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  • Calcium  (121)
  • man  (90)
  • Industrial Chemistry
  • Seismology
  • Springer  (226)
  • 2005-2009  (7)
  • 1975-1979  (110)
  • 1970-1974  (109)
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  • 1
    Unknown
    Kent and Riegel’s Handbook of Industrial Chemistry and Biotechnology (2007)
    Springer
    Details
    Keywords: Biomass conversion ; Biotechnology ; Chemical Engineering ; Chemistry industry ; Industrial Chemistry ; Kent ; Riegel ; biochemical engineering
    Description / Table of Contents: Substantially revising and updating the classic reference in the field, this handbook offers a valuable overview and myriad details on current chemical processes, products, and practices. No other source offers as much data on the chemistry, engineering, economics, and infrastructure of the industry. The Handbook serves a spectrum of individuals, from those who are directly involved in the chemical industry to others in related industries and activities. It provides not only the underlying science and technology for important industry sectors, but also broad coverage of critical supporting topics. Industrial processes and products can be much enhanced through observing the tenets and applying the methodologies found in chapters on Green Engineering and Chemistry (specifically, biomass conversion), Practical Catalysis, and Environmental Measurements; as well as expanded treatment of Safety, chemistry plant security, and Emergency Preparedness. Understanding these factors allows them to be part of the total process and helps achieve optimum results in, for example, process development, review, and modification. Important topics in the energy field, namely nuclear, coal, natural gas, and petroleum, are covered in individual chapters. Other new chapters include energy conversion, energy storage, emerging nanoscience and technology. Updated sections include more material on biomass conversion, as well as three chapters covering biotechnology topics, namely, Industrial Biotechnology, Industrial Enzymes, and Industrial Production of Therapeutic Proteins.
    Pages: Online-Ressource (XIV, 1562 pages)
    ISBN: 9780387278438
    URL: https://doi.org/10.1007/978-0-387-27843-8
    Language: English
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    E-BOOK
  • 2
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    Fractal Behaviour of the Earth System (2005)
    Springer
    In:  Norwell, Springer, vol. 6, no. 3, pp. 2-203, (ISBN: 3-540-26532-5, XVI + 208 p. 72 illus.)
    Details
    Publication Date: 2005
    Keywords: FractureT ; Seismology ; Geoelectrics ; Electromagnetic methods/phenomena ; Geothermics ; Non-linear effects ; Dynamic ; Earth ; system ; geophysics ; Inhomogeneity ; scaling
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    BIBLIOGRAPHY SEISMOLOGY
  • 3
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    The Dead Sea fault and its effect on civilization (2005)
    Springer
    In:  Professional Paper, Perspectives in Modern Seismology, Dordrecht, Springer, vol. 65, no. 16, pp. 145-168, (ISBN 0080419208)
    Details
    Publication Date: 2005
    Keywords: paleo ; Seismicity ; Fault zone ; DSTF ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania ; Earthquake risk
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    BIBLIOGRAPHY SEISMOLOGY
  • 4
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    Velocity field of the Aegean-Anatolian region from 3D finite element models (2005)
    Springer
    In:  Bull., Polar Proj. OP-O3A4, Perspectives in Modern Seismology, London, Springer, vol. 201, no. XVI:, pp. 169-184, (ISBN: 3-540-23712-7)
    Details
    Publication Date: 2005
    Keywords: Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Geodesy ; Finite Element Method ; Modelling ; Three dimensional ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania ; Earthquake risk
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    BIBLIOGRAPHY SEISMOLOGY
  • 5
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    Nonlinear seismology - the seismology of the XXI century (2005)
    Springer
    In:  Bull., Polar Proj. OP-O3A4, Perspectives in Modern Seismology, Dordrecht, Springer, vol. 20, no. 4, pp. 47-65, (ISBN 0080419208)
    Details
    Publication Date: 2005
    Keywords: Non-linear effects ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania ; Earthquake risk
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    BIBLIOGRAPHY SEISMOLOGY
  • 6
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    Small-scale mantle plumes: Imaging and geodynamic aspects (2005)
    Springer
    In:  Bull., Open-File Rept., Perspectives in Modern Seismology, Arnsberg-Neheim, Springer, vol. 10, no. 87-17, pp. 69-94, (ISBN 0080419208)
    Details
    Publication Date: 2005
    Keywords: Plate tectonics ; hot ; spots ; GeodesyY ; Tomography ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania
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    BIBLIOGRAPHY SEISMOLOGY
  • 7
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    An earthquake early warning system for the Romanian capital (2005)
    Springer
    In:  Professional Paper, Open-File Rept., Perspectives in Modern Seismology, Berlin, Springer, vol. 1, no. 16, pp. 1-12, (ISBN 0080419208)
    Details
    Publication Date: 2005
    Keywords: Review article ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania ; Earthquake risk
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    BIBLIOGRAPHY SEISMOLOGY
  • 8
    Electronic Resource
    Electronic Resource
    Intestinal calcium binding protein in uremia (1979)
    Springer
    Calcified tissue international 27 (1979), S. 205-210 
    Details
    ISSN: 1432-0827
    Keywords: Intestine ; Calcium ; Binding ; Protein ; Uremia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In order to assess the usefulness of intestinal biopsies as indicators of end-organ responsiveness to vitamin D in uremic patients, calcium binding activity and calcium binding protein (CaBP) content were measured in intestinal biopsies from 12 uremic patients (glomerular filtration rate〈5.0 ml/min) and 12 adult controls. Values for both were found to vary with the site of biopsy, highest values being obtained in the duodenal bulb, with lower values distally. Values for activity correlated with values for CaBP content in both normals and uremics and no difference was observed between groups. Levels of calcium binding activity and content of CaBP did not correlate with serum immunoreactive parathormone levels, but were directly related to circulating 25-hydroxycholecalciferol (25-OHD) levels. The data show that intestinal CaBP is normal in activity, quantity, and affinity for calcium in malabsorbing uremic patients, and are consistent with the hypothesis that calcium malabsorption in uremia is unrelated to deficiency of intestinal calcium binding protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441187
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  • 9
    Electronic Resource
    Electronic Resource
    Precipitation of calcium phosphates from electrolyte solutions V. The influence of citrate ions (1979)
    Springer
    Calcified tissue international 28 (1979), S. 131-136 
    Details
    ISSN: 1432-0827
    Keywords: Calcium ; Phosphate ; Citrate ; Precipitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The influence of citrate ions on the precipitation of crystalline apatitic precipitates with low Ca/P molar ratios [octacalcium phosphate (OCP) and calcium-deficient apatites (DA) (system A)] and of the intercrystalline mixtures of calcium hydrogen phosphate dihydrate (DCPD) and DA (system B) was investigated. Samples were prepared by direct mixing of calcium chloride solutions (A, 6·10−3 mol dm−3; B, 1·10−1 mol dm−3) and sodium phosphate solutions (A, 6·10−3 mol dm−3; B, 2·10−2 mol dm−3) containing citrate (0–2·10−3 mol dm−3) and preadjusted to pH 7.4. In the presence of citrate ions: (a) crystal growth of OCP and DA was slowed down; (b) habit modification of DCPD crystals occurred; and (c) equilibration in intercrystalline mixtures of DCPD and DA's was slowed down. All phenomena were caused by surface adsorption of negatively charged ions, most probably CaC6H5O7-, which is the prevalent calcium citrate species under the given experimental conditions. Habit modification of DCPD was induced by preferential adsorption at the (001) crystal plane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441231
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  • 10
    Electronic Resource
    Electronic Resource
    Eine Verbesserung von Alsops Methode zur Bestimmung der Reflexions- und Transmissionskoeffizienten von Oberflächenwellen (1979)
    Springer
    Pure and applied geophysics 117 (1979), S. 1045-1049 
    Details
    ISSN: 1420-9136
    Keywords: Seismology ; Surface waves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Description / Table of Contents: Summary Alsop's method (1966) for the non-normal passage of surface waves through a vertical discontinuity is improved by using a new functional to be made stationary on the plane of discontinuity. The modified functional has the dimension of an energy flux and is characterized by the discontinuous surface wave displacements and stresses on the vertical discontinuity. Model calculations which were carried out for SV-waves and Love waves show that the new version of Alsop's method yields in all respects more consistent results than the old one.
