-0827
    Keywords: Bone ; Growth ; Rat ; Remodeling ; Tetracyclines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Cortical bone remodeling along the femur diaphysis was determined in normal female rats (Sprague-Dawley) with the tetracycline technique. Three segments on the cortical bone circumference (the anterolateral, the medial, and the posterior) were found to be most suitable for the study of the remodeling process. Oxytetracycline was administered at age 60 and 75 days, and groups of animals were killed at age 75, 85, 95, and 105 days. The accumulated endosteal growth during age 60 to 75 days in the anterolateral segment was found to increase uniformly in the distal direction along the femur diaphysis. A method is described where this accumulated endosteal growth is used. This method eliminates the use of calipers to determine the section level and makes it possible to study comparable sections even after varying periods of time. The proximal part of the diaphysis showed periosteal apposition in all three segments. The periosteal apposition turned into resorption in the distal part of the diaphysis in the anterolateral and medial segments, whereas the periosteal appsition increased in the posterior segment. The endosteal growth increased in the distal direction in the anterolateral and medial segments. Irregular OTC bands made measurements of endosteal remodeling in the posterior segment impossible. The cortical width decreased in the distal direction along the femoral shaft. Comparison between the different age groups is described and also the relation between the accumulated endosteal growth and the diameter of the medullary cavity.
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  • 27
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    Calcified tissue international 27 (1979), S. 161-164 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Ovary ; Rat ; Vitamin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Fifty adult female rats were used to study the effect of 1-alpha-hydroxyvitamin D3 (1α-OH-D3)on bone after oophorectomy. The experimental period was 6 months. At the end of the experiment the femurs and the tibias were investigated for bone mass and composition. Significant signs of osteopenia occurred as a result of oophorectomy. The treatment with 1α-OH-D3 induced only minor changes in blood chemistry but increased bone mass significantly. The findings support the view that 1α-OH-D3 may be a valuable tool in the treatment of osteoporosis resulting from ovarian insufficiency.
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    Calcified tissue international 50 (1992), S. 524-526 
    ISSN: 1432-0827
    Keywords: Verapamil ; Bone ; Osteopenia ; Rat ; Female ; Intestinal calcium absorption
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    Topics: Biology , Medicine , Physics
    Notes: Summary Verapamil inhibits the intestinal absorption of calcium (Ca) and increases serum parathyroid hormone in rats. The effects of verapamil on bone tissue after long-term treatment is, however, not well described. Adult female and male Sprague-Dawley rats received verapamil in their drinking water at a dosage of 0.075 mg/ml (low dose) or 0.75 mg/ml (high dose) for 12 weeks; control rats received only drinking water. All rats were fed a diet containing 0.1% Ca and 0.5% P. In female rats, the amount of bone ash per volume was significantly reduced from 0.742 g/ml in controls to 0.713 g/ml after low-dose treatment of verapamil, and to 0.667 g/ml following high-dose treatment (P〈0.01). The tibial length was increased from 39.7 mm in controls to 40.3 mm or to 40.7 mm after low or high doses (P〈0.01). The tibial volume increased from 0.385 ml in controls to 0.397 ml after low doses and to 0.429 ml after high doses (P〈0.01). In contrast, in male rats the amount of bone ash per volume was significantly increased from 0.578 g/ml in controls to 0.580 g/ml after low doses and to 0.620 g/ml after high doses of verapamil (P〈0.01). The tibial bone volume in males as decreased from 0.633 ml in controls to 0.641 ml after low doses and to 0.583 ml after high doses (P〈0.05). The tibial length in the males was not changed by verapamil. The intestinal absorption of Ca was reduced in male rats from 5.28 in controls to 4.03 (serosa/mucosa) after low-dose treatment and to 2.46 after high-dose treatment with verapamil (P〈0.05). In female rats, the intestinal absorption of Ca did not change after verapamil treatment. Thus, chronic treatment with verapamil in female rats induced osteopenia whereas in male rats bone growth was inhibited.
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  • 29
    ISSN: 1432-0827
    Keywords: Rat ; Osteoblast-like culture ; Ovariectomy ; Estrogens ; Bone blood supply
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    Topics: Biology , Medicine , Physics
    Notes: Summary Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n=6–8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from shamoperated and ovariectomized animals (n=10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.
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    Calcified tissue international 52 (1993), S. 361-364 
    ISSN: 1432-0827
    Keywords: Calcitonin ; Sustained release ; Copolymer depot ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Studies were carried out to determine whether monolithic depot formulations, prepared using lactide:glycolide copolymers, could be used to administer salmon calcitonin (sCT) to rats in vivo. Formulations containing 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of peptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma calcium concentrations and cumulative weight gain of the animals were used to measure pharmacological effects of the released sCT. Release of sCT from the depots was controlled by the copolymer and was sustained for periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading of the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day period postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between days 11 and 18. Release of peptide from the depots was essentially complete by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have application for the convenient clinical administration of sCT in metabolic bone diseases.
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  • 31
    ISSN: 1432-0827
    Keywords: Bone ; Nandrolone decanoate ; Ovariectomy ; Bone mechanics ; IGF-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or Stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on Serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the Start of the experiment) were Studied for 6 months. The results were compared with those obtained in agematched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of Serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were Significantly reduced. Treatment of OVX rats with 1 mg ND/14 days resulted in a Significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and Strength, and bone IGF-I content, and a decrease in Serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVX to the level of the intact controls. These results indicate that ND acts as an antiresorptive drug and as a bone formation Stimulating drug. Furthermore, the increased bone mass and bone mineral density is associated with improved bone Strength and stiffness and the presence of an increased amount of IGF-I. IGF-I is a growth factor considered to play a role in the maintenance of normal skeletal balance by a paracrine or autocrine mechanism.
