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  • Immunocytochemistry  (69)
  • Drosophila melanogaster  (67)
  • man  (57)
  • Springer  (193)
  • American Chemical Society
  • Periodicals Archive Online (PAO)
  • 1975-1979  (193)
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  • Springer  (193)
  • American Chemical Society
  • Periodicals Archive Online (PAO)
  • Wiley-Blackwell  (4)
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  • 1
    Digitale Medien
    Digitale Medien
    Localization of cells capable of transdetermination in a specific region of the male foreleg disk ofDrosophila (1977)
    Springer
    Development genes and evolution 182 (1977), S. 69-74 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Drosophila melanogaster ; Male foreleg disk ; Capacity of transdetermination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary In the male foreleg disk ofDrosophila melanogaster the cells capable of transdetermination are clustered in a specific region within the upper half of the disk. Cells outside this region cannot transdetermine under any of the experimental conditions thus far applied. Transdetermination occurs when cells capable of transdetermination are stimulated to a certain extent of additional proliferation. This can be achieved either by exposing these cells at a wound surface of an intact fragment, or by dissociation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848088
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  • 2
    Digitale Medien
    Digitale Medien
    Localized synthesis of specific proteins during oogenesis and early embryogenesis inDrosophila melanogaster (1979)
    Springer
    Development genes and evolution 187 (1979), S. 151-165 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Oogenesis ; Embryogenesis ; Two-dimensional gels ; Protein synthesis ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Protein synthesis in egg follicles and blastoderm embryos ofDrosophila melanogaster has been studied by means of two-dimensional gel electrophoresis. Up to 400 polypeptide spots have been resolved on autoradiographs. Stage 10 follicles (for stages see King, 1970) were labelled in vitro for 10 to 60 min with35S-methionine and cut with tungsten needles into an anterior fragment containing the nurse cells and a posterior fragment containing the oocyte and follicle cells. The nurse cells were found to synthesize a complex pattern of proteins. At least two proteins were detected only in nurse cells but not in the oocyte even after a one hour labelling period. Nurse cells isolated from stages 9, 10 and 12 follicles were shown to synthesize stage specific patterns of proteins. Several proteins are synthesized in posterior fragments of stage 10 follicles but not in anterior fragments. These proteins are only found in follicle cells. No oocyte specific proteins have been detected. Striking differences between the protein patterns of anterior and posterior fragments persist until the nurse cells degenerate. In mature stage 14 follicles, labelled in vivo, no significant differences in the protein patterns of isolated anterior and posterior fragments could be detected; this may be due to technical limitations. At the blastoderm stage localized synthesis of specific proteins becomes detectable again. When blastoderm embryos, labelled in vivo, are cut with tungsten needles and the cells are isolated from anterior and posterior halves, differences become apparent. The pole cells located at the posterior pole are highly active in protein synthesis and contribute several specific proteins which are found exclusively in the posterior region of the embryo. In this study synthesis of specific proteins could only be demonstrated at those developmental stages which are characterized by the presence of different cell types within the egg chamber, while no differences were detected when stage 14 follicles were cut and anterior and posterior fragments analyzed separately. The differences in the pattern of protein synthesis by pole cells and blastoderm cells indicate that even the earliest stages of determination are reflected by marked changes at the biochemical level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848268
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  • 3
    Digitale Medien
    Digitale Medien
    Genetic analysis of pattern-formation in the embryo ofDrosophila melanogaster (1977)
    Springer
    Development genes and evolution 183 (1977), S. 249-268 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Pattern-formation ; Embryogenesis ; Maternal-effect mutants ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The mutationbicaudal (Bull, 1966) causes embryos to develop a longitudinal mirror image duplication of the posteriormost abdominal segments, while head and thorax are missing. These embryos occur with varying frequencies among eggs laid by mutant females, irrespective of the paternal genotype. Recombination and deletion mapping indicate thatbicaudal (bic) is a recessive, hypomorphic, maternal-effect mutation mapping at a single locus on the second chromosome ofDrosophila melanogaster close tovg (67.0±0.1). The frequency of bicaudal embryos depends on the age of the mother, her genetic constitution and the temperature at which she is raised. Best producers are very young females hemizygous forbic (bic/Df(2)vg B ) at 28° C. Under these conditions 80% to 90% of the eggs which differentiate can show the bicaudal embryo phenotype. Upon ageing of the mother the frequency of bicaudal embryos declines rapidly, and most of the eggs develop the normal body pattern. Temperature shift experiments suggest a temperature-sensitive period at the onset of vitellogenesis. The mutation causes several types of abnormalities in the segment pattern of theDrosophila embryo, which are interpreted as various degrees of expression of the mutant character. The most frequent abnormal phenotype is the symmetrical bicaudal embryo with one to five abdominal segments duplicated. Less frequent are asymmetrical types, in which the smaller number of segments is always in the anterior reversed part. Other phenotypes are embryos with missing or rudimentary heads, and embryos with irregular gaps in the segment pattern. In bicaudal embryos, the pole cells, formed at the posterior pole of the egg prior to blastoderm formation, are not duplicated at the anterior. The significance of thebicaudal phenotypes for embryonic pattern-formation inDrosophila is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00867325
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  • 4
    Digitale Medien
    Digitale Medien
    Detection of clones in the nervous system ofDrosophila melanogaster (1977)
    Springer
    Development genes and evolution 183 (1977), S. 165-169 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Clones ; Nervous system ; Shibire ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Mitotic recombination was induced, by X-irradiation at the blastoderm stage, in flies heterozygous for one of the temperature-sensitive paralytic mutationsshibire andtp-2. The results show that these mutations can be used to detect the presence of clones in the central nervous system through the temperature-sensitive paralysis of individual legs. Mitotic recombination can also be used to examine the effects of these mutations in the peripheral nervous system; shibire is thus shown to affect the function of sensory neurons.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848786
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  • 5
    Digitale Medien
    Digitale Medien
    Isozymic patterns and functional states of cell lines ofDrosophila melanogaster cultured in vitro. II (1976)
    Springer
    Development genes and evolution 180 (1976), S. 107-119 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Drosophila melanogaster ; Cell lines ; Isoenzymes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Our previous isoenzyme investigation ofDrosophila melanogaster cell lines in vitro has been completed with twelve further enzyme systems. The “enzyme profiles” seem to be in good agreement with a previous hypothesis concerning the precise origin of these cell lines (probably from imaginal discs or nervous tissues). Our results have been summarized with reference to the biochemical genetic map ofDrosophila melanogaster in order to consider a possible functional organization of the genome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848101
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  • 6
    Digitale Medien
    Digitale Medien
    A study of the female germ line in mosaics ofDrosophila (1978)
    Springer
    Development genes and evolution 184 (1978), S. 41-56 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Drosophila melanogaster ; Female germ line ; Mosaics ; Stem cell divisions ; Metafemale ; Sterility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Our report presents an analysis of the development and dynamics of the female germ line inDrosophila. Females were produced that were mosaic either for attached-X chromosomes $$(\widehat{XX})$$ and a ring-X (triplo-X-diplo-X), or for $$\widehat{XX}$$ and a marked Y-chromosome $$(\widehat{XX}/Y - \widehat{XX}/O)$$ . The germ-line and genitalia of these females were analysed by direct microscopic observation or by examination of the progeny. Eggs derived from triplo-X germ cells were hardly capable of supporting development, with most of the zygotes dying during embryonic development. The analysis of the germ line was therefore carried out mainly by direct observation of histochemically stained developing oocytes in the ovaries of mosaic females. The total germ cell population of both ovaries of a female was mosaic in 22–29% of the tested animals. From this frequency of mosaicism we estimated the number of functional primordial germ cells to be betwen 3 and 6 cells at the blastoderm stage. At this stage the cell lineages for the left and right ovary are not yet separated. The germ cell population of individual ovarioles was frequently mosaic which shows that the few stem cells in an ovariole are recruited as a group and are not clonal descendants of a single ancestor cell per ovariole. An analysis of the sequential pattern of oocyte-nurse cell cysts in mosaic ovarioles revealed that neighbouring cysts tend to be of the same genotype. This suggests that the stem cells of the adult ovaries preferentially divide in bursts, one of them giving rise to two, three and sometimes even more cystocytes in a row. In addition, the foci for lethality and sterility of the triplo-X condition were determined. Non-mosaic triplo-X females (metafemales) are hardly viable and invariably sterile. Using our mosaics, the focus forlethality could be mapped to a region very near the ventral prothoracic discs. The focus forsterility resides in the genitalia, since flies with triplo-X genitalia never laid any eggs, regardless of the genotype of their ovaries.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848668
