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  • pharmacokinetics  (760)
  • Ultrastructure  (600)
  • Electron microscopy  (470)
  • kinetics
  • man
  • Springer  (1,983)
  • American Chemical Society
  • 1985-1989  (944)
  • 1975-1979  (1,039)
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  • 1
    Electronic Resource
    Electronic Resource
    Das Rückstandsverhalten von Chloramphenicol nach intramuskulärer Applikation beim Schwein (1985)
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    Details
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020458
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  • 2
    Electronic Resource
    Electronic Resource
    Human vitamin C requirements (1987)
    Springer
    European journal of nutrition 26 (1987), S. 125-137 
    Details
    ISSN: 1436-6215
    Keywords: vitamin C ; functions ; kinetics ; pool ; saturation ; requirements ; RDA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Die Bedeutung von Vitamin C für den menschlichen Organismus wird aus den wichtigen Funktionen ersichtlich, an denen das Vitamin beteiligt ist, wie zum Beispiel Kollagen- und Karnitinsynthesen. In neuerer Zeit entdeckt wurde seine Rolle bei der Noradrenalinsynthese, der Inaktivierung von freien Radikalen sowie der Verhinderung der Nitrosaminbildung. Die Vielfalt dieser Vitamin-C-abhängigen Funktionen läßt erkennen, daß die Bedarfsfestsetzung für Vitamin C nicht nur die Verhütung der Mangelkrankheit Skorbut anvisieren, sondern auch berücksichtigen sollte, daß alle diese Funktionen jederzeit genügend Vitamin C zur Verfügung haben müßten, um optimal reagieren zu können. Das Konzept der Gewebesättigung kommt diesem Ziel am nächsten. Studien mit einem kinetischen Modell haben ergeben, daß eine Sättigung mit täglicher Einnahme von 100 mg Vitamin C bei Nichtrauchern und von 140 mg bei Rauchern eintritt, Mengen, die als optimale Werte gelten können. Bei verschiedenen Krankheiten dürfte der Bedarf höher sein; die genauen Mengen müssen jedoch erst noch ermittelt werden.
    Notes: Summary The importance of vitamin C is reflected in its multifunctional roles which include participation in collagen and carnitine syntheses, promotion of iron absorption and the more recently discovered participation in noradrenaline synthesis, inactivation of free radical chain reactions, prevention of N-nitroso compound formation and more. Given the many extra-antiscorbutic functions of the vitamin, the Recommended Dietary Allowances (RDA) should not just prevent deficiency disease but should aim at providing sufficient amounts for all vitamin C-dependent functions to operate at full capacity. The concept of vitamin C tissue saturation is best able to meet this demand. The use of kinetic models has shown that the body pool is saturated with a daily intake of 100 mg vitamin C in non-smokers and 140 mg in smokers, amounts that may be regarded as optimal RDA values. Certain disease states may be accompanied by still higher vitamin C requirements but the exact amounts are not yet known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02019608
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  • 3
    Electronic Resource
    Electronic Resource
    On the theory of photoadsorption kinetics of a-Se colloids: The thermal activation energy and compensation effect (1988)
    Springer
    Colloid & polymer science 266 (1988), S. 958-964 
    Details
    ISSN: 1435-1536
    Keywords: a-Se colloids ; photoadsorption ; kinetics ; activation energy ; compensation effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract In this study, a model is developed to explain in microscopic terms the results obtained from thermally activated photoadsorption experiments in a-Se colloids. The observed compensation effect can be described for two different cases. At low efficiency adsorption, the process is controlled by the potential at the boundary layer. In the high efficiency adsorption case, the process is controlled by diffusion transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01410853
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  • 4
    Electronic Resource
    Electronic Resource
    On the morphology of oriented nylon-12 (1985)
    Springer
    Colloid & polymer science 263 (1985), S. 116-119 
    Details
    ISSN: 1435-1536
    Keywords: Electron microscopy ; staining ; morphology ; nylon-12 ; orientation
    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 morphology of drawn and annealed sheets of nylon-12 was investigated by transmission electron microscopy of stained sections, and the results compared with equivalent small-angle X-ray scattering (SAXS) patterns. A three-component structure was observed, consisting of crystalline (C) and amorphous (A) regions in the microfibrils and an interfibrillar component whose density was deduced to be intermediate between that of the C and A regions. The crystallite width was given satisfactorily by a Guinier analysis of the SAXS profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01412785
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  • 5
    Electronic Resource
    Electronic Resource
    Laser temperature jump experiments with fluorescence polarization and turbidity detection on the phase transition of single shell vesicles of dimyristoylphosphatidylcholine (1985)
    Springer
    Colloid & polymer science 263 (1985), S. 484-493 
    Details
    ISSN: 1435-1536
    Keywords: Phospholipid bilayer ; kinetics ; laser temperature jump ; phase transition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The iodine-laser temperature-jump technique has been used to investigate the main phase transition in single shell vesicles of dimyristoylphosphatidylcholine. The probe molecules DPH and TMA-DPH were incorporated into the lipid bilayer and laserT-jump experiments with turbidity and flourescence polarization detection were performed. We found three well separated relaxation processes between 5 μs and 10 ms. The relaxation signals showed strong cooperativity in the relaxation times as well as in their corresponding amplituedes. We attributed the relaxation to the formation and dissolution of clusters of different order inside the bilayer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01458339
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  • 6
    Electronic Resource
    Electronic Resource
    Radical desorption in the emulsion polymerisation of vinyl monomers (1987)
    Springer
    Colloid & polymer science 265 (1987), S. 58-64 
    Details
    ISSN: 1435-1536
    Keywords: Polymerisation ; emulsion ; styrene ; methylmethacrylate ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The dependence of emulsion polymerisation rates on a number of important parameters is considered. Attention is paid to the use of seeded emulsion systems for the evaluation of radical desorption coefficients (k o). Experimental conditions are shown to be important. When the average number of radicals per particle is low, large changes in the rate coefficient for chain termination do not have a large effect on the kinetics. With styrene and methylmethacrylate, radical re-absorption by the polymer particles is shown to be important and radical capture efficiences can be high. Consistency is established between the results of a number of workers and values fork o are shown to be lower than those calculated from chain transfer rates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01422665
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  • 7
    Electronic Resource
    Electronic Resource
    The effects of aqueous solvent structure on the mutarotation kinetics of glucose (1977)
    Springer
    Journal of solution chemistry 6 (1977), S. 203-216 
    Details
    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
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00646739
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  • 8
    Electronic Resource
    Electronic Resource
    Solvent effects on the acid-catalyzed hydrolysis of tetramethylurea (1976)
    Springer
    Journal of solution chemistry 5 (1976), S. 163-169 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00654333
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  • 9
    Electronic Resource
    Electronic Resource
    Ultrasonic absorption of the oxyethylene group in aqueous nonelectrolyte solutions (1986)
    Springer
    Journal of solution chemistry 15 (1986), S. 221-229 
    Details
    ISSN: 1572-8927
    Keywords: Ultrasonics ; kinetics ; aqueous solution ; triethylene glycol monobutyl ether
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The ultrasonic absorption from 6.5 to 220 MHz and velocities at 2.5 MHz have been measured in aqueous solution of triethylene glycol monobutyl ether as a function of concentration at 25°C. A single relaxational excess absorption, observed from 0.60 to 2.5 mol-dm−3, is attributed to a perturbation of an equilibrium associated with solute-solvent interaction. Rate constants for the forward and reverse processes have been determined from the concentration dependence of the relaxation frequency, and the influence on the water structure by an addition of the solute has been considered. Solution densities were also measured in order to obtain the expansivity of the solution. The standard volume and enthalpy changes of the reaction have been estimated from the concentration dependence of the maximum excess absorption per wave length. A linear relationship between the number of oxyethylene groups and the free energy change between bonded water and nonbonded water is established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00646689
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  • 10
    Electronic Resource
    Electronic Resource
    The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 432-433 
    Details
    ISSN: 1420-9071
    Keywords: Interferon ; immunomodulator ; catabolism ; pharmacokinetics ; administration routes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary When human recombinant interferon-α2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02118644
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  • 11
    Electronic Resource
    Electronic Resource
    Coquille de l'oeuf de caille: Étude ultrastructurale et cristallographique (1978)
    Springer
    Calcified tissue international 25 (1978), S. 145-159 
    Details
    ISSN: 1432-0827
    Keywords: Bird egg shell ; Ultrastructure ; Calcification ; Electron diffraction ; Microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The egg-shell of Japanese quail was studied by several techniques. Semithin sections (1μm thick) of non-decalcified shell were observed by normal and polarized light microscopy. Thin sections of non-decalcified shell, examined by transmission electron microscopy, permitted us to observe the forms and dimensions of crystals of calcite within different layers of the shell: mammilary layer, layer of cones, palissade layer and surface crystal layer. There appears to be two distinct zones in the layer of cones as well as in the superficial crystal layer. Electron microdiffraction revealed the orientation of calcite crystals in the columns. Some crystal defects (twins?) were described and the possibility of their artefactual formation during ultramicrotomy is discussed. Localization of Ca, Mg, P and S were made by X-ray microanalysis of semithin sections. This technique shows that shell membranes, and chiefly the true cuticle, are also mineralized but, in these layers, minerals are not crystallized. Otherwise the distribution of Mg is not uniform throughout the shell thickness; it is less concentrated in the external zone of the layer of cones. These results together with observation of developing shells by scanning electron microscopy allowed us to propose a scheme for shell organization of the quail egg. This organization was related with decalcification which occurs during hatching.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02010763
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  • 12
    Electronic Resource
    Electronic Resource
    The morphology of bone mineral crystals (1978)
    Springer
    Calcified tissue international 25 (1978), S. 217-222 
    Details
    ISSN: 1432-0827
    Keywords: Bone mineral ; Electron microscopy ; X-ray diffraction ; Dark field
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Electron microscopical observations of the size and shape of bone mineral crystallites have not been in complete agreement with X-ray diffraction findings. The two prevalent viewpoints consider bone mineral crystals to be either rod, or plate like in habit. There appears to be agreement that the smallest dimension of the crystals is about 5 nm, but there is discrepancy in the reported c-axial lengths. The method of dark field imaging is used to obtain a quantitative measurement of the c-axial length distribution in rabbit, ox and human bone: mean c-axial lengths 32.6 nm, 36.2 nm and 32.4 nm, respectively, show no significant difference at the 5% level to the mean c-axial length measured by X-ray line broadening. Both bright and dark field images strongly suggest that bone mineral has a plate like form. Reasons for past discrepancies are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02010772