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  • 32
    ISSN: 1432-0827
    Keywords: Hyperthyroidism ; Osteopenia ; Bisphosphonate ; Rat
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    Topics: Biology , Medicine , Physics
    Notes: Summary Hyperthyroidism, either endogenous or iatrogenic, leads to increased bone turnover and osteopenia. This study was conducted to examine (1) whether thyroid hormone excess in rats causes bone changes similar to those seen in patients with hyperthyroidism, and (2) the effects of the aminobisphosphonate alendronate on the thyroid hormone-induced bone changes. Sprague-Dawley male rats, divided into four groups, received L-thyroxine (T4) 250 μg/kg/day (+T4) or vehicle (-T4) subcutaneously six times per week and alendronate 1.75 mg/kg (+ALN) or vehicle (-ALN) orally twice a week. Rats were sacrificed after 3 weeks of treatment, blood samples were analyzed for serum T4, triiodo-L-thyronine (T3), and osteocalcin, and the proximal tibiae were processed for histomorphometric analysis. Serum T4 and T3 levels measured 20–24 hours after the last injection were 2 to 2.5-fold higher in +T4 groups than in-T4 groups. Serum osteocalcin was significantly (P 〈 0.05) higher in +T4/-ALN group than in the other groups, which were not statistically different from each other. T4 treatment (+T4/-ALN) significantly decreased the amount of cancellous bone volume (-45%) and increased osteoid surface (+254%), osteoblast surface (+111%), and osteoclast surface (+176%) relative to control values. Alendronate increased the bone volume above control values in both T4-treated (+ T4/ +ALN) and untreated (-T4/ +ALN) rats, and prevented the T4-induced increase in bone turnover in +T4/+ALN rats. It is concluded that (1) excess thyroid hormone induces cancellous bone loss associated with high bone turnover in the rat, and (2) this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity.
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    Journal of molecular evolution 33 (1991), S. 442-449 
    ISSN: 1432-1432
    Keywords: Humans ; Mouse ; Rat ; Codon usage ; Mutation bias ; Selection
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    Topics: Biology
    Notes: Summary A new statistical test has been developed to detect selection on silent sites. This test compares the codon usage within a gene and thus does not require knowledge of which genes are under the greatest selection, that there exist common trends in codon usage across genes, or that genes have the same mutation pattern. It also controls for mutational biases that might be introduced by the adjacent bases. The test was applied to 62 mammalian sequences, the significant codon usage biases were detected in all three species examined (humans, rats, and mice). However, these biases appear not to be the consequence of selection, but of the first base pair in the codon influencing the mutation pattern at the third position.
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  • 34
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    Journal of comparative physiology 170 (1992), S. 645-650 
    ISSN: 1432-1351
    Keywords: Milk ejection reflex ; Positive pressure oscillations ; Motor activity of pups ; Tactile stimulation of nipples ; Rat
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    Topics: Biology , Medicine
    Notes: Summary Changes of positive pressure exerted by pups on nipples during sucking were investigated using anesthetized, lactating dams. It was found that, every 50–60 s, individual pups performed bouts of pressure oscillations (3/s) of high amplitude which lasted about 10–12 s and coincided with periods of increased motor activity. During the intervals, when pups were quiet, series of low-amplitude oscillations (3/s) were also observed. Using a strain measuring method to record the activity of sucking pups, synchronization of activity of two or more pups was found to occur periodically every 25–30 s and, most frequently, 10–30 s before the reflex increase of milk pressure. In further experiments, artificial tactile stimulation was applied to the dam's nipples using the joint action of suction and positive pressure. Following a short-term (10–20 s) increase in frequency and amplitude of artificial nipple stimulation, 60%–80% of all reflexive peaks of milk pressure were elicited with a latency of 19 ± 5 s. This suggests that there are specific conditions under which the stimulation of nipples by pups may trigger the formation of the milk ejection reflex in the rat.
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  • 35
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    Journal of comparative physiology 171 (1992), S. 657-664 
    ISSN: 1432-1351
    Keywords: Inferior olivary complex ; Cerebellum ; 3-acetylpyridine ; Harmaline ; Learning ; Memory ; Rat
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    Topics: Biology , Medicine
    Notes: Summary DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3-acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures.
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  • 36
    ISSN: 1436-5073
    Keywords: flow injection analysis (FIA) ; mercury ; porphyrin ; kinetics ; spectro-photometry
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    Topics: Chemistry and Pharmacology
    Notes: Abstract 5,10,15,20-tetrakis(3-chloro-4-sulfophenyl)porphine (m-Cl-TPPS4) was synthesized and used for the Spectrophotometric determination of mercury by flow injection analysis. A pseudo-first-order reaction kinetic mechanism was proposed with a rate constant of 0.8 min−1 for Hg(II) withm-Cl-TPPS4 in the presence of 8-hydroxyquinoline in a medium of 1.0M acetic acid and sodium acetate buffer solution (pH 6.22). In the optimum conditions of reaction temperature (85 ° C), stopped-flow time (60 s) and sampling volume (100 μl), the method's relative standard deviation was 0.82% (n = 12) at 5.0 μg ml−1 mercury, with a linear range of 0–12.0 μg ml−1 and an analytical frequency of 60h−1. The detection limit (3σ) was 0.025 μg ml−1. Interference studies showed that most metal ions co-existing with Hg2+ could be tolerated at 100-fold excess levels, but Zn2+, Cu2+ and Mn2+ needed to be masked. The method has been applied to the analysis of water samples with satisfactory results.
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  • 37
    ISSN: 1436-5073
    Keywords: atrazine ; terbuthylazine ; sequential binding ; kinetics ; cross-reactivity
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Immunoassays for triazine herbicides were tested for their reaction to the variation of the tracer incubation time. By application of a sequential technique the measuring range of atrazine could be expanded to five decades and the total duration of the test could be reduced to about 30 min. In an optimized version a lower detection limit of 9 pmol/l (2 ng/l) was achieved. The detection limit of a sensitive immunoassay for terbuthylazine is also below the concentration limit demanded of the German drinking water regulation (100 ng/l) and reaches 130 pmol/l (30 ng/l). Short tracer incubation times did not lead to increased cross-reactivities in contrast to theoretical models [1, 2]. Different mechanisms, which could cause a shift of the center point of the calibration curve, are discussed, including kinetic considerations.
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    Biodegradation 4 (1993), S. 163-170 
    ISSN: 1572-9729
    Keywords: factorial analysis ; kinetics ; methane ; methanotrophs ; nutrients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The effect of different mineral nutrients on the kinetics of methane biodegradation by a mixed culture of methanotrophic bacteria was studied. The substrate factors examined were ammonia, iron, copper, manganese, phosphate, and sulphide. The presence of iron in the growth medium had a strong effect on the yield coefficient. Yield coefficients up to 0.49 mg protein per mg methane were observed when iron was added at concentrations of 0.10–5.0 mg/l. Iron addition also increased the maximum methane utilization rate. The same effect was observed after addition of ammonium to a medium where nitrate was the only nitrogen source. The observed Monod constant for methane utilization increased with increasing concentration of ammonia. This shows that ammonia is a weak competitive inhibitor as observed by other researchers. Relatively high levels of both ammonia (70 mg/l) and copper (300 µg/l) inhibited the methane degradation, probably due to the toxic effect of copper-amine complexes.