    Notes: Zusammenfassung Die Methode von Alsop (1966) für den Durchgang von schräg einfallenden Oberflächenwellen durch eine vertikale Diskontinuität wird durch Verwendung eines neuen Funktionals, das auf der Diskontinuitätsfläche stationär sein soll, verbessert Das modifizierte Funktional hat die Dimension eines Energieflusses und wird durch diejenige Spannungs- und Verschiebungsdiskontinuität charakterisiert, die durch das Oberflächenwellenfeld auf der Diskontinuitätsfläche erzeugt wird. Modellrechnungen für SV-Wellen und Lovewellen zeigen, daß die neue Version von Alsoos Verfahren in jeder Hinsicht konsistentere Ergebnisse als die bisherige liefert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00876084
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  • 11
    Electronic Resource
    Electronic Resource
    Disordered mineral metabolism produced by ketogenic diet therapy (1979)
    Springer
    Calcified tissue international 28 (1979), S. 17-22 
    Details
    ISSN: 1432-0827
    Keywords: Anticonvulsant ; Ketogenic diet ; Calcium ; Vitamin D ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Vitamin D and mineral metabolism status was examined in five children maintained chronically on combined ketogenic diet-anticonvulsant drug therapy (KG), and the results compared to those obtained in 18 patients treated with anticonvulsant drugs alone (AD) and 15 normal controls. KG patients exhibited biochemical findings of vitamin D deficiency osteomalacia: decreased serum 25-hydroxyvitamin D (25OHD) and calcium concentrations, elevated serum alkaline phosphatase and parathyroid hormone concentrations, decreased urinary calcium and increased urinary hydroxyproline excretion, and decreased bone mass. Although the KG and AD groups demonstrated similar reductions in serum 25OHD concentration, the KG patients exhibited a significantly greater reduction in bone mass. In response to vitamin D supplementation (5000 IU/day), mean bone mass in the KG group increased by 8.1±0.9% (P〈0.001) over a 12-month period. These results suggest that ketogenic diet and anticonvulsant drug therapy have additive deleterious effects on bone mass and that these effects are partially reversible by vitamin D treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441213
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  • 12
    Electronic Resource
    Electronic Resource
    Precipitation of calcium phosphates under conditions of double diffusion in collagen and gels of gelatin and agar (1979)
    Springer
    Calcified tissue international 27 (1979), S. 171-176 
    Details
    ISSN: 1432-0827
    Keywords: Calcium ; Phosphate ; Precipitation ; Double diffusion ; Collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary One-dimensional double diffusion was applied to determine critical concentrations at which the precipitation of calcium phosphates occurs in reconstituted connective tissue collagen and agar gels at 37°C and in gelatin gels at 25°C. Experiments were performed in the presence of unbuffered 0.15 mol dm−3 NaCl, or 0.15 mol dm−3 NaCl-veronal adjusted to pH 7.4. It was found that critical concentrations of precipitation of both precipitating components, CaCl2 and phosphate buffer (pH 7.4), were equimolar and independent of the ratios of initial concentrations of the components. Critical concentrations of precipitation were not affected by the concentrations and kinds of gels used. The first-formed precipitates showed amorphous structure by X-ray diffraction analyses. Infrared (IR) spectra of the precipitates indicated CaHPO4 · H2O to be their predominant species. The molar Ca/P ratio obtained by chemical analyses was 1.08. This precipitate transformed in time into octacalcium phosphate. In all experiments, two very thin membranes of precipitate were formed in the gel column at the onset of precipitation simultaneously on both sides of the actual disc of precipitate. IR spectra and chemical analyses showed that both membranes were identical to the actual precipitation discs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441181
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  • 13
    Electronic Resource
    Electronic Resource
    Factors affecting parathyroid hormone-induced hypophosphatemia and32P specific activity in thyroparathyroidectomized rats (1979)
    Springer
    Calcified tissue international 27 (1979), S. 239-246 
    Details
    ISSN: 1432-0827
    Keywords: Parathyroid hormone ; Calcium ; Plasma phosphate ; Bone phosphate ; Plasma32P ; Specific activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Plasma changes in calcium, phosphate, and their radionuclides were studied in thyroparathyroidectomized (TPTX) rats treated with parathyroid hormone (PTH) for 8 h, this treatment starting 10 h after injection of45Ca and32P. Prior to intravenous infusion or hourly injections of PTH (10 mU/g/h), rats were maintained in one of three ways: on an extended fast (24 h); on a partial fast (10 h); or provided with 10% glucose and 1% calcium lactate overnight as a substitution for solid food. The pattern of change for plasma calcium,45Ca, and45Ca specific activity (S.A.) produced by PTH was not affected by these dietary conditions. The changes in phosphate were as follows: During the experimental (8 h) period, the rate of loss of32P from plasma in control rats was proportional to the length of the fast. This suggests that32P was released into plasma during the experimental period proportional to the ready availability of soft tissue glucose. In rats on an extended fast, PTH was phosphaturic, hypophosphatemic, and increased the rate of loss of32P from plasma without affecting32P S.A. values. In rats fasted for only 10 h, PTH produced similar effects on plasma phosphate and plasma32P values, but also caused a significant fall in plasma32P S.A. After glucose and calcium lactate treatment, PTH-induced phosphaturia was temporarily lost and the marked hypophosphatemia was replaced with a slight hyperphosphatemia. Plasma32P values also rose slightly; therefore, no effect on32P S.A. was produced. It is concluded from these studies that as the result of the phosphaturia caused by PTH, the hypophosphatemia which is produced automatically changes the phosphate gradient between various body compartments, causing phosphate entry into plasma. The authors postulate that this phosphate entering plasma is withdrawn primarily from bone fluid and bone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441192
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  • 14
    Electronic Resource
    Electronic Resource
    Anticonvulsant drug-induced osteomalacia: Alterations in mineral metabolism and response to vitamin D3 administration (1979)
    Springer
    Calcified tissue international 27 (1979), S. 13-18 
    Details
    ISSN: 1432-0827
    Keywords: Anticonvulsants ; Calcium ; Vitamin D ; Parathyroid hormone ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Parameters of mineral metabolism were examined in 6 patients with moderately severe anticonvulsant drug-induced osteomalacia. Compared to 15 matched controls, the patients exhibited significantly reduced serum calcium, inorganic phosphate, and 25-hydroxyvitamin D concentration, elevated serum alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) concentration, reduced intestinal47Ca absorption, reduced urinary calcium and increased urinary hydroxyproline excretion, and reduced forearm bone mass. Intestinal absorption of vitamin D3 was normal. Following 4 months of treatment with vitamin D3 (4000 units/day), serum 25-OHD concentration was increased to 3 times mean normal values and all parameters except serum iPTH, urinary calcium excretion, and forearm bone mass were returned to levels not significantly different from normal. Serum iPTH concentration was reduced by 39% (P〈0.05); 24-h urinary calcium excretion rose by 98% (P〈0.001), and forearm bone mass increased by 5.6% (P〈0.05). It is concluded that moderate-dose vitamin D3 supplementation is effective in normalizing parameters of mineral metabolism in this disorder, despite evidence of resistance to the biologic effects of vitamin D.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441155
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  • 15
    Electronic Resource
    Electronic Resource
    The calciuria of increased fixed acid production in humans: Evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D (1979)
    Springer
    Calcified tissue international 28 (1979), S. 233-238 
    Details
    ISSN: 1432-0827
    Keywords: Calcium ; PTH ; 1,25(OH)2D ; Acid ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N=3) or by increased dietary protein intake (N=4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. We conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441241
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  • 16
    Electronic Resource
    Electronic Resource
    Vaterite, a constituent of the eggshells of the nonparasitic cuckoos,Guira guira andCrotophagi ani (1979)
    Springer
    Calcified tissue international 29 (1979), S. 63-69 
    Details
    ISSN: 1432-0827
    Keywords: Vaterite ; Calcium ; Eggshells ; Cuckoos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The crystalline spherules occurring in patches on the outer surface of the eggshells ofGuira guira and the bloom on the entire outer surface of those ofCrotophagi ani were shown by X-ray diffraction analysis to be vaterite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02408056
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  • 17
    Electronic Resource
    Electronic Resource
    Regulation of calcium transport in isolated periosteal cells, effects of hormones and metabolic inhibitors (1979)
    Springer
    Calcified tissue international 29 (1979), S. 155-161 
    Details
    ISSN: 1432-0827
    Keywords: Periosteal cells ; Calcium ; PTH ; CT ; Metabolic inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Calcium transport was studied in cells isolated from cultured periostea of 18-day-old chick embryos. Net calcium uptake was stimulated by iodoacetate (IAA) and inhibited by dinitrophenol (DNP). Calcium efflux from the intracellular compartment was inhibited by IAA. Changes in the extra-or intracellular sodium concentration had only minor effects on calcium transport. This indicates that calcium efflux from periosteal cells is probably directly dependent on ATP hydrolysis, whereas calcium-sodium exchange is of less importance. The cation ionophore A23187 stimulated calcium uptake during short incubations but was inhibitory in long incubations. The possible involvement of the mitochondria in this effect is discussed. Parathyroid hormone (PTH) and calcitonin (CT) stimulated the net uptake of calcium in relatively low doses (both 0.01 U/ml or higher). The effects of the hormones on net calcium uptake were not additive. Calcium efflux was not changed in the presence of PTH or CT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02408071
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  • 18
    Electronic Resource
    Electronic Resource
    Phytochrome-mediated uptake of calcium in Mougeotia cells (1979)
    Springer
    Planta 146 (1979), S. 31-39 
    Details
    ISSN: 1432-2048
    Keywords: Autoradiography ; Calcium ; Mougeotia ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Ca2+ is proposed to function as a messenger in such phytochrome-mediated responses as localized cell growth, intracellular movements, and control of plasma membrane properties. To test this hypothesis, the uptake of Ca2+ in irradiated and non-irradiated regions of individual threads of the green alga Mougeotia was studied with the aid of 45Ca2+ and low temperature autoradiography: 10–20 cells within 40–60 cell-long threads were irradiated for up to 1 min, transferred to darkness for 3 to 10 min, submersed in a radioactive medium for 1 min, washed in an unlabelled medium for 30 min, and then autoradiographed at-80° C for several days. The autoradiographs show that those cells which had been pre-irradiated with red light did take up 2–10 times more Ca2+ than the adjacent non-irradiated cells of the same thread. Cells pre-irradiated with farred light or red light followed by far-red light showed no enhanced uptake of Ca2+. These results might be interpreted to indicate, firstly, that phytochrome-Pfr is involved in the enhanced uptake of Ca2+ and secondly, that the accumulation of radioactive Ca2+ in red light irradiated cells is an expression of an increased intracellular concentration of Ca2+. This interpretation is based on the data that (i) the dark interval between irradiation and labelling precluded the involvement of photosynthesis, (ii) the effect of red light was reversible with far-red light, and (iii) the accumulation of Ca2+ persisted during the long wash-out period. We speculate, that the red light-enhanced accumulation of Ca2+ in Mougeotia cells is caused by a Pfr-mediated increase of the Ca-permeability of the plasma membrane, and perhaps by a Pfr-impeding of an active Ca2+-extrusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381252
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  • 19
    Electronic Resource
    Electronic Resource
    Forced calcium entry and polarized growth of Funaria spores (1979)
    Springer
    Planta 144 (1979), S. 401-406 
    Details
    ISSN: 1432-2048
    Keywords: A23187 gradients ; Calcium ; Germination (moss spores) ; Electric fields-Funaria ; Ionophore gradient ; Moss spores-Polarization ; Spores (moss)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have used both steady electric fields, and gradients of the divalent ionophore, A23187, to control the point at which rhizoids emerge from spores of the common moss Funaria hygrometrica. The spores were grown in a medium containing calcium nitrate as the only major salt. Spores tend to form rhizoids towards the positive electrode, with a half maximal response to a difference of 4–8 mV across each cell. They also tend to form rhizoids towards the end of higher ionophore concentration in response to A23187 gradients. Both of these responses are the same at pH 5.5 and 8.0. Our tentative explanation is that Funaria spores tend to form rhizoids where most calcium enters. However, the point of chloronema emergence is scarcely affected by steady fields of up to 45 mV/cell. Moreover, when steady fields are applied across already developed rhizoids or chloronemata, their subsequent growth is directed towards the negative electrode in both cases, with rhizoids giving a 50% response at only 3—5 mV/cell, and chloronemata being less responsive.
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    URL: http://dx.doi.org/10.1007/BF00380114
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  • 20
    Electronic Resource
    Electronic Resource
    Interaction of bovine rhodopsin with calcium ions (1979)
    Springer
    European biophysics journal 5 (1979), S. 33-41 
    Details
    ISSN: 1432-1017
    Keywords: Rhodopsin ; Calcium ; Reaction kinetics ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract The formation of metarhodopsin II in various bovine rhodopsin preparations (rod outer segment (ROS) suspensions and rhodopsin-detergent solutions) was measured by means of flash spectrophotometry. The half-lifetime and formation of metarhodopsin II in ROS did not depend on the calcium concentration in the range of less than 10−9 M (using EGTA or EDTA) to 15×10−3 M calcium at pH values of 5.0, 7.1, and 9.0 (Table 1). The regeneration of rhodopsin from opsin by adding 11-cis retinal to ROS-suspensions and rhodopsin digitonin solutions was measured spectrophotometrically. It was not substantially different in either saline, one containing less than 10−7 M calcium (by adding EGTA), the other containing 10−3 M calcium (Table 2).