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  • 7
    Digitale Medien
    Digitale Medien
    Rudimentary mutants ofDrosophila melanogaster (1979)
    Springer
    Development genes and evolution 187 (1979), S. 167-177 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Pyrimidine biosynthesis ; rudimentary mutants ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The X-linkedrudimentary (r) mutants ofDrosophila melanogaster are pyrimidine auxotrophs and require exogenous pyrimidines (Nørby, 1970; Falk, 1976). We have established a set ofrudimentary cell lines that are derived from embryos, homozygous for eitherr 1 orr 36. The enzymatic activities of the pyrimidine synthesizing enzymes were measured in the mutant lines. We have further investigated the nutritional requirements of the mutant cells in vitro by using a pyrimidine free culture medium. Ther 1 cell lines were found to express 3–7%dihydroorotase (DHOase) activity as compared to a wildtype cell line. Reducedaspartate transcarbamylase (ATCase) activity was measured in somer 1 cell lines whereas wildtypecarbamylphosphate synthetase (CPSase) activity is expressed in allr 1 cell lines. Ther 36 cell line expresses wildtype activity ofDHOase andCPSase. ATCase activity was found to be reduced to 10% of the wildtype activity. The mutant cell lines do not proliferate in pyrimidine free minimal medium and cell proliferation is obtained by the addition of crude RNA. Proliferation of ther 1 cells is restored by the supplementation of the minimal medium withdihydroorotate whereas proliferation of ther 36 cells is restored by supplementation with eitherdihydroorotate orcarbamylaspartate. The results demonstrate that therudimentary phenotypesr 1 andr 36 are expressed at the cellular level and that the two mutant cell types behave as cellular pyrimidine auxotrophs in vitro.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848269
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  • 8
    Digitale Medien
    Digitale Medien
    The effect of fat body on the differentiation in vitro of wing imaginal discs ofDrosophila melanogaster (1976)
    Springer
    Development genes and evolution 180 (1976), S. 73-77 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Ecdysones ; Imaginal discs ; Fat body ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The effect of suboptimal levels of α-ecdysone on the differentiation in vitro ofDrosophila melanogaster wing discs was enhanced by the addition of larval fat body to the cultures. However, similar experiments with β-ecdysome showed no enhancement. It is suggested that a partial conversion of α-ecdysone to β-ecdysone by the fat body may well account for these results.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848885
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  • 9
    Digitale Medien
    Digitale Medien
    Developmental potentials of the cells of the male foreleg disc ofDrosophila (1977)
    Springer
    Development genes and evolution 181 (1977), S. 309-320 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Drosophila melanogaster ; Male foreleg disc ; Pattern regulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary 1. The developmental potentials of the four quadrants of the male foreleg disc ofDrosophila melanogaster were analysed by culturing excised quadrants for 3 days and 10 days in adult hosts prior to metamorphosis. 2. The cultured pieces underwent different types of pattern regulation in a circular direction. The upper medial piece was able to regenerate the missing structures of the disc, thus confirming the findings of earlier reports. The three remaining pieces could undergo pattern duplication in mirror-image symmetry. The lower medial piece revealed in addition a slight capacity for regeneration from the vertical cut surface. 3. The duplicating pieces differed markedly in their frequencies of pattern duplication: duplications occurred with very high frequencies in lower medial pieces, with intermediate frequencies in upper lateral pieces, and with very low frequencies in lower lateral pieces. 4. Both lower lateral and upper lateral pieces underwent a progressive loss of most markers with increasing culture time. 5. Claws were regenerated solely by upper medial pieces. 6. Transdetermined structures, too, were encountered only in upper medial pieces. 7. The results are discussed with respect to the two major current models of pattern regulation in imaginal discs, the “gradient model” and the “clock model”. 8. It is suggested that the differences in the frequencies of pattern duplication reflect the unequal spacing of circular positional values within the three duplicating quadrants. Under this assumption the data indicate a progressive decrease in the density of circular positional values with increasing distance from the upper medial quadrant of the disc.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00848058
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  • 10
    Digitale Medien
    Digitale Medien
    Demonstration of enamel matrix proteins on root-analogue surfaces of rabbit permanent incisor teeth (1977)
    Springer
    Calcified tissue international 24 (1977), S. 223-229 
    Details
    ISSN: 1432-0827
    Schlagwort(e): Enamel-cementum-morphology ; Immunocytochemistry ; Biochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The continuously erupting rabbit incisor tooth is normally thought of as having an enamel covered “crown” on its labial surface and a cementum covered “root” on its lingual surface. We have examined both surfaces of continuously erupting rabbit incisor teeth taken from near term embryos by a variety of means, including transmission and scanning electron microscopy, biochemical fractionation, and immunohistochemistry. In all cases, we could detect no qualitative difference in the early extracellular matrices taken from the labial and lingual surfaces of the teeth. Both matrices were shown to be composed of dentin and enamel, although the thickness and geometry of the enamel matrix on the lingual surface was somewhat different from that on the labial surface.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02223320
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  • 11
    Digitale Medien
    Digitale Medien
    Phytochrome photoreversibility: Empirical test of the hypothesis that it varies as a consequence of pigment compartmentation (1978)
    Springer
    Planta 141 (1978), S. 129-134 
    Details
    ISSN: 1432-2048
    Schlagwort(e): Avena ; Immunocytochemistry ; Phytochrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Phytochrome of oat (Avena sativa L., cv. Garry) coleoptile cells in the red-light-absorbing form, Pr, is diffusely distributed while after conversion to the far-red-light-absorbing form, Pfr, it is observed only in very small areas within the cell. Comparison of phytochrome photoversibility measurements to the distribution of the pigment within the cell indicates that the spectral assay is not influenced by the observed compartmentalization of the chromoprotein. However, the observed compartmentalization of phytochrome is correlated with a loss in spectrophotometrically detectable Pr.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00387878
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  • 12
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561557
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  • 13
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sympathetic activity ; plasma catecholamine concentration ; dopamine-β-hydroxylase activity ; graded physical exercise ; heart rate ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567112
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  • 14
    Digitale Medien
    Digitale Medien
    Bioavailability of m-octopamine in man related to its metabolism (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 33-39 
    Details
    ISSN: 1432-1041
    Schlagwort(e): m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00616412
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  • 15
    Digitale Medien
    Digitale Medien
    Excretion of norephedrine by man after oral administration of oxyfedrine (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 161-166 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Oxyfedrine ; norephedrine ; man ; urinary excretion ; sympathomimetic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567109
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  • 16
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567123
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  • 17
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562660
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  • 18
    Digitale Medien
    Digitale Medien
    Delayed absorption of lithium in intoxication (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 285-285 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Lithium ; intoxication ; man ; delayed absorption ; gastric contents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567130
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  • 19
    Digitale Medien
    Digitale Medien
    Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 277-282 
    Details
    ISSN: 1432-1041
    Schlagwort(e): QX-572 ; quaternary ammonium compound ; plasma level ; urinary excretion ; man ; anti-arrhythmic drug
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567128
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  • 20
    Digitale Medien
    Digitale Medien
    Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 135-145 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614010
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  • 21
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 155-159 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614012
