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  • Ultrastructure  (94)
  • pharmacokinetics  (41)
  • Evolution
  • Springer  (146)
  • MDPI Publishing
  • PANGAEA
  • 1995-1999
  • 1975-1979  (146)
  • 1978  (146)
Collection
Keywords
Publisher
  • Springer  (146)
  • MDPI Publishing
  • PANGAEA
Years
  • 1995-1999
  • 1975-1979  (146)
Year
  • 1
    Electronic Resource
    Electronic Resource
    Coquille de l'oeuf de caille: Étude ultrastructurale et cristallographique (1978)
    Springer
    Calcified tissue international 25 (1978), S. 145-159 
    Details
    ISSN: 1432-0827
    Keywords: Bird egg shell ; Ultrastructure ; Calcification ; Electron diffraction ; Microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The egg-shell of Japanese quail was studied by several techniques. Semithin sections (1μm thick) of non-decalcified shell were observed by normal and polarized light microscopy. Thin sections of non-decalcified shell, examined by transmission electron microscopy, permitted us to observe the forms and dimensions of crystals of calcite within different layers of the shell: mammilary layer, layer of cones, palissade layer and surface crystal layer. There appears to be two distinct zones in the layer of cones as well as in the superficial crystal layer. Electron microdiffraction revealed the orientation of calcite crystals in the columns. Some crystal defects (twins?) were described and the possibility of their artefactual formation during ultramicrotomy is discussed. Localization of Ca, Mg, P and S were made by X-ray microanalysis of semithin sections. This technique shows that shell membranes, and chiefly the true cuticle, are also mineralized but, in these layers, minerals are not crystallized. Otherwise the distribution of Mg is not uniform throughout the shell thickness; it is less concentrated in the external zone of the layer of cones. These results together with observation of developing shells by scanning electron microscopy allowed us to propose a scheme for shell organization of the quail egg. This organization was related with decalcification which occurs during hatching.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02010763
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  • 2
    Electronic Resource
    Electronic Resource
    Amino acid-directed nucleic acid synthesis (1978)
    Springer
    Journal of molecular evolution 11 (1978), S. 109-120 
    Details
    ISSN: 1432-1432
    Keywords: Origin of Life ; Genetic code ; Protein synthesis ; Evolution ; Prebiotic reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fact that proteins contain onlya-amino acids and that protein structure is determined by 3′ → 5′ linked ribonucleotides is postulated to be the result of the copolymerization of these molecules in the prebiotic environment. Ribonucleotides therefore represent partial degradation products and proteins represent a side reaction developing from copolymerization. The basic structural unit of copolymerization is a nucleotide substituted with an amino acid at the 2′ position. Characteristics of modern amino and ribonucleic acid structure are all consistent with and necessary for this hypothesis. The characteristics and individual base assignments of the code also provide strong support for origin from the postulated copolymers. All characteristics of the code can be accounted for by this single hypothesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733887
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  • 3
    Electronic Resource
    Electronic Resource
    A measure of the denseness of a phylogenetic network (1978)
    Springer
    Journal of molecular evolution 11 (1978), S. 225-231 
    Details
    ISSN: 1432-1432
    Keywords: Phylogenetic denseness ; Phylogenetic trees ; Topology ; Molecular reconstructions ; Evolution ; Paleogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The concept of phylogenetic denseness bears critically on the accuracy of evolutionary pathways inferred from experimentally sequenced proteins isolated from extant species. In this paper I develop an objective measure,ρ, of denseness to supplement previous intuitive concepts and which permits one to use this concept in comparing the quality of different evolutionary reconstructions. This measure is used to examine several published phylogenetic trees: insulin, a-hemoglobin,β-hemoglobin, myoglobin, cytochromec, and the parvalbumin family. The paper emphasizes 1) the importance of denseness in accurately estimating the number of nucleotide replacements which separate homologous sequences when this estimation is made by the method of parsimony, 2) the value of this concept in assessing the quality of those estimates, and 3) the use of this concept as a biologically practical heuristic method for identifying poorly studied regions in a phylogenetic tree, whether or not the tree was obtained by the parsimony method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01734483
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  • 4
    Electronic Resource
    Electronic Resource
    Are extreme halophiles actually “bacteria”? (1978)
    Springer
    Journal of molecular evolution 11 (1978), S. 1-8 
    Details
    ISSN: 1432-1432
    Keywords: Halobacteria ; Archaebacteria ; Phylogeny ; 16S rRNA catalog ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Comparative cataloging of the 16S rRNA ofHalobacterium halobium indicates that the organism did not arise, as a halophilic adaptation, from some typical bacterium. Rather,H. halobium is a member of the Archaebacteria, an ancient group of organisms that are no more related to typical bacteria than they are to eucaryotes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01768019
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  • 5
    Electronic Resource
    Electronic Resource
    Relationship between gene function and gene location inEscherichia coli (1978)
    Springer
    Journal of molecular evolution 11 (1978), S. 47-56 
    Details
    ISSN: 1432-1432
    Keywords: Genome duplication ; Genome topography ; Evolution ; Gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Genes ofEscherichia coli were grouped according to the “biochemical relatedness” of the enzymes they specifiy, using two schemes to determine relatedness: similarity of reaction or similarity of reactants. The tendency of biochemically related genes as so defined to lie approximately 90° or 180° from one another on the circular genetic map was analyzed statistically. Of the classes analyzed, only the genes for the enzymes of glucose catabolism showed a significant departure from random distribution in this respect. The glucose catabolism genes showed a pronounced tendency to lie either 90° or 180° from one another (P = ca. 10−9), and, furthermore, most of these genes were found to lie in only four gene clusters on theE. coli genome. The significance of this observation is discussed in relation to evolutionary mechanisms and to mechanisms of gene expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01768024
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  • 6
    Electronic Resource
    Electronic Resource
    The asymmetry of life (1978)
    Springer
    Journal of molecular evolution 11 (1978), S. 313-332 
    Details
    ISSN: 1432-1432
    Keywords: Evolution ; Optical activity ; Photolysis ; Circularly ; polarized radiation ; Selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Stereoselective physical phenomena and their possible importance for the prevalence of D-sugars and L-aminoacids in living matter are reviewed. A classification is presented according to which a selective force provides a microscopic or macroscopic selection depending on its generality when taken over a macrosystem (a ‘unitary biosphere’ such as the Earth). The microscopic ‘selections’ are not genuine selections because the final sense of asymmetry is here determined by chance, in other words the initial choice is ‘random’, while it is ‘directed’ in the macroscopic selection. Two macroscopic selections appear possible: 1. selection due to an intrinsic energy difference between enantiomorph configurations, 2. selection accomplished by elliptically polarised radiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733840
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  • 7
    Electronic Resource
    Electronic Resource
    Étude en microscopie électronique et par cytophotométrie à balayage de la structure et de la distribution de la chromatine dans les noyaux des cellules cartilagineuses deTriturus cristatus âgés au cours de la régénération (1978)
    Springer
    Development genes and evolution 184 (1978), S. 195-211 
    Details
    ISSN: 1432-041X
    Keywords: Ultrastructure ; Scanning cytophotometry ; Chromatin ; Chondrocytes ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les cellules cartilagineuses des membres postérieurs deTriturus cristatus en régénération après amputation, ont été étudiées en microscopie électronique et par cytophotométrie à balayage. Nous nous sommes intéressés à la structure et à la distribution de la chromatine mais aussi à différents organites cytoplasmiques. Dans l'étude de cytophotométrie à balayage, la chromatine a été considérée à travers son constituant majeur, l'ADN, coloré par la réaction de Feulgen. Au cours de la régénération du membre, l'hétérochromatine initialement condensée, essentiellement accolée à la membrane nucléaire se décondense. Les vacuoles du cytoplasme, caractéristiques des animaux âgés par rapport aux animaux jeunes, disparaissent, les mitochondries et le reticulum endoplasmique rugueux deviennent plus abondants. Les caractéristiques nucléaires de l'activation cellulaire apparaissent précocement, précédent les modifications cytoplasmiques et conduisent à des cellules en tous points identiques aux cellules d'animaux jeunes en dehors de tout processus régénératif. Cette phase d'euchromatisation et de restructuration cytoplasmique est peut-être nécessaire à l'accroissement d'activité métabolique et à la division cellulaire qui suivent. Son déroulement peut expliquer tout au moins le ralentissement de la régénération observé chez les animaux âgés par rapport aux animaux jeunes.