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    URL: http://dx.doi.org/10.1007/BF00535771
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  • 21
    Electronic Resource
    Electronic Resource
    The effects of Mn2+ and Ca2+ on the prolonged depolarising after-potential in barnacle photoreceptor (1979)
    Springer
    European biophysics journal 5 (1979), S. 223-230 
    Details
    ISSN: 1432-1017
    Keywords: Prolonged depolarising after-potential (PDA) ; Visual pigment ; Invertebrate photoreceptor ; Manganese ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract We have studied the effects on the PDA of modifying intracellular and extracellular concentrations of Ca2+ and Mn2+. The effect of decreased Ca2+ concentration or addition of EGTA is mainly an increase in the PDA amplitude and length. Raising Ca2+ concentration using ruthenium red or high external Ca2+ has the opposite effect. The effect of Mn2+ is much more striking: In the presence of 50–100 mM Mn2+ the PDA is initially greatly depressed but can rise slowly for up to 20 or 30 s (in the dark) until it approaches its original amplitude and time course. Bridge measurements showed that the depression of the PDA corresponds to a depressed conductance and so is not due to an increase in K+ conductance. The Mn2+ effect is potentiated by decreased Ca2+. Appropriate stimulation suppresses the rising PDA as promptly as it does a normal PDA, suggesting that if lateral diffusion is the source of the slow rise, the PDA and PDA-depressing processes must be spatially linked. The action of the anti-PDA is apparently prolonged by both Ca2+ and Mn2+.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00535450
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  • 22
    Electronic Resource
    Electronic Resource
    Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 395-399 
    Details
    ISSN: 1432-1041
    Keywords: cyproheptadine ; metergoline ; glucose tolerance ; insulin secretion ; chemical diabetes ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
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    Pharmacokinetics of quinidine related to plasma protein binding in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 187-192 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
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    URL: http://dx.doi.org/10.1007/BF00563104
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    Use of a simulation model to study the acute haemodynamic effects of diazoxide in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 73-81 
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    ISSN: 1432-1041
    Keywords: simulation model ; diazoxide hypotension ; haemodynamics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute haemodynamic effects of injected diazoxide (Hyperstat® Schering) have been studied in 8 hypertensive subjects. Aortic blood pressure was measured and cardiac output and peripheral conductance were assessed continuously using a simulation model. In six of the patients pulmonary artery end-diastolic pressure was also measured. Blood pressure fell in all subjects 5–10 min after injection of the drug cardiac output increased in all patients studied. However, the initial change in cardiac output differed, as it decreased in two subjects and did not change in one. The largest initial increases in cardiac output were seen in the subjects with the highest pulmonary artery end-diastolic pressure. Patients with an initial decrease in cardiac output were those with the least compliant (stiffest) aortas. We consider that the responsiveness of the baroreceptors determines the size of the increase in cardiac output immediately after reduction of blood pressure by diazoxide. Thus in a patient with a stiff aorta, particularly at low cardiac filling pressure, diazoxide might cause a fall in blood pressure to an unacceptable level.
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    URL: http://dx.doi.org/10.1007/BF00609868
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    Effect of external factors on phototaxis of Chlamydomonas reinhardtii (1979)
    Springer
    Archives of microbiology 123 (1979), S. 93-99 
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    ISSN: 1432-072X
    Keywords: Movement ; Phototaxis ; Cations ; Chlamydomonas ; Calcium ; Lanthanum ; Circadian rhythms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects of several cations on phototaxis of Chlamydomonas reinhardtii have been studied with the aid of an automated phototaxis monitoring device, coupled with a continuous culture. Sodium, potassium and magnesium ions, if added to the complete nutrient medium, have only slight effects on phototaxis at lower concentrations (10-3 mol), but inhibit at higher concentrations (10-2 mol). This inhibitory effect is not specific because motility is also impaired. Addition of 10-3 mol calcium enhances the phototactic reaction for some hours, but then the stimulation decreases gradually. Addition of 10-2 mol calcium causes strong inhibition. However, the reactivity recovers gradually during the following hours. If 10-3 mol potassium which does not influence phototaxis if added alone is applied simultaneously with calcium, the stimulation by calcium is enhanced. By the addition of 5·10-4—2·10-3 mol Ca2+ or Ca2++K+ cicadian rhythms with an average period length of 24 h are initiated which damp out after 1–2 weeks. If the cells are grown in a calcium deficient medium or if calcium is removed, phototactic activity decreases to very low reaction values or to zero, but is drastically increased immediately after the addition of calcium. The stimulatory effect of Ca2+ ions is specific. Ca2+ cannot be fully substituted by Ba2+ or Sr2+, and phototaxis is reversibly inhibited by lanthanum which is known to inhibit the calcium pump.
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    Calcium binding sites in the vesicles of the carotid and aortic body chief cells (1979)
    Springer
    Cell & tissue research 199 (1979), S. 145-151 
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    ISSN: 1432-0878
    Keywords: Carotid body ; Aortic body ; Calcium ; X-ray microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chief cells of the carotid and aortic body chemoreceptors possess numerous cytoplasmic dense-core vesicles which are known to contain primarily dopamine. Following fixation in solutions containing 50 mM CaCl2, a 20–30 nm electron-dense particle (EDP) is often observed eccentrically located in many of the vesicles. Approximately 44 % of the carotid body and 16 % of the aortic body vesicles contain an EDP. The EDP probably represents the Ca+ + binding site critical to the stimulus-secretion coupling events culminating in exocytosis of these vesicles. The presence of Ca+ + in the cytoplasmic vesicles was verified by electron probe X-ray microanalysis.
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    The influence of humidity on the mineral composition of tomato plants with special reference to calcium distribution (1979)
    Springer
    Plant and soil 52 (1979), S. 427-435 
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    ISSN: 1573-5036
    Keywords: Ash alkalinity ; Calcium ; Cation distribution ; Humidity ; Magnesium ; Mineral composition ; Oxalate ; Pectate ; Tomato
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Tomato plants grown in water culture under two different humidity regimes (50% R.H. and 95% R.H.) were harvested at intervals over the growth period and cation uptake and calcium distribution investigated. The following results were obtained: 1. Plants in the high humidity regime initially grew faster but at the final harvest after 22 days, dry matter yields were the same. 2. In the high humidity treatment particularly towards the end of the experiment, the growth of the young leaves was disturbed and the plants showed symptoms resembling Ca or B deficiency. Analysis revealed that these tissues were lower in Ca than comparative tissues of the low humidity plants. The converse was true for B. 3. Cation uptake was little affected by the humidity treatment. However, the distribution of calcium within the plant was markedly influenced by humidity. In the high humidity treatment the level of Ca in the young leaves was very low and Ca accumulated in the stems. A high proportion of both Ca and Mg in these younger Ca deficient leaves was found to be associated with pectate. The same trend was observed in the stems, more of the Ca and Mg in this case being bound to oxalate as well as pectate. These results further indicate the possible significance of exchange movement of Ca particularly under low transpiration conditions when Ca transport by mass flow is restricted. 4. Xylem sap analysis showed a close cation-anion balance in all samples. NO3-ion was the predominant anion and the two major cations were K and Ca. This provides further evidence that the upper plant parts provide the major site of NO3-reduction in the tomato plant.
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    Higher mode dispersion measurement (1978)
    Springer
    Pure and applied geophysics 116 (1978), S. 1274-1283 
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    ISSN: 1420-9136
    Keywords: Seismology ; Surface-wave dispersion ; Higher mode surface waves ; Italy, phase vel. of surface waves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract A new method is presented for the determination of higher mode dispersion over small distances, using two stations. From an intermediate focus earthquake it has been possible to measure the dispersion of the first and second Rayleigh modes in the period range 25–35 sec and 25–70 sec respectively. Using the almost linear array of Italian long-period stations TRI, BLZ, OLB an estimate of the average errors is also made.
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    URL: http://dx.doi.org/10.1007/BF00874686
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    Contribution to phase velocity investigations of Rayleigh-waves in middle Europe (1978)
    Springer
    Pure and applied geophysics 116 (1978), S. 1299-1306 
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    ISSN: 1420-9136
    Keywords: Seismology ; Rayleigh wave dispersion ; Phase velocity of Rayleigh waves ; German Dem. Rep., Rayleigh waves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Summary The phase velocity curve of Rayleigh-waves is determined for a profile crossing the area of GDR from south to north. Two different methods of seismogram processing are used which are discussed in detail. The phase velocities found are checked for compatibility. An inversion of a common phase velocity curve is done by using hedgehog procedure.
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    An upper mantleP-wave velocity model for eastern and southern Africa (1978)
    Springer
    Pure and applied geophysics 116 (1978), S. 1262-1273 
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    ISSN: 1420-9136
    Keywords: Seismology ; African Rift ; P-wave velocity beneath Africa ; Upper mantle structure for Africa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract AP-wave velocity model for the upper mantle beneath eastern and southern Africa is proposed. The top 250 km of the model is characterized by relatively low velocities similar to those deduced for the upper mantle beneath the western United States of America. At greater depths, the velocities gradually change to normal mantle values.
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    Transient disturbance produced in an elastic half-space by impulsive shearing traction distributed over a circular region (1978)
    Springer
    Pure and applied geophysics 116 (1978), S. 198-211 
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    ISSN: 1420-9136
    Keywords: Seismology ; theoretical ; Cagniard's technique ; Elastic waves produced by shearing traction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The displacement produced in a semi-infinite, homogeneous, isotropic elastic medium by the application of shearing traction over a circular portion of the half-space has been evaluated in exact form by Cagniard's Technique (Cagniard, 1962;Gakenheimer andMiklowitz, 1969).
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    The intestinal handling of calcium by the rat in vivo, as affected by cortisol. Effect of dietary calcium supplements (1978)
    Springer
    Calcified tissue international 25 (1978), S. 1-6 
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    ISSN: 1432-0827
    Keywords: Calcium ; Intestine ; Growth ; Cortisol ; Hydroxyproline ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This paper reports the effects of cortisol on intestinal management of calcium and on related changes on bone metabolism. Five groups of 12 rats each fed a standard diet (0.8% Ca) received 2, 6, 16, 32, and 128 mg/kg/day of cortisol hemisuccinate, subcutaneously. After 16 days, intestinal absorption and excretion of Ca were measured with the aid of45Ca. True Ca absorption increased as a function of dose up to 16 mg/kg/day and remained high with the larger doses. Endogenous fecal Ca excretion increased exponentially as a function of the dose from 16 mg/kg/day onwards. Therefore, a dual effect was observed: (a) an increase in true Ca absorption at low cortisol doses (which increased net Ca absorption); and (b) an increase in endogenous fecal Ca excretion at high doses (which reduced net Ca absorption). In no case was a depression of true Ca absorption observed. Growth rate and food conversion efficiency were depressed only with a cortisol dose of 128 mg/kg/day. The urinary excretion of hydroxyproline, pyrophosphate, and aminopolysaccharides decreased with low doses and increased above normal levels with the highest dose. When animals treated with 128 mg/kg/day of cortisol were fed Ca-enriched diets, net Ca absorption improved. Simultaneously, growth rate and food conversion efficiency approached normal values. In these experiments, net absorption of Ca was found to be inversely related to urinary excretion of hydroxyproline. The urinary rate of excretion of hydroxyproline is suggested as an indicator of the effect of a Ca supplement on cortisol affected connective tissue turnover.