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  • 13
    Electronic Resource
    Electronic Resource
    Ultrastructural and microanalytical aspects of developing osteodentin in rat incisors (1977)
    Springer
    Calcified tissue international 24 (1977), S. 215-222 
    Details
    ISSN: 1432-0827
    Keywords: Mineralization ; Osteodentin ; Intracellular ; Ultrastructure ; Microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Newly formed osteodentin obtained from the anterior extremities of fetal or young rat incisors was observed by means of electron microscopy and electron probe X-ray microanalysis. Cells related to osteodentin formation frequently showed membrane bound intracellular bodies containing varying amounts of fine, needle-shaped crystals, which were identified as apatite. The intracellular clusters of apatite crystals were extruded from the cells through membrane fusion or cellular degeneration. These extracellular clusters seemed to be gradually incorporated into the mineralizing collagenous matrix, which developed around them. Frequent occurrence of dense, dotshaped or filamentous profiles suggested that the dense bodies seen in the perinuclear regions or in the Golgi area were the sites of crystal formation. Energy dispersive X-ray point analysis showed that the intracellular or extracellular apatite clusters contained sulfur in a concentration higher than was present in the mineralizing collagenous matrix. Furthermore, wave dispersive X-ray line analysis showed that the concentration of sulfur was higher in the osteodentin matrix than in the dentin matrix. The sulfur detected is presumed to be contained in acid mucopolysaccharides, which were distributed more heavily in the osteodentin matrix than in the dentin matrix. On the basis of these data, it was concluded that the unique chemical and structural characteristics of the osteodentin result primarily from the incorporation of apatite clusters of intracellular origin and associated acid mucopolysaccharides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02223319
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  • 14
    Electronic Resource
    Electronic Resource
    Studies on the biology of fish bone. III. Ultrastructure of osteogenesis and resorption in osteocytic (cellular) and anosteocytic (acellular) bones (1979)
    Springer
    Calcified tissue international 28 (1979), S. 43-56 
    Details
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteogenesis ; Fish bone ; Osteocytes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The comparative ultrastructure of fish bone osteogenesis and resorption induced by scale removal was described in the osteocytic (cellular-boned)Carassius auratus and the anosteocytic (acellular-boned)Tilapia macrocephala. Osteocytes, present in osteocytic bone, were lacking in anosteocytic bone. In osteocytic bone the osteoblast secreted a collagenous preosseous matrix in which it became enmeshed and then was termed a preosteocyte. When the preosseous matrix mineralized, the preosteocyte was termed an osteocyte and was completely surrounded by bone. In anosteocytic bone the osteoblasts receded from the mineralizing front and never became trapped as osteocytes. During resorption, types A and B resorptive cells, present in both bone types, invaded the matrix and demineralized the osseous zone. These cells were characterized by large amounts of granular endoplasmic reticulum and intracellular inclusions containing crystal-like material. Although functionally similar to mammalian osteoclasts, these cells lacked a characteristic ruffled border and were not multinucleated. The osteocytes of cellular bone did not appear to be involved during demineralization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441217
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  • 15
    Electronic Resource
    Electronic Resource
    Time-related changes in the ultrastructure of osteoclasts after injection of parathyroid hormone in young rats (1979)
    Springer
    Calcified tissue international 27 (1979), S. 129-135 
    Details
    ISSN: 1432-0827
    Keywords: Parathyroid hormone ; Osteoclasts ; Electron microscopy ; Morphometry ; Metaphysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of parathyroid hormone (PTH) on the size of the osteoclasts, nuclei, ruffled borders, and clear zones in long bones of thyroparathyroidectomized (TPTX) rats were quantitated as a function of time. These data were compared with the number of osteoclasts in the bone and with plasma calcium levels. A significant increase in the average size of the ruffled borders was demonstrated 30 min after injection of 50 U of purified bovine PTH, and of the clear zones 30–90 min after PTH. This was followed at 90 min by an increase in the average size of the cells. The sizes of ruffled borders and clear zones dropped sharply to control levels after 6 h, whereas the size of the cells remained elevated up to 12 h and returned to control values at 24 h. Plasma calcium levels were increased, but not significantly, between 30 min and 6 h. An increase in the number of osteoclasts was significant after 12 h. Removal of the parathyroid glands did not diminish the normal activity of osteoclasts. In animals with intact glands injection of 50 U of PTH did not cause a significant change in cell size or resorbing apparatus. It is concluded that PTH acts to rapidly stimulate the bone resorptive activity of osteoclasts and to cause a delayed increase in their number.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441175
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  • 16
    Electronic Resource
    Electronic Resource
    Origin and direction of replication in mitochondrial plasmid DNAs of broad bean,Vicia faba (1988)
    Springer
    Current genetics 14 (1988), S. 163-170 
    Details
    ISSN: 1432-0983
    Keywords: Plant mtDNA ; Electron microscopy ; Restriction enzymes ; Hairpin structures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Broad bean (Vicia faba) mitochondrial DNA (mtDNA) includes three circular plasmids: mt-plasmid 1 (1,704 ntp), mt-plasmid 2 (1,695 ntp) and mt-plasmid 3 (1,476 ntp). Partially replicated circular forms of these mt-plasmids have been observed in electron microscope preparations. Restriction enzymes that cleave either mt-plasmid 2 (but not mt-plasmids 1 and 3) or mt-plasmid 3 (but not mt-plasmids 1 and 2) were used to generate linear forms of partially replicated mt-plasmid 2 and mt-plasmid 3 molecules. Analyses of these linearized replicative intermediates, observed by electron microscopy, indicated that in both mt-plasmid 2 and mt-plasmid 3 replication originates at a specific location and proceeds in the same, single direction around the molecules. The replication origins of mt-plasmid 2 and mt-plasmid 3 map close to sequences that can fold into hairpin structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569340
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  • 17
    Electronic Resource
    Electronic Resource
    Heterogeneity of circular mitochondrial DNA molecules from sugar beet with normal and male sterile cytoplasms (1986)
    Springer
    Current genetics 10 (1986), S. 695-700 
    Details
    ISSN: 1432-0983
    Keywords: Sugar beet ; Cytoplasmic male sterility ; Mitochondrial DNA ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Mitochondrial (mt) DNAs from normal (N) and male sterile (S) cytoplasms of sugar been have been isolated and investigated by electron microscopy. The results showed that mtDNA was composed of a heterogeneous population of circular molecules. Their contour lengths varied from 0.28 to 51 μm, but unlike in the case of maize, a large difference was not observed in the distribution of molecular classes greater than 1.0 μm between N and S cytoplasms of sugar beet. On the other hand, N and S cytoplasms were shown to contain their own characteristic combinations of small circular mtDNA species with lengths between 0.28 μm and 0.6 μm. Mitochondrial DNAs from various sources of male-sterile cytoplasms were analyzed by agarose gel electrophoresis to determine the extent of cytoplasmic variation. Additional low molecular weight DNA bands appeared in all male-sterile lines examined, and as a result, three distinctive banding patterns were recognized. These data are in general agreement with those based upon restriction endonuclease digestion of mt and chloroplast DNAs and the genetic analysis of fertility restoration in test crosses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410918
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  • 18
    Electronic Resource
    Electronic Resource
    Characteristic views of prokaryotic 50S ribosomal subunits (1987)
    Springer
    Journal of molecular evolution 26 (1987), S. 347-357 
    Details
    ISSN: 1432-1432
    Keywords: Ribosome structure ; Electron microscopy ; Image analysis ; Evolutionary lineages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Multivariate statistical analysis and classification techniques are powerful tools in sorting noisy electron micrographs of single particles according to their principal features, enabling one to form average images with an enhanced signal-to-noise ratio and a better reproducible resolution. We apply this methodology here to determining the characteristic views of the large (50S) ribosomal subunits from the eubacteriumEscherichia coli and the archaebacteriaMethanococcus vannielii, Sulfolobus solfataricus, andHalobacterium marismortui. Average images were obtained of the subunit in the common crown and kidney projections, but views of the particle in orientations intermediate between these two extremes were also elucidated for all species. These averages show reproducible detail of up to 2.0 nm resolution, thus enabling the visualization and interspecies comparison of many structural features as a first step toward comparing the actual three-dimensional structures. Our results disprove evolutionary lineages recently postulated on the basis of electron microscopical images of ribosomal subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02101154
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  • 19
    Electronic Resource
    Electronic Resource
    Ultrastructure of cells in the cambial region during winter hardening and spring dehardening in Salix dasyclados Wim. grown at two nutrient levels (1987)
    Springer
    Trees 1 (1987), S. 151-163 
    Details
    ISSN: 1432-2285
    Keywords: Cambial activity ; Frost hardiness ; Phenology ; Salix ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The ultrastructure of cells in the cambial region of Salix dasyclados Wim. (clone 78056) was studied during the development of winter hardiness and the onset of cambial activity in spring. Plants were grown at relative growth rates (RG) of 8% and 12% respectively, resulting in different nitrogen content in the stems. Frost hardiness of the plants was estimated by standardized freezing tests. Plants with a higher nitrogen status ceased growth later and started re-growth earlier in spring than plants with lower nitrogen content. Differences in ability to withstand low temperatures during autumn and spring were found between plants grown in the two nutrient treatments. During the development of frost hardiness in the autumn, the number of meristematic cells in the cambial region decreased. The cessation of meristematic activity was accompanied by cell wall thickening and ultrastructural changes in the cells. Frost hardiness increased from the ability to survive -6° C in October to survival of -80° C at the beginning of December. From November to February the cambial region comprised a layer of 2–3 thick-walled cells with conspicuous ultrastructural features. Starch accumulated in plastids in September, decreased during November to March and then increased again in accordance with changes of frost hardiness. Onset of cambial activity began between the end of March and the beginning of April, as shown by increased vacuolization of meristematic cells and mitotic activity. By April, the starch content had increased and lipolysis was observed. Frost hardiness had decreased, and plants with low and high nitrogen content were able to survive -15° C and -10° C, respectively. After budburst, all axillary shoot parts were damaged at temperatures below-3° C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193558
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    Temperature-jump FT-IR time-resolved spectrometry (1988)
    Springer
    Microchimica acta 94 (1988), S. 277-278 
    Details
    ISSN: 1436-5073
    Keywords: kinetics ; FT-IR ; temporal resolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A system for performing gas-phase rapid scanning Fourier transform infrared time-resolved Spectrometry (FT-IR/TRS) has been evaluated. This technique can be applied to the study of the lifetimes and reactivity of transient species and can provide detailed information regarding reaction rate constants. Temperature-jump experiments have been initiated and preliminary results are presented.