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  • 39
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    Mycopathologia 123 (1993), S. 149-154 
    ISSN: 1573-0832
    Keywords: Ascending pyelonephritis ; Candida albicans ; Experimental model ; Rat
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    Topics: Biology , Medicine
    Notes: Abstract We developed a new experimental model of ascendingCandida pyelonephritis in female rats with leukopenia and vesicoureteral reflux. Rats were treated transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days before and transurethrally with diluted acetic acid solution to induce vesicoureteral reflux 1 day before inoculation ofCandida albicans strain, ATCC 10259 (containing 107 cells). Microscopy revealed acute pyelonephritis in whichCandida cells invaded from the fornix and/or papilla into the medulla within 3 days after inoculation. Between 7 and 28 days after inoculation, chronic pyelonephritis reached the cortex. The incidence of pyelonephritis increased gradually and was approximately 80% after 7 days.Candida colony counts of bladder urine specimens obtained by direct puncture were significantly greater in rats with pyelonephritis extending into the parenchyma than in those with pyelonephritis located along the pelvis (p〈0.01). These results suggest that this rat model shows the characteristic feature of ascending pyelonephritis due toC. albicans and that the severity ofCandida pyelonephritis can be estimated fromCandida counts of bladder urine.
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    Mycopathologia 55 (1975), S. 53-55 
    ISSN: 1573-0832
    Keywords: Rubratoxine B ; Mitochondria ; Rat
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    Topics: Biology , Medicine
    Notes: Abstract The in vitro effect of rubratoxin B on the electron transport system of rat liver mitochondria was investigated. This mycotoxin depressed oxygen consumption in ADP-lacking mitochondria and in ADP-coupled mitochondria, using succinate or β-hydroxybutyrate as substrats. Rubratoxin B is neither an oxidative-phosphorylation inhibitor nor uncoupling agent. Its effect is compared with aflatoxin B1.
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  • 41
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    Nutrient cycling in agroecosystems 39 (1994), S. 39-42 
    ISSN: 1573-0867
    Keywords: Controlled release fertilizers ; kinetics ; mechanism ; nutrient supply ; rate of release ; slow release fertilizers (SRF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Individual granules within a given granule population of a slow-release fertilizer (SRF) have a different release pattern. The populations studied differed both in relation to the time delay before the start of the release process and to the duration of the release. An association between a short delay period and a rapid release was found. The random reease distribution can be approximated using first-order rate equations. In cases, a term describing a “lag” period should be added. The distribution of release timing among the fertilizer granules may allow a long-lasting nutrient supply to the plant, as long as there are enough granules within the root zone to allow a uniform supply pattern.
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    Antonie van Leeuwenhoek 60 (1991), S. 175-191 
    ISSN: 1572-9699
    Keywords: growing systems ; kinetics ; murein wall ; nucleic acid ; protein ; turnover
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    Topics: Biology
    Notes: Abstract Living organisms do not just grow by synthesizing cellular components. As part of the necessary steps for existence, some components are degraded after synthesis. Even for bacteria in balanced, exponential growth some substances, under some conditions, are turned over. In other phases of growth turnover can be much more extensive, but it is still selective. This review covers studies with animals as a way to put the studies on microorganisms in perspective. The history, the mathematics, and experimental design of turnover experiments are reviewed. The important conclusion is that most of the proteins during balanced growth are very stable in bacteria, although ribosomal proteins are degraded under starvation conditions. Another generalization is that the process of wall enlargement in general is associated with obligatory turnover of the peptidoglycan.
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    Journal of biomedical science 1 (1994), S. 201-203 
    ISSN: 1423-0127
    Keywords: Hypertension ; Eicosanoid ; Rat ; Genetics ; Kidney
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    Topics: Biology , Medicine
    Notes: Abstract The present paper reviews the evidence for a possible involvement of renal eicosanoids in the pathophysiology of high blood pressure in genetically hypertensive rats of the Lyon strain. Both in vivo and in vitro experiments suggest that an increased ability to synthesize the vasoconstrictor prostaglandin H2 and/or thromboxane A2 in renal vessels (1) acts as an autocrine amplifier of pressor agents and (2) may contribute to resetting the pressure natriuresis curve which is a prerequisite for the development and maintenance of hypertension.
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  • 44
    ISSN: 1420-9071
    Keywords: Rat ; cerebrospinal fluid, human ; analgesia ; naloxone ; pain indifference, congenital ; opiates, endogenous
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    Notes: Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
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  • 45
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    Cellular and molecular life sciences 40 (1984), S. 1368-1369 
    ISSN: 1420-9071
    Keywords: Rat ; kidney ; hypertensive ; prostaglandin dehydrogenase ; hexokinase
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    Topics: Biology , Medicine
    Notes: Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
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  • 46
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    Cellular and molecular life sciences 47 (1991), S. 1104-1118 
    ISSN: 1420-9071
    Keywords: Transaminase ; decarboxylase ; serine hydroxymethyltransferase ; pyridoxal 5′-phosphate ; enzyme mechanism ; stereochemistry ; kinetics
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    Topics: Biology , Medicine
    Notes: Abstract Pyridoxal 5′-phosphate is a coenzyme for a number of enzymes which catalyse reactions at Cα of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-α-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.
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  • 47
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    Aquatic sciences 55 (1993), S. 103-111 
    ISSN: 1420-9055
    Keywords: iron(III) (hydr)oxide ; fulvic acid ; iron redox cycling ; dissolution ; surface reactivity ; kinetics
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    Topics: Biology
    Notes: Abstract The kinetics of conversion of iron(III) (hydr)oxides to ferrous iron mediated by fulvic acid have been investigated in order to improve the understanding of the redox cycling of iron at the oxic-anoxic boundary in natural waters. Under the conditions similar to natural waters, fulvic acid is able to reduce the iron(III) (hydr)oxide. The kinetics of the reaction depend on the reactivity of iron(III) (hydr)oxides and the reducing power of the fulvic acid. The rate of reaction is 60 nm/h obtained under following conditions: total concentration of Fe(III) 1.0 × 10−4 M, pH 7.5, fulvic acid 5 mg/L. The rate is considered as a net result of reduction and oxidation in the 〉 FeIII-OH/Fe(II) “wheel” coupled with fulvic acid. In a real natural water system, reductants other than fulvic acid may be of importance. The results obtained in the laboratory, however, provide evidence that the Fe(OH)3(s)/Fe(II) redox couple is able to act as an electron-transfer mediator for the oxidation of natural organic substances, such as fulvic acid by molecular oxygen either in the absence of microorganisms or as a supplement to microbial activity.