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  • 22
    Digitale Medien
    Digitale Medien
    The metabolism of (−)-ephedrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 193-198 
    Details
    ISSN: 1432-1041
    Schlagwort(e): (−)-[14C]-ephedrine ; metabolism ; urinary excretion ; tolerance ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic fate of orally administered (−)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 µCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53–74%), with N-demethylation occurring to a variable extent (8–20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4–13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614017
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  • 23
    Digitale Medien
    Digitale Medien
    Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 219-227 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Rifampicin ; induction of drug metabolism ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614021
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  • 24
    Digitale Medien
    Digitale Medien
    Disposition of quercetin in man after single oral and intravenous doses (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614022
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  • 25
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Aldosterone ; renin ; aldosterone antagonist ; canrenone ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561657
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  • 26
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Tricyclic antidepresent ; lofepramine ; single- and multiple-dose kinetics ; noradrenaline and 5-hydroxytryptamine uptake ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561663
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  • 27
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Absorption ; man ; β-methyl-digoxin ; serum concentration ; urinary excretion ; radio-immunoassay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561665
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  • 28
    Digitale Medien
    Digitale Medien
    Metabolism of digitoxin in man and its modification by spironolactone (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 345-354 
    Details
    ISSN: 1432-1041
    Schlagwort(e): 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606547
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  • 29
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Serum zinc concentration ; intestinal absorption ; portal vein ; transumbilical catheterization ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606559
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  • 30
    Digitale Medien
    Digitale Medien
    Effects of dixyrazine and methaqualone on the sleep pattern in normal man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 227-231 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dixyrazine ; methaqualone ; etodroxizine ; Isonox® ; sleep stages ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox® (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox® (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567120
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  • 31
    Digitale Medien
    Digitale Medien
    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561556
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  • 32
    Digitale Medien
    Digitale Medien
    Haemodynamic effects of intravenous disopyramide in heart failure (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 167-173 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Disopyramide ; haemodynamic effect ; negative inotropic effect ; anticholinergic effect ; hear failure ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The haemodynamic effects of disopyramide have been studied in 11 patients with manifest or imminent heart failure. Disopyramide, 2 mg per kg body weight, was given intravenously during right and left heart catheterisation. The cardiac index decreased by an average of 28% (p〈0.01); mean maximal left and right ventricular end-diastolic pressures were increased by 5.0±0.9 mm Hg (〈0.01) and 5.0±0.6 mm Hg (p〈0.05), respectively; and left ventricular systolic pressure fell slightly but significantly (p〈0.05). No significant change in right ventricular systolic pressure was seen. Pulmonary wedge pressure rose on average by 2.7 mm Hg (p〈0.05). No significant change in heart rate was observed in 5 patients with sinus rhythm. In 6 patients with atrial fibrillation, there was a significant (p〈0.01) increase in heart rate; the average increase in heart rate for the entire group was 19,6 heats per minute. The maximum effect on all the parameters occurred 7–11 minutes after the injection, and it gradually subsided during the following 10 minutes. It was concluded that disopyramide had a potentially serious myocardial depressant effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00567110
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  • 33
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562662
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  • 34
    Digitale Medien
    Digitale Medien
    Bioavailability studies with Digoxin-Sandoz® and Lanoxin® (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 371-376 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; bioavailability ; plasma levels ; cumulative urinary excretion ; particle size ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz® tablets have been compared with Lanoxin® manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to “new” Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562665
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  • 35
    Digitale Medien
    Digitale Medien
    On the pharmacokinetics of proscillaridin A in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 421-425 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Proscillaridin ; enteric-coated tablets ; plasma levels ; urine excretion ; 86Rb-erythrocyte assay ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration of proscillaridin was measured by a modified86Rd method during treatment with multiple doses of a commercial preparation of proscillaridin. Despite high doses, very low plasma levels were found, and there were only minute amounts of glycoside activity in urine and faeces. Administration of an enteric-coated proscillaridin preparation gave higher plasma levels, which raises the possibility of inactivation of the glycoside by acid gastric juice. The results suggest that proscillaridin has low biological availability when given orally, and that it is extensively metabolised in the body.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562316
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  • 36
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558337
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  • 37
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Phenothiazine ; thioridazine ; plasma level ; metabolic pattern ; half life ; man ; schizophrenia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562906
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  • 38
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): cyproheptadine ; metergoline ; glucose tolerance ; insulin secretion ; chemical diabetes ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561737
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  • 39
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Acetylsalicylic acid ; surgery ; man ; bleeding ; pain ; wound-healing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558332
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  • 40
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and bioavailability of indoprofen in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558338
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  • 41
    Digitale Medien
    Digitale Medien
    Inhibition of tetracycline absorption by zinc (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 59-62 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tetracycline absorption ; zinc sulphate ; zinc citrate ; complex formation ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561551
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  • 42
    Digitale Medien
    Digitale Medien
    Effect of analgesic agents on emptying of the gallbladder in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 127-131 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Gallbladder emptying ; analgesics ; indoprofen ; pentazocine ; morphine ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609471
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  • 43
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558329
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  • 44
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Twin study ; ethanol metabolism ; intra-individual variation ; pharmacogenetics ; plasma level ; man ; heritability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00566530
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  • 45
    Digitale Medien
    Digitale Medien
    Disposition and oxidative metabolism of phenylbutazone in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 359-366 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00566533
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  • 46
    Digitale Medien
    Digitale Medien
    A sensitive radioimmunoassay for fentanyl (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 153-158 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Fentanyl ; radioimmunoassay ; cross-reaction ; plasma level ; dog ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00645137
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  • 47
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Activated charcoal ; acute intoxication ; digoxin ; phenytoin ; aspirin ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609985
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  • 48
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tetracycline absorption ; EDTA ; milk ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607444
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  • 49
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00560462
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  • 50
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): quinidine ; plasma protein binding ; pharmacokinetics ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00563104