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    URL: http://dx.doi.org/10.1007/BF01205888
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    Dynamic Fourier transform infrared spectroscopy in polymer research (1988)
    Springer
    Microchimica acta 94 (1988), S. 323-328 
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    ISSN: 1436-5073
    Keywords: FTIR spectroscopy ; kinetics ; polymers ; rheo-optics ; variable-temperature measurements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The rapid-scanning capability of FTIR instrumentation has revitalized the field of vibrational spectroscopy in polymer research and will be discussed with reference to the study of polyurethane kinetics, the temperature dependence of hydrogen bonding in polyamide 6 and strain-induced crystallization in a polydimethylsiloxane elastomer.
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    URL: http://dx.doi.org/10.1007/BF01205899
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    The ultrastructure of the zygospore in Endogone flammicorona Trappe & Gerdemann (1976)
    Springer
    Mycopathologia 59 (1976), S. 117-123 
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    ISSN: 1573-0832
    Keywords: Ultrastructure ; Zygospore ; Mycorrhizal fungus ; Flaming crown
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The ultrastructural organization of the spores of the sporocarp of Endogone flammicorona was studied. Two types of organization are described. Initially the spore possessed a vacuolate protoplasm and was bound by two cell wall layers. The spore was surrounded by a hyphal mantle formed of a sheet of vacuolized hyphae with uniformly thin walls. Secondly, although the ultrastructural features of the spore appeared the same, it was now surrounded by a hyphal mantle with unevenly thickened walls (i. e., the so-called flaming crown) due to the gradual and irregular deposition of granules and lamellae. This crown gives the spore its most commonly observed morphological feature and is the preminent character employed taxonomically to speciate Endogone flammicorona Trappe & Gerdemann.
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    Sporulation and spore liberation in Aspergillus fumigatus (1977)
    Springer
    Mycopathologia 60 (1977), S. 175-177 
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    ISSN: 1573-0832
    Keywords: Aspergillus fumigatus ; Spore formation ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00448412
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    An ultrastructural survey of the genus Prototheca with special reference to plastids (1977)
    Springer
    Mycopathologia 61 (1977), S. 117-119 
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    ISSN: 1573-0832
    Keywords: Prototheca ; Colorless alga ; Plastids ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract An ultrastructural investigation of six different species of Prototheca showed that all of them contained starch grains enclosed in double-membrane-bounded structures recognized as plastids. It is concluded that these unicellular species of Prototheca must be considered as non-photosynthetic algae.
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    On the fungitoxicity of some new thiocyanatopyrazole derivatives: Electron microscopical study in trichophyton mentagrophytes (1976)
    Springer
    Mycopathologia 58 (1976), S. 39-47 
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    ISSN: 1573-0832
    Keywords: Trichophyton mentagrophytes ; Thiocyanatopyrazole derivatives ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Four thiocyanatopyrazole derivatives were synthesized and their fungistatic activity was demonstrated in vitro against a number of dermatophytic fungi. In Trichophyton mentagrophytes, the most active compound induced an unusual increase of the plasma membrane with production of intra and extracytoplasmic complexes, a deterioration of nuclear and mitochondrial membranes and a formation of autophagic-like vacuoles. Plasmolysis, accompanied by an almost complete disorganization of cytoplasmic structures, seemed to be the final event. A possible mechanism of action of the compounds was discussed.
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    Formation and nature of swirl defects in silicon (1975)
    Springer
    Applied physics 8 (1975), S. 319-331 
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    ISSN: 1432-0630
    Keywords: Self-interstitials in silicon ; Swirls ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Point defect agglomerates in dislocation-free silicon crystals, usually called “swirls”, have been investigated by means of high-voltage electron microscopy. It was found that a single swirl defect consists of a dislocation loop or a cluster of dislocation loops. By contrast experiments it could be shown that these loops are formed by agglomeration of self-interstitial atoms. Generally the loops have a/2〈110〉 Burgers vectors, but in specimens with high concentrations of carbon (∼1017 cm−3) and oxygen (∼1016 cm−3) also dislocation loops including a stacking fault were observed. In crystals grown at growth rates higher thanv=4 mm/min no swirls are observed; lower growth rates do not markedly affect the size and shape of the dislocation loops. With decreasing impurity content (particulary of oxygen and carbon) the swirl density decreases, whereas the dislocation loop clusters become larger and more complex. A model is presented which describes the formation of swirls in terms of agglomeration of silicon self-interstitials and impurity atoms.
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    Étude en microscopie électronique et par cytophotométrie à balayage de la structure et de la distribution de la chromatine dans les noyaux des cellules cartilagineuses deTriturus cristatus âgés au cours de la régénération (1978)
    Springer
    Development genes and evolution 184 (1978), S. 195-211 
    Details
    ISSN: 1432-041X
    Keywords: Ultrastructure ; Scanning cytophotometry ; Chromatin ; Chondrocytes ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les cellules cartilagineuses des membres postérieurs deTriturus cristatus en régénération après amputation, ont été étudiées en microscopie électronique et par cytophotométrie à balayage. Nous nous sommes intéressés à la structure et à la distribution de la chromatine mais aussi à différents organites cytoplasmiques. Dans l'étude de cytophotométrie à balayage, la chromatine a été considérée à travers son constituant majeur, l'ADN, coloré par la réaction de Feulgen. Au cours de la régénération du membre, l'hétérochromatine initialement condensée, essentiellement accolée à la membrane nucléaire se décondense. Les vacuoles du cytoplasme, caractéristiques des animaux âgés par rapport aux animaux jeunes, disparaissent, les mitochondries et le reticulum endoplasmique rugueux deviennent plus abondants. Les caractéristiques nucléaires de l'activation cellulaire apparaissent précocement, précédent les modifications cytoplasmiques et conduisent à des cellules en tous points identiques aux cellules d'animaux jeunes en dehors de tout processus régénératif. Cette phase d'euchromatisation et de restructuration cytoplasmique est peut-être nécessaire à l'accroissement d'activité métabolique et à la division cellulaire qui suivent. Son déroulement peut expliquer tout au moins le ralentissement de la régénération observé chez les animaux âgés par rapport aux animaux jeunes.
    Notes: Summary Cartilaginous cells of aged newts (Triturus cristatus) were studied during hind limb regeneration. The electron microscope was used to study the structure and distribution of chromatin in the cell nuclei, while the DNA content of the chromatin was measured by means of a scanning cytophotometer. Changes in the ultrastructure of the cytoplasm during regeneration were also studied. It was observed that the structure and distribution of chromatin in the activated cell is greatly modified. In the non-activated cell of the aged newt, the chromatin is found highly condensed and distributed peripherally close to the nuclear membrane. In contrast, in the activated cells, the chromatin is much less condensed and is distributed throughout the nucleus. Moreover, cytoplasmic vacuoles, found only in the non-activated aged cells, disappear and an increase in the mitochondria and rough endoplasmic reticulum is also observed. Changes in the nuclear structure are observed prior to the cytoplasmic modifications. It is interesting to note that the process of activation induces structural changes in the aged cells which make these cells appear to be structurally identical to the young cells. This process of rejuvenation takes 3–5 days in the newt. We suggest that these structural changes of the chromatin and cytoplasm in the aged cells are necessary to increase the metabolic activity which precedes cell division. It may also explain why regeneration takes a longer time in the aged animals than in the young ones.
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    Effect of pyrophosphate and orotidine monophosphate on cytosine deaminase regulatory properties (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1563-1564 
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    ISSN: 1420-9071
    Keywords: Cytosine deaminase ; kinetics ; pyrophosphate ; orotidine monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The maximal velocity of the reaction (Vmax) and the half-saturation constant (K0.5) values of theS. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.
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    Monoamine oxidase activity in single nerve cell bodies from substantia nigra of rat and man (1988)
    Springer
    Cellular and molecular life sciences 44 (1988), S. 710-712 
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    ISSN: 1420-9071
    Keywords: MAO A ; MAO B ; substantia nigra ; rat ; man ; MPTP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In single nerve cell bodies isolated from the substantia nigra of man and rat the active forms of MAO A and MAO B were found by the use of the microdiver technique and specific inhibitors.
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    URL: http://dx.doi.org/10.1007/BF01941038
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    The cytoplasmic architecture of the egg cell ofSmittia spec. (Diptera, Chironomidae) (1977)
    Springer
    Development genes and evolution 183 (1977), S. 233-248 
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    ISSN: 1432-041X
    Keywords: Cytoplasmic architecture ; Ultrastructure ; Insect egg ; Pattern formation ; Yolk ; Cytoplasma-Architektur ; Ultrastruktur ; Insekten-Ei ; Musterbildung ; Dotter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung 1. Das Ei der ZuckmückeSmittia spec. wurde licht- und elektronenmikroskopisch untersucht. Die vorliegende Arbeit beschreibt den Bau des Periplasmas und des Dotter-Endoplasma-Systems vor Bildung der Polzellen. 2. Das Periplasma, nach außen vom Oolemm und einer mehrschichtigen Eihülle begrenzt, besteht aus einer ribosomenreichen cytoplasmatischen Matrix, in die vor allem Mitochondrien und ER-Zisternen, wenig annulate lamellae und gelegentlich Golgi-Apparate eingelagert sind. Mikrotubuli wurden nur selten nachgewiesen. Öfters sind Anhäufungen einer dichten granulierten Substanz zu beobachten, die in ihrer Struktur dem Oosom-Material ähnelt. 3. Das Dotter-Endoplasma-System stellt ein Netzwerk aus Cytoplasma dar, in das Proteid-Dotterkugeln, Lipidtröpfchen sowie Glycogen-Anhäufungen eingelagert sind. Das Endoplasma, das sich zu 3–7 Plasma-Inseln erweitern kann und unmittelbar in das Periplasma übergeht, besteht wie dieses aus einer cytoplasmatischen Matrix und enthält die gleichen Zellelemente wie das Periplasma. Rosettenförmige Membran-Strukturen werden als “nuclear envelope organizing center” gedeutet. 4. Drei der sorgfältig analysierten Eier enthielten je 2 Kerne; sie lagen in Plasma-Inseln in der hinteren Eihälfte. 5. Sowohl im Periplasma wie im Dotter-Endoplasma-System sind alle Zellelemente unregelmäßig verteilt. Eine besondere Anordnung oder Zonierung ist nicht zu erkennen. 6. Die räumliche Verteilung der erfaßten Eikomponenten liefert keine Hinweise auf eine Funktion dieser Komponenten als Determinanten für die embryonale Musterbildung.