    Notes: Summary Cartilaginous cells of aged newts (Triturus cristatus) were studied during hind limb regeneration. The electron microscope was used to study the structure and distribution of chromatin in the cell nuclei, while the DNA content of the chromatin was measured by means of a scanning cytophotometer. Changes in the ultrastructure of the cytoplasm during regeneration were also studied. It was observed that the structure and distribution of chromatin in the activated cell is greatly modified. In the non-activated cell of the aged newt, the chromatin is found highly condensed and distributed peripherally close to the nuclear membrane. In contrast, in the activated cells, the chromatin is much less condensed and is distributed throughout the nucleus. Moreover, cytoplasmic vacuoles, found only in the non-activated aged cells, disappear and an increase in the mitochondria and rough endoplasmic reticulum is also observed. Changes in the nuclear structure are observed prior to the cytoplasmic modifications. It is interesting to note that the process of activation induces structural changes in the aged cells which make these cells appear to be structurally identical to the young cells. This process of rejuvenation takes 3–5 days in the newt. We suggest that these structural changes of the chromatin and cytoplasm in the aged cells are necessary to increase the metabolic activity which precedes cell division. It may also explain why regeneration takes a longer time in the aged animals than in the young ones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848254
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  • 8
    Electronic Resource
    Electronic Resource
    Retention of the differentiated state by larvalXenopus liver cells in primary culture (1978)
    Springer
    Development genes and evolution 185 (1978), S. 235-248 
    Details
    ISSN: 1432-041X
    Keywords: Liver ; Primary culture ; Ultrastructure ; Albumin synthesis ; Xenopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Electron microscopic analysis of primary cultures derived from larvalXenopus liver has shown that these cells, although they form only two-dimensional aggregates, retain and presumably also develop structural characteristics typical of liver parenchyma cells, such as bile canaliculi with microvilli and epithelial junctional complexes. As judged from structural criteria, primary cultures contain 80–90% hepatocytes. In contrast to the intact tissue, primary cultures showed excessive development of microfilaments, however. Incorporation of labeled amino acids has revealed further that the capacity for protein synthesis is maintained in culture and that synthesis of liverspecific protein albumin is maintained in vitro, even in liver cultures derived from thyrostatic tadpoles. This latter result suggests that initiation of albumin synthesis in the larval liver is probably not dependent upon thyroid hormones but rather reflects the protodifferentiated state of this tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848354
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  • 9
    Electronic Resource
    Electronic Resource
    Ultrastructure, histology, and innervation of the mantle edge of the freshwater pulmonate snailsLymnaea stagnalis andBiomphalaria pfeifferi (1978)
    Springer
    Calcified tissue international 26 (1978), S. 271-282 
    Details
    ISSN: 1432-0827
    Keywords: Shell formation ; Free nerve endings ; Ultrastructure ; Lymnaea stagnalis ; Biomphalaria pfeifferi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The mantle edge of the freshwater pulmonate snailsLymnaea stagnalis andBiomphalaria pfeifferi was investigated with histochemical and ultrastructural methods. The mantle edge gland, which is involved in shell formation, consists of the periostracal groove and the belt. This belt appears to be composed of various regions. In the area of the periostracal groove a number of subepithelial gland cell types occur; these release their products into the groove. Between the groove cells ciliated free nerve endings terminate; the corresponding perikarya occur in the subepidermal connective tissue. Also in the posterior belt region free nerve endings were observed between the epithelial cells; in addition, a particular type of subepithelial gland cell was found in this area. The epithelial cells of this part of the belt have the ultrastructural characteristics of ion and water transporting cells; they are probably involved in calcium deposition and resorption. The possible role of the free nerve endings and of the subepithelial gland cells is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02013270
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  • 10
    Electronic Resource
    Electronic Resource
    The disposition kinetics of diazepam in pregnant women at parturition (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; pharmacokinetics ; pregnant women ; plasma clearance ; blood/plasma concentration ratio ; placental transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of diazepam has been studied in pregnant women at parturition. The plasma concentration of diazepam was monitored for at least 3 days in 18 women who received a single intravenous injection of 10 mg during the 10 h-period prior to delivery. Fourteen mothers had uneventful puerperia (Group I) and in 13 of these cases there was a pronounced postnatal increase in the plasma concentration of diazepam. The terminal phase half-life (t1/2) was significantly greater for Group I (mean = 65 h; range = 24–114 h) than for age-matched non-pregnant patients (mean = 29 h; range = 18–44 h from literature). The prolonged t1/2 appeared to be related to changes in the distribution of diazepam and not to a reduction in hepatic elimination since the total plasma clearance (Cltp) in these 14 pregnant patients (mean = 28 ml/min; range = 18–43 ml/min) was not reduced compared to that reported for non-pregnant controls (mean = 30 ml/min; range = 22–45 ml/min). Four mothers underwent postnatal surgery for tubal ligation (Group II) and the plasma concentration-time profiles for this group did not show the same postnatal phenomenon as did the profiles obtained for Group I. The t1/2 for Group II was shorter (mean = 31 h; range = 24–37 h) than for Group I and similar to that for the non-pregnant controls. The Cltp for Group II was greater (mean = 56 ml/min; range = 48–63 ml/min) than for both Group I and non-pregnant controls. These results suggest that delivery alters the disposition of diazepam and is generally associated with a postnatal re-distribution of diazepam into the systemic circulation. The blood/plasma concentration ratio was determined in 9 patients (mean = 0.62; range = 0.54–0.77). There was no difference in the total blood clearance between the pregnant patients of Group I and the non-pregnant controls. In most cases the umbilical venous plasma concentration (Cpuv) of diazepam was greater than the peripheral maternal venous plasma concentration (Cpmv) at delivery. The foetus appears to constitute a slowly equilibrating tissue-group in which diazepam does not reach equilibrium with the maternal systemic circulation for at least 5–10 h at which time the diazepam concentration in maternal and foetal plasma is similar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716363
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  • 11
    Electronic Resource
    Electronic Resource
    Bioavailability of p-chlorophenoxyisobutyric acid (clofibrinic acid) after repeated doses of its calcium salt to humans (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606682
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  • 12
    Electronic Resource
    Electronic Resource
    Metabolism of phenazone in man after hydrocortisone administration (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 69-72 
    Details
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; hydrocortisone ; elimination rate ; distribution volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a high plasma concentration of hydrocortisone on the metabolism of phenazone in humans has been studied. Two series of experiments were carried out, Group A to demonstrate any enzyme-inducing effect of hydrocortisone, and Group B to study the immediate effect of hydrocortisone on the metabolism of phenazone. 9 subjects (Group A) received a total 250–400 mg hydrocortisone i.m. twice daily for three days and the 24-hour elimination of phenazone was studied before and afterwards. In a further 5 subjects (Group B) the elimination of phenazone was examined during administration of hydrocortisone or placebo. The elimination rate and the apparent volume of distribution of phenazone remained unchanged under both experimental conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606685