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  • 51
    Digitale Medien
    Digitale Medien
    Preliminary studies of the kinetics of citalopram in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 69-73 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00560260
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  • 52
    Digitale Medien
    Digitale Medien
    Investigation into the species-specific deacylation of penta-acetyl-gitoxin (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 425-430 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Penta-acetyl-gitoxin ; 16-acetyl-gitoxin ; gitoxin ; mass spectrometry ; species-specific deacylation ; man ; rabbit ; guinea-pig ; rat ; blood ; intestinal mucosa ; liver homogenate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00716384
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  • 53
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): simulation model ; diazoxide hypotension ; haemodynamics ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609868
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  • 54
    Digitale Medien
    Digitale Medien
    The fate of3H-terbutaline sulphate administered to man as an aerosol (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 1-7 
    Details
    ISSN: 1432-1041
    Schlagwort(e): 3H-terbutaline sulphate ; aerosol ; man ; absorption ; excretion ; spirometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561542
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  • 55
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): H 80/62 ; haemodynamic effects ; noninvasive techniques ; selectivity ; β1-adrenoceptor agonist ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609978
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  • 56
    Digitale Medien
    Digitale Medien
    Effect of delayed administration of activated charcoal on nortriptyline absorption (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 445-447 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Activated charcoal ; tricyclic antidepressants ; nortriptyline ; poisoning ; antidote ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00716388
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  • 57
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Intramuscular Clindamycin Phosphate ; serum levels ; half-lives ; renal Failure ; haemodialysis ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00716386
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  • 58
    Digitale Medien
    Digitale Medien
    Haemodynamic effects of intravenous verapamil at rest and during exercise in subjectively healthy middle-aged men (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 317-322 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Verapamil ; haemodynamics ; exercise ; man ; vascular resistance ; negative inotropism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Verapamil, 0.1 mg/kg body wt, was injected i.v. over 2 minutes in 8 subjectively healthy middle-aged men, followed by a continuous infusion of 0.007 mg/kg body wt per minute. Prior to the injection several of the subjects had raised pulmonary or systemic arterial pressures. At rest, the central pressures increased slightly, which was taken as a sign of a moderate negative inotropic effect, but there was no change in pre-ejection period or maximal dp/dt of the aortic pressure. The heart rate increased and there was a small decrease in systemic arterial pressure, probably due to a fall of systemic vascular resistance. The PQ time was prolonged. During exercise, with its positive inotropic stimulation, the moderate negative inotropic effect of verapamil disappeared, whereas the increase in heart rate and decrease in aortic pressures persisted. Some variables that reflected the oxygen demand of the heart decreased. The slight negative inotropic effect does not appear to be a particular contraindication to the use of verapamil, but it should be employed cautiously in conditions with a compensatory rise in systemic vascular resistance, or if atrioventricular conduction is impaired.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562656
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  • 59
    Digitale Medien
    Digitale Medien
    Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 337-341 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Carbamazepine ; carbamamazepine-10,11-epoxide ; pharmacokinetics ; induction of metabolism ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Carbamazepine (Tegretol®) was administered orally to four patients as a single dose, and one week later three times daily for 15–21 days. The plasma half-lives of the drug were shorter in all patients after multiple doses (20.9±5.0 hours) than after the initial single dose (35.6±15.3 hours). During multiple doses the plasma concentrations of the metabolite carbamazepine-10,11-epoxide followed those of the parent drug. The steady-state plasma concentrations expected during multiple doses were calculated from the pharmacokinetic parameters obtained in the single dose studies. The calculated levels were higher (17.2±7.2 µg/ml) than the observed maximal concentrations (8.4±1.6 µg/ml on day 4), which were obtained 3–4 days after starting the multiple doses. The levels tended to decrease further during the experimental period. The results suggest that carbamazepine induces its own metabolism in man.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562659
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  • 60
    Digitale Medien
    Digitale Medien
    Metabolism and excretion of methylproscillaridin by man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 427-432 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Methylproscillaridin ; urinary and faecal excretion ; polar and non-polar metabolites ; man ; glucuronides
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 0.5 mg3H-proscillaridin-4-methylether was administered orally to 5 healthy males. Maximum plasma levels of total radioactivity were reached after one to two hours. In two subjects a second peak was observed between 6 and 12 hours. The plasma half life of total radioactivity was 51 hours. 20% and 56% respectively of the dose were eliminated in urine and faeces during the following 7 days. 55% of the total radioactivity in plasma, 80% in urine and 20% in faeces consisted of CHCl3-insoluble compounds. 50 – 60% of the latter in plasma and urine could be hydrolysed by β-glucuronidase. More than 90% of the split products were identified as conjugates of methylproscillaridin. TLC-separation of the CHCl3-soluble fractions of plasma and urine yielded two unidentified metabolites, P2 and P3, as the main compounds, besides methylproscillaridin, proscillaridin and scillarenin. In faeces more than 90% of the non-polar fraction was identified as methylproscillaridin. Shortly after administration of3H-methylproscillaridin, the radioactivity in plasma consisted mainly of CHCl3-in-soluble conjugates and of the metabolite P2.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562317
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  • 61
    Digitale Medien
    Digitale Medien
    Clinical efficacy of BS 100-141 in essential hypertension (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 69-72 
    Details
    ISSN: 1432-1041
    Schlagwort(e): BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl)acetamide hydrochloride ; essential hypertension ; antihypertensive agent ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561553
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  • 62
    Digitale Medien
    Digitale Medien
    Plasma levels and half lives of thioridazine and some of its metabolites (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 135-140 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Phenothiazine ; thioridazine ; metabolites ; plasma-level ; metabolic pattern ; half-life ; man ; schizophrenia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562905
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  • 63
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): β-Methyl-digoxin ; digoxin ; intravenous administration ; man ; serum concentration ; renal clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606413
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  • 64
    Digitale Medien
    Digitale Medien
    Comparison of BS 100-141 and clonidine as antihypertensive agents (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 73-76 
    Details
    ISSN: 1432-1041
    Schlagwort(e): BS 100-141 ; N-amidino-2-(2,6-dichlorphenyl) acetamide hydrochloride ; clonidine ; essential hypertension ; antihypertensive agents ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561554
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  • 65
    Digitale Medien
    Digitale Medien
    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 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Oxprenolol ; smoking ; catecholamines ; coronary circulation ; man ; c-AMP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00645126
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  • 66
    Digitale Medien
    Digitale Medien
    Influence of nutritional status on plasma levels and relative bioavailability of tetracycline (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 281-284 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607427
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  • 67
    Digitale Medien
    Digitale Medien
    Bioavailability of norethindrone in human subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606680
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  • 68
    Digitale Medien
    Digitale Medien
    Nutritional control of xanthine dehydrogenase. II. Effects on xanthine dehydrogenase and aldehyde oxidase of culturing wild-type and mutant Drosophila on different levels of molybdenum (1975)
    Springer
    Biochemical genetics 13 (1975), S. 53-64 
    Details
    ISSN: 1573-4927