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    Effects of a single dose of fluoride on calcium metabolism (1978)
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    Calcified tissue international 26 (1978), S. 199-202 
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    ISSN: 1432-0827
    Keywords: Fluoride ; Calcium ; Phosphate ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Fluoride 27 mg was given perorally to 14 subjects. It was found that the serum fluoride concentration increased followed by a decrease to normal levels during 24 h. Serum concentrations of calcium and phosphate decreased initially whereas those of serum immunoreactive parathyroid hormone increased. After 24 h the measured quantities were within normal limits. The results are discussed with reference to mineralization of hard tissues and to fluoride treatment of osteoporotic patients.
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    Potentiation of the effects ofSolanum malacoxylon extracts on rat intestinal phosphate and calcium absorption by incubation with ruminal fluid (1978)
    Springer
    Calcified tissue international 26 (1978), S. 215-219 
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    ISSN: 1432-0827
    Keywords: Solanum malacoxylon ; Vitamin D metabolites ; Rickets ; Phosphate ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of a partially purified aqueous extract ofSolanum malacoxylon (SM) leaves and of an SM extract incubated with ruminal fluid (RF) prior to administration on intestinal phosphate and calcium absorption in rachitic rats were compared with 1α, 25-dihydroxy-vitamin D3[1α,25-(OH)2-D3] using a duodenal loop in situ method. The time course responses elicited by both extracts were qualitatively similar to that of 1α, 25-(OH)2-D3. However, a single dose of SMRF was significantly more effective in stimulating32P absorption than an equivalent dose of SM. Part of this difference can be accounted for by incomplete saturation of the phosphate transport system with the level of SM employed. Treatment with rumen potentiated the effects of SM on45Ca absorption to a lesser extent. Extraction of SMRF with nonpolar organic solvents and purification of the lipid extract by chromatography on Silica Gel G thin-layer plates and on Sephadex LH-20 columns yield two fractions which promote intestinal32P absorption. The bioactive fraction eluting first from the Sephadex LH-20 column migrates similarly as 1α,25-(OH)2-D3. The greater effectiveness of SMRF extracts on intestinal phosphate and calcium absorption may be tentatively attributed to the release of 1α,25-(OH)2-D3 from the corresponding glycoside, shown previously to be present in SM, and to steroid modification during incubation with rumen.
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    Selective stimulation of net calcium efflux from chick embryo tibiae by parathyroid hormone in vitro (1978)
    Springer
    Calcified tissue international 25 (1978), S. 227-232 
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    ISSN: 1432-0827
    Keywords: Parathyroid hormone ; Bone ; Calcium ; Chick embryo ; Organ culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this study was to measure in an in vitro system the movement of Ca and phosphate (Pi) out of bone when treated with parathyroid hormone (PTH). Tibiae from 13-day chick embryos were incubated for up to 8 h in a defined medium containing 1.8 mM Ca. Medium samples were collected every 2 h and were analyzed for Ca, Pi and lactate. Net effluxes from the bones were calculated. When bones were incubated with PTH in the medium (1 U/ml), net Ca efflux was increased 44, 60 and 100% at 4, 6 and 8 h, respectively. At no time was net Pi efflux affected by the hormone. The well known PTH-stimulated lactate production was not seen until 8 h. Lower doses of PTH (0.1 and 0.3 U/ml) were also effective. Comparing PTH (1 U/ml) responsiveness at higher (2.2 mM) and lower (0.9 mM) medium Ca concentrations, showed that with 2.2 mM Ca no increased Ca efflux was seen, while with 0.9 mM Ca significant elevation in medium Ca occurred 2 h sooner than in the experiments using 1.8 mM Ca. In another experiment, varying the medium Pi level from 1 to 2 mM had no effect on the Ca response to PTH. In neither experiment was Pi release affected by PTH. The results of this study have led to the following conclusions: (1) PTH acts on bone to cause an early dose related increase in net Ca efflux; (2) the effect is specific for Ca, since it is not accompanied by an increased Pi efflux, and may be saturated by raising the medium Ca level; and (3) PTH-stimulated Ca efflux in this system is not correlated with, and is probably not a result of increased lactate production.
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    Influence of partially purified extracts ofSolanum malacoxylon on bone resorption in organ culture (1978)
    Springer
    Calcified tissue international 26 (1978), S. 39-45 
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    ISSN: 1432-0827
    Keywords: Solanum malacoxylon ; Bone culture ; Resorption ; Calcium ; Osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The water-soluble active principle of the plantSolanum malacoxylon (SM) was partially purified by column chromatography, and its bone-resorbing activity was tested by using an organ culture system of 18-day fetal mouse fibulae prelabeled with45Ca. Three series of experiments were performed. In the first series, the aqueous extract of SM was submitted to Sephadex G-25 chromatography to separate the active substances. From six collected fractions only two exhibited reproducible bone-resorbing activity as indicated by an increased release of45Ca from bone rudiments. In the second series, the active fractions were combined and lyophilized to a powder which was dissolved in the culture media to obtain the concentrations of 5, 25, 50, and 100 μg/ml. The addition of this saltfree material resulted in a dose-related accentuation of45Ca release from fetal mouse bones into the medium. Histologically, the treated fibulae showed greater numbers of osteoclasts than the controls and a disappearance of bone trabeculae. In the third series, the active material was further purified on Sephadex LH-20 column. From four collected fractions, only one showed bone-resorbing activity in vitro. It is concluded that the purified active factor of SM exerts a direct effect on bone. It stimulates the mobilization of bone calcium in vitro by increasing the population of osteoclasts. The nature of the active principle remains unknown.
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    A proposed cellular mechanism for calcium transport in the intestinal epithelial cell (1978)
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    Calcified tissue international 26 (1978), S. 71-79 
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    ISSN: 1432-0827
    Keywords: Absorption ; Calcium ; Mitochondria ; Intestinal epithelium ; Potassium-pyroantimonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Intracellular transport of calcium from the apical to the basal-lateral region of the intestinal epithelial cell was invetigated in duodenum from normal fed, fasted, and calcium-loaded rats. The process was followed with time using electron microscopy with potassium pyroantimonate to precipitate calcium. The observations made were subjected to morphometric analysis. The specificity of the method was demonstrated in the villus cell by resistance to micro-incineration and by absence of deposits following exposure to EGTA. Using this method calcium was seen in cells from calcium-fed rats at the microvillus border, in the Golgi zone, and within the internal compartments of the mitochondria. In cells from fasted rats calcium was not seen. Mitochondria were found largely at the apex of the cell and were free of detectable calcium. By 5 min, in the cells of fasted rats given a calcium load, the calcium had reached the Golgi apparatus and the inner mitochondrial compartment. After 15 min mitochondria were heavily loaded with calcium and had moved to the basal region of the cell. These observations suggest that mitochondria play an important role in absorption of calcium and appear to transport this ion from the apex to the basal region of the cell where entry into the capillaries takes place.
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    Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 213-218 
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    ISSN: 1432-1041
    Keywords: Activated charcoal ; acute intoxication ; digoxin ; phenytoin ; aspirin ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of activated charcoal 50 g suspended in water on the absorption of digoxin, phenytoin and aspirin was studied in six healthy volunteers in a cross-over manner. The absorption of digoxin and phenytoin were almost completely prevented (about 98%) when activated charcoal was ingested immediately after the drug. The total absorption of aspirin was inhibited by 70%, with clear postponement of absorption and partial release of aspirin from the charcoal in the gut: The peak serum concentration of aspirin was reduced by 95% by charcoal. When activated charcoal was ingested 1 hour after the drugs the inhibition of absorption was considerably less. However, since the absorption of larger doses of the drugs is often slow, the administration of an adequate dose of activated charcoal will be of definite value in the treatment of acute intoxication, even if delayed for several hours.
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    Compensation of dietary induced reduction of tetracycline absorption by simultaneous administration of EDTA (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 129-131 
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    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; EDTA ; milk ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of tetracycline in man under the influence of concomitantly administered EDTA, milk and a combination of EDTA and milk has been investigated. Urinary excretion of the drug was measured for 30 h. The inhibitory effect of milk could be counteracted by simultaneous ingestion of EDTA, which resulted in almost equivalent urinary excretion of tetracycline compared to experiments done in the fasting state. Administration of EDTA alone, in a neutral dosage form, did not significantly change absorption of the drug, which contradicted previous findings. The possible use of EDTA during tetracycline therapy is discussed.
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    Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 277-280 
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    ISSN: 1432-1041
    Keywords: Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.
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    Preliminary studies of the kinetics of citalopram in man (1978)
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    European journal of clinical pharmacology 14 (1978), S. 69-73 
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    ISSN: 1432-1041
    Keywords: Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.
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    Investigation into the species-specific deacylation of penta-acetyl-gitoxin (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 425-430 
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    ISSN: 1432-1041
    Keywords: Penta-acetyl-gitoxin ; 16-acetyl-gitoxin ; gitoxin ; mass spectrometry ; species-specific deacylation ; man ; rabbit ; guinea-pig ; rat ; blood ; intestinal mucosa ; liver homogenate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penta-acetyl-gitoxin (PAG) shows species-specific deacylation to 16-acetyl-gitoxin (16-AG; I and III) or gitoxin (II and IV) by homogenates of liver and intestinal mucosa of man (I), rabbit (II), guinea-pig (III) and rat (IV), whereas it is degraded into tri- and tetra-acetates by homogenates of guinea-pig myocardium as well as by human blood and serum. The identity of the principal and chloroform-extractable metabolites in human urine after PAG administration with 16-AG has been demonstrated by mass spectrometry.
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    Haemodynamic and tolerance studies in man of a new, orally active, selectiveβ 1-adrenoceptor agonist H 80/62 (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 163-170 
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    ISSN: 1432-1041
    Keywords: H 80/62 ; haemodynamic effects ; noninvasive techniques ; selectivity ; β1-adrenoceptor agonist ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The selective β1-adrenoceptor agonist H 80/62 was administered intravenously and orally to healthy subjects and its effects on systolic time intervals, arterial blood pressure and heart rate were studied. Side-effects were noted too, and continuous ECG-recordings were made in order to study its arrhythmogenic effect. After i.v. administration of H 80/62 20 µg/kg body weight there was shortening of total electromechanical systole, the pre-ejection period and of the left ventricular ejection time, systolic blood pressure tended to increase, and diastolic blood pressure and heart rate were essentially unchanged. When administered orally as a sustained-release preparation in doses between 20 and 40 mg the haemodynamic effects were qualitatively the same as after i.v. administration, but in some studies there was a slight increase in heart rate. During exercise the systolic blood pressure and heart rate were identical after H 80/62 and placebo. The effect of the drug was maximal immediately after cessation of the i.v. infusion and basal values were regained within 60 min. After oral administration of a sustained-release formulation the effect was maximal after one hour and persisted for at least five to seven hours. The drug was well tolerated on repeated administration. The incidence of ventricular extrasystoles was possibly increased in one subject out of eight (11 ventricular extrasystoles during 18 h). The results of this Phase I study of H 80/62 warrant further evaluation of the drug in man.