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  • 13
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and side-effects of clonidine (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 97-101 
    Details
    ISSN: 1432-1041
    Keywords: Clonidine ; plasma level ; pharmacokinetics ; steady state ; urinary excretion ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single oral dose of clonidine 300 µg was administered to 8 healthy, normotensive subjects and the time course of its plasma concentrations was followed for 24 h. The plasma concentration of clonidine rose to a peak of 1.17±0.12 ng/ml at about 2 h: the absorption half-life was 0.6±0.2 h. Elimination followed first order kinetics with a half-life of 7.7±2.0 h. The correlation between the two most common side-effects of clonidine, sedation and dryness of the mouth, with the time course of its plasma concentrations was highly significant, p〈0.01. All the subjects complained of severe sedation. During continuous administration of clonidine (75 µg t.i.d.) for one week a steady state serum level of 0.30–0.35 ng/ml was achieved. One 75 µg tablet of clonidine raised the serum level to about 0.69±0.13 ng/ml in two hours. After cessation of dosing, the serum level declined with a half-life of 7.5±1.5 h. The urinary excretion of unchanged clonidine was found to be about onethird of the administered dose in 24 h during continuous administration and in the first 24 h after the single oral dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609752
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  • 14
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 203-212 
    Details
    ISSN: 1432-1041
    Keywords: Mepivacaine ; pharmacokinetics ; neonates ; healthy adults ; metabolism ; renal excretion ; lignocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of mepivacaine has been studied in premature neonates dosed subcutaneously and in healthy adults dosed intravenously. The pharmacokinetics of mepivacaine in four neonates (N) was compared with that in six adults (A). Newborns had a significantly longer terminal phase half-life than adults (N mean 8.69 h; A mean 3.17 h). Total plasma clearance normalized on body weight was significantly smaller in neonates (mean 2.34 ml/min/kg) than in adults (mean 5.47 ml/min/kg), as was the hepatic blood clearance (N mean 1.37 ml/min/kg; A mean 5.10 ml/min/kg). The renal plasma clearance, however, was significantly greater in neonates (mean 0.76 ml/min/kg) than adults (mean 0.20 ml/min/kg). There was an average six-fold increase in the fraction of the dose excreted unchanged in newborns (mean 43.3%) compared to adults (mean 7.1%) with acidified urine (pH 5.5–6.0). There was significantly more of the mono-N-demethylated metabolite of mepivacaine excreted by newborns (mean 11.4%) than by adults (mean 2.2%), but their capacity to carry out aromatic hydroxylation of mepivacaine was negligible. These results for mepivacaine were compared with those previously reported for lignocaine in premature infants. The immaturity of hepatic function appears to have diminished more profoundly the ability of premature infants to metabolize mepivacaine than lignocaine. These findings are discussed in terms of perfusion theory of hepatic drug elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02089961
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of high-dose methotrexate treatment in children (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 143-147 
    Details
    ISSN: 1432-1041
    Keywords: Children ; leukemia ; high-dose methotrexate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous high-dose methotrexate were studied in two groups of children being treated for malignant diseases, mostly acute lymphatic leukemia. The peak serum level of methotrexate of 2.32·10−5 mol/l was found in children given 500 mg methotrexate/m2 by a 24 h infusion, and another group given 2790 mg/m2 during a 6 h infusion had serum levels as high as 2.16·10−4 mol/l. The decay of serum concentration of methotrexate after completion of the infusion followed a diphasic curve, with an initial serum half-life of 4.8 h, followed by a second half-life of 34.4 h at distribution equilibrium. The apparent volume of distribution was 56.8 litres/m2. Significant levels of methotrexate were found in cerebrospinal fluid, but penetration into cerebrospinal fluid was slow. Urinary excretion of methotrexate was considerable. Four to five days after commencement of the infusion, urinary concentrations of methotrexate still exceeded the serum levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607446
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  • 16
    Electronic Resource
    Electronic Resource
    Binding of drugs to human muscle (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 335-340 
    Details
    ISSN: 1432-1041
    Keywords: Drug binding to muscle ; interindividual differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Binding of 22 drugs to human muscle tissue has been determined by ultrafiltration. All drugs tested were bound, the bound fraction ranging from 13% (aminophenazone) to 〉98% (desipramine). Both linear and nonlinear binding was observed. For chemically related substances, binding to muscle tissue correlated with plasma binding and lipid solubility. There were significant differences in binding to muscle from different individuals. With respect to pharmacokinetics of drugs, it is suggested that binding to muscle tissue may be at least as important as plasma binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00611903
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  • 17
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of furosemide in anephric patients and in normal subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 41-48 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; pharmacokinetics ; anephric patients ; metabolism ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min · kg and 2.96 ml/min · kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDss. In the patients, but not in the normal subjects, there was a significant positive correlation between $$V_{D_{ss} } $$ and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoylanthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606681
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  • 18
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 29-33 
    Details
    ISSN: 1432-1041
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
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    Pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. 11 etidocaine (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 365-371 
    Details
    ISSN: 1432-1041
    Keywords: Etidocaine ; pharmacokinetics ; metabolism ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary elimination of etidocaine and several of its metabolites was investigated in neonates whose mothers had received one or more doses of etidocaine during labour. The urine collection period ranged among the neonates from 21.4 to 47.0 h post-partum. The total amounts of etidocaine and its metabolites recovered in neonatal urine represented a mean of 0.12 per cent of the maternal dose. Some differences in the pattern of urinary metabolites were observed between neonates and adults. Mean half-life of elimination of etidocaine calculated from sigma-minus plots of the neonatal urinary data was 6.42 h. This is greater than that previously reported following intravenous administration of etidocaine to adults (2.6 h). The slower rate of elimination in neonates is probably due to an increased neonatal volume of distribution since there is evidence to show that etidocaine is extensively metabolised by the neonate.
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  • 20
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    Influence of bed rest on the pharmacokinetics of phenazone (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 379-383 
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    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; phenzone ; posture ; immobilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of phenazone was studied in six subjects while ambulant and during bed rest for 3 days. Elimination of the drug was followed for 12 h after oral and intravenous administration. The elimination rate constant and total body clearance were significantly increased during bed rest as compared to the ambulant period, but the differences were small. The apparent volume of distribution decreased significantly. No consistent change due to bed rest was found in the rate of absorption or bioavailability of the oral dose.