    Schlagwort(e): aldehyde oxidase ; xanthine dehydrogenase ; Drosophila melanogaster ; molybdenum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Two new mutants, deficient in aldehyde oxidase and xanthine dehydrogenase, have been isolated from a wild-type stock of Drosophila melanogaster and have been provisionally termed lxd c and lxd d, respectively, as both mutants appear to be allelic with lxd (low xanthine dehydrogenase). An analysis has been made of the effects of dietary molybdenum on lxd, lxd c, lxdd, lao (low aldehyde oxidase), mal (maroon-like eye color), and pac (Pacific) wild-type flies. On the lower dietary levels of 10 −3 M and 10 −2 M molybdenum, increases in specific activity of both enzymes were observed only in lxd. Furthermore, two- to three-fold increases in specific activity of both enzymes occurred in all strains, except mal, when cultured on 5×10 −2 M molybdenum. The lxd and lxd c strains failed to survive on this high concentration of the ion. Similar concentrations of molybdenum had no effect in vitro. An extra electrophoretic band of xanthine dehydrogenase was observed on polyacrylamide gel from extracts of wild-type flies cultured on certain levels of molybdenum, but its appearance was not always correlated with the increases in specific activity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00486006
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  • 69
    Digitale Medien
    Digitale Medien
    The size of poly(A)-containing RNAs in Drosophila melanogaster embryos (1976)
    Springer
    Biochemical genetics 14 (1976), S. 357-371 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; poly(A)-containing RNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The size range of poly(A)-containing RNA from Drosophila melanogaster embryos has been estimated by hybridization with 3H-labeled poly(U) and subsequent fractionation on sucrose gradients. The median size of nuclear poly(A)-containing RNA is about 30 S (6000 nucleotides), and the median size of cytoplasmic poly(A)-containing RNA is about 17 S (1800 nucleotides). The relationship of these sizes to messenger RNA needed to code for protein and to the length of DNA contained in a chromomere is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484774
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  • 70
    Digitale Medien
    Digitale Medien
    Partial purification and properties of guanosine triphosphate cyclohydrolase from Drosophila melanogaster (1976)
    Springer
    Biochemical genetics 14 (1976), S. 259-270 
    Details
    ISSN: 1573-4927
    Schlagwort(e): GTP cyclohydrolase ; Drosophila melanogaster ; pteridines ; dihydroneopterin triphosphate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The first enzyme (named GTP cyclohydrolase) in the pathway for the biosynthesis of pteridines has been partially purified from extracts of late pupae and young adults of Drosophila melanogaster. This enzyme catalyzes the hydrolytic removal from GTP of carbon 8 as formate and the synthesis of 2-amino-4-hydroxy-6-(d-erythro-1′,2′,3′-trihydroxypropyl)-7,8-dihydropteridine triphosphate (dihydroneopterin triphosphate). Some of the properties of the enzyme are as follows: it functions optimally at pH 7.8 and at 42 C; activity is unaffected by KCl and NaCl, but divalent cations (Mg2+, Mn2+, Zn2+, and Ca2+) are inhibitory; the K m for GTP is 22 μm; and the molecular weight is estimated at 345,000 from gel filtration experiments. Of a number of nucleotides tested, only GDP and dGTP were used to any extent as substrate in place of GTP, and these respective compounds were used only 1.8% and 1.5% as well as GTP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484765
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  • 71
    Digitale Medien
    Digitale Medien
    The suppressor of forked mutation in Drosophila melanogaster: Interactions with the lozenge gene (1976)
    Springer
    Biochemical genetics 14 (1976), S. 611-617 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; phenol oxidases ; spectrophotometry ; electrophoresis ; suppression ; ribosomal proteins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract An interaction between the lozenge gene and the suppressor of forked gene of Drosophila melanogaster has been investigated both spectrophotometrically and electrophoretically. The nature of this interaction is such that certain lozenge alleles appear to be phenotypically suppressed while others are enhanced or unaffected, and the results reported demonstrate that the effect can clearly be observed at the biochemical level. Earlier observations have suggested that the suppressor of forked gene codes for a ribosomal protein, and this hypothesis is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00485839
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  • 72
    Digitale Medien
    Digitale Medien
    Selection against homozygotes in the ADH polymorphic system of Drosophila melanogaster associated with the lethal factor l(2) Stm (1977)
    Springer
    Biochemical genetics 15 (1977), S. 93-100 
    Details
    ISSN: 1573-4927
    Schlagwort(e): alcohol dehydrogenase (ADH) ; genetic polymorphism ; selection ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract In the natural populations +Tüb, +Prov, and +Rov, similar Adh F allele frequencies occur (q F=0.11, 0.18, and 0.08, respectively). However, there is a discrepancy in that the Adh F allele in +Tüb is closely linked to the lethal factor 1(2)Stm, which reduces relative fitness of the F phenotype to zero. In spite of this, polymorphism is maintained also in +Tüb, because the heterozygotes are superior to the homozygous S type (relative fitness=0.88). Under laboratory culture conditions, in +Tüb the relative fitness of the S genotype further decreases to 0.6. After outcrossing the lethal factor, relative fitnesses for S, FS, and F become 0.6, 1, and 0.48, respectively, implying that fitness for S remains the same. Relative values for S, FS, and F in +Prov, not affected by the lethal factor, are calculated by the maximum average fitness method to be 1, 1.2, and 0.2 under the assumption that heterozygous FS are similarly superior to S as in the natural +Tüb population and all allele frequencies found are stable equilibrium values.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484551
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  • 73
    Digitale Medien
    Digitale Medien
    Origin of α-glycerophosphate dehydrogenase isozymes in Drosophila melanogaster and their functional relationship in the α-glycerophosphate cycle (1977)
    Springer
    Biochemical genetics 15 (1977), S. 235-251 
    Details
    ISSN: 1573-4927
    Schlagwort(e): l-glycerol-3-phosphate dehydrogenase (α-GPDH) ; isozymes ; development ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The basis for the differentiation of l-glycerol-3-phosphate dehydrogenase (α-GPDH) into larval and adult isozymes in Drosophila melanogaster was investigated by the correlation of a lack of appearance of each isozyme during development within Drosophila bearing α-GPDH “null” alleles and by the study of a putative conversion factor. Conversion studies indicate the presence of a heat-labile RNase-resistant conversion factor present in crude larval extracts with the ability to convert GPDH-1 to GPDH-2 and GPDH-3 but not vice versa. In addition, “null” mutations at the Gpdh locus obliterate all isozymatic species of α-GPDH in all developmental stages. These observations suggest that all α-GPDH isozymes are the product of a single structural gene and that the multiple forms of this enzyme arise during successive developmental stages through an epigenetic modification of the primary Gpdh + polypeptide. Finally, observations are reported which bear on the functional divergence of the α-glycerophosphate cycle in the adult and larval stage of development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484456
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  • 74
    Digitale Medien
    Digitale Medien
    Isolation and genetic characterization of alcohol dehydrogenase thermostability variants occurring in natural populations of Drosophila melanogaster (1977)
    Springer
    Biochemical genetics 15 (1977), S. 971-988 
    Details
    ISSN: 1573-4927
    Schlagwort(e): allozymes ; thermostability ; alcohol dehydrogenase ; Drosophila melanogaster ; natural populations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Drosophila melanogaster collected from natural populations were examined fo thermostability variants within electrophoretic mobility classes of two enzymes. In alcohol dehydrogenase, two discrete forms of the “slow” allozyme and three discrete forms of the “fast” allozyme were revealed by postelectrophoretic treatments ranging from 15 sec at 40 C to 40 sec at 43 C. All variants have been mapped to within 0.7 unit of the Adh locus. Results of a geographic survey indicate that two alleles giving rise to fast-moderate and slow-moderate allozymes are common everywhere; other variants have a collective frequency ranging from 0% to 7%. In a test of the possibility that the rare Adh alleles could be generated by intragenic recombination between the two common alleles, electrophoresis and heat treatment of progeny recombinant for flanking markers of Adh revealed no new allozymes. Among 27 stocks containing slow α-glycerophosphate dehydrogenase allozymes and 109 fast stocks, heat treatments revealed no additional variation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00483992
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  • 75
    Digitale Medien
    Digitale Medien
    Control of drosopterin synthesis in Drosophila melanogaster: Mutants showing an altered pattern of GTP cyclohydrolase activity during development (1978)
    Springer
    Biochemical genetics 16 (1978), S. 13-26 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; GTP cyclohydrolase ; development ; pteridine biosynthesis ; mutants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The reaction catalyzed by GTP cyclohydrolase is the first unique step of pteridine biosynthesis in Drosophila melanogaster and is therefore likely to be an important control point. GTP cyclohydrolase activity varies during development, showing two distinct peaks of activity—one at pupariation and a much larger peak at emergence. Most of the early pupal enzyme is located in the body region, whereas in late pupal and early adult life most of the activity is found in the head. Mixing experiments indicate that developmental changes in activity are not due to changes in the level of a direct effector of GTP cyclohydrolase. The mutants raspberry and prune show an increased GTP cyclohydrolase activity at pupariation relative to wild type, but a decreased enzyme activity at emergence. The changes in GTP cyclohydrolase activity are reflected in changes in pteridine levels in these mutants. Several lines of evidence suggest that neither locus is the structural gene for GTP cyclohydrolase. The raspberry and prune gene products may play a specific role in regulating GTP cyclohydrolase activity during development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484381