    Notes: Summary 1. Eggs of the midgeSmittia were investigated by light microscopy and transmission electron microscopy. This paper describes elements and architecture of periplasm and yolk endoplasm before the formation of pole cells. 2. The periplasm is coated externally by the oolemma and a multilayered egg shell. The periplasm consists of a cytoplasmic matrix rich in ribosomes; it contains mitochondria and ER cisternae, some annulate lamellae and an occasional Golgi complex. Microtubuli were demonstrated only rarely. Accumulations of a dense granulated substance resembling in its structure the oosome material were frequently observed. 3. The yolk endoplasm is a cytoplasmic network embodying proteid yolk particles, lipid droplets and accumulations of glycogen. The endoplasm is continuous with the periplasm and shows the same cell constituents. It may form between 3 and 7 cytoplasmic islands free of yolk particles. Rosette-shaped membranous structures in the yolk endoplasm are interpreted as nuclear envelope organizing centres. 4. Three carefully analysed eggs contained 2 nuclei each. both nuclei were situated in the posterior egg half. 5. Periplasm and yolk endoplasm are characterized by random distribution of cell elements. No zonation or special accumulations could be recognized. 6. The spatial distribution of the egg components studied did not indicate that any of these components could function as a determinant in embryonic pattern formation.
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    Ultrastructure of a fertilized barnacle egg (Pollicipes polymerus) with peristaltic constrictions (1977)
    Springer
    Development genes and evolution 181 (1977), S. 333-355 
    Details
    ISSN: 1432-041X
    Keywords: Barnacle eggs ; Constriction rings ; Microfilaments ; Ultrastructure ; Peristalsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. The egg ofPollicipes polymerus, the common intertidal gooseneck barnacle, has been studied by electron microscopy. Constriction rings, similar to the contractile rings of cleaving cells and polar lobes, move unidirectionally from the animal to the vegetal pole of newly fertilized eggs. This is referred to as peristaltic constriction. The present paper describes the fine structure of the egg during first polar body formation and peristalsis. 2. During formation of the polar body, dense bodies are produced by the Golgi and extracellular plaques are observed. Thin microfilaments (40–60 Å) are in the egg adjacent to the polar body. 3. In eggs undergoing peristalsis, the appearance of extracellular spheres, flocculent material and filaments is observed. Intracellularly large numbers of multivesiculate bodies, glycogen granules, mitochondria and protein-carbohydrate and lipid yolk bodies are seen at the level of constriction. 4. Thin microfilaments are found in the cortical area of newly-fertilized eggs exclusively in peristaltic constriction rings. Filaments are oriented primarily in a meshwork, although circumferentially-oriented filaments are also found in rings near the vegetal pole. Microvilli extend into the space created between a constriction and the elevated egg membrane. 5. A model is proposed to explain the peristalsis in this species. It is suggested that information from a pacemaker region activates peristalsis by affecting filament polymerization and orientation. One function of peristalsis may be elongation of the egg from a sphere to an ovoid, although other possibilities such as elevation of the egg membrane, segregation of the lipid yolk to the vegetal pole and predetermination of the first cleavage plane are also discussed.
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    Ultrastructure of collagen in sea urchin embryos (1979)
    Springer
    Development genes and evolution 186 (1979), S. 65-70 
    Details
    ISSN: 1432-041X
    Keywords: Sea urchin ; Embryo ; Collagen ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Collagen fibrils with a main period banding of 610 Å and 220 Å in width were observed in the blastocoel of 72-h embryos of the sea urchin,Strongylocentrotus purpuratus. Non-striated fibrils of 50 Å diameter were also observed. The collagen is seen in highest concentration in the vicinity of mesenchyme cells which are richly endowed with endoplasmic reticulum and secretory vesicles. A role for collagen in cell attachment, orientation and spicule formation is discussed.
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    Retention of the differentiated state by larvalXenopus liver cells in primary culture (1978)
    Springer
    Development genes and evolution 185 (1978), S. 235-248 
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    ISSN: 1432-041X
    Keywords: Liver ; Primary culture ; Ultrastructure ; Albumin synthesis ; Xenopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Electron microscopic analysis of primary cultures derived from larvalXenopus liver has shown that these cells, although they form only two-dimensional aggregates, retain and presumably also develop structural characteristics typical of liver parenchyma cells, such as bile canaliculi with microvilli and epithelial junctional complexes. As judged from structural criteria, primary cultures contain 80–90% hepatocytes. In contrast to the intact tissue, primary cultures showed excessive development of microfilaments, however. Incorporation of labeled amino acids has revealed further that the capacity for protein synthesis is maintained in culture and that synthesis of liverspecific protein albumin is maintained in vitro, even in liver cultures derived from thyrostatic tadpoles. This latter result suggests that initiation of albumin synthesis in the larval liver is probably not dependent upon thyroid hormones but rather reflects the protodifferentiated state of this tissue.
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    Quantitative morphogenetic investigations on fine structural changes in the optic tectum of the rainbow trout (Salmo gairdneri) during ontogenesis (1978)
    Springer
    Development genes and evolution 184 (1978), S. 83-94 
    Details
    ISSN: 1432-041X
    Keywords: Synaptogenesis ; Electron microscopy ; Visual acuity ; Fish development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The morphogenetic differentiation of synapses of the optic tectum of the rainbow trout was investigated at different stages of development (from hatching to adult) and compared with the improvement in visual discrimination (minimum separable). (1) The main phase of synaptogenesis (increase in number of synapses, length of contact zone and number of vesicles) begins about one week after hatching and continues up to the age of one month, when the larvae start swimming freely. (2) Myelination begins 26 days after hatching and induces the end of the synaptogenesis period. (3) The visual discrimination (minimum separable) of trout larvae improves from 30 degrees of arc on the 10th day after hatching to 1 degree on day 30, then to about 14 to 18 min of arc in the adult. The results are discussed with special reference to previous biochemical investigations on changes in the ganglioside composition of the trout brain during comparable periods of development.
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    Ultrastructural changes in the distal wing bud of the chick embryo after removal of the apical ectodermal ridge (1979)
    Springer
    Development genes and evolution 185 (1979), S. 333-346 
    Details
    ISSN: 1432-041X
    Keywords: Chick embryo ; Limb bud ; Ultrastructure ; Cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The ultrastructural changes in the wing bud afterapical ectodermal ridge (A.E.R.) removal was studied to re-examine the issue of distal mesenchymal cell death. The A.E.R. of the right wing bud was removed microsurgically from chick embryos of stages 18 to 22 (HH 1951). The wing buds were examined at three hour intervals up to twelve hours after the operation with light, transmission and scanning electron microscopy. The main findings were: (1) Immediate and temporary shrinkage of the mesenchymal extracellular space 100 to 150 μm and chromatin condensation in the cells 50 to 75 μm from the wound. (2) Death of ectodermal and mesenchymal cells in the immediate vicinity of the wound. (3) Formation of a single squamous-like layer of mesenchymal cells to cover the wound. (4) Occasional evidence of cell death in the distal mesenchyme at later times after the operation. The pattern of cell death observed suggests only a traumatic etiology, and gives little evidence for the postulated developmental significance of cell death following A.E.R. removal.
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    Membranes during yolk-platelet development in oocytes of the toad Bufo marinus (1987)
    Springer
    Development genes and evolution 196 (1987), S. 367-371 
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    ISSN: 1432-041X
    Keywords: Vitellogenesis ; Bufo marinus oocyte ; Yolk-platelet membrane ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Oocytes of the toad Bufo marinus have been studied by means of thin section and particularly freeze-fracture electron microscopy to characterize the cytoplasmic membranes around the yolk organelle, and the storage of yolk material in precursors and platelets. This appears to be a previously unknown type of yolk-platelet formation. During yolk-organelle development from the primordial precursor to the bi-partite fully grown yolk platelet, numerous lipoid droplets are attached to the periphery of the platelet, indicating an intense uptake of lipids. As is typical for amphibians, the fully grown yolk platelet has a crystalline internum covered by a dense osmiophilic externum, and the whole organelle is enveloped by a plasma membrane that shows no direct connection or fusion with endocytotic vesicles. The yolk membrane exhibits few intramembraneous particles (IMPs) at the core areas and some more where it borders fields of lipoid droplets. Here the IMPs show a net-like arrangement in the furrows between adjacent droplets.
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    Yolk organelles and their membranes during vitellogenesis ofXenopus oocytes (1989)
    Springer
    Development genes and evolution 198 (1989), S. 92-102 
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    ISSN: 1432-041X
    Keywords: Vitellogenesis ; Xenopus oocyte ; Yolk-platelet membrane ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The yolk platelets ofXenopus laevis have been studied by thin-section and freeze-fracture electron microscopy to characterize the boundary membrane during yolk formation. Throughout vitellogenesis, large yolk platelets are in close contact with smaller nascent yolk organelles. Two types of primordial yolk platelets (I and II) have been discriminated. After membrane fusion these precursors can be completely incorporated into the main body of existing platelets, numerous yolk crystals then merge and form one uniformly stratified core. Lipid droplets are tightly attached to the membrane at all developmental stages of yolk platelets. A direct connection of endoplasmic reticulum to the membranes of yolk platelets was not observed. On freezeetching replicas, yolk-platelet membranes present fracture faces with intramembranous particles (IMP) of various sizes and a heterogeneous distribution of approximately 200–600 IMP/μm2 at the E face, and 1200–2100 IMP/μm2 at the P face. Again, this presentation of the membrane exhibits neither anastomoses to the endoplasmic reticulum, nor caveolae that exclude the uptake of yolk-containing vesicles into these yolk organelles. Proteinaceous yolk platelets tend to fracture along their periphery through the superficial layers.