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    URL: http://dx.doi.org/10.1007/BF00644612
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  • 21
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    Paracetamol (acetaminophen) kinetics in patients with Gilbert's syndrome (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 209-212 
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    ISSN: 1432-1041
    Keywords: Paracetamol ; acetaminophen ; Gilbert's syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of paracetamol after intravenous and oral administration has been studied in 6 patients with Gilbert's syndrome, and 6 healthy controls. Paracetamol clearance was significantly less in the patients (255 ml/min SE±23 ml/min) than in the normal subjects (352 ml/min SE±40 ml/min). Moreover, whilst paracetamol concentrations declined monoexponentially in the patients, the decline was biexponential in the controls. No difference in the bioavailability of 500 mg paracetamol given orally was observed between the two groups. The results suggest that not only is paracetamol elimination impaired in Gilbert's syndrome, but that its distribution kinetics are also abnormal. Both these findings could be attributed to a decrease in hepatic glucuronyl transferase activity.
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  • 22
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    Output of14CO2 in breath after oral administration of (14C-methyl) aminopyrine in hepatitis, cirrhosis and hepatic bilharziasis: Its relationship to aminopyrine pharmacokinetics (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 223-229 
    Details
    ISSN: 1432-1041
    Keywords: Aminopyrine ; pharmacokinetics ; 14CO2 breath test ; hepatic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of aminopyrine in plasma and of14CO2 in breath was determined for 6 hours after oral administration of (14C-methyl) aminopyrine to healthy controls and to patients with hepatitis and hepatic fibrosis, cirrhosis and hepatic bilharziasis.14CO2 in breath declined about 1.8 times more slowly than aminopyrine plasma levels, which suggests the occurrence of metabolite demethylation. This was confirmed by the slow elimination of14C from plasma, the formation of14CO2 after aminopyrine had disappeared and the presence of a considerable amount of monomethyl-aminopyrine in plasma. The mean14CO2 concentration in breath was correlated with but was not proportional to aminopyrine clearance, which was attributed to individual differences in aminopyrine half-life. Both a correlation and proportionality were found when14CO2 extrapolated to zero time was used as a parameter of14CO2 production. Hepatic disease affected aminopyrine clearance to a variable extent. In the hepatitis and fibrosis group, aminopyrine clearance was affected in 2 out of five subjects. In all except one cirrhotic subject aminopyrine clearance was markedly decreased. Moreover, in three out of seven cases aminopyrine absorption was impaired, presumably due to decreased gastrointestinal blood-flow. This may produce an erroneously low14CO2 concentration in breath during the first two hours after aminopyrine administration. Hepatic bilharziasis was accompanied by very low aminopyrine clearance in all four cases. In two patients high apparent Vd values were observed, probably due to “first-pass” metabolism. Patients with ascites had Vd values within normal limits.
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    Pharmacokinetics of sulfadiazine and trimethoprim in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 57-67 
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    ISSN: 1432-1041
    Keywords: Chemotherapy ; sulfadiazine ; trimethoprim ; pharmacokinetics ; acetylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual “peak” concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 µg/ml for SDZ and 0.3 to 1.1 µg/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h) – 145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 µg/ml for SDZ and from 13.8 to 93.4 µg/ml for TMP. The fraction acetylated SDZ/acetylated SDZ + SDZ was 21% during the 0–8 h period, 33% during the 8–15 h period and 41% during the 15–24 period. The average values for the notional volume of distribution, Vd, were 0.36±0.13 1/kg for SDZ and 1.39±0.25 1/kg for TMP. The average “t1/2” was 15.2±7.4 h for SDZ and 7.4±1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p〈0.01) and also between the renal clearance of the two drugs (p〈0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ Vd was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for “acetylated SDZ”. The renal clearance of “acetylated SDZ” averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.
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    Distribution, elimination and natriuretic effect of furosemide in patients with severe arterial hypertension (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 237-244 
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    ISSN: 1432-1041
    Keywords: Furosemide ; arterial hypertension ; protein binding ; sodium excretion ; renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was injected intravenously in 7 patients with severe hypertension and vascular complications. A two compartment, open model was used to describe the disappearance of the drug from serum. The mean serum clearance (Cls=1.83 ml/min · kg) was significantly reduced compared to the mean Cls-value of a group of normals (2.96 ml/min · kg). A significant correlation was found between Cls and mean blood pressure, as well as between Cls and renal clearance (mean Clr=0.83 ml/min · kg); extrapolation of the regression line yielded a Cls-value of 50 ml/min for Clr=0. The Clr was also significantly negatively correlated with mean blood pressure. Protein binding of furosemide was normal, except in one patient, who had considerable impairment of renal function. Apparently more than 90% of unchanged furosemide passed in urine was excreted by tubular transport. A highly significant negative correlation was found between Cls and the fraction of furosemide excreted as a glucuronide. During the first two hours, significantly less sodium was excreted by the patients than by a comparable group of normal subjects. The correlation between serum concentration of furosemide and the amount excreted of sodium was not significant, but highly significant correlations were found between the amounts of furosemide and sodium excreted by the kidney in 0–30 and 0–60 min. In all the individual patients an approximately linear relationship with wide variation in the slope was found between the cumulative excretion of furosemide and sodium from 0–30 min to 0–60 and to 0–120 min. After 120 min deviations were observed in the curves from 4 of the patients, which indicated that smaller and smaller additional amounts of sodium were excreted with constant additional amounts of furosemide.
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    Pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients after acute dosage (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 267-271 
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    ISSN: 1432-1041
    Keywords: Lithium ; sustained-release ; pharmacokinetics ; manic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An ordinary and a sustained-release lithium carbonate preparation were administered acutely at equivalent dosage (1.80 g=24.3 mmol) in a crossover fashion to manic patients. Serum lithium levels were determined by atomic absorption spectroscopy and pharmacokinetic parameters were calculated. Maximum mean serum levels of 1.13 mmol/l and 0.78 mmol/l were achieved at 6 h and 12 h respectively with the ordinary and sustained-release forms. The mean half-lives of absorption, redistribution and elimination were 0.78 h±0.05 (SE), 5.06 h±0.23, 26.8 h±4.5 and 3.73 h±0.37 (SE), 4.42 h±0.28 and 25.6 h±5.5 for the ordinary and sustained-release forms respectively. In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects. Lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.
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    Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 277-280 
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    ISSN: 1432-1041
    Keywords: Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.
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    Preliminary studies of the kinetics of citalopram in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 69-73 
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    ISSN: 1432-1041
    Keywords: Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.
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    Plasma timolol levels after oral and intravenous administration (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 431-434 
    Details
    ISSN: 1432-1041
    Keywords: Timolol ; pharmacokinetics ; oral and intravenous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volume of distribution was 3.5 l/k. It is suggested that timolol is little affected by the ‘first pass effect’, even though there is marked interindividual variation in availability and peak plasma level.
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    The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 143-152 
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    ISSN: 1432-1041
    Keywords: Lignocaine ; pharmacokinetics ; neonates ; metabolism ; renal excretion ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of lignocaine in premature neonates was studied after subcutaneous administration. The collection of serial urine together with a limited number of blood samples from neonates enabled simultaneous computer fitting of data to a pharmacokinetic model. The disposition kinetics of lignocaine in four neonates were compared with similar data reported for adults. Neonates had prolonged t1/2 (neonate mean: 3.16 h; adult mean: 1.80 h), and an increased total volume of distribution (neonate mean: 2.75 l/kg; adult mean: 1.11 l/kg) compared with adults. Total plasma clearance (Cltp) normalised on body weight showed no significant difference between neonates (mean: 0.610 l/h/kg) and adults (mean: 0.550 l/h/kg). The urinary excretion of lignocaine and several of its metabolites was studied in 8 neonates and 11 adults. Neonates were shown to excrete much more unchanged lignocaine (mean: 19.67%) compared with adults (mean: 4.27%) and the proportion of the dose excreted as 4-hydroxyxylidine is considerably reduced in neonates (neonate mean: 8.89%; adult mean: 63.78%). The use of the two pharmacokinetic parameters, t1/2 and Cltp, as indices of drug elimination ability are discussed.