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  • 76
    Digitale Medien
    Digitale Medien
    A genetic and developmental analysis of an acid deoxyribonuclease in Drosophila melanogaster (1978)
    Springer
    Biochemical genetics 16 (1978), S. 1113-1134 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; isozymes ; position effect ; segmental aneuploidy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A deoxyribonuclease, called DNase-1, that is active at acid pH in the presence of EDTA has been studied in Drosophila melanogaster. The locus for the enzyme maps genetically to 61.8 on the right arm of the third chromosome. Cytogenetically, DNase-1 has been localized to within five to ten bands between 90C-2 and 90E. This analysis utilizes both electrophoretic variants and the Y-autosome translocations of Lindsley et al. (1972). DNase-1 is present in all stages of the life cycle, and the paternal genome actively contributes DNase-1 to the embryo between 0 and 1 hr after fertilization.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484532
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  • 77
    Digitale Medien
    Digitale Medien
    Variation in amount of enzyme protein in natural populations (1978)
    Springer
    Biochemical genetics 16 (1978), S. 159-170 
    Details
    ISSN: 1573-4927
    Schlagwort(e): alcohol dehydrogenase ; allozyme properties and amounts ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Among strains of Drosophila melanogaster each derived from a single fertilized female taken from natural populations, there is variation in both alcohol dehydrogenase (ADH) activity and the amount of ADH protein. The correlation between ADH activity and number of molecules over all strains examined is 0.87 or 0.96 in late third instar larvae depending on whether the substrate is 2-propanol or ethanol. With respect to the two common electrophoretic allozymic forms, F and S, segregating in these populations, the FF strains on the whole have higher ADH activities and numbers of ADH molecules than the SS strains. Over all strains examined, enzyme extracts from FF strains have a mean catalytic efficiency per enzyme molecule higher than that of enzyme extracts from SS strains when ethanol is the substrate, and much higher when 2-propanol is the substrate. One FF strain had an ADH activity/ADH protein ratio characteristic of SS strains.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484075
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  • 78
    Digitale Medien
    Digitale Medien
    Alcohol metabolism in Drosophila melanogaster: Uselessness of the most active aldehyde oxidase produced by the Aldox locus (1978)
    Springer
    Biochemical genetics 16 (1978), S. 203-211 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; alcohol tolerance ; alcohol utilization ; alcohol dehydrogenase ; aldehyde oxidase ; allozymes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Alcohol dehydrogenase is necessary for ethanol detoxification and metabolic utilization. It has been generally assumed that aldehyde oxidase (AO) produced by the Aldox locus (3–56.7) is necessary for a further transformation of acetaldehyde into acetate. We find that various mutant strains (ma-l or Aldox n) which do not produce an active enzyme show about the same tolerance to alcohol as do wild strains. This physiological paradox is probably to be explained by the discovery of another locus (not localized) which produced a small amount of AO in all tested strains. The adaptive significance of the genetically polymorphic Aldox locus is probably to be looked for in physiological pathways other than ethanol metabolism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484078
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  • 79
    Digitale Medien
    Digitale Medien
    A simple approach for discovering common nonelectrophoretic enzyme variability: A heat denaturation study in Drosophila melanogaster (1978)
    Springer
    Biochemical genetics 16 (1978), S. 299-305 
    Details
    ISSN: 1573-4927
    Schlagwort(e): nonelectrophoretic structural variability ; Drosophila melanogaster ; phosphoglucomutase ; genetic polymorphism ; heat denaturation study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A simple procedure is described to detect genetic heterogeneity within electrophoretic classes at a locus in Drosophila, based on electrophoresis and heat denaturation studies. Temperature-resistant (tr) and temperature-sensitive (ts) isoelectrophoretic alleles at the phosphoglucomutase locus (Pgm) are present at polymorphic frequencies in natural and in laboratory populations of Drosophila melanogaster.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484086
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  • 80
    Digitale Medien
    Digitale Medien
    Developmental changes of sepiapterin synthase activity associated with a variegated purple gene in Drosophila melanogaster (1979)
    Springer
    Biochemical genetics 17 (1979), S. 197-206 
    Details
    ISSN: 1573-4927
    Schlagwort(e): sepiapterin synthase ; variegation ; purple ; Drosophila melanogaster ; pteridine eye pigments ; drosopterin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A variegated position effect on the autonomous gene, purple, has been studied enzymologically in Drosophila melanogaster. Sepiapterin synthase, the enzyme system associated with pr +, was examined for activity in different developmental stages of the fly. The results indicate that T(Y:2) pr c5, cn/prc4 cn flies (flies in which pr + has been translocated and which exhibit variegation) have a reduced amount of enzyme activity as compared with both Oregon-R and pr 1 flies. This reduction in activity was not found in larval stages, which suggests that the inactivation process probably occurs in late larval or early pupal stages. The phenotype of the variegated adult has white eyes with red-colored spots and patches where drosopterins occur. The phenotype of the fly carrying the translocation is modified by the presence of additional Y chromosomes. This extends the observation from other systems that extra heterochromatin acts to suppress the variegated position effect. The advantages of studying the variegation by measuring enzyme activity, as well as the phenotypic expression, are several; for example, the developmental time at which variegation occurs may be estimated even though drosopterin synthesis is not occurring.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484485
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  • 81
    Digitale Medien
    Digitale Medien
    Polymorphism at the G6pd and 6Pgd loci in Drosophila melanogaster. III. Developmental and biochemical aspects (1979)
    Springer
    Biochemical genetics 17 (1979), S. 1131-1144 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; enzyme polymorphism ; G6PD ; 6PGD ; enzyme activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The electrophoretic variants of G6PD and 6PGD isolated from the Bogota Drosophila melanogaster population were characterized developmentally and biochemically. Changes in in vitro enzyme activity during development were comparable to those found for other dehydrogenases: an increase in the larval and adult stage and a decrease in the pupal stage. During the whole life cycle the “S” enzyme of both loci showed a higher activity than the “F” enzyme. MgCl2 had a stimulating effect on the activity of both enzymes whereas their heat stability was decreased. The allozymes of 6PGD had different Vmax's but were comparable with respect to Km values, pH optimum, and stability at 45 C. the allozymes of G6PD showed different Vmax's and differed in stability at 35 C, but had similar Km values and pH optima. As the difference in stability was probably due to differences in molecular structure of the allozymes, the differences in activity found at high pH and high MgCl2 concentration were most probably due to this difference in stability.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00504350
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  • 82
    Digitale Medien
    Digitale Medien
    Transport defects as the physiological basis for eye color mutants of Drosophila melanogaster (1975)
    Springer
    Biochemical genetics 13 (1975), S. 603-613 
    Details
    ISSN: 1573-4927
    Schlagwort(e): transport mutants ; eye color mutants ; kynurenine ; Drosophila melanogaster ; Malpighian tubules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Kynurenine-H 3 transport and conversion to 3-hydroxykynurenine were studied in organ culture using the Malpighian tubules and developing eyes from wild type and the eye color mutants w, st, 1td, ca, and cn of Drosophila melanogaster. Malpighian tubules from wild type have the ability to concentrate kynurenine and convert it to 3-hydroxykynurenine. The tubules from w, st, 1td, and ca are deficient in the ability to transport kynurenine, as are the eyes of the mutants w, st, and 1td. This defect in kynurenine transport provides a physiological explanation for the phenotypic properties of the mutants. The relationship of these measurements to previous observations on these eye color mutants is discussed and the transport defect hypothesis is consistently supported. We have concluded that several of the eye color mutants in Drosophila are transport mutants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484918
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  • 83
    Digitale Medien
    Digitale Medien
    Correlation of guanosine triphosphate cyclohydrolase activity and the synthesis of pterins in Drosophila melanogaster (1976)
    Springer
