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  • 1
    Electronic Resource
    Electronic Resource
    Laser diagnostic in molecular beams (1975)
    Springer
    Applied physics 8 (1975), S. 65-70 
    Details
    ISSN: 1432-0630
    Keywords: Nozzle beams ; Laser Diagnostic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The output from a stabilized, tunable single-mode laser is split into two beams which cross the molecular beam perpendicularly and at an angle of β to the beam axis. Tuning the laser frequency across the unshifted and Doppler-shifted absorption profile of the molecular transition yileds the velocity distribution of the molecules in the beam for individual quantum states. The internal state distribution among vibrational and rotational levels in the beam can be determined by comparing the fluorescence simultaneously induced in the beam and in a cell with molecules in thermal equilibrium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00883672
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  • 2
    Electronic Resource
    Electronic Resource
    Disposition of β-methyldigoxin in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 105-114 
    Details
    ISSN: 1432-1041
    Keywords: Methyldigoxin ; excretion ; deep compartment ; O-demethylation ; glycosides ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of radioactivity in plasma and the excretion in urine and faeces over 7 days were determined in 12 healthy subjects after single oral and intravenous doses of a solution of3H-β-methyldigoxin. 62.2±2.1 and 29.0±5.2 per cent of the dose were excreted in urine and faeces, respectively, within 7 days of intravenous administration, compared with 55.2±2.8 and 28.6±5.7 per cent after oral administration. This indicates almost complete absorption of the glycoside when given in solution. 12 hours after its administration a pseudo-distribution equilibrium was reached and the average half life of tritiated compounds was 1.3 days. By 48 – 96 hours after treatment the average half life was 2.8 days. O-demethylation was revealed as the main metabolic degradation step in man. The rate of Demethylation was higher after oral than i.v. administration. Thus, only 31% of the radioactivity excreted in the urine consisted of unchanged β-methyldigoxin after oral administration compared to 51% after i.v. dosing. Only traces of bis- and monoglycosides were excreted in urine, but there were considerable amounts in faeces, where they accounted for more than 35% of the total excretion. Up to 40% of the radioactivity in plasma and urine consisted of polar conjugates during the first 12 hours after administration of β-methyldigoxin. The mono- and bisglycosides were identified as the main products of conjugation. During the 7 days approximately 15% of the administered dose was metabolized by splitting off glycosidic bonds and conjugation to polar compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614005
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  • 3
    Electronic Resource
    Electronic Resource
    Acrodermatitis enteropathica: Recent findings concerning clinical features, pathogenesis, diagnosis and therapy (1976)
    Springer
    European journal of pediatrics 121 (1976), S. 247-261 
    Details
    ISSN: 1432-1076
    Keywords: Acrodermatitis enteropathica ; Small bowel ; Oxyquinoline ; Metabolism of fatty acids ; Paneth cells ; Zinc deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 2 Geschwistern, einem Jungen und einem Mädchen, wurde die Diagnose der Acrodermatitis enteropathica (AE) im Alter von 10 bzw. 6 Wochen gestellt. Bis auf eine Blutsverwandtschaft, die 5 Generationen zurückliegt, ist die Familienanamnese anauffällig. Beide Kinder boten bei Diagnosestellung die für AE typischen Hautveränderungen. Symptome von seiten des Magen-Darm-Kanals waren weniger ausgeprägt und traten mit zunehmendem Alter in den Hintergrund. Bei dem jüngeren Patienten konnten während eines Rezidivs eine Erniedrigung des Serumspiegels der Ölsäure (18:1) sowie eine leichte Vermehrung der Linolsäure (18:2) festgestellt werden, während die Arachidonsäure (20:4) vermindert war. Bei beiden Patienten waren die Serumzinkspiegel mit und ohne Oxychinolinbehandlung deutlich erniedrigt. Eine Substitutionstherapie mit Zinkaspertat brachte weder eine klinische Besserung noch einen wesentlichen Anstieg des Serumzinkspiegels. Durch Gabe von Zinksulfat konnten eine völlige Remission der Hautveränderungen sowie eine weitgehende Normalisierung der Serumzinkspiegel erreicht werden. Untersuchungen der Dünndarmschleimhaut zeigten lichtmikroskopisch keine Besonderheiten. Elektronenmikroskopisch fanden sich in den Enterocyte sogenannte multi-vesicular bodies. Die Paneth-Zellen zeigten teilweise unregelmäßig geformte, inhomogene Strukturen im Cytoplasma. Die pleomorphen Sekretgraula wanen plump und groß und wiesen eine ausgeprägte Heteromorphie ihrer Matrix auf. Da bei Ratten unter zinkarmer Ernährung ähliche ultrastrukturelle Veränderungen bekannt sind, muß durch weitere Untersuchungen geklärt werden, ob die Veränderungen in den Paneth-Zellen typisch für die AE sind. Die adäquate Therapie der AE besteht zur Zeit in der Substitution von Zink. Dadurch wurde die mit toxischen Augenschädigungen belastete Therapie mit Oxychinolinen überflüssig.