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    Preliminary data on the pharmacokinetics of Glaziovine in man (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 219-222 
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    ISSN: 1432-1041
    Keywords: Glaziovine ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; enteral absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of Glaziovine, a pro-aporphine alkaloid with neuropharmacological properties, were investigated in healthy human volunteers. Glaziovine-14C 20 mg was administered in capsules (oral route) and in vials (i.v. route). Total radioactivity was measured in plasma, urine and faeces. When administered orally, peak plasma levels were encountered at 2 h. The cumulative urinary excretion of total radioactivity over a 24 h period was 38% after oral and 50% after i.v. administration. Investigation of metabolites in urine revealed Glaziovine glucuronide as the sole metabolite of the drug. By comparing the percentage of urinary excretion or the area under the plasma level-time curve (AUC) obtained in the first 24 hours after i.v. and oral administration, enteral absorption was found to range from 78 to 84%. Thus, glaziovine appears to show very high enteral absorption.
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    Disposition of valproic acid in patients with liver disease (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 55-60 
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    ISSN: 1432-1041
    Keywords: Valproic acid ; pharmacokinetics ; liver disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of valproic acid (di-n-propylacetate; VA) has been studied after a single oral dose of a solution of 450 mg in 7 patients with alcoholic cirrhosis and in 4 patients recovering from acute hepatitis. The diagnosis was based on biochemical function tests and histological findings. The pharmacokinetic parameters were compared with those reported for healthy volunteers. VA in therapeutic concentration (80 µg/ml) in plasma was less bound to plasma proteins in patients with alcoholic cirrhosis (70.7±11.3%) and in patients recovering from acute hepatitis (78.1±14.1%) than in controls (88.7±5.2%). The reduced binding affected the blood/plasma concentration ratio and the apparent distribution volume Vd(β); the latter was increased from the normal value of 0.14±0.05 l/kg to 0.22±0.09 (p〈0.05) in alcoholic cirrhotics, and to 0.20±0.07 (p=0.056) in patients recovering from acute hepatitis. The half-life of elimination T1/2 (β) (controls=12.2±3.7 h) was significantly (p〈0.05) prolonged in cirrhotics (18.9±5.1 h) and in patients recovering from acute hepatitis (17.0±3.7 h). The plasma $$\overline {Cl} $$ of total drug was not impaired, which can best be explained by the lower plasma protein binding, which might have increased the $$\overline {Cl} $$ of this drug which shows restricted clearance. In addition, the plasma $$\overline {Cl} $$ of free drug was significantly (p〈0.02) reduced in alcoholic cirrhotics. During a two day urine collection no measurable amount of unchanged VA was recovered. There was considerable excretion of VA-conjugates, which could be hydrolyzed either by HCl or by β-glucuronidase/arylsulphatase (4–23% of the dose). These percentages were in the same range as in normals (26.7±16.1%). The study indicates that elimination of VA is slightly impaired in patients with dysfunction of the liver.
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    Absorption of oral and intramuscular chlordiazepoxide (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 267-274 
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    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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    Model for retrospective estimation of serum levels of phenylbutazone: Application to two cases of digestive tract hemorrhage (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 439-443 
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    ISSN: 1432-1041
    Keywords: Phenylbutazone ; pharmacokinetics ; model ; retrospective analysis ; digestive-tract hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Phenylbutazone treatment can cause digestive-tract hemorrhages, but its concentration in the blood at the time of hemorrhage is generally not known. In two patients who had had digestive tract hemorrhages, the variation in the serum phenylbutazone concentration throughout treatment and just before hemorrhage was simulated by a two-compartment model based on assays (gas-liquid chromatography) made after the hemorrhage. Identification of the parameters of the model and simulation of changes in concentration during therapy suggested that the phenylbutazone level in serum at the time of hemorrhage was 101 and 125 µg/ml respectively.
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    Pharmacokinetics of a single oral dose of hydroflumethiazide in health and in cardiac failure (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 29-37 
    Details
    ISSN: 1432-1041
    Keywords: Hydroflumethiazide ; pharmacokinetics ; cardiac failure ; renal drug excretion ; metabolism ; 2,4-disulfamyl-5-trifluoro-methylaniline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydroflumethiazide (HFT) were investigated after single oral doses of 6 µmoles/ per kg body weight in five healthy subjects and in nine patients with moderate cardiac failure. HFT was excreted in urine together with 2,4-disulfamyl-5-trifluoromethylaniline (DTA), which was also present in the blood after administration of HFT. HFT and DTA were determined by TLC and spectrofluorodensitometry. Mean cumulative urinary excretion of HFT was 46.5 and 47.5 per cent of the dose both in healthy subjects and in patients. Distribution half-life (t1/2α) was about 2 h in both groups of subjects, while biological half-life (t1/2β) ranged from 12.4 to 26.9 h (mean 16.6) in healthy subjects, and from 6.3 to 13.7 h (mean 9.6) in patients. Mean renal clearance was 0.33 and 0.211 · h−1 · kg−1 in normal subjects and patients, respectively, and was almost equal to the total body clearance. HFT had a large apparent volume of distribution (Vβ), with mean values of 6.4 and 3.11 · kg−1 in normal subjects and patients. Mean cumulative urinary excretion of DTA was 1.8 and 1.9 per cent in healthy subjects and patients with cardiac failure. The apparent half-life of DTA, determined from urinary excretion rate in eleven subjects, ranged from 16 to 56 h but half-lives in three others were more than 100 h. The results indicate that HFT is partly metabolized in the body to DTA, and DTA and HFT are excreted in urine. The half-life of DTA was longer than that of the parent drug. The apparent volume of distribution, clearance and biological half-life of HFT were lower in patients with cardiac failure than in healthy subjects.
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    Pharmacokinetics of furosemide in gestosis of pregnancy (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 361-366 
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    ISSN: 1432-1041
    Keywords: Furosemide ; gestosis of pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 50 mg was administered orally and intravenously to twelve gestotic women for brief periods as a part of a randomized, multicentre clinical trial comparing the efficacy of bed rest and pharmacological treatment. The pharmacokinetic profile was investigated using a gas-liquid chromatographic technique. The plasma half-life after oral and intravenous administration was 115±37.1 and 71.8±26.3 min and plasma clearance was 153±48 and 152±23 ml/min, respectively (mean±SD). Comparative data from healthy pregnant women cannot be obtained for ethical reasons. The results show that gestosis has only a marginal if any effect on the kinetics of furosemide in comparison with published kinetic parameters in healthy volunteers and patients with renal failure. The new-born babies where checked for side effects according to a protocol in use in a larger regional surveillance programme. No clinical side-effects were attributable to furosemide, but the small size of the group does not permit any definitive conclusions about this aspect.