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    Effect of delayed administration of activated charcoal on nortriptyline absorption (1978)
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    European journal of clinical pharmacology 14 (1978), S. 445-447 
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    ISSN: 1432-1041
    Keywords: Activated charcoal ; tricyclic antidepressants ; nortriptyline ; poisoning ; antidote ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, ‘Medicoal’ was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought.
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    Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 435-439 
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    ISSN: 1432-1041
    Keywords: Intramuscular Clindamycin Phosphate ; serum levels ; half-lives ; renal Failure ; haemodialysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal failure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 8 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.
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    Bioavailability of norethindrone in human subjects (1978)
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    European journal of clinical pharmacology 13 (1978), S. 35-39 
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    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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    Calcium uptake and survival of Bacillus stearothermophilus (1978)
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    Archives of microbiology 119 (1978), S. 17-24 
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    ISSN: 1432-072X
    Keywords: Thermophilic bacteria ; Bacillus stearothermophilus ; thermostability ; Calcium ; Transport ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The calcium transport in resting vegetative cells of Bacillus stearothermophilus was studied by determining the retention of 45Ca in a membrane filter assay. The kinetics of death by vegetative cells, when suspended in buffer at 55°C, was also investigated. The calcium influx required the presence of an energy source, e.g. glucose-1-phosphate and the system exhibited saturation kinetics. The requirements for survival of the thermophilic cells reflected those of the calcium transport system. Thus, cells treated with nitrogen gas showed an increased thermal stability and a decreased efflux of calcium. The initial velocity of calcium influx correlated linearly with the survival of the cells after 1 min heating at 55° C. Lanthanum inhibited calcium influx and reduced survival. Magnesium did not inhibit calcium influx but could replace calcium as a stabilizing agent. The results suggest that the thermophilic cells are not intrinsically heat stable but survive due to a high cellular concentration of divalent ions.
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    Catharanthine: A novel stimulator of pancreatic enzyme release (1978)
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    Cell & tissue research 192 (1978), S. 277-284 
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    ISSN: 1432-0878
    Keywords: Pancreas ; Calcium ; Vinca alkaloids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The plant alkaloid, catharanthine, was shown to stimulate release of amylase from pancreatic fragments and to cause extensive degranulation of pancreatic acinar cells with accumulation of membrane material in the Golgi region. The extent and time course of maximal catharanthine stimulation was comparable to that induced by the cholinergic analog bethanechol. Antimycin inhibited the action of catharanthine while atropine did not. Removal of Ca2+ from the incubation medium inhibited amylase release induced by catharanthine but did not affect release induced by bethanechol. Catharanthine induced a delayed release of 45Ca2+ from prelabeled pancreatic fragments as compared to bethanechol. It is suggested therefore that catharanthine activates the physiological pathway controlling amylase release by causing a rise in cytoplasmic Ca2+ but the mechanism by which this occurs is different from that caused by physiological secretagogues.
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    Cold-induced insulin release in vitro: Evidence for exocytosis (1978)
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    Cell & tissue research 194 (1978), S. 387-398 
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    ISSN: 1432-0878
    Keywords: Isolated pancreatic islets ; Temperature ; Exocytosis ; Insulin ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Exposure of isolated pancreatic islets (mouse or rat) to low temperature (2° C) evoked a threefold increase in insulin release irrespective of the glucose concentration in the incubation medium. Cold-induced release was transient and rewarming to 37° C restored the sensitivity of B-cells to glucose stimulation. In islets cooled to 2° C, exocytotic profiles could easily be detected both by thin-section and freeze-fracture electron microscopy. As revealed by the freeze-fracture technique, the number of exocytotic profiles per membrane area was increased three-to fourfold as compared to islet cells incubated at 20° C. This was paralleled by intracellular fusion of secretory vesicles. Cold-induced insulin release was not affected by theophylline, cytochalasin B, omission of extracellular Ca++ or D600. Replacement of extracellular Na+ with choline or sucrose suppressed the increase in insulin release and in frequency of exocytotic profiles recorded after exposure to 2° C. It is suggested that a redistribution of Ca++ from intracellular stores, possibly mediated by an increase in intracellular Na+, triggers exocytosis of insulin granules upon exposure to cold.
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    The effect of the ionophore A23187 on amylase release, cellular integrity and ultrastructure of mouse pancreatic acini (1978)
    Springer
    Cell & tissue research 186 (1978), S. 287-295 
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    ISSN: 1432-0878
    Keywords: Pancreas ; Calcium ; Ionophore
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of the Ca2+ ionophore A 2317 on pancreatic amylase and lactate dehydrogenase (LDH) release, cellular electrolyte balance and ultra-structure were studied with the use of incubated pancreatic fragments. A 23187 (0.3 μM) in the presence of Ca2+, increased amylase release but at higher concentrations (1–10 μM) also increased LDH release and increased uptake of 14C-sucrose with concomitant loss of tissue K+ and gain in Na +. The ultrastructure of the majority of acini appeared normal and showed depletion of zymogen granules. Microtubules and microfilaments which have been implicated in the release process were normal or increased in number. In the absence of Ca+ the ionophore had no effect on secretion, cellular integrity or ultrastructure. It is concluded that A 23187 in the presence of Ca2+ increases amylase release by a mechanism comparable to the terminal steps in stimulussecretion coupling induced by physiological secretagogues. This provides further evidence that amylase release is mediated by a rise in cell Ca2+ although the mechanisms of the ionophore- and physiological secretagogue-induced rise in Ca+ are probably different. High concentrations of ionophore (〉 1 μM) also induce Ca2+ dependent damage in a fraction of the cells.
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    Calcium and sulphur in neurosecretory granules and calcium in mitochondria as determined by electron microscope X-ray microanalysis (1978)
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    Cell & tissue research 186 (1978), S. 453-463 
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    ISSN: 1432-0878
    Keywords: Neurosecretory granules (Insects) ; Mitochondria ; Calcium ; Sulphur ; Microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Sections of neurosecretory cells fixed in glutaraldehyde and osmium tetroxide were studied by means of an EMMA-4 analytical microscope. Secretory granules in neurosecretory cells of the corpus cardiacum and of the brain, both in the desert locust Schistocerca and in the blowfly Calliphora, as well as neurosecretory granules in posterior pituitaries of the frog Rana and of the albino rat all contain a high concentration of calcium. A distinct sulphur peak was also a constant feature. In neurosecretory cells of the corpus cardiacum of Schistocerca the chromatin contained a high concentration of calcium. The mitochondria also contained much calcium, but part of this disappeared during preparation except when fixative and wash contained calcium chloride. By block staining with uranyl acetate most calcium is displaced from the mitochondria, whereas most of the calcium remains in the neurosecretory granules. Since the calcium peaks in spectra from neurosecretory granules appear of similar size, regardless of variations in the preparative procedure, this calcium must be firmly bound. The possible role of the calcium bound to the neurosecretory substance is discussed. The presence of sulphur in insect neurosecretory granules indicates the presence of a protein besides the hormone, i.e., an insect neurophysin.
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    The temperature dependency of45Ca diffusion in bovine enamel (1977)
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    Calcified tissue international 24 (1977), S. 173-177 
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    ISSN: 1432-0827
    Keywords: Enamel ; Calcium ; Diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The diffusion of45Ca ions in sound bovine enamel at pH 7.0 was studied as a function of temperature in the range 20°–40°C. The experimental data show that the diffusion is governed by two processes with activation energies of about 0.7 and 1.3 eV respectively. These values are considerably larger than the activation energy of calcium ion diffusion in water (0.2 eV). The diffusion process with the activation energy of 1.3 eV is dependent upon the calcium concentration in solution. A model based on the complex pore structure of enamel and on interactions of diffusing ions with the enamel constituents is discussed.
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    Determination of focal coordinates of near earthquakes in an area of unknown crustal parameters (1977)
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    Pure and applied geophysics 115 (1977), S. 667-673 
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    ISSN: 1420-9136
    Keywords: Seismology ; Hypocenter determination ; Focal coordinate determination ; Near earthquakes location
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Summary A new computation method is described which determines the focal coordinates, theP n-andP G-velocity, the focal time and the Moho-depth in the case of near earthquakes. The method is provided especially for areas where the crustal parameters are insufficiently known. It presumes that the standard error ofP n-andP G-arrival times is a minimum. The problem turns out to represent the solution of a set of at least seven equations with seven unknown parameters. Four of these unknowns can be separated in advance. This leads to a considerable simplification. The three remaining unknowns are the focal coordinates. Their best fitting values are found by the gradient method. An example is presented which shows how errors can arise if the initial trial coordinate is chosen at an unfavourable position.
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    A lithospheric model to interpret focal properties of intermediate and shallow shocks in central greece (1977)
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    Pure and applied geophysics 115 (1977), S. 655-666 
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    ISSN: 1420-9136
    Keywords: Seismology ; Greece ; Plate tectonics ; Focal mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Summary An attempt has been made to interpret the striking difference, in focal properties, between the intermediate and shallow earthquakes in Central Greece and an observed time sequence of these shocks by a lithospheric model. This model consists of a lithospheric slab descending from the Ionian to the Aegean and a back-arc expanding Aegean lithosphere. Thrust faulting near the top surface of the slab, caused by the sinking of the slab, triggers spreading and normal faulting in the back-arc Aegean region.
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    Systematic variations of mean travel-time residuals in space and time (1977)
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    Pure and applied geophysics 115 (1977), S. 675-692 
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    ISSN: 1420-9136
    Keywords: Seismology ; P wave residuals ; Travel-time anomalies ; Earthquake prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Summary Mean travel-time residuals of P waves for the period 1964–1970 at stations in North America and Europe are well separated into large domains of positive and negative values. The spatial distribution of residuals in North America is in good agreement with the structure of the upper mantle obtained from Rayleigh wave dispersion and is in accord with magnitude anomalies and heat flow data. A systematic variation of residuals in time is found to be sensitive to major changes in the nature of the earthquake source distribution, as for example aftershocks, as well as to changes in methods of detection of first arrivals. Residuals at neighboring stations are correlated up to distances of the order of 2°. Half year mean residuals at stations within 2° distance from the epicenters of strong earthquakes have a sudden jump 1.5 years before the occurrence of an earthquake. A formal algorithm based on this pattern permits prediction of the times of all 16 earthquakes with magnitudeM≥7.5 occurring during the interval 1966–1972. Although the average duration of the alarm periods is about half the total time interval of the catalog, so that the algorithm has no practical importance, these results are statistically significant on a 99% level of confidence.