    Notes: Abstract Acrodermatitis enteropathica (AE) was diagnosed in 2 siblings, boy and girl, at the age of 10 and 6 weeks. The family history is unremarkable except for consanguinity 5 generations previously. The clinical symptoms of the 2 patients conformed to the known features of AE, the gastrointestinal involvement loosing its significance with increasing age. In one patient in a stage of exacerbation the serum level of oleic acid (18:1) was lowered and of linoleic (18:2) acid slightly increased while that of arachidonic acid was decreased (Fig. 4). In both patients the serum zinc levels were significantly lowered. Under substitution with ZnSO4 the clinical condition improved and the serum zinc levels returned to normal. Histologically the small bowel mucosa was practically normal. Ultrastructural examination of jejunal biopsies revealed rather unspecific changes in the enterocytes in the form of numerous multivesicular bodies. The Paneth cells sometimes contained irregularly formed inhomogeneous structures within their cytoplasm. In addition the secretory granules varied in size and displayed a granular heteromorphic matrix. Frequently they were confluent and formed giant granules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00443018
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  • 4
    Electronic Resource
    Electronic Resource
    Acrodermatitis enteropathica (1977)
    Springer
    European journal of pediatrics 125 (1977), S. 153-162 
    Details
    ISSN: 1432-1076
    Keywords: Acrodermatitis enteropathica therapy ; Small bowel ; Zinc malabsorption ; Zinc deficiency ; Paneth cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Als Ursache der klinischen Erscheinungen bei der Akrodermatitis enteropathica (A.E.) muß ein Zinkmangel als Folge einer Zinkmalabsorption angesehen werden. Durch orale Substitution mit Zink lassen sich die Krankheitserscheinungen beseitigen. Es wird über 2 Geschwister mit A.E. berichtet, die lange Zeit mit Oxychinolinpräparaten mit wechselndem Erfolg vorbehandelt waren. Durch orale Substitution mit Zinksulfat in der Dosis von 110–220 mg täglich wurde eine vollständige und anhaltende Remission erzielt. Gleichzeitig normalisierten sich die vorher stark erniedrigten Serumzinkspiegel. Keine so strenge Korrelation bestand zwischen dem Zinkgehalt der Haare und der Art Der Zinksubstitution. — Wie wir in unserer 1. Mitteilung zeigten, lassen die Paneth-Zellen der Dünndarmmukosa bei A.E. ultrastrukturelle Veränderungen in Form von inhomogenen Strukturen des Zytoplasmas, der Bildung von Riesengranula und Einschlüssen erkennen. Unter der Zinksubstitution kommt es zu einer vollkommenen Normalisierung des ultrastrukturellen Bildes der Paneth-Zellen. Die Veränderungen an den Paneth-Zellen können daher nur die Folge, jedoch nicht die Ursache des Zinkmangels bzw. der Zinkmalabsorption sein.