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    Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 281-291 
    Details
    ISSN: 1432-1041
    Keywords: Phase I clinical trial ; complex protocol ; tolerance ; pharmacokinetics ; praziquantel ; anthelmintic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1×20 mg/kg, 1×50 mg/kg, 3×10 mg/kg and 3×25 mg/kg body weight (τ=4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinicopsychological parameters and subjective comments, the largest daily dose tested (3×25 mg/kg=75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1– h, and the elimination half-life for the period 2–8 h was 1–1.5 h.
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    Bioavailability of norethindrone in human subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
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    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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    Pharmacokinetics of bendroflumethiazide in hypertensive patients (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 119-124 
    Details
    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; pharmacokinetics ; hypertension ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml−1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg−1. Non-renal clearance averaged 200 ml · min−1. The renal clearance of bft was significantly lower (p〈0.05) after 5 mg (48 ml · min−1) than after 2.5 mg bft (93 ml · min−1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.
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    Pharmacokinetics of cephacetrile in patients with normal or impaired renal function (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 445-448 
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    ISSN: 1432-1041
    Keywords: Cephacetrile ; pharmacokinetics ; renal Impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cephacetrile, administered as a single i. v. injection of 15 mg/kg, have been determined in 8 patients with normal renal function and in 12 patients with a varying degree of renal impairment. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of antibiotic in the central and peripheral compartments. In patients with normal renal function the following values were obtained for various pharmacokinetic parameters: α=3.971 h−1; β=0.343 h−1; K12=1.745 h−1; K21=0.763 h−1; Kel=1.793 h−1; Vc=8.181; Vp=18.401 and Vdss=26.581. Cephacetrile had some of the highest apparent distribution volumes of all the cephalosporins. Impaired renal function significantly affected α, β, K12, and Kel. A linear relationship between Kel of cephacetrile and creatinine clearance was demonstrated. The elimination of cephacetrile in anuric patients was about ten times slower than in patients with normal renal function.
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  • 40
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    Rate of drug metabolism in man measured by14CO2-breath analysis (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 293-299 
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    ISSN: 1432-1041
    Keywords: Breath analysis ; 14CO2 exhalation ; drug metabolism ; glycodiazine ; liquid chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Exhalation of14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of14C-demethylation breath tests. In particular, they are consistent with the hypothesis that14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.
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  • 41
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    Elimination of hexamethylene diisocyanate cross-linked polypeptides in patients with normal or impaired renal function (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 405-412 
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    ISSN: 1432-1041
    Keywords: Colloidal plasma substitutes ; cross-linked polypeptides ; Haemaccel® ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Infusions of 3.5% isocyanate cross-linked polypeptide solution 500 ml were given to 52 patients with normal or impaired renal function: glomerular filtration rate (GFR)=0–133 ml/min. The serum concentration and urinary excretion of hydroxyproline were measured and the equivalent polypeptide concentrations were calculated from the results. In patients with normal renal function (GFR〉90 ml/min) the proportion of polypeptide excreted in the urine up to 12 h was 45.4±2.6% ( $$\bar X$$ ±SEM), up to 24 h 47.7±2.9% and up to 48 h 49.3±3.4%. In patients with moderate renal insufficiency (GFR=30–90 ml/min) there was no decrease in polypeptide excretion and even in patients with more serious impairment of GFR (11–30 ml/min) 48-h urinary polypeptide excretion was still 40.6±5.9%. In patients with GFR of 2–10 ml/min polypeptide excretion fell to 10.7±3.2% during the first 12 h, although there was an increase in later collection periods as compared to patients with normal renal function −19.9±3.9% in 24 h and 27.0±3.5% in 48 h. The elimination half-life (t1/2) calculated from serum concentrations was 505±30 min ( $$\bar X$$ ±SEM) in patients with normal renal function (GFR〉90 ml/min). Only when the GFR fell below 30 ml/min did it slowly begin to increase. In patients with minimal residual renal function (GFR=0–0.5 ml/min), who were on haemodialysis, the elimination half-life was 985±49 min, i.e. approximately twice the normal. Twice weekly infusion of 3.5% polypeptide solution 500 ml over a period of 6 weeks did not produce any significant cumulation in haemodialysis patients (GFR=0–0.5 ml/min). A weekly dose of polypeptide 35 g appeared to be quite safe when given for several weeks, even to anuric patients. As no significant amount of polypeptide was lost during haemodialysis, the dose can be chosen without taking into account any effect of intermittent haemodialysis.
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    Disappearence of the intracytoplasmic membranes inRhodopseudomonas sphaeroides (1978)
    Springer
    Archives of microbiology 117 (1978), S. 293-295 
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    ISSN: 1432-072X
    Keywords: Rhodopseudomonas sphaeroides ; Intracytoplasmic membranes ; Membranes ; Ultrastructure ; Bacteriochlorophyll ; Chromatophores
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The photosynthetic bacterium,Rhodopseudomonas sphaeroides, can be grown phototrophically (light, anaerobiosis), of chemotrophically (dark, aerobiosis). In the first case, it contains intracytoplasmic membranes with photosynthetic pigments. When shifted from phototrophy to chemotrophy these membranes disappear in an unknown fashion. In the present experiment, samples were taken for electron microscopy, cell density and bacteriochlorophyll determinations after shift from phototrophy to chemotrophy. The density of intracytoplasmic vesicles was measured on micrographs. During the first 2h growth is very slow and the ultrastructure remains unaltered. As growth resumes, the vesicles disappear at a rate which implies that they are not incorportated into the cytoplasmic membrane, nor actively digested, but remain intact and become increasingly diluted in the cytoplasm as the culture grows. The size of the vesicles was estimated to about 500 Å. The number of vesicles in phototrophically grown cells was calculated to about 575 per cell, and after 6h chemotrophic growth to about 100. The areas of the cytoplasmic and intracytoplasmic membranes are roughly calculated.
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    Sporogenesis in Streptomyces melanochromogenes (1978)
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    Archives of microbiology 118 (1978), S. 309-316 
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    ISSN: 1432-072X
    Keywords: Streptomyces melanochromogenes ; Sporogenesis ; Formation of sporulation septum ; Delimitation, separation, and release of spores ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The mode of spore differentiation in a strain of Streptomyces melanochromogenes was followed by analysis of ultrathin sections of sporulating aerial hyphae at various stages of sporogenesis. A special accent was laid on the formation of the sporulation septum and its alterations in the course of spore delimitation and separation. Distinct differences in formation and substructure have been observed between the cross walls of vegetative hyphae and the sporulation septa. Cross walls of vegetative hyphae are formed in a way typical for Gram-positive bacteria by a centripetal annular ingrowth of cytoplasmic membrane, on which wall material immediately is deposited. The development of the sporulation septa is characterized by the accumulation of amorphous material in addition to the newly synthesized wall layer inside the invaginating cytoplasmic membrane. This amorphous septal material will later be decomposed presumably by two lytic systems which cause the separation of the spores. The central region of the finished sporulation septum is perforated by microplasmodesmata. Spores are released by a break down of the surface sheath. The complete spores are enveloped by a twolayered cell wall and the spiny surface sheath.