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    Ultrastructural localization of catalase and D-amino acid oxidase in ‘normal’ fetal mouse liver (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 144-147 
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    ISSN: 1420-9071
    Keywords: Ultrastructure ; catalase ; D-amino acid oxidase ; fetal mouse liver ; hepatocytes ; peroxisomes ; muscular dysgenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the hepatocytes of ‘normal’ fetal mice from mothers which were carriers of muscular dysgenesis, catalase and D-amino acid oxidase (DAAO) positive as well as negative peroxisomes were observed. DAAO reaction product was occasionally localized in patches around cell membranes and DAAO-positive peroxisomes were frequently observed near mitochondria.
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    Cellular calcium distribution in fetal bones studied with K-pyroantimonate (1978)
    Springer
    Calcified tissue international 26 (1978), S. 181-190 
    Details
    ISSN: 1432-0827
    Keywords: Cellular calcium ; Electron microscopy ; Osteoblasts ; Chondrocytes ; Mineralization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The calcium distribution in cartilage and bone cells during beginning ossification of fetal mouse long bones was studied after fixation with 2% K-pyroantimonate in 1% osmium. In the developing periosteum, the future osteoblasts showed a sparse cation-antimonate precipitate over the cytoplasm. In young osteoblasts the precipitate was accumulated on the mitochondrial membranes and the plasmalemma. Both organelles were sharply outlined by precipitate in the mature osteoblasts at the onset of mineralization. X-Ray microprobe analysis of these organelles demonstrated the presence of both Sb and Ca. In the extracellular compartment, a collagen-associated precipitate with 50 to 60 nm periodicity appeared during osteoblastic differentiation. During the initial phase of matrix mineralization, a random gross precipitate appeared in the matrix and seemed to be accumulated by osmiophilic matrix vesicles while the collagen fibrils lost their precipitate. Subsequently, during the confluent phase of matrix mineralization, the precipitate rapidly disappeared from the cells, leaving them devoid of precipitate once they were surrounded by mineralized matrix. Similar changes were found in the chondrocytes of the growth plate, but cartilage collagen, unlike osteoid collagen, did not bind precipitate. The results indicate that both osteoblasts and calcifying cartilage cells bind calcium prior to matrix mineralization. Bone collagen has strong pyroantimonate binding capacity, but it is not directly involved with initial stages of matrix mineralization, which starts in close association with matrix vesicles.
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    URL: http://dx.doi.org/10.1007/BF02013254
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    Ultrastructure, histology, and innervation of the mantle edge of the freshwater pulmonate snailsLymnaea stagnalis andBiomphalaria pfeifferi (1978)
    Springer
    Calcified tissue international 26 (1978), S. 271-282 
    Details
    ISSN: 1432-0827
    Keywords: Shell formation ; Free nerve endings ; Ultrastructure ; Lymnaea stagnalis ; Biomphalaria pfeifferi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The mantle edge of the freshwater pulmonate snailsLymnaea stagnalis andBiomphalaria pfeifferi was investigated with histochemical and ultrastructural methods. The mantle edge gland, which is involved in shell formation, consists of the periostracal groove and the belt. This belt appears to be composed of various regions. In the area of the periostracal groove a number of subepithelial gland cell types occur; these release their products into the groove. Between the groove cells ciliated free nerve endings terminate; the corresponding perikarya occur in the subepidermal connective tissue. Also in the posterior belt region free nerve endings were observed between the epithelial cells; in addition, a particular type of subepithelial gland cell was found in this area. The epithelial cells of this part of the belt have the ultrastructural characteristics of ion and water transporting cells; they are probably involved in calcium deposition and resorption. The possible role of the free nerve endings and of the subepithelial gland cells is discussed.
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    The ultrastructure of the extracellular phase of bone as observed in frozen thin sections (1977)
    Springer
    Calcified tissue international 23 (1977), S. 215-223 
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    ISSN: 1432-0827
    Keywords: Amorphous mineral ; Bone ; Electron microscopy ; Ultracryotomy ; Ultramicro-incineration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The fine structure of the extracellular phase of avian medullary bone and embryonic chick femur was examined in thin sections prepared by ultracryotomy and ultramicroincineration. Since contact with solutions was completely avoided, little or no loss or dislocation of mineral constituents could occur. Amorphous bone mineral (ABM) was present in two forms: as 15–30 nm spheres and as a structure-free haze. Removal of all organic material by low temperature ashing left the ABM intact. Crystals were usually associated with the ABM. In newly ossifying regions clusters or nodules of randomly oriented crystals and ABM appeared to coalesce when they reached approximately 1 μm in diameter. In highly calcified regions crystals appeared to be oriented along collagen fibers. ABM did not appear to be associated with collagen. Unmineralized collagen was visible in osteoid after staining with dry OsO4 vapor and it appeared to be diverted around nodules. Structures which resembled matrix vesicles were present. Selected area electron diffraction patterns indicated the presence of hydroxyapatite.
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    The fine structure of decalcified cartilage and bone: A comparison between decalcification procedures performed before and after embedding (1978)
    Springer
    Calcified tissue international 25 (1978), S. 179-190 
    Details
    ISSN: 1432-0827
    Keywords: Decalcification ; Electron microscopy ; Calcified matrices
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The ultrastructure of calcifying cartilage and bone has been examined under the electron microscope after using three different methods of decalcification. The first was carried out before embedding (by soaking specimens in EDTA or formic acid), the second after embedding (by floating ultrathin sections on formic acid), and the third after embedding (by soaking embedded specimens in EDTA or formic acid), and with later re-embedding. The first procedure invariably induces drastic changes in the fine structure of the cells and calcified matrix, probably as a results of the extraction of organic material along with extraction of mineral. The second and third procedures make it possible to preserve ultrastructural details perfectly in both cells and calcified matrix. Of the two, the third procedure is preferable because of its greater simplicity. In areas that are still calcifying, these post-embedding decalcification techniques reveal the presence of crystal-associated, filamentous organic structures which are not recognizable in specimens decalcified before embedding. These structures, which could have a key role in inducing and regulating crystal formation and growth, are less evident in fully calcified areas (but not at their borders). This may partly be due to the loss of glycan components in the matrix during calcification. The most important determinant, however, seems to be the fact that during calcification the components of the matrix, including collagen fibrils, are involved in an aggregation process which reduces the amounts of free chemical groups available for reaction with the stain solution. Because post-embedding decalcification does not disturb this state of aggregation, the stainability of the matrix and the electron microscopic evidence of its components remain very low.
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    Ultrastructural study of amelogenesis imperfecta (1977)
    Springer
    Calcified tissue international 24 (1977), S. 191-197 
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    ISSN: 1432-0827
    Keywords: Amelogenesis imperfecta ; Hypocalcification ; Hypoplasia ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary An ultrastructural study of teeth with amelogenesis imperfecta revelaed various aspects of microcavities in the enamel surface, which ranged from isolated imprints of ameloblasts corresponding to the mildest lesions at the end of amelogenesis, to pits caused by the death of 20 to 30 ameloblasts at the beginning of amelogenesis. Abnormalities in the shape of the prisms can be observed. Further, crystals are distributed randomly within a prism or at the junction of 2 contiguous prisms while intercrystalline spaces are widened, indicating in various places the lack of a preferred orientation of the crystals. In amelogenesis imperfecta, two different crystalline periods are found: 1 of about 250 Å, the other of about 500 Å and over. The fact that amorphous areas are found among the crystals of enamel may be related to different stages of crystallization. However, it was not possible to find any lattice defect.
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    Further observations on the fine structure of cellular cementum from deciduous teeth of pigs (1977)
    Springer
    Calcified tissue international 24 (1977), S. 239-242 
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    ISSN: 1432-0827
    Keywords: Cementum ; Lysis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Examination of microradiographs from the deciduous teeth of pigs revealed large lacunae or radiolucent zones close to the cemento-dentinal junction. Electron microscopic studies of the ground sections showed areas or irregularly shaped zones devoid of mineral and filled with collagen fibers. In the wide unmineralized zones, spherical clusters of crystallites were noted. Several cementum lacunae bordered by a broad rim of unmineralized collagen fibers were noted and some lacunae also contained zones of a moderately electron dense material. This material did not yield a diffraction pattern, while the mineralized part of the cementum gave the diffraction pattern typical of hydroxyapatite.
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    The crystal sheaths from bivalve hinge ligaments (1978)
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    Calcified tissue international 25 (1978), S. 45-51 
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    ISSN: 1432-0827
    Keywords: CaCO3 ; Amino acids ; Sheaths ; Ligament ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The aragonite crystals in the molluscan bivalve hinge ligament are surrounded by an organic sheath which is distinct from the remainder of the ligament matrix. Methods have been developed to isolate these sheathed crystals from the ligaments ofSpisula solidissima andMercenaria mercenaria employing a papain digestion of the matrix protein. The sheathed crystals fromSpisula have a CaCO3/protein ratio of 11.1 and those fromMercenaria a ratio of 29.6. The sheathed crystals and the empty crystal sheaths have been examined by electron microscopy for structural integrity. The sheath proteins exhibit much smaller proportions of the amino acids glycine and methionine than the hinge ligaments. These are characteristic amino acids of high concentration in the hinge ligaments of both species. The concentrations of acidic and basic amino acids are increased about two fold in the sheaths over those of the ligaments. Otherwise there is little similarity in the amino acid composition of the sheaths in the two species. However, SDS electrophoresis shows the sheaths of both to contain a major protein component with a molecular weight of about 25,000. The sheath protein from theMercenaria ligament contains about 5% carbohydrate and that ofSpisula sheaths less than 1% carbohydrate.