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  • 48
    ISSN: 1432-041X
    Keywords: Inner cell mass ; Blastocyst ; Morula ; Implantation ; Rat
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    Topics: Biology
    Notes: Summary The number of trophectoderm (TE) and inner cell mass (ICM) cells was determined by complementmediated lysis and differential staining in rat embryos collected at different times during in vivo preimplantation development. At 90 h after fertilization, two groups of morulae were discriminated according to the presence or absence of detectable ICM cells, and the analysis of their total cell number indicated that acquisition of a permeability seal between TE cells begins at the 14-cell stage. On the other hand, our data confirmed that blastocoele formation occurs after the fourth cleavage division in the rat. The total cell number increased exponentially with time in blastocysts recovered between 90 h and 127 h but the cell kinetics of TE and ICM cells were different. The proportion of ICM cells consequently varied throughout blastocyst development, with a peak value for expanded blastocysts at 103 h. Finally, a linear-quadratic relationship was found between the numbers of TE and ICM cells when all the embryos with a detectable ICM were analysed together.
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  • 49
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    Cellular and molecular life sciences 40 (1984), S. 1008-1010 
    ISSN: 1420-9071
    Keywords: Rat ; ethanol preference ; acetaldehyde self-administration
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    Topics: Biology , Medicine
    Notes: Summary Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.
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  • 50
    ISSN: 1432-0827
    Keywords: Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
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  • 51
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    Calcified tissue international 34 (1982), S. 211-213 
    ISSN: 1432-0827
    Keywords: Rat ; incisor ; ameloblasts ; enamel ; 45Ca autoradiography
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    Topics: Biology , Medicine , Physics
    Notes: Summary Rats were injected with45Ca and horseradish peroxidase to determine the patterns of45Ca incorporation into incisor enamel and the morphological types of the overlying maturation ameloblasts.45Ca autoradiography showed no differences in the patterns of incorporation into enamel between routinely embedded and freeze-dried specimens. Enamel overlaid by ruffle-ended ameloblasts was much more heavily labeled while that overlaid by smooth-ended ameloblasts showed only moderate labeling. The observations lend further support to the hypothesis that the ruffle-ended cells are very active in mineralizing enamel and that the smooth-ended cells are in a passive, restorative phase.
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    Calcified tissue international 51 (1992), S. 137-142 
    ISSN: 1432-0827
    Keywords: Swimming exercise ; Bone histomorphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swin training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2–6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. “Normal” gravity would be an important cofactor in the osteogenic effects of exercise.
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  • 53
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    Keywords: Connective Tissue ; Vitamin D deficiency ; Hydroxyproline excretion ; Glycosaminoglycan excretion ; Rat
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    Topics: Biology , Medicine , Physics
    Notes: Summary The urinary excretion of two connective tissue metabolites was studied in both control and vitamin D deficient rats. Hydroxyproline (HyPRO) excretion was determined after 2, 13 and 22 months (experiment I). It decreased with aging in animals receiving the control diet. On the contrary, this excretion increased as a function of age in vitamin D deficient animals. At the age of 22 months, HyPRO excretion was respectively 31 and 1708 µg a day in control and deficient animals. HyPRO and glycosaminoglycans (GAG) excretion was measured on a group of both control and vitamin D deficient rats at the age of 21 months (experiment II). These results confirm the high excretion of HyPRO in deficient animals. On the contrary, the GAG excretion was higher in control animals than in deficient ones, the mean excretion being respectively 412 and 234 µg a day.
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  • 54
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    Calcified tissue international 25 (1978), S. 75-83 
    ISSN: 1432-0827
    Keywords: Rat ; Fluorosis ; Enamel ; Scanning electron microscopy ; Low temperature incineration
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    Topics: Biology , Medicine , Physics
    Notes: Summary Sixteen 58-day-old male rats of Wistar strain, with a mean body weight of 179 g, were divided into two equal groups. Each group of eight animals was maintained for 70 days on drinking water, ad lib., containing no fluorine (control group) and 100 ppm of fluorine (experimental group). All specimens examined were obtained from the incisal portions of the incisors. The following types of enamel specimens were prepared for scanning electron microscopy: (1) acid-etched specimens; (2) acid-etched specimens followed by low temperature microincineration; and (3) fractured specimens. The enamel formed during high fluoride exposure showed marked hypocalcification, that is, the crystallite density in the prism core and interprismatic region was lower than that of control animals. The organic substances appeared to increase in these regions. These changes were prominent in the outer and middle enamel layers. Such changes following fluoride administration appear to indicate an inhibition of enamel maturation, that is, an inhibition of the mineral deposition and/or an inhibition of organic matrix withdrawal.
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  • 55
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    Calcified tissue international 32 (1980), S. 63-68 
    ISSN: 1432-0827
    Keywords: Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
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  • 56
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    Calcified tissue international 32 (1980), S. 113-122 
    ISSN: 1432-0827
    Keywords: Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
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  • 57
    ISSN: 1432-0827
    Keywords: Rat ; Hypophysectomy ; Dietary phosphorus deprivation
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    Topics: Biology , Medicine , Physics
    Notes: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
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  • 58
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    Keywords: Cortisol ; Cortical bone ; Bone biomechanics ; Rat ; Femur
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    Topics: Biology , Medicine , Physics
    Notes: Summary Doses of 8, 16 (low), 32, 48, 64 (medium), and 150 (high) mg/kg/day of cortisol were administered to groups of 8 growing rats each during 16 days, and their femurs were then submitted to 3-point bending tests at low strain rate. Low doses had no effect. Medium doses, previously shown to improve calcium (Ca) balance and weight gain in the species, augmented diaphyseal elastic and ultimate strength, stiffness, and plastic-to-elastic deformation ratio with respect to untreated controls. This effect was achieved either by enhancing bone mass (volume, sectional moment of inertia, wall/lumen ratio) without changes in material quality parameters (32 mg/kg/day) or, conversely, by increasing bone tissue mechanical properties (stress, modulus of elasticity) not affecting bone geometry (48 and 64 mg/kg/day). The highest dose, known to depress Ca balance and weight gain, impaired diaphyseal mechanical performance in controls by substantially reducing bone mass without major variation in bone material properties, that is, developing a true osteopenic state in mechanical terms. The energy elastically absorbed per unit volume (proportional to the risk of comminute fractures) was greater with the highest dose because of enhanced deformability and diminished bone mass. The biphasic dose-response curves obtained, grossly parallel to those previously demonstrated for metabolic actions of cortisol in the same species, showed that biomechanical repercussion of this treatment on bone depends on different, dose-dependent effects which vary independently in temporal course, intensity, and sign.