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    Ultrastructural study of microcyclic macroconidiation in Neurospora crassa (1978)
    Springer
    Archives of microbiology 116 (1978), S. 279-288 
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    ISSN: 1432-072X
    Keywords: Neurospora crassa ; Macroconidia ; Microcycle ; Heat ; Ultrastructure ; Nucleolus ; Proconidia ; Septa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Heat-shock of macroconidia of Neurospora crassa at 46°C followed by shift-down to 25°C determines premature conidiogenesis. The nuclei and cytoplasm of heat-treated, swollen conidia contain spots of a dense material especially concentrated around the nucleolus in short time treated ones. In the first proconidium apically budding on the enlarged tip of the premature conidiophore, small vesicles are peripherally spread. A few such vesicles are later seen lining the initially simple septum separating the proconidial units into conidia. The doubling of this interconidial septum is surface viewn as a thick annulus. Disarticulation of the conidial units intervenes along a septal furrow of electroluscent material. Interconidial continuity through the septal pores is transiently insured by a connective which is ruptured for final liberation of the conidia.
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    Reduced sulfur and nitrogen compounds and molecular hydrogen as electron donors for anaerobic CO2 photoreduction in Anacystis nidulans (1978)
    Springer
    Archives of microbiology 119 (1978), S. 313-322 
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    ISSN: 1432-072X
    Keywords: Cyanobacteria ; Anacystis ; Anoxygenic photosynthesis ; Reducing agents ; Electron donors ; Anaerobiosis ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Photosynthesis by Anacystis nidulans was studied in presence of reduced sulfur or nitrogen compounds, or of hydrogen. O2 evolution and CO2 fixation were depressed by sulfide, sulfite, cysteine, thioglycollate, hydroxylamine and hydrazine. Sulfite, cysteine and hydrazine inhibited O2 evolution much more strongly than CO2 fixation, indicating ability to supply electrons for CO2 photoreduction; DCMU suppressed these photoreductions. In contrast, some anoxygenic photosynthetic CO2 fixation insensitive to DCMU was found with sulfide, thiosulfate and hydrogen. Emerson enhancement studies confirmed that sulfite, cysteine and hydrazine acted on photosystem II, while photoreduction supported by sulfide, thiosulfate and hydrogen needed photosystem I only. Sulfite was photooxidized to sulfate, sulfide to elemental sulfur, and thiosulfate to sulfate plus elemental sulfur; the sulfur accumulated inside the cells. Results on the stoichiometries of the photoreductions were consistent with the photooxidation products determined. Inhibitor studies suggested photosynthetic CO2 fixation through the Calvin cycle. While photoreduction by all reductants used was found to be constitutive in Anacystis, the process was stimulated by anaerobic preincubation with the reductants only in the cases of hydrogen and thiosulfate; this adaptation was prevented by chloramphenicol and by O2. Anaerobic photoautotrophic growth of Anacystis was, however, not observed; the increase in dry weight with H2 and thiosulfate was not accompanied by cell multiplication or by an increase in chlorophyll content. Parallel short-term experiments with Chlorella did not reveal any constitutive photoreduction in this eukaryotic alga.
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    Some principles governing selection in self-reproducing macromolecular systems (1978)
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    Journal of mathematical biology 6 (1978), S. 169-175 
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    ISSN: 1432-1416
    Keywords: Selection ; Evolution ; Biological macromolecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Summary Starting with Eigen's model we discuss some principles pertaining to the selection of biological macromolecules. The principles have a certain analogy to Fisher's fundamental theorem for natural selection.
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    Elucidation of the evolution and taxonomy of cultivated potatoes with electrophoresis (1978)
    Springer
    Theoretical and applied genetics 52 (1978), S. 217-220 
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    ISSN: 1432-2242
    Keywords: Page ; Proteins ; Cultivated potatoes ; Evolution ; Taxonomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A recently developed polyacrylamide gel electrophoresis technique for tuber proteins is used to help elucidate the evolution and taxonomy of some cultivated potatoes. The results substantiate the theory that Group Tuberosum evolved from Group Andigena, that Group Andigena evolved from a cultivated diploid × wild diploid hybrid, and that Group Phureja evolved from Group Stenotomum. Furthermore, the results suggest these groups are closely enough related to merit classification within a single species.
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    A freeze-fracture study of tight junctions in the pars convoluta and pars recta of the renal proximal tubule (1978)
    Springer
    Cell & tissue research 186 (1978), S. 121-133 
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    ISSN: 1432-0878
    Keywords: Proximal tubule ; Tight junctions ; Ultrastructure ; Electron microscopy ; Freeze fracturing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphology of tight junctions of the renal proximal tubule was studied comparing the pars convoluta and pars recta of rat, golden hamster, rabbit, cat, dog and tupaia. Though some interspecies variations were observed, the convoluted portions of the proximal tubules revealed quite uniformly very leaky tight junctions with mainly 1–2 strands. Along the whole proximal tubule of the rabbit kidney including the pars recta only minor differences of the zonulae occludentes were found. By contrast, the tight junctions of the pars recta in other species were much more elaborate, especially in cat and tupaia, having up to 6 strands and an overall depth of more than 150 nm. The implications of these findings are discussed with special regard to the functional differences between the pars convoluta and pars recta of the proximal tubule.
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    Exocrine pancreas under experimental conditions (1978)
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    Cell & tissue research 186 (1978), S. 227-240 
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    ISSN: 1432-0878
    Keywords: Pancreas (rat) ; Pancreatic duct ligation ; Cell membrane ; Intercellular junctions ; Ultrastructure ; Freeze fracture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Exocrine pancreatic tissue was investigated during various intervals after pancreatic duct ligation. Concomitant to the increase of the intraluminal pressure, alterations are found in the arrangement of the luminal membrane surface and the zonulae occludentes of the acinar cells. The zonulae occludentes exhibit a disarrangement of their strands. The number of strands diminishes and small interruptions as well as large discontinuities of the strands are observed in most regions of the acinar cells. Furthermore, gap junctions are found very infrequently between acinar cells. The ultrastructural alterations of the zonulae occludentes suggest a gradual adaptation to the increasing unilateral pressure. However, a leakage of the paracellular permeability barrier occurs which contributes to the known shunt between the compartments of the pancreatic juice and the interstitial space following pancreatic duct obstruction. The present investigation is a further example of alterations in the paracellular permeability and intercellular communication of epithelial cells under pathological conditions.
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    Fine structure of the eyes of orb-weavers, Argiope amoena L. Koch (Aranea: Argiopidae) (1978)
    Springer
    Cell & tissue research 186 (1978), S. 435-452 
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    ISSN: 1432-0878
    Keywords: Photoreceptors ; Arthropod ; Spider (Argiope amoena) ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The anterolateral eye, the posterolateral eye and the posteromedial eye of the web-building spider, Argiope amoena have been examined by light and electron microscopy. The dioptric apparatus of all three eyes is similar in structure, and consists of a cornea, a lens and a vitreous body. The retina contains monopolar receptor cells, the cell bodies of which are present beneath the vitreous body in all three eyes. Proximal processes of the receptor cells form rhabdoms beneath the cell body layer and then extend toward the first optic glomerulus as an ocellar nerve. Two distinct patterns of retinal organization are present in the three eyes. In one type the rhabdomic layer of the retina is backed by a pigmented layer. In the other type the rhabdomic layer is backed by a tapetal reflecting layer. Rhabdomic structure and cytoplasmic inclusions of the receptor cells differ greatly between the two types. The anterolateral eye possesses a single type of retina with the rhabdoms backed by the tapetum. Both the posterolateral and the posteromedial eye are similar in structure, each possessing beneath the common dioptric apparatus retinae of both types.