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    Orientation of apatite in single osteon samples as studied by pole figures (1979)
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    Calcified tissue international 29 (1979), S. 101-105 
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    ISSN: 1432-0827
    Keywords: Osteon ; X-ray diffraction ; Pole figures ; Electron microscopy ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The X-ray diffraction method based on pole figures has been applied to single osteon samples in order to obtain information about the texture of the inorganic bone fraction and the way it changes during calcification. The osteon samples were cylindrically shaped, with axes corresponding to those of the haversian canals. Selection was carried out according to the degree of calcification and the orientation of collagen bundles and inorganic particles. Osteons at both the initial and final stages of calcification were chosen. Arrangements of fiber bundles and inorganic particles in successive lamellae characteristic of three types of osteons were selected: longitudinal, alternate, and transversal. The results indicate that in all three types of osteons, the long axis of the sample is apparently the only direction of orientation because the transversally oriented crystallites give an isotropic diffuse scattering as would be expected if all the inorganic particles were irregularly oriented around the osteon axis. The number of longitudinally oriented crystallites increases progressively from transversally oriented osteons to alternately and longitudinally oriented ones. The crystallite orientation in an axial direction increases in fully calcified osteons. This last result is in agreement with the electron microscopic finding that the long needle-shaped crystallites covering much more than a major collagen period and measuring 40–45 Å in width increase in number as calcification proceeds.
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    X-ray diffraction and electron microscope study of osteons during calcification (1978)
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    Calcified tissue international 25 (1978), S. 133-143 
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    ISSN: 1432-0827
    Keywords: Osteon ; X-Ray diffraction ; Electron microscopy ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To obtain information on the changes in the inorganic bone fraction during calcification, low- and wide-angle X-ray diffraction techniques and electron microscopy have been applied to single osteon samples. The samples were cylindrically shaped and their axes corresponded to the axes of the Haversian canals. The selection was made according to the degree of calcification and the orientation of collagen bundles and inorganic particles. Osteons at both the initial and final stages of calcification were chosen. Arrangements of fiber bundles and inorganic particles in successive lamellae characteristic of three types of osteon were selected, that is, longitudinally structured osteons, transversely structured osteons, and alternately structured osteons. The results indicate that in osteonic lamellar bone there are two types of inorganic particles: (1) granules arranged in linear or needle-shaped entities with maximum width 40–45 Å, which are regularly distributed at the level of the main band of the collagen fibrils where their maximum length reaches the length of the main band itself; that is, about 400 Å; and (2) very long crystallites, with a diameter of 40–45 Å, which grow with their crystallographicc-axis parallel to the collagen fibrils and cover much more than a major collagen period.
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    Ultrastructural damage due to freezing followed by thawing in shoot meristem and leaf mesophyll cells of tall fescue (Festuca arundinacea Schreb.) (1977)
    Springer
    Planta 134 (1977), S. 159-168 
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    ISSN: 1432-2048
    Keywords: Festuca ; Frost damage ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Tillers of Festuca arundinacea Schreb. were subjected to-8°C in a bath of methylated spirits for three-quarters of an hour. They were thawed at room temperature and some material taken from the shoot apical meristem and leaf blade for electron microscopy. Similar material was taken from control plants for electron microscopy. Nine tillers subjected to-8°C and thawed subsequently failed to regrow. Nine control tillers regrew. All the treated meristem cells and about half the treated leaf mesophyll cells were extensively altered. Their nuclei were contracted, organelles were swollen or partly disrupted, plasmalemma and nuclear membranes were broken or absent and vacuoles were sometimes disrupted. Strongly osmiophilic material accumulated in the vicinity of membranes. About half the leaf mesophyll cells differed from the control mesophyll cells only in having more spherosomes and narrower thylakoids. Parallels with other ultrastructural studies of stress damage and the indications the results give of possible primary damaging events are discussed.
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    An electron microscope study on in vitro parthenogenesis in sunflower (1989)
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    Sexual plant reproduction 2 (1989), S. 154-166 
    Details
    ISSN: 1432-2145
    Keywords: Helianthus annuus ; Unfertilized ovule culture ; Parthenogenesis ; Ultrastructure ; Proembryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Electron microscope studies have been conducted on the parthenogenesis induced by in vitro culture of unfertilized ovules of sunflower (Helianthus annuus). In comparison with the state of the egg prior to inoculation, some eggs 5 days after culture show striking ultrastructural changes, which include, among others, nuclear migration, an increase in the number and activity of the organelles, a loss of polarity and wall formation at the chalazal end of the cell. Most of these changes are similar to those that occur normally in the zygote, indicating that parthenogenic development has been triggered in these eggs. Such eggs have been termed activated and are presumed to be capable of undergoing parthenogenesis. The parthenogenic proembryos which result share some features in common with zygotic proembryos. In addition, some parthenogenic proembryos exhibit unique properties not found in zygotic proembryos. These include embryos that consist of two parts differing markedly in density, an inversion of polarity, the frequent occurrence of autophagic vacuoles, the thickening of cell walls, a centripetal growth mode of wall formation, the appearance of an incomplete cell wall, free nuclear division, amitosis and degeneration. We believe that these ultrastructural peculiarities are the effects of in vitro culture.
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    The ultrastructure of polymorphic pollen grains of Canna indica L. (1989)
    Springer
    Sexual plant reproduction 2 (1989), S. 193-198 
    Details
    ISSN: 1432-2145
    Keywords: Polymorphism ; Ultrastructure ; Pollen grains ; Canna indica L ; Tannin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Our investigations on Canna indica L. indicate that the pollen of this species is polymorphic: there are two types of pollen — a larger type and a comparatively smaller type. Transmission electron microscopy (TEM) revealed the presence of small vacuoles containing tannic substances in the generative cell (GC) of the larger grains: the GC of the mature grain contained a higher quantity of tannins than the GC of the immature grain. Mitochondria, lipid bodies, rough endoplasmic reticulum (RER) and microtubular bundles were present in the cytoplasm of the GC. Numerous mitochondria, lipid bodies and plastids were also present in the vegetative cell (VC), with the mitochondria clustered around the vegetative nucleus. The plastids were observed to be associated with the RER cisterns. During the maturation process, the number of starch grains contained in the plastids decreased.
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    Pre-fertilization degeneration of both synergids in Brassica campestris ovules (1988)
    Springer
    Sexual plant reproduction 1 (1988), S. 208-216 
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    ISSN: 1432-2145
    Keywords: Megagametophyte ; Synergids ; Brassica campestris ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In Brassica campestris, both synergids of the ovule degenerate before the arrival of the pollen tube. Synergid degeneration does not depend on pollination. At the non-degenerated stage, the synergids are completely filled with a complexly organized cytoplasm containing numerous mitochondria with many cristae, a large number of dictyosomes with many associated vesicles, and a very extensive rough endoplasmic reticulum. The degenerative changes that occur in the cytoplasm of the synergids are characterized by a loss of visibility of the membranes of the endoplasmic reticulum and the simultaneous formation of dense deposits on the surrounding membranes of the mitochondria. Locally, the plasma membranes of the synergids disappear, and some ground plasma of the synergids penetrates into the space between the plasma membranes of the egg cell and the central cell.
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    Early embryogenesis in Tropaeolum majus L.: Diversification of plastids (1976)
    Springer
    Planta 133 (1976), S. 15-19 
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    ISSN: 1432-2048
    Keywords: Tropaeolum, Embryogenesis ; Differentiation ; Plastids ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Embryogeny in the nasturtium is characterized by the development of a large, tripartite suspensor and storing cotyledons. A light and electron microscopic study revealed an early diversification of the plastids in the various regions of the suspensor and the embryo proper. Amyloplasts are found in the developing cotyledons of the heart-like embryo, while chloroplasts occur within the meristematic part of the embryo and the adjacent portion of the suspensor. The cells between the meristem and the storing cotyledons display undifferentiated leukoplasts, whereas leukoplasts with an electron-dense matrix occur in the basal cell mass of the embryo-suspensor. Etioplasts develop in several cells of the placental haustorium of the suspensor. The carpel haustorium shows rather undifferentiated leukoplasts, which are transformed into electron-dense plastids during autolysis of the suspensor. This early plastidal differentiation in discussed with respect to its control and functional significance.
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    Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
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    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
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    Comparative pharmacokinetics of ceftazidime in young, healthy and elderly, acutely ill males (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 179-186 
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    ISSN: 1432-1041
    Keywords: ceftazidime ; pharmacokinetics ; elderly patients ; young volunteers ; acute infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected by posture and were similar to what has been reported earlier. In contrast, elderly patients had longer t1/2β (3.1 vs 1.9 h), larger AUC (414.0 vs 276.6 h·mg/l), lower total and renal clearances, reduced urinary recovery over 12 h and enlarged Vss. Total serum clearance of ceftazidime was closely correlated with the51Cr-EDTA clearance. There was no significant change in51Cr-EDTA clearance after seven days of treatment. A reduction in the dose of betalactam antibiotics eliminated by the kidney is advisable in elderly patients with an acute bacterial infection.
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    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
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    European journal of clinical pharmacology 8 (1975), S. 97-105 
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    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
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    Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 157-160 
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    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; pharmacokinetics ; metabolism ; pharmacological action ; nitrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
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    Correlation between increased dopamine-β- hydroxylase activity and catecholamine concentration in plasma: Determination of acute changes in sympathetic activity in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 181-188 
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    ISSN: 1432-1041
    Keywords: Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy untrained volunteers the increase in plasma dopamine-β-hydroxylase (DBH) activity during graded physical exercise has been examined as a true measure of increased activity of the sympathetic nervous system. The correlation between DBH activity, catecholamine concentration (CA) in plasma and heart rate was studied. When work on an electrically braked bicycle ergometer was gradually increased from 12.5 to 100, 200 and 300 watts there was a linear increase in DBH activity and heart rate; the increase in CA concentrations followed an exponential function. The peak values for DBH activity and CA concentration in plasma after the 300 watt work load (as percentages of the resting levels) were 130±3% and 820±71%, respectively; the adrenaline concentration in plasma increased only to 150±19% (p〉0.05). There were significant correlations between heart rate and work load, DBH and work load and log CA and work load. The data imply direct correlations between heart rate and DBH, heart rate and log CA and DBH and log CA. The exponential increase in noradrenaline concentration in plasma might be due either to a greater net “overflow” from sympathetic nerve endings, and/or to increased secretion by the adrenal medulla. In the latter case, the release of noradrenaline would not be accompanied by secretion either of adrenaline or DBH. After work ceased there were sharp falls in heart rate and CA concentration, which indicate an immediate drop in sympathetic activity. DBH activity in plasma returned to normal very slowly; it reached half maximum values after 20 – 22 min. It is concluded that increased sympathetic activity in man can be estimated in vivo as changes in DBH and/or CA concentration in plasma. In contrast, a rapid decrease in sympathetic activity is directly reflected only by a rapid fall in the plasma concentrations of CA.