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  • 59
    ISSN: 1432-0827
    Keywords: Loading ; Strain ; Modeling ; Rat ; Ulna
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    Topics: Biology , Medicine , Physics
    Notes: Abstract Adaptive changes in bone modeling in response to noninvasive, cyclic axial loading of the rat ulna were compared with those using 4-point bending of the tibia. Twenty cycles daily of 4-point bending for 10 days were applied to rat tibiae through loading points 23 and 11 mm apart. Control bones received nonbending loads through loading points 11 mm apart. As woven bone was produced in both situations, any strain-related response was confounded by the response to direct periosteal pressure. Four-point bending is not, therefore, an ideal mode of loading for the investigation of strain-related adaptive modeling. The ulna's adaptive response to daily axial loading over 9 days was investigated in 30 rats. Groups 1–3 were loaded for 1200 cycles: Group 1 at 10 Hz and 20 N, Group 2 at 10 Hz and 15 N, and Group 3 at 20 Hz and 15 N. Groups 4 and 5 received 12,000 cycles of 20 N and 15 N at 10 Hz. Groups 1 and 4 showed a similar amount of new bone formation. Group 4 showed the same pattern of response but in reduced amount. The responses in Groups 2 and 3 were either small or absent. Strains were measured with single-element, miniature strain gauges bonded around the circumference of dissected bones. The 20 N loading induced peak strains of 3500–4500 μstrain. The width of the periosteal new bone response was proportional to the longitudinal strain at each point around the bone's circumference. It appears that when a bone is loaded in a normal strain distribution, an osteogenic response occurs when peak physiological strains are exceeded. In this situation the amount of new bone formed at each location is proportional to the local surface strain. Cycle numbers between 1200 and 12,000, and cycle frequencies between 10 and 20 Hz have no effect on the bone's adaptive response.
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  • 60
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    Calcified tissue international 55 (1994), S. 33-37 
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Rat ; Orchidectomy ; Exercise ; Strength
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    Topics: Biology , Medicine , Physics
    Notes: Abstract The effect of exercise on castration-induced osteoporosis in 3-month-old male rats weighing 264±4 g at the beginning of the experiment was studied. A testosterone deficiency was induced by orchidectomy (ORC), and the exercise group ran 10 m/minute for 1 hour a day on a treadmill at 0% grade. There were seven groups of eight rats (n=56) randomized into a control group killed at time 0, and sham, ORC and ORC and exercise groups killed at 4 and 8 weeks. ORC reduced body weight gain (with analysis of variance (ANOVA) P〈0.001), and at 4 weeks the body weight was 343±14 g in ORC group and 301±4 g in the ORC and exercise group (P〈0.01). The increase in femoral length was slower in the ORC+exercise groups. The ash weight of the tibia did not decrease significantly after ORC or ORC+ exercise. ORC did not affect 45Ca incorporation, but exercise slightly increased it in the whole tibia 8 weeks after ORC (with ANOVA P=0.057). ORC had significantly lowered the trabecular bone volume in the secondary spongiosa of the distal femur at 4 and 8 weeks, and exercise did not prevent this. This is an opposite finding to our previous study with ovariectomized female rats [12]. ORC also significantly had reduced the osteoblast-lined trabecular bone surface and the number of osteoclasts by 8 weeks after the operation. Exercise increased the osteoblast-lined surface and the number of osteoclasts. The mechanical strength of the femoral neck also was reduced after ORC and this was not prevented by exercise either. In conclusion, ORC reduces bone growth and turnover which leads to osteopenia in growing rats. Moderate treadmill exercise does not reverse the ORC-induced loss of trabecular bone and the reduced mechanical strength of the femoral neck, although it has a positive effect on the osteoblast and osteoclast indices and on calcium incorporation into bone.
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  • 61
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    Calcified tissue international 33 (1981), S. 223-231 
    ISSN: 1432-0827
    Keywords: Protein deficiency ; Bone formation ; Skeletal development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Protein deficiency was produced by freely feeding young rats a 1% lactalbumin diet for 12 weeks in order to study the effects of protein-calorie malnutrition on skeletal development. During the experiment the food and caloric intake and weight of the experimental animals decreased, while those parameters of the control animals progressively increased. However, when gross caloric intake was expressed as a function of the metabolic size of the animal, the caloric consumption was similar for both groups of animals. The protein-deficient animals exhibited micro-radiographic and histological features of an abnormal pattern of endochondral bone formation. Appositional bone growth, as determined by the daily appositional rate and the percentage of endosteal surfaces undergoing active bone formation, was significantly decreased in these animals, as was the percentage of periosteal surfaces exhibiting resorption. Both chemical analyses of the whole bone and electron probe microanalysis in the specific area of actively calcifying bone revealed no significant differences between the mineral content of control and protein-deficient animals. This study distinguishes the effects of protein deficiency from that of combined protein-calorie deprivation and demonstrates that the abnormal skeletal development observed was the result of a decrease in the quantity of bone formed rather than an altered mineral content.
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  • 62
    ISSN: 1432-0827
    Keywords: Rat ; Incisor ; Amelogenesis ; Acid phosphatase ; Ferritin
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    Topics: Biology , Medicine , Physics
    Notes: Summary Acid phosphatase was localized in rat incisor ameloblasts without prior decalcification. Whenβ-glycerophosphate was used as the substrate, an intense reaction was observed in the supranuclear region of the secretory ameloblasts. But the reaction was dramatically reduced at the transitional stage and was very weak in the maturation ameloblasts. Whenp-nitrophenylphosphate was the substrate, the reaction product was consistently seen in the Golgi cisternae and the vesicular components of the ameloblasts at all stages of enamel development. These observations suggest that there are two acid phosphatases in ameloblasts. One is in the secretory ameloblasts and the other in the transition and maturation ameloblasts. X-ray micro-analyses for Fe and Pb showed that Fe and acid phosphatase were in the ferritin-containing vesicles at the later stage of enamel maturation. This evidence suggests that ferritin is digested in these vesicles for the release of the Fe pigment to the enamel. An increase in the number of intercellular bridges between ameloblasts was correlated with the dramatic decrease in height of ameloblasts at the pigment release stage. The ameloblast membranes were acid phosphatase positive at the intercellular bridges whenp-nitrophenylphosphate was the substrate. This activity may be involved in the reduction in the surface area of the ameloblast membranes.
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  • 63
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    Calcified tissue international 22 (1977), S. 77-84 
    ISSN: 1432-0827
    Keywords: Fluoride ; Blood plasma ; Enamel mineralization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract It is postulated that tissue fluid F concentrations are the primary determinants of fluoride effects on bones and developing teeth and that these concentrations are dependent on, or mirrored by, blood plasma F. It has earlier been shown that the plasma F levels are dependent on the dietary F supply as well as on skeletal F concentration. Fasting and post-ingestion or postinjection plasma F levels have been determined in rats on F doses that cause different degrees of enamel fluorosis. The results indicate that temporary peak values rather than elevated fasting values are responsible for the occurrence of enamel fluorosis and that the peak values must approach about 10 μM in order to block enamel formation by the ameloblasts. The diagnostic and prognostic importance of plasma F determinations is discussed.