    Notes: Abstract The basic defect in acrodermatitis enteropathica (A.E.) is zinc deficiency caused by zinc malabsorption. The clinical symptoms disappear and serum zinc levels normalize after oral treatment with zinc. A report is given on two siblings suffering from A.E., both treated with oxyquinolines for a long period with changing clinical success. A permanent clinical remission could be achieved by treatment with zinc-sulphate at doses of 110–220 mg daily. The serum zinc levels normalized. The correlation between the zinc concentration of the hair and the kind of therapy was not very close. As we have shown in our first communication, the Paneth cells of the intestinal mucosa display ultrastructural changes in form of an unhomogeneous structure of the cytoplasm, formation of giant granules, and inclusion bodies. The zinc-therapy led to a complete normalization of the pathological changes in the Paneth cells. Thus, the changes in the Paneth cells in A.E. are the result and not the cause of zinc deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00489988
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  • 5
    Electronic Resource
    Electronic Resource
    Long-term occupational inhalation of organic dust — Effect on pulmonary function (1978)
    Springer
    International archives of occupational and environmental health 42 (1978), S. 119-127 
    Details
    ISSN: 1432-1246
    Keywords: Organic dusts ; Allergic alveolitis ; Bird fancier's lung ; Immunology ; Counter-immunoelectrophoresis ; Sensitisation ; Pulmonary function diagnosis ; Ventilation ; Respiratory mechanics ; Diffusion ; Distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Studies to detect disorders of pulmonary function were performed on 42 workers at a poultry farm. All the subjects were exposed to organic dusts and sensitised to poultry antigens. Typical signs of bird fancier's lung were recorded in two of them. Included in all examinations were immunological diagnosis by means of counter-immunoelectrophoresis, systematic interviewing for case histories, and registration of respiratory symptoms. Pulmonary function was recorded by means of the following techniques: analysis of ventilation (flow-volume indices), respiratory mechanics of the larger airways and lung (body box plethysmography, oesophago-balloon technique), respiratory mechanics of the small airways (closing volume), distributional analysis, diffusion analysis, and blood gas analysis. A disorder of pulmonary function was recordable in 40 sensitised individuals. Such disorder being characterised by obstruction of the larger airways and slight inhomogeneity. The small airways were not narrowed. No restriction nor disturbed diffusion were established. The severity of obstruction was found to be related to the degree of sensitisation. The following more clearly pronounced changes in terms of functional diagnosis were recordable from two poultry workers with allergic alveolitis: obstruction of larger airways with concomitant restriction, marked inhomogeneity, and disorder of diffusion. The disorders, relatively discrete, led to mild PO2-reduction in sensitised individuals, whereas mild hypoxaemia was recorded from subjects with allergic alveolitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01297550
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  • 6
    Electronic Resource
    Electronic Resource
    Demethylation and cleavage of glycosidic bonds of 4‴-methyldigoxin in man (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 450-453 
    Details
    ISSN: 1432-1912
    Keywords: Urinary Excretion ; Methyldigoxin ; Digoxin ; Metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In man the oral or intravenous administration of 4‴-methyldigoxin yields metabolites in urine which are soluble either in chloroform or in water. The chromatographic analysis reveals demethylation as the main metabolic reaction in man. In addition to methyldigoxin and digoxin small amounts of digoxigenin-bisdigitoxoside and digoxigenin-mono-digitoxoside can be detected. The water soluble metabolites represent 7% of the radioactivity excreted in 7 days reaching a maximum within the first 8 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501252
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  • 7
    Electronic Resource
    Electronic Resource
    Quantitative analysis of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin and their metabolites in bile and urine of rats (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 273 (1972), S. 154-167 
    Details
    ISSN: 1432-1912
    Keywords: Digoxin and Derivatives ; Bis- and Monodigitoxosides ; Biliary Excretion ; Renal Excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolism of digoxin (D), 4‴-acetyldigoxin (AD) and 4″-methyldigoxin (MD) was studied in biliary fistula rats by quantitative analysis of the excretion of these glycosides after intraduodenal administration. The total activity excreted within 12 h in bile amounts to 45.1; 40.5; 21.3 and in urine to 11.6; 14.3; 17.6% of the dose of D, AD and MD respectively. AD undergoes a rapid, but incomplete desacetylation in the organism. The highest desacetylation activities were found in liver, in intestinal mucosa and in kidney. Yet considerable amounts of unchanged AD were found in portal vein blood and still another 1–2% of the dose in bile and urine. In contrast MD is very slowly demethylated. 15 min after intraduodenal administration portal vein blood contains almost exclusively MD. A stepwise cleavage of digitoxoses from D as well as of AD and MD is indicated. The absolute amounts of digoxigenin-bis-digitoxoside (4–8% of the dose), digoxigenin-mono-digitoxoside (2.5–8.5%) excreted in bile and urine were in the same range for all three glycosides examined, although the relative amounts of these metabolites in bile and urine were much higher after administration of MD than of the two other glycosides. In addition a water-soluble fraction could be detected in bile and urine after administration of D, AD and MD. The absolute quantities of polar metabolites (4.5–7.0%) excreted in bile and urine were identical for all three glycosides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508087