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    Bioavailability of m-octopamine in man related to its metabolism (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 33-39 
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    ISSN: 1432-1041
    Keywords: m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of3H-m-octopamine to eight patients. Identical amounts of3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinarym-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways form-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in themeta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting “first pass effect”, i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
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    Excretion of norephedrine by man after oral administration of oxyfedrine (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 161-166 
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    ISSN: 1432-1041
    Keywords: Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75–100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2–4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30–150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the directβ-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.
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    URL: http://dx.doi.org/10.1007/BF00567109
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    Pharmacokinetics — Uses and abuses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 241-248 
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    ISSN: 1432-1041
    Keywords: pharmacokinetics ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.
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    URL: http://dx.doi.org/10.1007/BF00567122
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    Pharmacokinetics and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
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    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
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    URL: http://dx.doi.org/10.1007/BF00567123
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    Anticoagulant effect and plasma kinetics of fluorophenindione after a single dose in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 271-275 
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    ISSN: 1432-1041
    Keywords: Fluorophenindione ; vitamin K antagonist ; pharmacokinetics ; loading dose ; anticoagulant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After administration of a single loading dose (80 mg p.o.) of fluorophenindione, the prothrombin level decreased to 37 % in 24 h, and the effect lasted for 48 h. Accordingly, fluorophenindione can be classified as an anticoagulant with an “intermediate” effect. Its elimination half-life was 31 h, which is longer than that of phenindione, because of the greater stability of the fluorinated derivate.
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    URL: http://dx.doi.org/10.1007/BF00567127
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    Kinetics of nortriptyline in man according to a two compartment model (1975)
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    European journal of clinical pharmacology 8 (1975), S. 343-347 
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    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
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    URL: http://dx.doi.org/10.1007/BF00562660
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    Delayed absorption of lithium in intoxication (1975)
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    European journal of clinical pharmacology 8 (1975), S. 285-285 
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    ISSN: 1432-1041
    Keywords: Lithium ; intoxication ; man ; delayed absorption ; gastric contents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.
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    Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 277-282 
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    ISSN: 1432-1041
    Keywords: QX-572 ; quaternary ammonium compound ; plasma level ; urinary excretion ; man ; anti-arrhythmic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
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    Disposition of placentally transferred carbamazepine (Tegretol®) in the newborn (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 283-284 
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    ISSN: 1432-1041
    Keywords: Newborn infants ; carbamazepine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma elimination of carbamazepine (Tegretol®) was studied in five newborns who had got the drug transplacentally from their epileptic mothers. The half-lives ranged from 8.2 – 27.7 hours which is comparable or even shorter than those found in adults after a single oral dose, but in the same range as those found in adults after multiple oral doses. This suggests that the newborns' drug metabolizing capacity has been induced during fetal life.
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    The serum level approach to individualization of drug dosage (1975)
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    European journal of clinical pharmacology 9 (1975), S. 1-8 
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    ISSN: 1432-1041
    Keywords: Serum concentrations ; individual drug dosage ; pharmacokinetics ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be “titrated” directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships — the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement.
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    On the fate of furosemide in man (1975)
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    European journal of clinical pharmacology 9 (1975), S. 57-61 
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    ISSN: 1432-1041
    Keywords: Furosemide ; gastrointestinal absorption ; diuretics ; glucuronides ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 35S-furosemide was administered orally (n=7) or i.v. (n=2) to healthy subjects. The average gastrointestinal uptake estimated by comparison of the urinary recovery of label and the areas under the plasma curves after the two routes of administration was 65%. The half life of radioactivity in the plasma after oral35S-furosemide was 90 ± 17 min (estimated on the slope between 2 and 6 h); the corresponding figure after35S-furosemide i.v. was 47–53 min (slope 0.5–4 h). There was probably a slower phase after 4–6 h. Fractionation of labelled material in urine from two subjects demonstrated that approximately two thirds of the label recovered at 24 h had the same chromatographic properties as furosemide. A major part of the metabolite(s) was probably furosemide glucuronide. There was no evidence that 4-chloro-5-sulfamoylanthranilic acid was formed in man. The total urinary recovery of label (5–7 d) after oral and intravenous administration was 55.1±3.2 (mean±SD) and 82–84%, respectively. After35S-furosemide i.v., 6–9% of the label was recovered in faeces, and it could not be accounted for solely by biliary excretion of furosemide.
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    Serum concentrations of ampicillin and probenecid and ampicillin excretion after repeated oral administration of a pivampicillin-probenecid salt (MK-356) (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 125-129 
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    ISSN: 1432-1041
    Keywords: Pivampicillin ; ampicillin ; probenecid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.
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    Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 135-145 
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    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
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    Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 155-159 
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    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
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    The metabolism of (−)-ephedrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 193-198 
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    ISSN: 1432-1041
    Keywords: (−)-[14C]-ephedrine ; metabolism ; urinary excretion ; tolerance ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate of orally administered (−)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.
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    The physiological disposition of etilefrine in man (1975)
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    European journal of clinical pharmacology 9 (1975), S. 179-187 
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    ISSN: 1432-1041
    Keywords: Etilefrine ; pharmacokinetics ; metabolism ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and metabolic studies with3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, β) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with the hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.
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    Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 169-178 
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    ISSN: 1432-1041
    Keywords: Heptabarbital ; heptabarbital sodium ; pharmacokinetics ; plasma concentration ; single and multiple dose kinetics ; relative bioavailability ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 – 5.0 µg/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets was quite slow and peak level times varied from 1.5 to 4 h. The sodium salt was absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 – 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 – 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin® tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.
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    Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 219-227 
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    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
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    Interaction of indomethacin and acetylsalicylic acid as shown by the serum concentrations of indomethacin and salicylate (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 199-207 
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    ISSN: 1432-1041
    Keywords: Indomethacin ; acetylsalicylic acid ; drug interaction ; oral and rectal dosing ; serum levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A clinical-pharmacological study was performed to determine the effect of acetylsalicylic acid upon the serum concentration of indomethacin. 14 rheumatic patients were given indomethacin orally (25 mg × 4 for 4 days) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily), and 21 rheumatic patients were given indomethacin rectally in the morning (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily). On comparison with treatment with oral or rectal indomethacin alone, it was found that peak serum concentrations of indomethacin were significantly reduced (1% level), the times of the peaks were not shifted, and the areas beneath the serum concentration curves of indomethacin were smaller, but significantly so only if compared with rectal administration. In 12 rheumatic patients given indomethacin by rectum in the evening (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g (0.9 g × 3 and 1.0 g × 1 daily), the serum level of indomethacin on the following morning (after 11 h) did not differ from that found after rectal treatment. A statistically but not biologically significant difference was observed between the mean serum half-lives of indomethacin given orally and rectally. For unknown reasons, concurrent doses of acetylsalicylic acid and indomethacin made the mean serum half-life of indomethacin longer than after its oral administration, but shorter than when the same dose of indomethacin was given rectally. There was no difference between serum levels of salicylate after oral administration of acetylsalicylic acid alone or after a concurrent oral or rectal dose of indomethacin. The results have been related to those reported previously, with respect to the interaction between indomethacin and acetylsalicylic acid, the serum levels of indomethacin after oral and rectal dosing, and the serum half-life of indomethacin based upon a one- or two-compartment model. The clinical relevance of the study is discussed.
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    Disposition of quercetin in man after single oral and intravenous doses (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
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    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
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    URL: http://dx.doi.org/10.1007/BF00614022
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    Effect of the aldosterone antagonist canrenone on plasma aldosterone concentration and plasma renin activity, and on the excretion of aldosterone and electrolytes by man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 253-257 
    Details
    ISSN: 1432-1041
    Keywords: Aldosterone ; renin ; aldosterone antagonist ; canrenone ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Canrenone was administered in doses of 2×82 mg and 2×164 mg per day over a period of 10 days to diabetic patients without cardiovascular, liver or kidney involvement. Aldosterone excretion and plasma aldosterone increased only slightly during both regimes. There was a clear-cut increase in aldosterone excretion only after discontinuation of carenone. Excretion of sodium potassium and fluid was not significantly changed either during or after treatment. The lack of effect of canrenone on the kidney was in contrast to the significant decrease in serum sodium and increase in serum potassium, and the significant, dose-dependent rise in plasma renin activity following canrenone administration. The increased plasma renin activity persisted for some days after discontinuation of canrenone. It is suggested that canrenone primarily exerted its effect in the distal part of the large intestine where ionic movements are most affected by aldosterone. The disproportionately slight increase in plasma aldosterone concentration and aldosterone excretion, in spite of the greatly elevated plasma renin activity and serum potassium level, is considered to be due to a direct inhibitory effect of canrenone on aldosterone production in the adrenals.
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    URL: http://dx.doi.org/10.1007/BF00561657
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  • 79
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    Pharmacokinetics of lofepramine in man: Relationship to inhibition of noradrenaline uptake (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 291-298 
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    ISSN: 1432-1041
    Keywords: Tricyclic antidepresent ; lofepramine ; single- and multiple-dose kinetics ; noradrenaline and 5-hydroxytryptamine uptake ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lofepramine, an imipramine analogue, have been studied by administering single oral doses to volunteers, determination of plasma levels of lofepramine and desmethylimipramine after ten days of oral administration to patients, and by relating plasma levels to the effect on uptake of noradrenaline by isolated rat irides and brain slices of plasma samples collected during treatment. The results indicate that lofepramine undergoes pronounced first pass elimination and that desmethylimipramine is a major metabolite of it. During steady-state conditions the plasma level of lofepramine fluctuates considerably between doses. A linear relation was found between inhibition of neuronal uptake of noradrenaline and the plasma concentration of desmethylimpramine. No effect was seen on the uptake of 5-hydroxytryptamine in brain slices incubated in patients' plasma which suggests that neither lofepramine nor its metabolites formedin vivo in man affect neuronal uptake of this amine. Lofepramine belongs to the group of tricyclic anti-depressants which preferentially inhibit noradrenaline uptake.