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    Diffusion of45Ca in bovine enamel (1977)
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    Calcified tissue international 24 (1977), S. 59-64 
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    ISSN: 1432-0827
    Keywords: Enamel ; Calcium ; Exchange ; Diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The penetration of45Ca ions into whole bovine enamel from an aqueous solution was studied as a function of the Ca content in the solution. A sectioning technique was employed to measure the penetration of45Ca into the enamel. Probably only Ca ions occupying surface positions in the hydroxyapatite crystallites participate in the exchange process at the solution-enamel interface. The fraction of Ca ions participating in the exchange was 2% of the total number of Ca ions. Two different diffusion processes occur; firstly, a process governed by a diffusion coefficient, D1 ranging from about 5×10−14 to 2×10−12 cm2/s and strongly dependent on the calcium concentration in the solutions; and secondly a process with a concentration-independent diffusion coefficient, D2, with a value of 2.8×10−12 cm2/s. It is assumed that the 2 diffusion types correspond to intra-and interprismatic transport, respectively. A model based on the pore structure of dental enamel and on surface charges on hydroxyapatite crystallites is discussed.
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    The measurement of Ca2+ effluxes from bone (1977)
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    Calcified tissue international 24 (1977), S. 113-117 
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    ISSN: 1432-0827
    Keywords: Bone membrane ; Calcium ; Ion fluxes ; Calvarium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To facilitate the study of membrane function in the control of the flow of ions into and out of bone, it was desirable to develop a system for the direct quantitation of unidirectional effluxes of calcium and phosphate from bones. Based on a mathematical analysis of the problem, a specially designed Ussing chamber was developed which proved successful. Calvaria from 2-day-old rat pups, 3-day chicks and adult mice were evaluated. Calcium influxes which exceeded the corresponding effluxes were observed in the neonatal calvaria but not with those from adult mice. Also, an asymmetry in efflux was observed in rat calvaria, the inner side of the skull showed a higher efflux than did the external side. no such asymmetry was seen with calvaria from chicks or mice. This new technology should permit a further exploration of the role of the bone membrane in electrolyte homeostasis.
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    The effect of fluoride on bone of rats fed diets deficient in calcium or phosphorus (1977)
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    Calcified tissue international 22 (1977), S. 9-17 
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    ISSN: 1432-0827
    Keywords: Bone ; Fluoride ; Calcium ; Phosphorus ; Mechanical Strength
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Four groups of weanling rats were fed for 2 weeks on a diet sufficient or insufficient in calcium and/or phosphorus. Each group was divided into four subgroups which were offered distilled water supplemented with 0, 50, 75, or 150 ppm fluoride. High levels of fluoride in drinking water inhibited weight gain. This inhibition was less in rats deficient in phosphorus than when normal-phosphorus diets were offered. At a low level, fluoride was without any effect on bone ash, thickness of femoral cortical bone, and mechanical strength, as measured by maximal load, ultimate stress to breaking, and limit of elasticity. Modulus of elasticity was decreased. At higher levels fluoride tended to decrease most of these parameters, except in rats deprived of both calcium and phosphorus. The effect of fluoride was modified by lack of dietary calcium and/or phosphorus and appeared to be weaker in rats deficient in these nutrients. Lack of dietary calcium and/or phosphorus decreased bone strength more than did fluoride content of water and of bone mineral. Concentration of bone ash and thickness of femoral cortical bone were closely correlated with parameters of mechanical strength.
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    On the state of anionic groups of demineralized matrices of bone and dentine (1977)
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    Calcified tissue international 22 (1977), S. 275-284 
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    ISSN: 1432-0827
    Keywords: Bone ; Calcium ; Collagen ; Dentine ; Phosphoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Calcium-binding and biochemical studies have been applied to characterize the state of the carboxylate and protein-bound phosphate groups in the EDTA-demineralized matrices of rat bone and dentine. The organic phosphate and carboxylate content of demineralized bone is virtually identical to that of purified steer skin collagen whereas demineralized dentine has a significantly higher phosphate and carboxylate content, presumably due to the presence of an acidic non-collagenous phosphoprotein. Two classes of calcium-binding sites can be detected in demineralized bone, demineralized dentine, and purified, reconstituted collagen. The number of strong calcium-binding sites correlates with the number of protein-bound phosphate groups. Depending on the preparative procedure, seven to nine such sites (per collagen molecule) are present in dentine, and one to two in the purified reconstituted collagen and in bone. The binding constant for the dentinal sites (1.1×104 M−1), however, is 20 times greater than that for bone or reconstituted collagen fibrils from skin. We tentatively conclude that the strong calcium-binding site in bone and reconstituted collagen is of the form protein-PO 4 − Ca++ whereas in dentine it is of the form the weak binding sites in bone and dentine are of the form protein-COO-Ca++; and that approximately 160 of the 217 carboxylate groups of the collagen molecules of dentine or bone are present as electrostatic linkages of the form protein-COO−+H3N-protein.
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    A new tracer method for the calculation of rates of bone formation and breakdown in osteoporosis and other generalised skeletal disorders (1977)
    Springer
    Calcified tissue international 22 (1977), S. 191-206 
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    ISSN: 1432-0827
    Keywords: Bone ; Calcium ; Strontium ; Apposition ; Tracer analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract 1. Evidence has accumulated that the rate of acceretion (A) of calcium to bone is the sum of two fluxes; apposition involving the laying down of new bone and augmentation which is the result of slow exchange of non-surface bone calcium with plasma calcium pools as the result of solid state diffusion. 2. A method has been devised for separating A into its two components. It requires the use of45Ca or, for clinical studies,85Sr as a calcium tracer. Studies which are initiated with a combined accretion rate-calcium balance study, are concluded with an estimate of the exponent of the power function which has been found to describe the whole body retention of tracer from the second month onward. 3. The impulse response function of the skeleton for the tracer is then calculated, making the assumption that in any uniform volume of bone, osteoclastic resorption is a first order process. Making in addition certain simplifying assumptions, which are shown to have a modest influence on the final results, a mean rate of bone resorption can be calculated using a development of the well known Stewart-Hamilton formula. The apposition rate is calculated as the sum of the resorption rate and the calcium balance. Augmentation and diminution, defined as equal and opposite exchange processes, are given by the difference between A and the apposition rate. 4. The results of our first thirteen studies in normal subjects and patients with metabolic bone disease are presented, together with analyses of some data from the literature. It is concluded that the development of an atraumatic method for measuring rates of bone formation and resorption in the whole body would be an important advance in the study of metabolic bone disease, and this work is presented so that critical comparisons may be initiated between this tracer method and independent histological methods for measuring these parameters.
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    Calcium deficiency, pregnancy, and lactation in rats (1977)
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    Calcified tissue international 23 (1977), S. 87-94 
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    ISSN: 1432-0827
    Keywords: Calcium ; Osteoporosis ; Lactation ; Chemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The calcium homeostatic mechanism was challenged in adult female rats by feeding them a calcium-deficient diet containing oxalate, and by subjecting them to pregnancy and lactation. The regimen caused a substantial weight loss, especially in those animals which reared their young well. Severe hypocalcaemia was observed in the lactating rats. Serum-P was slightly elevated. The content of hydroxyproline in serum was considerably elevated, reflecting the degree of calcium deprivation. Serum proteins were least influenced. The calcium depriving regimen reduced the growth of long bones, but did not stop it. The ash content of the bones was considerably reduced, the degree of reduction depended on the degree of calcium deprivation. Ash as percentage of total bone organ was reduced, but not to the same extent as total ash. Analyses of different parts of femur showed that the proximal and distal parts had lost more bone mineral than the diaphyseal shaft. The ash content of cortical bone tissue from the femur was estimated by a volumetric method. No differences were observed between test groups and controls, indicating that no measurable amounts of bone mineral had been removed from the walls of the vascular canals or by osteocytic osteolysis. Planimetric determinations on cross sections from femora disclosed that a great amount of bone had been removed from the endosteal surface of the diaphysis, while the periosteal surface demonstrated reduced bone apposition.
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    The early mineralization of enamel (1977)
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    Calcified tissue international 24 (1977), S. 271-274 
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    ISSN: 1432-0827
    Keywords: Enamel ; Mineralization ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The potassium pyroantimonate technique was used to study the cellular distribution of calcium during the early mineralization of enamel in rat molar tooth germs at the electron microscope level. Differing patterns of calcium distribution were observed in the ameloblast seemingly associated with the appearance of Tomes' process. In the early secretory ameloblast calcium pyroantimonate deposits were observed within the Golgi apparatus, within coated vesicles, within mitochondria and associated with the inner aspect of the cell membrane. However, with the development of Tomes' process the ameloblasts no longer demonstrated these discrete deposits of calcium pyroantimonate. Instead they showed a diffuse cytoplasmic staining pattern with no preference for any particular organelle.
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    A model-independent comparison of the rates of uptake and short term retention of47Ca and85Sr by the skeleton (1977)
    Springer
    Calcified tissue international 22 (1977), S. 183-189 
    Details
    ISSN: 1432-0827
    Keywords: Calcium ; Strontium ; Bone ; Mathematical modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract 1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for47Ca and85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the47Ca and85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewera priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of*Ca and*Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies.85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.
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    Localisation histochimique du calcium dans la colloïde des vésicules thyroïdiennes du rat (1977)
    Springer
    Calcified tissue international 24 (1977), S. 275-278 
    Details
    ISSN: 1432-0827
    Keywords: Calcium ; Thyroid ; Calcium ; Thyroïde
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Les auteurs utilisent une solution de Glyoxal bis 2-hydroxyanil à basse température pour localiser le calcium dans la thyroïde. Grâce à cette technique qui limite les mouvements ioniques, ils observent que le calcium situé principalement dans la colloïde est résorbé en même temps qu'elle lors d'une stimulation par le froid.
    Notes: Summary With a Glyoxal bis 2-hydroxyanil alcoholic solution at −25°C, the calcium was localized in frozen thyroid slices. The limited ionic movement permits seeing that the calcium situated principally in the colloid is resorbed at the same time by a low temperature stress.
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    Our present knowledge of calcium or hydrogen ions as transmitters in the vertebrate rod outer segments (1977)
    Springer
    European biophysics journal 3 (1977), S. 55-58 
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    ISSN: 1432-1017
    Keywords: Rhodopsin ; Rods ; Phototransduction ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Difficulties in testing the possible role of calcium as a Transmitter in the R.O.S. are discussed. A comparison is made with the Sarcoplasmic Reticulum system where calcium flux are easily measured. The latest results reviewed on intact cellular structures are highly indicative but not yet conclusive.