    Biochemical genetics 14 (1976), S. 271-280 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; GTP cyclohydrolase ; pteridine biosynthesis ; development ; mutants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The enzyme guanosine triphosphate cyclohydrolase (GTP cyclohydrolase), which in bacteria is known to be the first enzyme in the biosynthetic pathway for the synthesis of pteridines, has been discovered in extracts of Drosophila melanogaster. Most of the enzyme (80%) is located in the head of the adult fly. An analysis of enzyme activity during development in Drosophila has revealed the presence of a relatively small peak of activity at pupariation and a much larger peak that appears at about the time of eclosion. Enzyme activity declines rapidly as the fly ages. Analyses for the production of the typical pteridine pigments of Drosophila have indicated that the small peak of GTP cyclohydrolase activity evident at pupariation coincides with the appearance of isoxanthopterin, sepiapterin, and pterin, and the larger peak at eclosion roughly corresponds to the accumulation of drosopterin as well as to the appearance in larger amounts of pterin and sepiapterin. These observations strongly suggest that in Drosophila, like bacteria, GTP cyclohydrolase is involved in the biosynthesis of pteridines. Analyses of a variety of zeste mutants of Drosophila melanogaster have shown that these mutants all contain GTP cyclohydrolase equal approximately to the amount found in the wild-type fly. These observations do not support the suggestions made by Rasmusson et al. (1973) that zeste is the structural locus for GTP cyclohydrolase.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484766
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  • 84
    Digitale Medien
    Digitale Medien
    Genetics and physiological expression of β-hydroxy acid dehydrogenase in Drosophila (1978)
    Springer
    Biochemical genetics 16 (1978), S. 333-342 
    Details
    ISSN: 1573-4927
    Schlagwort(e): β-hydroxy acid dehydrogenase ; chromosome ; dosage compensation ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A mutant Had nl was induced in Drosophila melanogaster and found to be deficient in β-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had +. Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene-enzyme system are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484089
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  • 85
    Digitale Medien
    Digitale Medien
    Dietary rescue of a lethal “null” activity allele of 6-phosphogluconate dehydrogenase in Drosophila melanogaster (1978)
    Springer
    Biochemical genetics 16 (1978), S. 469-475 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; 6-phosphogluconate dehydrogenase ; Pgd n lethal alleles ; rescue by dietary supplements ; hexose monophosphate shunt
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The genetic rescue of Pgd n lethal alleles, accomplished by combining them with mutations lacking glucose-6-phosphate dehydrogenase activity, has led to the hypothesis that Pgd n lethality may be due to the accumulation of 6-phosphogluconate. In this article we report the rescue of Pgd n /Y males by dietary supplements (fructose and linolenate) designed to minimize 6-phosphogluconate production.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484212
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  • 86
    Digitale Medien
    Digitale Medien
    Biochemical properties of esterase 6 in Drosophila melanogaster (1979)
    Springer
    Biochemical genetics 17 (1979), S. 1-22 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; esterase 6 ; allozymes ; biochemical properties
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Biochemical properties of esterase 6 in Drosophila melanogaster were investigated using partially purified preparations from three genotypes, 1/1, 1/2, and 2/2. The molecular weight of the enzyme is estimated to be about 90,000, and treatment with sodium dodecylsulfate cleaves the enzyme into four units with a molecular weight of about 22,000. The activity toward 28 naturally occurring esters was assayed and shown to vary considerably with substrate, the 1/1 preparation having in general higher activity than 1/2 and 2/2, which were very similar. Heat sensitivity, the effect of metal ions, and the effects of the presence or absence of an end product were also studied. The differences demonstrated between allozymes would allow considerable scope, under appropriate conditions, for differential selection to operate between genotypes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484470
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  • 87
    Digitale Medien
    Digitale Medien
    Properties of the two common electrophoretic variants of phosphoglucomutase in Drosophila melanogaster (1979)
    Springer
    Biochemical genetics 17 (1979), S. 825-836 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; phosphoglucomutase ; polymorphism ; enzyme kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Phosphoglucomutase (PGM) of adult stage in Drosophila melanogaster has been characterized by gel filtration, ion-exchange chromatography, and isoelectric focusing. The two common electrophoretic variants, PGMA and PGMB, differ with respect to their kinetic and stability parameters. PGMA is more thermostable than PGMB but shows the same pH optimum, equal dependence on Mg2+, and identical molecular weight. There is no significant kinetic difference between the two allozymes at the optimum pH value, but at pH 6.0 the K m value for glucose-1,6-diphosphate of PGMB is significantly higher than that of PGMA. This difference might explain the observed selective advantage of the Pgm A allele in population studies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00504306
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  • 88
    Digitale Medien
    Digitale Medien
    Biological role of alcohol dehydrogenase in the tolerance of Drosophila melanogaster to aliphatic alcohols: Utilization of an ADH-null mutant (1976)
    Springer
    Biochemical genetics 14 (1976), S. 989-997 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; alcohol dehydrogenase ; enzyme biological activity ; toxicity of alcohols
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The toxicity of the first eight primary alcohols and of four secondary alcohols was compared in a wild-type strain (having active ADH) and an ADH-negative mutant. Differences between lc 50 measured in the two strains allowed an evaluation of the biological activity of the enzyme. In vitro, ADH is mainly active on secondary alcohols, while in vivo its main role is the detoxification and metabolism of ethanol. These observations suggest that originally ADH was involved in unknown metabolic pathways and that its utilization in ethanol metabolism could be a recent event.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00485131
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  • 89
    Digitale Medien
    Digitale Medien
    Preparation of specific antisera to Drosophila acid phosphatase without rigorous protein purification (1976)
    Springer
    Biochemical genetics 14 (1976), S. 237-243 
    Details
    ISSN: 1573-4927
    Schlagwort(e): null alleles ; antibody purification ; Drosophila melanogaster ; immunological methods
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Extracts from an acid phosphatase CRM− null mutant of Drosophila melanogaster were used to eliminate contaminating antibodies in a nonspecific preparation of anti-acid phosphatase serum. This method of producing specific antisera makes unnecessary the rigorous purification of an antigen prior to immunization attempts in those cases where CRM− null mutants of the antigen are available. Antisera so prepared could be used for a wide variety of purposes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484763
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  • 90
    Digitale Medien
    Digitale Medien
    Association and the Adh locus with a lethal factor (l(2) Stm) in Drosophila melanogaster (1976)
    Springer
    Biochemical genetics 14 (1976), S. 299-308 
    Details
    ISSN: 1573-4927
    Schlagwort(e): allozymes ; alcohol dehydrogenase ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Keeping Drosophila cultures at 28 C results in elimination of all minor multiple ADH bands, thought to be due to conformational change. Thus in diploid and triploid adults heterozygous for the Adh F and Adh Salleles, relative staining intensities are found for the three bands which were in conformity with the assumption that both alleles are equally expressed. Among all polymorphic strains derived from natural Central European and Mediterranean populations, the strain +Tüb is unique in that its Adh Fallele is closely linked to a new recessive lethal factor, named 1(2)Stm. All Adh F 1/AdhF 1 pupae are unable to emerge, and die. The lethal effect is obvious 50 hr earlier by retarded eye, bristle, and body wall pigmentation. Although all pupae of the phenotype F die, Adh F allele frequency scarcely seems to be lowered in this natural population.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484769
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  • 91
    Digitale Medien
    Digitale Medien
    Further evidence of thermostability variation within electrophoretic mobility classes of enzymes (1976)
    Springer
    Biochemical genetics 14 (1976), S. 383-387 
    Details
    ISSN: 1573-4927
    Schlagwort(e): allozymes ; thermostability ; alcohol dehydrogenase ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Two Drosophila melanogaster strains, each heterozygous for “fast” and “slow” alleles at the Adh locus, and each having balanced second chromosomes, were found to differ in the apparent thermostability of the slow allozyme. The two strains were crossed, and F1heterozygotes were separated on the basis of the origin of the slow allele. After electrophoresis, the cellulose acetate strips were treated 1 1/2 min at 35 C. The putatively more sensitive allozyme showed a strikingly greater response to heat. These findings further support the conclusion that electrophoretically cryptic allelic differences exist which are expressed in thermostability differences. Further application of this approach has revealed one similar sensitive slow allozyme and three cases of a relatively resistant fast ADH allozyme in wild-caught flies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484776
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  • 92
    Digitale Medien
    Digitale Medien
    Demonstration of 6-phosphogluconolactonase activity in Drosophila melanogaster using a null allele of 6-phosphogluconate dehydrogenase (1978)
    Springer