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    URL: http://dx.doi.org/10.1007/BF00561663
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  • 80
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    Absorption of β-methyl-digoxin determined after a single dose and under steady state conditions (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 307-314 
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    ISSN: 1432-1041
    Keywords: Absorption ; man ; β-methyl-digoxin ; serum concentration ; urinary excretion ; radio-immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of β-methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum® or Lanitop® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of β-methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with β-methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop® ampoules or oral treatment with Lanitop® tablets. For a standard daily dose of 0.2 mg β-methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.
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    URL: http://dx.doi.org/10.1007/BF00561665
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  • 81
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    Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 327-332 
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    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; half-life ; blood ; plasma ; saliva ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). The levels in blood and saliva were comparable to those in plasma at every time studied. The half life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n=5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.
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  • 82
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    Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 319-325 
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    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
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  • 83
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    Observations on the efficacy and pharmacokinetics of sotalol after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
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    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
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  • 84
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    Metabolism of digitoxin in man and its modification by spironolactone (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 345-354 
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    ISSN: 1432-1041
    Keywords: 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of spironolactone on the metabolism of intravenously administered3H-digitoxin (80 µCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79 % was unaltered drug and 12 % consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (〈2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p〈0.05). In addition spironolactone caused a 20 % reduction in the half-life of serum radioactivity (p〈0.01) and a 16 % reduction in the volume of distribution (p〈0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
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    Some aspects of the intestinal absorption of zinc in man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 423-428 
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    ISSN: 1432-1041
    Keywords: Serum zinc concentration ; intestinal absorption ; portal vein ; transumbilical catheterization ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum zinc concentrations in peripheral venous blood were determined in 8 healthy volunteers at various times after oral administration of 50 mg Zn++. The same dose was given to 6 patients surgically treated for obesity by jejuno-ileostomy. In the healthy volunteers the mean serum zinc concentration before dosing was 0.89 µg/ml and a mean peak concentration of 2.39 µg/ml was found after 3 h. In the patients the starting level was lower, 0.67 µg/ml, and a mean peak concentration of 1.31 µg/ml was found 90 min after treatment. In the patients the areas under the serum concentration-time curve was approximately 1/3 of that in the healthy subjects. Zn++ 50 mg was also given to 3 patients undergoing transumbilical catheterization of the portal vein for diagnostic purposes and serum zinc concentrations were measured in portal and peripheral venous blood sampled simultaneously. No significant differences were found between the concentration of zinc in portal and peripheral venous blood during absorption, which suggests slow passage of zinc across the intestinal wall.
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    Pharmacokinetics and relative bioavailability of cyclobarbital calcium in man after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 443-450 
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    ISSN: 1432-1041
    Keywords: Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
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  • 87
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    Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 77-82 
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    ISSN: 1432-1041
    Keywords: N-acetylcysteine ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l·kg−1 and a plasma clearance of 0.84 l·h−1·kg−1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l·kg−1 and its plasma clearance was 0.11 l·h−1·kg−1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.
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  • 88
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    A preliminary study of the pharmacodynamics and pharmacokinetics of a novel enkephalin analogue [Tyr-D.Arg-Gly-Phe(4NO2)·Pro·NH2 (BW443C)] in healthy volunteers (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 67-71 
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    ISSN: 1432-1041
    Keywords: BW443C ; enkephalin ; opioid peptide ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 µg·kg−1 for 60 min and increasing to a maximum of 2.0 µg·kg−1·min−1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 µg·kg−1·min−1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations 〉0.8 µg·ml−1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60–90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accomodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean ± SD plasma clearance of 123±18 ml·min−1 and a half-life of 2.0±0.4 h.
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    Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child of an oxcarbazepine-treated mother (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 311-313 
    Details
    ISSN: 1432-1041
    Keywords: oxcarbazepine ; newborns ; antiepileptic ; placental transfer ; 10-hydroxy-carbazepine ; pharmacokinetics ; breast milk transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gaschromatography — mass spectrometry (GC/MS) was used to determine plasma levels of oxcarbazepine (OCB) and its main metabolite in a newborn girl and her OCB-treated mother during the first five post partum days. At delivery the maternal and neonatal plasma concentrations were in the same range, indicating considerable placental transfer of both substances. In spite of ingestion of both substances via breast milk, there was no accumulation in the baby. On the fifth post partum day OCB and 10-hydroxy-carbazepine (10-OH-CB) levels in plasma in the newborn were only 12 and 7%, respectively, of the values found on the first day after delivery.
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  • 90
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    The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 439-443 
    Details
    ISSN: 1432-1041
    Keywords: doxifluridine ; colorectal carcinoma ; 5′-deoxy-5-fluorouridine ; 5-fluorouracil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of a new 5-fluorouracil prodrug, 5′-deoxy-5-fluorouridine (5′dFUR, doxifluridine), were investigated in six patients with colorectal carcinoma. Each patient randomly received two single intravenous doses of 5′dFUR (2 and 4 g · m−2) on separate days. Plasma concentrations of 5′dFUR fell rapidly with terminal half-lives ranging from 16.1 to 27.7 min. A disproportionate increase in the area under the curve with increasing dose was seen in most patients. Doubling the dose resulted in a 40% decrease in nonrenal clearance (0.60 to 0.37 l · min−1) but no apparent change in renal clearance (0.32 to 0.29 l · min−1) or steady-state apparent volume of distribution (19.8 to 20.4 l). The mechanism for dose-dependence of 5′dFUR appears to be primarily due to nonlinear elimination associated with nonrenal processes rather than nonlinear plasma protein or tissue binding.
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    Kinetics and disposition of fluorescein-labelled liposomes in healthy human subjects (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 475-479 
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    ISSN: 1432-1041
    Keywords: liposomes ; sodium fluorescin ; pharmacokinetics ; clinical studies ; drug delivery ; normals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vivo kinetics and organ uptake of multilamellar liposomes have been studied in healthy volunteers. Sodium fluorescein-containing liposomes composed of equimolar amounts of egg phosphatidylocholine and cholesterol were injected into a peripheral vein in 4 healthy subjects. Blood samples collected from the femoral artery, hepatic vein and pulmonary artery, were analysed for liposomal dye content. The results, showing involvement of the reticuloendothelial system (RES) in the removal of liposomes, confirmed those previously obtained with radiolabelled preparations. Use of an innocuous liposomal marker (sodium fluorescein) and conventional vascular catheterization techniques, as employed here, may provide a reliable and clinically acceptable approach to establishing disease-induced changes in the kinetics of uptake of drug-containing liposomes by the RES, and thus help in the design of protocols for effective treatment.
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  • 92
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    Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 469-473 
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    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min−1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.
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    Effects of dixyrazine and methaqualone on the sleep pattern in normal man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 227-231 
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    ISSN: 1432-1041
    Keywords: Dixyrazine ; methaqualone ; etodroxizine ; Isonox® ; sleep stages ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.
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    Comparison of the pharmacokinetics of glipizide and glibenclamide in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 63-69 
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    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; sulfonylurea ; glipizide ; glibenclamide ; pharmacokinetics ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Four subjects received 5 mg14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00616416
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  • 95
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    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561556
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  • 96
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    Haemodynamic effects of intravenous disopyramide in heart failure (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 167-173 
    Details
    ISSN: 1432-1041
    Keywords: Disopyramide ; haemodynamic effect ; negative inotropic effect ; anticholinergic effect ; hear failure ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of disopyramide have been studied in 11 patients with manifest or imminent heart failure. Disopyramide, 2 mg per kg body weight, was given intravenously during right and left heart catheterisation. The cardiac index decreased by an average of 28% (p〈0.01); mean maximal left and right ventricular end-diastolic pressures were increased by 5.0±0.9 mm Hg (〈0.01) and 5.0±0.6 mm Hg (p〈0.05), respectively; and left ventricular systolic pressure fell slightly but significantly (p〈0.05). No significant change in right ventricular systolic pressure was seen. Pulmonary wedge pressure rose on average by 2.7 mm Hg (p〈0.05). No significant change in heart rate was observed in 5 patients with sinus rhythm. In 6 patients with atrial fibrillation, there was a significant (p〈0.01) increase in heart rate; the average increase in heart rate for the entire group was 19,6 heats per minute. The maximum effect on all the parameters occurred 7–11 minutes after the injection, and it gradually subsided during the following 10 minutes. It was concluded that disopyramide had a potentially serious myocardial depressant effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567110
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  • 97
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    Electronic Resource
    The dosage of Co-trimoxazole in childhood (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 217-222 
    Details
    ISSN: 1432-1041
    Keywords: Co-trimoxazole ; sulphamethoxazole ; trimethoprim ; pharmacokinetics ; paediatric-prescribing ; dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-trimoxazole, a mixture of one part trimethoprim (TMP) and five parts of sulphamethoxazole (SMX) in fixed ratio was given to 48 children aged between one and 48 months twice daily for up to seven days. Twenty were relatively healthy and 28 were very ill. Dosage was based on age. Plasma concentrations of both drugs were measured just before a dose was due and some three hours later. They were in the effective but not toxic range and serve to justify the simple regimen which generated them.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567118
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  • 98
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    Pharmacokinetics of 5,6-trans-25-hydroxycholecalciferol, a synthetic analogue of vitamin D3, in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 255-260 
    Details
    ISSN: 1432-1041
    Keywords: Vitamin D ; renal osteodystrophy ; 5,6-trans-25-hydroxycholecalciferol ; rickets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vitamin D analogues of high biological activity are probably useful in the treatment of renal osteodystrophy. The pharmacokinetics of the synthetic compound 5,6-trans-25-hydroxycholecalciferol have been studied in healthy subjects who were of normal vitamin D status. In comparison to natural 25-hydroxy-cholecalciferol, serum levels of the analogue were lower and its half-life in blood after oral or intravenous administration was considerably shorter. In normal subjects no increase of dihydroxylated metabolites in serum was observed within seven days of an intravenous dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567124
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  • 99
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    Electronic Resource
    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562662
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  • 100
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    Bioavailability studies with Digoxin-Sandoz® and Lanoxin® (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 371-376 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; bioavailability ; plasma levels ; cumulative urinary excretion ; particle size ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz® tablets have been compared with Lanoxin® manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to “new” Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562665
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