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    Calcium ion, a putative intracellular messenger for light-adaptation in Limulus ventral photoreceptors (1977)
    Springer
    European biophysics journal 3 (1977), S. 141-143 
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    ISSN: 1432-1017
    Keywords: Calcium ; Limulus ; Photoreceptors ; Adaptation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Calcium ion fulfills several criteria for identifying an intracellular messenger for light-adaptation in Limulus photoreceptors. Direct injection of Ca++ mimicks two aspects of light-adaptation; sequestration of intracellular calcium tends to prevent light-adaptation; and light induces an increase in intracellular Ca++ as demonstrated by two independent techniques.
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    On the mechanism of conductance control of the arthropod visual cell membrane (1977)
    Springer
    European biophysics journal 3 (1977), S. 145-151 
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    ISSN: 1432-1017
    Keywords: Visual cell membranes ; Invertebrates ; Ion channels ; Activation of light channels ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract It is assumed that “dark channels” determine a permanent dark conductance of the arthropod visual cell membrane. The light stimulus causes a transient opening of “light channels”. The ion selectivity of dark channels and light channels is roughly described. Factors influencing the activation of light channels, as membrane energy metabolism, membrane potential and adjusted calcium ion concentration are specified. The mechanism of the action of calcium ions on the conductance of the visual cell membrane is discussed.
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    Plasma levels and half lives of thioridazine and some of its metabolites (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 141-147 
    Details
    ISSN: 1432-1041
    Keywords: Phenothiazine ; thioridazine ; plasma level ; metabolic pattern ; half life ; man ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of “thioridazine plus metabolites” ranged from 43–74%. The mean “early disappearance half-life” of thioridazine was 5 hours, and its mean “late disapperance half-life” was 26 hours.
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    The kinetics of ethanol absorption and elimination in twins and supplementary repetitive experiments in singleton subjects (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 337-344 
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    ISSN: 1432-1041
    Keywords: Twin study ; ethanol metabolism ; intra-individual variation ; pharmacogenetics ; plasma level ; man ; heritability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of genetic and environmental factors on the metabolism of a single oral dose of ethanol 1.2 ml per kg body weight was analysed in 19 identical and 21 fraternal healthy, adult, un-selected male twin pairs. The heritability values of the rates of absorption, degradation and elimination of ethanol were 0.57, 0.41 and 0.46 respectively. Environmental factors, such as daily alcohol intake and smoking, increased the rate of elimination of blood alcohol. Intrasubject variation in ethanol metabolism was studied by repeated tests in 11 male volunteers at intervals of at least 2 months, under the same conditions as in the twins; the coefficients of variation for parameters of metabolism was about 8%. The results demonstrate both genetic control of ethanol absorption, degradation and elimination and the appreciable influence of environmental factors. The almost total genetic control of ethanol metabolism postulated by Vesell et al. (1971) could not be confirmed.
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    Disposition and oxidative metabolism of phenylbutazone in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 359-366 
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    ISSN: 1432-1041
    Keywords: Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.
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    A sensitive radioimmunoassay for fentanyl (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 153-158 
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    ISSN: 1432-1041
    Keywords: Fentanyl ; radioimmunoassay ; cross-reaction ; plasma level ; dog ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man.
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    Plasma levels and half lives of thioridazine and some of its metabolites (1977)
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    European journal of clinical pharmacology 11 (1977), S. 135-140 
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    ISSN: 1432-1041
    Keywords: Phenothiazine ; thioridazine ; metabolites ; plasma-level ; metabolic pattern ; half-life ; man ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of thioridazine and four of its metabolites were determined in a series of fifteen young acute schizophrenics. Consistent individually different metabolic patterns were detected in a group of patients who had the same value for the sum of thioridazine plus metabolites. The apparent volume of distribution and half life were calculated. Clinical evolution tended to correlate best with the level of mesoridazine.
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    Serum glycoside concentrations after single or repeated intravenous doses ofβ-methyl-digoxin and digoxin (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 213-218 
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    ISSN: 1432-1041
    Keywords: β-Methyl-digoxin ; digoxin ; intravenous administration ; man ; serum concentration ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present investigation was to estimate the ratio of the intravenous doses ofβ-methyl-digoxin and digoxin required to produce identical serum glycoside concentrations in man. 20 patients on intravenous maintenance therapy were changed fromβ-methyl-digoxin to the identical dose of digoxin or vice versa. Each drug was given for 7 days. Serum concentrations 13% higher were found during administration ofβ-methyl-digoxin. Assuming a half life of 60 h after with drawal, the dose of digoxin producing the same minimum serum concentration was estimated to be 1.16 times higher than that ofβ-methyl-digoxin. 18 healthy volunteers received 0.4 mg β-methyldigoxin, and 23 the same dose of digoxin, as an intravenous infusion over 2 h. The serum concentrations and urinary glycoside excretion were measured over a period of 32 hrs. During the first hour after the infusion the serum concentration of digoxin declined more rapidly than that ofβ-methyl-digoxin. Thereafter, the ratio of the serum concentrations did not change appreciably up to the end of the investigation. The area under the serum concentration/time curve was about 13% greater forβ-methyl-digoxin than for digoxin; this difference was not significant. The average renal clearance was 96±9 ml forβ-methyl-digoxin, 151±13 ml for digoxin. Since the total body clearance of digoxin is only about 1.16 times higher than that ofβ-methyl-digoxin, the lower renal clearance ofβ-methyl-digoxin must partly be compensated by higher extrarenal clearance. From the ratios of the areas under the serum concentration/time curves after single doses of β-methyldigoxin and digoxin, and the minimum serum concentrations during maintenance therapy, it was concluded that the dose of digoxin to produce the same average serum concentrations would be about 1.15 times higher than that ofβ-methyl-digoxin. In comparison with the large variations in individual dosage of digoxin andβ-methyl-digoxin, this difference is too small to be of practical importance.
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    Smoking and catecholamine and c-AMP concentrations in the coronary circulation of man and the effect of oxprenolol (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 81-87 
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    ISSN: 1432-1041
    Keywords: Oxprenolol ; smoking ; catecholamines ; coronary circulation ; man ; c-AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increased from 63±2 beats/min (control) to 74±3 (smoking) (P〈0.01), falling to 70±2 (10 min after smoking) (0.05〉P〉0.01), whilst coronary sinus c-AMP concentrations rose from 11±0.7 nmol/l (smoking) to 11.9±0.8 nmol/l (after smoing) (0.05〉P〉0.01; one tailed ‘t’ test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1±0.7 nmol/l (control) to 5.5±1.1 nmol/l (after smoking) (0.05〉P〉0.01; one tailed ‘t’ test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a β-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74±0.07 mmol/l (control) to 0.83±0.09 mmol/l (smoking).
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    Influence of nutritional status on plasma levels and relative bioavailability of tetracycline (1977)
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    European journal of clinical pharmacology 12 (1977), S. 281-284 
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    ISSN: 1432-1041
    Keywords: Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.
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    The sarcoplasmic reticulum and associated plasma membrane of trunk muscle lamellae in Branchiostoma lanceolatum (Pallas) (1977)
    Springer
    Cell & tissue research 181 (1977), S. 169-196 
    Details
    ISSN: 1432-0878
    Keywords: Skeletal muscle ; Branchiostoma lanceolatum ; Fibre types ; Sarcoplasmic reticulum ; Sarcolemma ; Calcium ; X-ray micro-analysis ; Freeze-fracturing ; Replica
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The trunk muscle lamellae of Amphioxus is made up of cross-striated lamellae about 1 μm thick. Transverse tubules are absent, but numerous subsarcolemmal vesicles are found in both tissue blocks and minced samples after aldehyde and osmium fixation, embedding and sectioning. The vesicles contain a granular matrix, range in diameter from 30 to 200 nm and constitute about 3 to 6% of the muscle fibre volume. 8 out of 10 vesicles are found above the Z and I-bands. In the presence of oxalate, electron dense precipitates form within the vesicles. Energy-dispersive X-ray microanalysis reveals the presence of Calcium in these precipitates. The area of the plasma membrane is about 2 μm2/μm3 muscle fibre volume. The corresponding area of sarcoplasmic membrane is ca. 1 μm2/μm3. About 20% of the plasma membrane is directly overlaid and coupled to the sarcoplasmic vesicles. A thin surface coat is present all over the lamellae, but ruthenium red staining indicates that the coat is slightly concentrated above the sarcoplasmic vesicles. Freeze-fracture replicas reveal tightly packed coarse granular material in the vesicular membrane and less concentrated and smaller particles in the plasma membrane. The latter particles are seen somewhat less commonly above the vesicles than on the rest of the plasma membrane. Likewise, direct replicas of lamella spread on glass slides and freeze-dried, reveal a distinct pattern in the surface coat or its underlying structures, corresponding to the Z and I-bands. In the scanning electron microscope the general arrangement of the sarcoplasmic vesicles could be examined. In addition, numerous defects in the plasma- and vesicular membranes indicate a strong adhesion between the two. It is concluded that the trunk muscle lamellae of Amphioxus have a sarcoplasmic reticulum consisting of subsarcolemmal vesicles with calcium sequestrating properties at Z and I-level. Further that the plasma membrane and its surface coat is probably specialized above the vesicles as compared to the rest of the surface.
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    Rheography of the stomach (1977)
    Springer
    Bulletin of experimental biology and medicine 84 (1977), S. 1060-1064 
    Details
    ISSN: 1573-8221
    Keywords: rheography ; stomach ; animals ; man ; sensitive probe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A practical method of rheography is suggested for studying the state of the human gastric circulation. The theoretical aspects of the use of a bipolar system of electrodes (external and internal) with essentially different sizes of contact surface are examined with respect to the stomach. A scheme and brief description of the simple apparatus are given. Control experiments were carried out on animals to confirm the validity of the basic assumptions. Mean values of some rheographic indices frequently used in clinical practice, based on rheograms of the stomach of 30 healthy subjects, are given.
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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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    Pharmacokinetics of lofepramine in man: Relationship to inhibition of noradrenaline uptake (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 291-298 
    Details
    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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    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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    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 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00606559
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    Clinical pharmacokinetics of sisomicin: Two-compartment model analysis of serum data after I.V. and I.M. administration (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 251-256 
    Details
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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    URL: http://dx.doi.org/10.1007/BF00558337
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    Double-blind crossover study of the effect of acetylsalicylic acid on bleeding and post-operative course after bilateral oral surgery (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 217-225 
    Details
    ISSN: 1432-1041
    Keywords: Acetylsalicylic acid ; surgery ; man ; bleeding ; pain ; wound-healing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylsalicylic acid (ASA) was tested against placebo in a double-blind crossover study, in which essentially the same operation was performed twice on 23 healthy patients who required surgical removal of bilateral “identically” impacted wisdom teeth. On the evening before one operation they received ASA 1.0 g (Globentyl®) followed by ASA 2.0 g daily for the next 3 days, and at the other operation placebo tablets. A number of objective and subjective parameters were recorded for paired comparison of the pre-, per-, and post-operative courses, including bleeding, pain, wound-healing, and preference. Tests of platelet aggregation before each operation indicated whether or not ASA had been taken. Pre-operative bleeding time was significantly increased (from 4.4 to 6.9 min) by ASA, as well as the per-operative blood loss (about 30%), and the post-operative bleeding tendency. Episodes of profuse post-operative haemorrhage were reported by 5 patients, always after the operation for which ASA had been given. ASA also significantly promoted the occurrence of ecchymosis and haematoma. The pre-operative bleeding time was not a reliable predictor for these complications. The drug was very well tolerated with respect to side effects such as abdominal discomfort. The post-operative pain scores were neither reduced nor increased significantly by ASA, and the preference scores were not in favour of the drug. The present patients were all young and denied any previous bleeding disorders; nevertheless, ASA resulted in post-operative haemorrhage, ecchymosis and haematoma formation in several cases.