    Biochemical genetics 16 (1978), S. 1023-1029 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; 6-phosphogluconolactonase ; hexose monophosphate shunt ; Pgd n Zw n mutants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Using a double mutant strain, Pgd n Zw n , we have developed an assay for 6-phosphogluconolactonase activity and have demonstrated its occurrence in adult Drosophila melanogaster.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00483752
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    Digitale Medien
    Digitale Medien
    Enumeration of Drosophila form II DNA-dependent RNA polymerase initiation sites on Drosophila DNA (1979)
    Springer
    Biochemical genetics 17 (1979), S. 97-104 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; form II RNA polymerase initiation sites ; chromomeres
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The in vitro incorporation of γ-32P-labeled nucleoside triphosphates into RNA by Drosophila melanogaster form II RNA polymerase from template sites which afford protection from the initiation inhibitor, polyriboinosinic acid (poly [I]), is used as a method for enumerating a specific class of transcription initiation sites on D. melanogaster DNA. Such sites number about 4000 per haploid genome for D. melanogaster. This value is in good agreement with the number of functional genetic units in the D. melanogaster genome as determined by classical cytogenetics.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484476
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    Digitale Medien
    Digitale Medien
    Purine transport by Malpighian tubules of pteridine-deficient eye color mutants of Drosophila melanogaster (1979)
    Springer
    Biochemical genetics 17 (1979), S. 565-573 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; Malpighian tubules ; purine transport ; eye color mutants ; riboflavin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Uptakes of guanine into Malpighian tubules of wild-type Drosophila and the eye color mutants white (w), brown (bw), and pink-peach (p p) have been compared. Tubules for each of these mutants are unable to concentrate guanine intracellularly. The transport of xanthine and riboflavin is also deficient in w tubules. The transport of guanosine, adenine, hypoxanthine, and guanosine monophosphate is similar in wild-type and white Malpighian tubules. These data and other information about these mutants make it likely that these pteridine-deficient eye color mutants do not produce pigments because of the inability to transport a pteridine precursor. This view supports the hypothesis that mutants which lack both pteridine and ommochromes do so because precursors to both classes of pigments share a common transport system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00498891
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Variants of α-glycerophosphate dehydrogenase in diploids and triploids of Drosophila melanogaster (1975)
    Springer
    Biochemical genetics 13 (1975), S. 263-271 
    Details
    ISSN: 1573-4927
    Schlagwort(e): allozymes ; α-glycerophosphate dehydrogenase ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract On the basis of band staining intensities in electrophoretic runs of single flies homozygous and heterozygous for two alleles at the autosomal locus for GPDH, F allele activity is believed to be 8% lower than S allele activity. Indeed, the intensity distribution in the patterns of FSS and FFS triploid females shows that both are not equally expressed. On a per fly or live weight basis, females with two and three doses of the Gpdh gene show bands with equal staining intensity, thus exhibiting a dosage effect when GPDH activity is estimated on a per cell basis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00486021
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Variation between electrophoretically identical alleles at the alcohol dehydrogenase locus in Drosophila melanogaster (1975)
    Springer
    Biochemical genetics 13 (1975), S. 721-731 
    Details
    ISSN: 1573-4927
    Schlagwort(e): Drosophila melanogaster ; enzyme variation ; alcohol dehydrogenase ; electrophoretically identical alleles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A new variant of alcohol dehydrogenase (ADH 71k) was found in a laboratory stock of Drosophila melanogaster. ADH in this stock had the same electrophoretic mobility as the F variant both on acrylamide and on agar. Activity levels were similar to the levels in F flies at temperatures between 15 and 25 C. But while ADH F enzyme is inactivated rapidly at 40 C, ADH 71k is still active. Also, ADH S is not inactivated at this temperature, but has a far lower activity per fly than ADH 71k. Genetic analysis showed that the new variant is an allele of the Adh locus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484929
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Isozyme variability in species of the genus Drosophila. VIII. The alcohol dehydrogenase polymorphism in north carolina populations of D. melanogaster (1976)
    Springer
    Biochemical genetics 14 (1976), S. 47-58 
    Details
    ISSN: 1573-4927
    Schlagwort(e): electrophoresis ; alcohol dehydrogenase ; Drosophila melanogaster ; isozymes ; genetic variation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Adult Drosophila melanogaster flies collected from populations broadly dispersed over ecological and geographic strata of North Carolina, and over a period of 4 years, were analyzed for alcohol dehydrogenase phenotypes by gel electrophoresis. Gene frequencies in spring-summer-fall field collections were remarkably stable over all strata. Two winter collections exhibited contrasting gene frequency changes. In one case the results are interpreted in terms of long-distance migration from Florida, while the other is explicable by assignment of a causal role to environmental factors which accompany the winter season.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484872
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Heat stability studies at the α-glycerophosphate dehydrogenase locus in populations of Drosophila melanogaster (1978)
    Springer
    Biochemical genetics 16 (1978), S. 769-775 
    Details
    ISSN: 1573-4927
    Schlagwort(e): hidden variation ; α-GPDH ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The level of hidden variation in populations of Drosophila melanogaster at the Gpdh + locus was determined by thermal stability studies of the protein. The results indicate a lack of variation using these methods both in and between the two common electrophoretic variants. It is suggested that α-GPDH is conserved in primary structure, which may be related to its critical role in flight muscle metabolism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484734
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Mutagenesis at the cinnabar locus in Drosophila melanogaster (1978)
    Springer
    Biochemical genetics 16 (1978), S. 855-865 
    Details
    ISSN: 1573-4927
    Schlagwort(e): kynurenine hydroxylase ; cinnabar locus ; EMS mutagenesis ; Drosophila melanogaster
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract A study was undertaken to isolate mutations affecting the temporal appearance of kynurenine hydroxylase in Drosophila melanogaster. Such mutations, lacking or having reduced enzyme activity at the larval or pupal stage only, could represent changes in regulatory functions. Mutagenesis was carried out using EMS. Potential mutations were isolated from mass F1 cultures. The screening of large numbers of individuals was made possible by the use of the mutant red, which allowed visual classification for the presence or absence of the enzyme at both stages. From a series of six mutagenesis experiments 111,561 chromosomes were tested, and 122 phenotypically mutant F1 individuals were found. From these, 38 inheritable mutations were isolated which, by phenotypic observation, lacked or had reduced enzyme activity at the larval and pupal stages. Assay of enzyme activity levels in several of the mutants confirmed the phenotypic data. All of the 27 mutations that could be tested further are recessive and behave as cinnabar alleles. Complementation tests were performed between these 27 mutant stocks, and no complementation in the production of eye color has been seen between the mutants examined. When extended collection periods were used, a significantly higher percentage of inheritable mutations was isolated from the first 3 days of the screen. Over 80% of the F1 phenotypic mutants could be classified as mosaics, which indicates that cinnabar can be autonomous under certain conditions. The failure to isolate mutations in possible regulatory function is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00483738
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Isolation and biochemical analysis of a temperature-sensitive scarlet eye color mutant of Drosophila melanogaster (1979)
    Springer
    Biochemical genetics 17 (1979), S. 149-158 
    Details
    ISSN: 1573-4927
    Schlagwort(e): xanthommatin synthesis ; scarlet mutants ; Drosophila melanogaster ; temperature-sensitive mutants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Six new EMS-induced scarlet mutants were selected. Four of these were partially pigmented, with xanthommatin levels ranging from 12% to 45% of normal. In one (st 754ts), pigment production was temperature sensitive; the level of xanthommatin changed from less than 10% of normal at 29 C to more than 70% at 18 C. In all of the new mutants tested, the level of early pupal 3-hydroxykynurenine was as low as low as that in st 1. Thus reduced larval accumulation of this metabolite also appears to be a characteristic feature of scarlet mutants. Temperature-pulse and temperature-shift experiments were carried out with st 754ts to determine the temperature-sensitive period for the scarlet gene during development. The major sensitive period commenced prior to the onset of pigmentation and was over before adult emergence. Thus the initiation of xanthommatin synthesis is not brought about by the activation of the scarlet gene. In similar experiments carried out with a temperature-sensitive white mutant (w bl), a similar temperature-sensitive period was obtained.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00484480
    Standort Signatur Erwartet Verfügbarkeit
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