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetic behaviour of 4‴-methyldigoxin in man (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 273 (1972), S. 172-174 
    Details
    ISSN: 1432-1912
    Keywords: 4′-Methyldigoxin ; Half Life ; Excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 10 patients the time course of specific activity in plasma, and the excretion rates in urine and feces after oral and intravenous administration of 12α-3H-4‴-methyldigoxin were studied. The determined biological half life of radioactivity in plasma averaged 43 h and corresponds with the renal excretion velocity (50 h). 32.5 ± 5.0 and 31.5 ± 6.3% of the dose were found in feces and 59.7 ± 1.3 and 52.9 ± 1.8% were excreted in urine within 7 days after intravenous and oral administration, respectively. These results together with the observed plasma concentrations suggest a rapid and almost complete absorption of 4′-methyldigoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508089
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of digoxin and its 4‴-acetyl-and methylderivates in the rat (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 274 (1972), S. 171-181 
    Details
    ISSN: 1432-1912
    Keywords: Digoxin ; 4‴-Acetyldigoxin ; 4‴-Methyldigoxin ; Absorption Velocities ; Blood Level ; Biliar Excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The kinetics of absorption, of changes in blood concentration, and of biliary excretion after the i.v. and i.d. administration of 40 μCi each, of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin were studied in biliary fistula rats. The highest blood concentrations were found after the i.v. administration of 4‴-methyldigoxin, which decline with a half life time of 10 h, compared with 5.6 and 4.5 h for 4‴-acetyldigoxin and digoxin respectively. 71%, 55% and 17% of the dose were excreted in the bile within 12 h after the i.v. administration of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin. The blood concentrations observed after the i.d. administration of digoxin and 4‴-acetyldigoxin show almost identical pharmacokinetics with respect to height and elimination velocity (half life 7.0 h for digoxin and 7.5 h for 4‴-acetyldigoxin). In contrast, following the i.d.administration of 4‴-methyldigoxin, blood concentrations, which were twice as high, were observed and declined with the same half life as after the i.v. administration. Determination of the disappearance rates of these glycosides from the intestinal lumen reveals a biphasic course of absorption. A first phase, with k values of 0.4, 0.5, 1.2 for digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin respectively is followed by a second phase with k values of 0.04, 0.04, 0.001 for digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin. Thus, 4‴-methyldigoxin is almost completely absorbed within the first two hours, while digoxin and 4‴-acetyldigoxin continue to be absorbed during the following hours. The absorption velocity of digoxin from the ileum was found to be one half of that seen in the duodenum. But this slow absorption, as well, follows a biphasic course. The data indicate that 4‴-methyldigoxin is absorbed at a distinctly higher rate than 4‴-acetyldigoxin and digoxin. Acetylation in 4‴ position evidently provides no important advantage with respect to absorption. While this study allows the determination of absorption and excretion velocities, no account of absorption quotes is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501851
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  • 10
    Electronic Resource
    Electronic Resource
    Evaluation of the enterohepatic circulation after 3H-digoxin administration in the rat (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 1-10 
    Details
    ISSN: 1432-1912
    Keywords: Enterohepatic Circulation ; Pharmacokinetics ; Digoxigenin-Bis- and Mono-Digitoxoside ; Polar Conjugates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After intraduodenal administration of 3H-digoxin (d) in biliary fistula (b.f.) rats, the total radioactivity in blood and bile is eliminated with t1/2 of 7 h in both fluids. In rats with intact enterohepatic circulation (e.c.), a t1/2 of 13.5 h was observed in blood and of 22 h in bile. To explain the much longer t1/2 in bile than in blood, the pharmacokinetics were studied of all substances, which might participate in e.c. after d administration. E.c. of the water soluble fraction is negligible since almost no absorption was found. Digoxigenin-bis- (b) and monodigitoxoside (m) showed approximately the same absorption kinetics as d. However, the blood levels of radioactivity after i.d. administration of these metabolites in b.f. rats were 5–6 times lower than those after d as a consequence of higher biliary excretion. 90–95% of the absorbed amounts of b and m were extrected in bile within 11 h compared with 61% after d administration. Thus the far longer t1/2 of elimination of radioactivity in bile than in blood after i.d. administration of d in rats with e.c. seemed to be due to a short circuit of b and m between intestine and liver. Evidence for this comes from the chromatographic analysis of the total radioactivity in the bile of these animals which shows that significantly more b is present in the bile of rats with e.c. than b.f. rats. No differences were found in the case of m, which on one hand is formed to a lesser extent and is on the other rapidly converted to polar metabolites, which are not reabsorbed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505063
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