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    URL: http://dx.doi.org/10.1007/BF00558332
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    Pharmacokinetics and bioavailability of indoprofen in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
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    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
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    URL: http://dx.doi.org/10.1007/BF00558338
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  • 86
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    Inhibition of tetracycline absorption by zinc (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 59-62 
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    ISSN: 1432-1041
    Keywords: Tetracycline absorption ; zinc sulphate ; zinc citrate ; complex formation ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of zinc on the gastrointestinal absorption of tetracycline has been investigated in 7 healthy volunteers. Zinc (45 mg Zn++) was given as a solution of zinc sulphate and as a zinc citrate complex; tetracycline (500 mg) was administered as a commercially available preparation. Serum tetracycline concentrations and the area under the serum tetracycline concentration-time curve (up to 6 h) were significantly reduced when tetracycline was taken with either zinc sulphate or the zinc citrate complex. Although the reduction of absorption seemed more pronounced after zinc sulphate, the difference between the inhibitory effects of the two forms of zinc was not significant. It is concluded that simultaneous administration of zinc and tetracycline may reduce absorption of tetracycline.
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    URL: http://dx.doi.org/10.1007/BF00561551
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  • 87
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    Effect of analgesic agents on emptying of the gallbladder in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 127-131 
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    ISSN: 1432-1041
    Keywords: Gallbladder emptying ; analgesics ; indoprofen ; pentazocine ; morphine ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A controlled study of the clinical pharmacology of the biliary tract has been made. The rate of gallbladder emptying induced by a fatty meal was taken as a parameter for assessment of the inhibitory effect of indoprofen, a new analgesic-anti-inflammatory drug, pentazocine and morphine. The compounds were administered as single doses by iv (indoprofen and pentazocine) or im (morphine) injection. Indoprofen up to 400 mg had no effect, whereas morphine and pentazocine exerted a significant inhibitory effect on emptying of the gallbladder. Adverse reactions of clinical significance were associated with morphine and pentazocine, but were negligible with indoprofen.
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    URL: http://dx.doi.org/10.1007/BF00609471
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  • 88
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    Plasma dopamine-β-hydroxylase activity and the pressor effect of dopamine infusion in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 197-200 
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    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the function of dopamine-β-hydroxylase (DBH) in human plasma, dopamine, its natural substrate, was infused intravenously in 22 healthy volunteers. Their plasma DBH activities showed great interindividual variations (31–301 units/ml). The infusion rates of dopamine required to increase systolic blood pressure (BP) by 30 mm Hg differed considerably between the subjects, and ranged from 3,0 to 11,6 µg/kg/min. No correlation could be shown between the various dopamine doses and individual plasma levels of DBH. It was concluded, therefore, that plasma DBH in the blood stream was enzymatically inactive. Experiments with human plasma DBH in vitro also support this interpretation. Consequently, interindividual differences in the effects on BP during dopamine infusion cannot be due to pressor effects of noradrenaline synthesized by plasma DBH.
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    URL: http://dx.doi.org/10.1007/BF00558329
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  • 89
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    The fate of3H-terbutaline sulphate administered to man as an aerosol (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 1-7 
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    ISSN: 1432-1041
    Keywords: 3H-terbutaline sulphate ; aerosol ; man ; absorption ; excretion ; spirometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six asthmatic patients and two healthy volunteers inhaled tritiated terbutaline sulphate delivered by a pressurized aerosol inhaler. Spirometric measurements were performed and the amounts of total radioactivity in plasma, urine and faeces were determined. The analysis of urine included determination of radioactivity due to metabolized drug. Depending on the amount of drug inhaled the peak plasma level varied from undetectable to 3.8 ng/ml. An early plasma peak was found in 7 out of 8 subjects. The main plasma peaks were observed 1 – 6 hours after administration. The results of urinalysis showed a metabolic profile similar to that after parenteral administration. Disregarding the amount of inhaled drug and sampling time, 3 – 35% of the delivered drug was recovered in the urine and 2 – 37% in the faeces. Immediately after treatment 4 subjects rinsed their mouths with water and it was found to contain 14.5 – 50% of the delivered dose. The adapters from the aerosol canisters contained 14 – 27.5% of the delivered dose of drug.
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    URL: http://dx.doi.org/10.1007/BF00561542
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  • 90
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    Clinical efficacy of BS 100-141 in essential hypertension (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 69-72 
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    ISSN: 1432-1041
    Keywords: BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl)acetamide hydrochloride ; essential hypertension ; antihypertensive agent ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of the guanidine derivative BS 100-141 (N-amidino-2-(2,6-dichlorphenyl)acetamide hydrochloride) has been studied in 11 hospitalized patients suffering from essential hypertension (WHO grade I – II). BS 100-141 1 mg tid was given in the first week and a larger dose in the second week. Mean 24-hour systolic and diastolic blood pressures were significantly lower at the end of the first and second weeks of active treatment than at the end of the placebo-week. The antihypertensive effect of BS 100-141 was stronger in the standing than in the supine position. It significantly reduced the heart rate. Treatment with BS 100-141 was well tolerated, although tiredness and dryness of the mouth appeared more often than during the placebo period. Extensive laboratory tests did not reveal any toxic effect on the liver, kidneys or haemopoietic tissues.
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    URL: http://dx.doi.org/10.1007/BF00561553
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    Comparison of BS 100-141 and clonidine as antihypertensive agents (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 73-76 
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    ISSN: 1432-1041
    Keywords: BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl) acetamide hydrochloride ; clonidine ; essential hypertension ; antihypertensive agents ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect and side effects of the guanidine derivative BS 100-141 (N-amidino-2-(2,6-dichlorphenyl) acetamide hydrochloride) and clonidine were compared in a single-blind, cross-over study. The study consisted of two active treatment periods of 6 weeks each, both preceded by a 2 week placebo period. Thirty ambulant, hypertensive patients, whose blood pressure was of WHO severity grades I – II, were admitted to the study, and the results are based on the 24 patients who completed it. In more than half the patients the optimal daily dose of BS 100-141 was 3 – 4 mg, and of clonidine 0.30 – 0.45 mg. An equally large and significant decrease in blood pressure was produced by both drugs. Both of them also caused bradycardia, but it was of no clinical significance. Both BS 100-141 and clonidine caused tiredness in about half the patients, but it diminished after a few weeks. Dryness of the mouth occurred in more than half the patients taking either drug, and it remained unchanged during the 6 weeks of treatment. A withdrawal syndrome was noted in one patient on discontinuation of clonidine.
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  • 92
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    Effect of calcium depletion and subsequent repletion on parathyroids, parafollicular (C) cells and bone in the growing pig (1976)
    Springer
    Cell & tissue research 168 (1976), S. 373-384 
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    ISSN: 1432-0878
    Keywords: Calcium ; Bone ; Parathyroid ; Parafollicular cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the chief cells of the parathyroid gland and thyroid parafollicular (C) cells and the morphology of bone in calcium depletion and subsequent repletion were examined in young growing pigs. A low calcium diet resulted in osteopenia, increased removal of the cartilaginous core, osteoclasia and osteocytic osteolysis. Subsequent repletion quickly returned bone to normal. In pigs fed the low calcium diet, there was a marked depletion of secretory granules but a striking increase in the number of microtubules in chief cells. Increasing the calcium content of the diet to normal quickly returned the ultrastructural appearance of chief cells to apparent normal. In the initial response to calcium repletion, chief cells exhibited large number of lysosomes and occasionally prominent paracrystalloid bodies. Electron microscopic examination of parafollicular (C) cells of the thyroid gland failed to reveal differences in ultrastructure between test and control pigs. These findings support the view that bone resorption following calcium deficiency may be the result of a secondary hyperparathyroidism rather than of calcium deficiency per se.
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    URL: http://dx.doi.org/10.1007/BF00215314
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    The subcellular localization of calcium in vertebrate smooth muscle: Calcium-containing and calcium-accumulating structures in muscle cells of mouse intestine (1976)
    Springer
    Cell & tissue research 169 (1976), S. 221-231 
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    ISSN: 1432-0878
    Keywords: Smooth muscle ; Calcium ; Sarcoplasmic reticulum ; Mitochondria ; Microprobe analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The intracellular localization of calcium by means of cytochemical techniques was studied in smooth muscle cells of mouse intestine. When the lead acetate method according to Carasso and Favard (1966) was used calcium was found in mitochondria and sarcoplasmic reticulum and occasionally between the myofilaments. The active ATP-dependent accumulation of calcium into cell structures was investigated by the oxalate method (Heumann and Zebe, 1967). After appropriate treatment the only structures of smooth muscle cells which contained calcium oxalate (identified by microprobe analysis) were elements of the sarcoplasmic reticulum. The results are discussed in relation to the role of calcium in the control of muscle activity during the contraction-relaxation cycle.
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    URL: http://dx.doi.org/10.1007/BF00214210
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  • 94
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    The effect of the ionophore A23187 on the ultrastructure and electrophysiological properties of frog skeletal muscle (1976)
    Springer
    Cell & tissue research 173 (1976), S. 193-209 
    Details
    ISSN: 1432-0878
    Keywords: Muscle ; Ionophore A23187 ; Calcium ; Muscular dystrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The divalent cation ionophore A23187 has three major effects on the thin cutaneous pectoris muscle of frog: (1) The membrane potential is depolarized, an action that is found only when the [Ca2+] of the bathing saline is very low. (2) It causes an increase in resting tension and the development of contraction. This action is produced at both normal and low values of [Ca2+]o and is, therefore, independent of Ca2+ entry and of changes in Em. The ionophore is believed to act primarily by releasing Ca2+ from intracellular stores. (3) It causes major ultrastructural damage to the muscle filaments. It is believed that this damage is the result of the action of A23187 on the sarcoplasmic reticulum and the elevation of [Ca2+]i and we suggest that the action of this ionophore may serve as a useful model for the study of certain myopathies.
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    URL: http://dx.doi.org/10.1007/BF00221375
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  • 95
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    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00561557
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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 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00616412
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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 and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
    Details
    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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  • 100
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    Kinetics of nortriptyline in man according to a two compartment model (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
    Details
    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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