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  • 64
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    Calcified tissue international 34 (1982), S. 376-381 
    ISSN: 1432-0827
    Keywords: Matrix vesicles ; Bone ; Actin ; Rat
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    Topics: Biology , Medicine , Physics
    Notes: Summary Preliminary indications of the occurrence of actin and myosin in crude matrix vesicle preparations have been reported previously. In the present study extracellular matrix vesicles from rat alveolar bone were isolated. They were further purified by a sucrose density gradient. SDS-polyacrylamide gel electrophoresis of the purified vesicles revealed the presence of a polypeptide with a molecular weight of 43 K daltons and with electrophoretic mobility identical to that of blood platelet actin. The limited proteolysis of both 43 K dalton vesicular polypeptide and actin byStaphylococcus aureus-V8-protease revealed three fragments with identical electrophoretic mobility. In addition, the vesicular preparations inhibited the activity of DNase I, a property typical of actin monomers. Filamentous material extracted from matrix vesicles showed ultrastructural features of F-actin. Reaction of this material with heavy meromyosin resulted in arrowhead formation, which is characteristic of acto-heavy meromyosin. The occurrence of actin in extracellular matrix vesicles may account for their budding from the osteoblastic plasma membrane, their possible motility in the matrix, and maintenance of the spherical shape.
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  • 65
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    Keywords: Bone alkaline phosphatase ; Rat ; Vitamin D ; Sorbitol
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    Topics: Biology , Medicine , Physics
    Notes: Summary In the femoral extremities of the adult rat containing the metaphysis, the epiphyseal cartilage, and the epiphysis, four alkaline phosphatase (AP) forms were distinguished on polyacrylamide gel electrophoresis. Two soluble forms were present in the 160,000 g supernatant: one of Mr 165 kDa and another of Mr 110–115 kDa, which exhibited a strong catalytical activity. Moreover, from the pellet, three membrane-bound forms of Mr 130, 110–115, and 100 kDa could be extacted with sodium deoxycholate. When denaturated AP was visualized by postelectrophoretic autoradiography of the phosphorylated intermediates, subunits always appeared as three monomers of Mr 75–80, 60–70, and 50–60 kDa. As four native forms but only three types of subunits were found to be present in the femur, it seems that, apart from homodimers, some heterodimers could also occur. Three types of diets were administered to three groups of rats for 5 weeks. Two are known to disturb bone mineralization: (1) a vitamin D3-deficient diet, and (2) the same as (1) but enriched with 12% sorbitol. The third was a normal diet containing vitamin D3. Concerning the effects on AP of dietary sorbitol and the vitamin D3-deficient diet, it was found that rats receiving the diet supplemented with sorbitol showed a substantial rise in the activity of the Mr 165 kDa form with the concomitant appearance of a new monomer of Mr 100 kDa. In contrast, rats fed the vitamin D3-deficient diet always displayed an increase in enzyme activity, principally of the Mr 100 and 110 kDa forms. In conclusion, the femur extracts of normal rats contained different forms of AP: either soluble 110–115 and 165 kDa forms or membrane-bound 130, 110–115, and 100 kDa forms. The administration of sorbitol-enriched diet induced a marked increase of the 165 kDa form whereas the administration of vitamin D3-deficient diet increased the 100 and 110 kDa forms.
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  • 66
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    Calcified tissue international 35 (1983), S. 107-110 
    ISSN: 1432-0827
    Keywords: Calcium ; Glucocorticoid ; Vitamin D ; Osteoporosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Eighty-eight adult male Sprague-Dawley rats were given a diet with either (a) 0.5% Ca and 0.6% P or (b) 0.01% Ca and 0.6% P. Osteopenia was created by adding prednisolone to the diet. The prophylactic effect of oral 1,25(OH)2D3 on the osteopenia was studied. It was found that prednisolone osteopenia in the rat was associated with defective Ca absorption. By giving an oral dose of 1,25(OH)2D3, it was possible to maintain normal Ca absorption during prednisolone treatment and to prevent the bone loss. No significant hypercalcemia or any kidney calcifications were seen. These results are in contrast to earlier findings, in which subcutaneous administration of 1,25(OH)2D3 failed to prevent prednisolone osteopenia because of its tendency to increase bone resorption.
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    Calcified tissue international 51 (1992), S. 30-34 
    ISSN: 1432-0827
    Keywords: PTHRP ; Anabolic ; Rat ; Bone ; Potency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1–34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1–34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1–74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1–74) (1 and 2 nmol/100 g body weight, bw), bPTH(1–34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxypro-line content. Results of these studies indicate that PTHRP (1–74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period.
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    Calcified tissue international 54 (1994), S. 150-154 
    ISSN: 1432-0827
    Keywords: Vitamin D analog ; KH1060 ; Kidney transplantation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract KH1060 is a new 20-epi-vitamin D3 analog, which has exerted a considerable immunosuppressive potency in vitro. We have tested in vivo the effect of KH1060 on the suppression of renal allograft rejection in the rat. Allogenic kidney transplantation from DA donor rats to Lewis recipient rats treated intraperitoneally with KH1060 in doses from 0.2 to 6 μg/kg/day, or saline (placebo group), or CyA 10 mg/kg/day for 10 days (positive control group), was performed. Median graft survival time in KH1060-treated groups was 7–9 days, in the placebo group 6 days, whereas CyA led to long-term graft survival, 34 days in 50% of rats and 〉100 days in 50% of rats. In vivo, KH1060 failed to prolong renal allograft survival considerably, and led to development of hypercalcemia. Our results stress the existence of a large discrepancy between the in vitro and in vivo immunoregulatory effects of this vitamin D analog.
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  • 69
    ISSN: 1432-0827
    Keywords: Bone mechanics ; Bone composition ; Vitamin D3 ; Corticosteroid ; Rat
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    Notes: Abstract The effects of 1α-vitamin D3 were studied for 6 months in 2-month-old male and female rats on a moderately low calcium diet with or without low-dose prednisolone treatment. Both cortical bone mechanical and biochemical properties were examined. Femoral bone specimens were subjected to torsional loading tests. With age, bone strength and stiffness increased in both sexes, accompanied by an increased degree of mineralization (bone ash and calcium concentrations). During growth, strength and stiffness increased more in male than in female rats. When 1α-vitamin D3 (0.5 μg/kg/day) was given alone, bone mechanical competence improved significantly whereas insulin-like growth factor-I (IGF-I) and calcium concentrations in the bone matrix were significantly reduced. Treatment with low-dose prednisolone (0.5 mg/kg/day) alone did not influence bone mechanical properties compared with intact control rats (without prednisolone) although a significant reduction in calcium concentration and an increased phosphorus concentration were measured. A combined therapy with prednisolone and 1α-vitamin D3 significantly increased bone strength, toughness, and stiffness compared with control bones. Both mineralization degree (ash and calcium concentration) and IGF-I concentration were decreased. We conclude that (1) mechanical properties of rat cortical bones improve relatively more in males compared with agematched females during growth which is related to increased bone mass and size, (2) low-dose prednisolone treatment does not change mechanical properties in males, and altered them only nonsignificantly in females despite a change in mineralization degree in both sexes; (3) treatment with 1α-vitamin D3 results in a consistent increase in mechanical competence of the bone accompanied by a significant decrease in IGF-I concentration in the bone matrix.
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    International journal of biometeorology 34 (1990), S. 24-27 
    ISSN: 1432-1254
    Keywords: Cold-induced thermogenesis ; Peripheral nervous system ; Respiratory quotient ; Rat
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    Topics: Geography , Physics
    Notes: Abstract Cold-exposed rats show a reduction in the respiratory quotient which is indicative of a relative shift from carbohydrates to lipids as substrates for oxidative metabolism. In the present study, the effects of food deprivation and cold exposure on the respiratory quotient were observed. In addition, the involvement of the three main branches of the peripheral nervous system (sympathetic, parasympathetic, and somatic) was investigated by means of synaptic blockade with propranolol, atropine, and quinine, respectively. Both propranolol and quinine blocked the cold-induced decrease in respiratory quotient and increase in heat production, whereas atropine had only minor and very brief effects. It is concluded that both the sympathetic and somatic branches are involved in the metabolic changes associated with cold-induced thermogenesis and that the increase in metabolic heat production involves a shift from carbohydrate to lipid utilization irrespective of which of the two branches is activated.
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    European journal of clinical pharmacology 42 (1992), S. 107-110 
    ISSN: 1432-1041
    Keywords: Phenobarbitone ; Cerebral malaria ; P.falciparum ; kinetics ; drug absorption ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of intramuscular phenobarbitone 7 mg·kg−1 was studied in 11 Karen children aged between 1.7 and 11 y with severe falciparum malaria. Eight of the children were comatose. Clinical findings were compared with those in 9 further children with severe malaria of similar age range (four of whom were unconscious), who received an identical placebo. One child, who had received placebo, had repeated convulsions and died 1 h after admission to hospital. The remainder made an uncomplicated recovery. There were no convulsions subsequent to treatment, although the study was too small to assess anticonvulsant efficacy. There was no observable toxicity, but phenobarbitone recipients had a significant tendency to deepen in their level of coma or to become sleepy within the 4 h after drug administration. Phenobarbitone was rapidly absorbed, reaching a mean (range) peak concentration of 34.2 [29.3–42.6] μmol·l−1 in a median (range) of 4 (2.5–12) h. These values are comparable to those previously reported in healthy children and in children with febrile convulsions. Intramuscular phenobarbitone is well absorbed in children with severe malaria; the optimum prophylactic anticonvulsant dose remains to be determined.
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  • 72
    ISSN: 1432-1041
    Keywords: Atrial natriuretic peptide ; kinetics ; ageing
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the influence of age on the kinetics of atrial natriuretic peptide (ANP) in man, human (99–126) ANP 2.0 μg·min−1 was infused IV for 60 min in 8 healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both baseline ANP values and the levels at the end of infusion were higher in the elderly subjects. The mean residence time of ANP in the two age groups was not significantly different, whereas total body clearance (CL) was markedly diminished in the elderly as compared to the young subjects (mean±SD 3.1±1.0 l·min−1 and 6.2±4.1 l·min−1, respectively). The apparent volume of distribution at steady state was lower in the elderly than in the young, but the difference was not significant (mean±SD 44±19 and 103±111, respectively. The decrease in CL largely explained the higher ANP levels found in the elderly subjects. The MRT and the plasma half-life of the terminal phase did not differ between the two groups. In the elderly but not in the young subjects the calculated endogenous creatinine clearance was closely correlated with the CL (r=0.90, P〈0.001), thereby emphasizing the importance of the kidney in the metabolic clearance of ANP in the elderly.
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  • 73
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    European journal of clinical pharmacology 42 (1992), S. 461-462 
    ISSN: 1432-1041
    Keywords: Talinolol ; Sulfasalazine ; β-adrenoceptor-blocking drugs ; absorption ; drug interaction ; kinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of talinolol (TA) 50 mg was investigated without and together with the co-administration of sulfasalazine (SASP) 4 g in 11 healthy young volunteers, in order to clarify gastrointestinal transit of TA. Without SASP, the tmax of TA was 2.8 h, Cmax was 112 ng·ml−1 and the half life was 12 h; the AUCo-t was 958 ng·ml−1·h. In the case of concomitant administration of SASP, TA was found only in serum from 3 individuals, with a Cmax of 23 ng·ml−1 and a mean AUCo-t of 84 ng·ml−1·h. TA was not detectable in 5 subjects and it was at the limit of detection (2 ng·ml−1) in 3 subjects. Pharmacokinetic analysis was not possible in any of those individuals. The reason for the interaction appears to be the adsorption of TA by SASP. An interval of 2–3 h should elapse between giving SASP and other drugs.
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  • 74
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    European journal of clinical pharmacology 44 (1993), S. 231-235 
    ISSN: 1432-1041
    Keywords: Carbamazepine ; kinetics ; population pharmacokinetics ; bioavailability ; controlled release ; non-linear model
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption properties of a conventional tablet of carbamazepine (T) and a controlled release form of carbamazepine (TCR) have been compared using a nonlinear mixed effect model (NONMEM). Plasma carbamazepine concentration data were obtained from an open, steady-state, crossover bioavailability study in which 494 measurements were obtained from 13 patients, with an equal number of samples per patient for each dosage form. The pharmacokinetic model used was a one-compartment open model with first-order absorption and elimination. The objective function was used as a measure of the goodness of fit of the model to the data. Body weight was an important determinant of carbamazepine clearance (CL) but not volume of distribution (V). Accounting for the interindividual variability in volume of distribution did not significantly influence the objective function. Including different rates of absorption (ka) for the two dosage forms resulted in a significant improvement in the objective function, as well as reducing the interindividual variability in the rate of absorption. Adding a parameter for relative bioavailability (f) of TCR improved the objective function statistically, but an unrealistic value for V was obtained, and the absorption and elimination rates appeared to be transposed in the classical “flip-flop” manner. Fixing V to the value obtained before introducing f did not change the objective function and permitted estimation of f without the confounding influence of excessive parameters. The final population parameter estimates (standard error of estimate) were: CL, 0.0522 (0.0019) l·h−1·kg−1; V, 63.7 (FIXED)l; kaT, 0.312 (0.064) h−1; kaTCR, 0.149 (0.016) h−1; f, 1.01 (0.0326); variance (additive) in CL, 0.291 (0.083) (l·h−1·kg−1)2; residual intrasubject error variance (additive), 0.572 (0.082) (mg·l−1)2. The 95% confidence interval of the extent of absorption (f) of 93.6%–107.4% was well within the generally accepted range of ±20%, while the rate of absorption of Tegretol CR was significantly slower than that of Tegretol, as expected for a controlled release product.
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  • 75
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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
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    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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  • 76
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    European journal of clinical pharmacology 22 (1982), S. 225-228 
    ISSN: 1432-1041
    Keywords: pinazepam ; N-desmethyldiazepam ; kinetics ; metabolism ; human
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    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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  • 77
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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
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    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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  • 78
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    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
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    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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  • 79
    ISSN: 1432-1041
    Keywords: prizidilol ; antihypertensive effect ; acute and long-term blood pressure control ; plasma renin activity ; acetylator phenotype ; antinuclear antibodies ; side effects ; kinetics
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    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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  • 80
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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
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    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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  • 81
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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
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    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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  • 82
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    European journal of clinical pharmacology 27 (1984), S. 491-494 
    ISSN: 1432-1041
    Keywords: amiodarone ; kinetics ; volunteers
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    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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  • 83
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    European journal of clinical pharmacology 10 (1976), S. 43-48 
    ISSN: 1432-1041
    Keywords: Spironolactone ; acetylsalicylic acid ; fludrocortisone ; kinetics ; pharmacology ; interaction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of 600 mg acetylsalicylic acid (ASA) on the renal excretion and clearance of canrenone, the principal unconjugated metabolite of spironolactone, was examined in a double-blind crossover study in six healthy subjects. ASA significantly reduced the urinary excretion, and the fractional excretion, of canrenone between 4 — 6 hours after administration of 50 mg spironolactone. The pharmacological activity of spironolactone, assessed simultaneously by alterations in fludrocortisone-induced urinary electrolyte changes, was slightly but not significantly reduced. The reductions in urinary canrenone excretion correlated with changes in the urinary log 10 Na/K ratio. The results suggest that canrenone may be actively secreted at the proximal renal tubule, and that secretion is blocked by ASA or its conjugates. This is a possible mechanism for the pharmacological interaction between ASA and spironolactone which has been described previously.
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  • 84
    ISSN: 1432-1041
    Keywords: Theophylline ; kinetics ; apnea ; premature newborns ; developmental pharmacology
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Aminophylline (theophylline-ethylenediamine) was administered to 27 premature newborns to prevent apneic spells. Of the 22 patients monitored for theophylline concentration, a therapeutic blood level was reached in 19 in 1–2 days, and 3 stayed below it. ‘Toxic’ blood levels (≥20 µg/ml) were reached in 3 cases, one of whom showed signs of toxicity. Theophylline treatment was not efficient in the prevention of apnea when a serious underlying disease was present. Theophylline blood half-life (mean : 27.0 h) and clearance (mean 12.9 ml/h/kg) confirmed the slow elimination pattern of the drug in the premature infant.
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  • 85
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 86
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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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  • 87
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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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    European journal of clinical pharmacology 24 (1983), S. 41-47 
    ISSN: 1432-1041
    Keywords: quinidine ; digoxin ; interaction ; kinetics ; absorption ; elimination
    Source: Springer Online Journal Archives 1860-2000
    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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  • 89
    ISSN: 1432-1041
    Keywords: lorcainide ; oral antiarrhythmic therapy ; nor-lorcainide ; first-pass metabolism ; kinetics ; alternative dosage ; regimens
    Source: Springer Online Journal Archives 1860-2000
    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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  • 90
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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
    Source: Springer Online Journal Archives 1860-2000
    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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    European journal of clinical pharmacology 23 (1982), S. 261-266 
    ISSN: 1432-1041
    Keywords: mexiletine ; rifampicin ; kinetics ; enzyme induction ; excretion ; antipyrine clearance ; dosage adjustment
    Source: Springer Online Journal Archives 1860-2000
    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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  • 92
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    Current genetics 23 (1993), S. 15-18 
    ISSN: 1432-0983
    Keywords: Yeast ; Rat ; Ribosomal protein ; 60S Ribosomal subunit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary This communication reports on a single-copy gene of Saccharomyces cerevisiae which is homologous to the rat ribosomal protein gene L21. The yeast and the rat genes show 59% identity in DNA sequences and in the predicted protein sequences. This yeast gene is, therefore, assumed to code for an as yet unassigned ribosomal protein (URP1). The URP1 open reading frame is 480 nucleotides long and can encode a protein of about Mr 18 200. Like most of the other known ribosomal protein genes, URP1 is interrupted by an intron in its 5′ terminal part and it is preceeded by upstream sequence elements which usually regulate transcription of these genes. Northern blot analysis reveals that the URP1 gene is actually expressed in vivo.
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  • 93
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    European journal of clinical pharmacology 23 (1982), S. 87-92 
    ISSN: 1432-1041
    Keywords: phenobarbital ; epilepsy ; kinetics ; bioavailability ; epileptic patients
    Source: Springer Online Journal Archives 1860-2000
    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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  • 94
    ISSN: 1432-1041
    Keywords: metoprolol ; age ; disposition ; elderly subjects ; kinetics ; metabolism ; alpha-OH-metoprolol
    Source: Springer Online Journal Archives 1860-2000
    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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  • 95
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    European journal of clinical pharmacology 21 (1981), S. 149-153 
    ISSN: 1432-1041
    Keywords: cinromide ; epilepsy ; kinetics ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    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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  • 96
    ISSN: 1432-1041
    Keywords: hyperthyroidism ; propranolol ; methimazole ; metoprolol ; atenolol ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    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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  • 97
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 98
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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
    Source: Springer Online Journal Archives 1860-2000
    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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  • 99
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    European journal of clinical pharmacology 27 (1984), S. 367-369 
    ISSN: 1432-1041
    Keywords: flurbiprofen ; syrup ; suppository ; kinetics ; children ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    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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  • 100
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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
    Source: Springer Online Journal Archives 1860-2000
    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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