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    Ultrastructure of the subfornical organ of the Japanese quail, Coturnix coturnix (1978)
    Springer
    Cell & tissue research 188 (1978), S. 19-33 
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    ISSN: 1432-0878
    Keywords: Subfornical organ ; Circumventricular organ ; Coturnix quail ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The structure of the subfornical organ (SFO) of the Japanese quail has been studied by light and electron microscopy. The SFO is a small semiglobular bulge in the midline on the rostrodorsal wall of the third ventricle between the anterior commissure and tela choroidea. The organ consists of three main parts, anterior stalk, the corpus and the posterior stalk. The anterior stalk is covered by ependymal cells with a few cilia, but the corpus and posterior stalk are characterized by a distinctive lack of cilia and by flat or bulging cell surfaces, which have the appearance of cobble stones. The large bulbous protrusions in the ependymal surface of the posterior stalk suggest a secretory function into the ventricle. In the subependymal layer, there are a few parvocellular neurons that contain small mitochondria, moderately developed Golgi apparatus, lysosomes, dilated cisternae of rER and a few dense-cored granules of 100–120 nm in diameter. They appear to be secretory in nature. Two types of glial cells occur in the subependymal and internal layers. One is small and spindle-shaped with a dense nucleus and elongated cytoplasmic processes; it may be microglial. The other is a small polygonal cell with rounded nucleus and clear cytoplasm containing bundles of filaments; it may be a protoplasmic astrocyte. The neuropil contains three types of axons. The first contains dense-cored granules, 80 nm in diameter, and clear vesicles, 40–60 nm in diameter and is involved in axosomatic synapses. The second type contains dense granules, 120 nm in diameter, and clear vesicles, 40–80 nm in diameter, and shows axodendritic synapses. The third contains peptidergic granules about 100–120 nm in diameter and seems to belong to the organ-specific nerve cells. These axons terminate at the perivascular space of the blood capillaries, suggesting secretion into the blood.
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    Origin of the glial processes responsible for the spontaneous postnatal phagocytosis of boutons on cat spinal motoneurons (1978)
    Springer
    Cell & tissue research 189 (1978), S. 203-217 
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    ISSN: 1432-0878
    Keywords: Astrocytes ; Development ; Phagocytosis ; Neuroplasticity ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous studies have demonstrated that astrocyte processes are responsible for a spontaneously occurring phagocytosis of boutons on cat spinal motoneurons during the second postnatal week. In the present investigation, the astrocytes and the astrocyte processes in contact with the motoneurons were studied qualitatively and quantitatively during the early postnatal period. It could be concluded that the cells responsible for the phagocytosis of boutons are immature astrocytes. These cells were present not only during the period of phagocytosis but also prior to this period. The type of process responsible for the phagocytosis was present not only during the period of phagocytosis but also prior to and after that period although the relative contribution of such processes to the glia-covered membrane area of the motoneurons was reduced in the older animals. On the basis of these results, the possible specificity of the immature astrocyte as the element responsible for the phagocytosis of boutons during normal development is discussed.
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    Synaptic junctions in the sinus gland of the freshwater prawn Palaemon paucidens (1978)
    Springer
    Cell & tissue research 189 (1978), S. 435-440 
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    ISSN: 1432-0878
    Keywords: Neurosecretion ; Sinus gland ; Synapses ; Palaemon ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two types of neurosecretory fibers, designated as Type 5 and Type 6 axons, in the sinus gland of the freshwater prawn, Palaemon, establish contact with other neurosecretory axons by means of synaptic junctions. This finding strongly supports the view that release of some neurohormones from the eyestalk may be regulated by neurosecretory neurons through synaptic transmission.
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    Structure of occluding junctions in ileal epithelial cells of suckling rats (1978)
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    Cell & tissue research 191 (1978), S. 449-462 
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    ISSN: 1432-0878
    Keywords: Ileum (Rat) ; Occluding junctions ; Freeze-fracture ; Ultrastructure ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two kinds of occluding junctions are found between ileal epithelial cells of suckling rats: apical zonulae occludentes (ZO) and fasciae occludentes (FO) which are associated with the lateral plasma membranes of many epithelial cells. In unfixed preparations, glycerol treatment induces the further proliferation of extensive fasciae occludentes. Both kinds of junction have identical structural elements when visualized in freeze fracture replicas, although the arrangement of these elements differs. Zonulae occludentes consist of networks of branching and anastomosing linear ridges or rows of ∼10 nm particles with 20–30 nm spaces between the rows which form narrow belt-like structures around the apical region of adjacent cells. Fasciae occludentes, on the other hand, consist of similar linear ridges or rows of particles but the junction strands are often discontinuous, open ended and only occasionally intersect with each other. Several different fracture planes through the plasma membrane in the region of the occluding junctions have been observed and these provide further evidence that two components, one from each membrane, fused at the level of the extracellular space, form the junction sealing element. Furthermore, we present evidence which indicates a staggered rather than an in-register arrangement of these two components.
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    URL: http://dx.doi.org/10.1007/BF00219808
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    Effects of hormone-releasing stimuli on the area of the perivascular space in the neural lobe of the rat (1978)
    Springer
    Cell & tissue research 191 (1978), S. 501-506 
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    ISSN: 1432-0878
    Keywords: Neurohypophysis ; Ultrastructure ; Perivascular space ; Hormonerelease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Neural lobes from rats subjected to neurohypophysial hormone-releasing stimuli were examined electron microscopically following fixation in 4 % tannic acid in 2.5 % glutaraldehyde. This fixation allowed the delineation of the perivascular space in the neural lobe tissue. Measurement of the area of the perivascular space showed that it was significantly increased in the rats subjected to vagal stimulation and intraarterial calcium ions compared to the control rats. The rats which had been subjected to haemorrhage as a hormonereleasing stimulus did not show any significant change in the area of the perivascular space. The significance of these findings in relation to hormone release is discussed.
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    URL: http://dx.doi.org/10.1007/BF00219812
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    Lymph node macrophages and reticulum cells in the immune response (1978)
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    Cell & tissue research 192 (1978), S. 1-23 
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    ISSN: 1432-0878
    Keywords: Lymph node (rat) ; Macrophages ; Dendritic reticulum cells ; Immune response to paratyphoid vaccine ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The reactivity of rat lymph node macrophages and reticulum cells has been studied in relation to the course of the immune response. Special attention was paid to the interdigitating cells (IDC) in the paracortex and the dendritic reticulum cells (DRC) in the germinal centre. Different types of macrophage predominate in the three different phases of the immune response. In the induction phase exudate macrophages predominate. They transform their morphology depending on the micro-environment in which they settle. These cells may contain Birbeck granules. Our experiments suggest, that these granules are immunologically specific organelles, associated with the induction of a primary humoral response. In the proliferation phase transitional cells between newly arrived macrophages and IDC predominate in the paracortex and the number of IDC decreases. In the memory phase IDC repopulate this thymus dependent area, indicating that the characteristic morphology of these cells results from the immune response in the T cell environment. The DRC are specifically related to the germinal centre, the morphological transformation of this peculiar reticulum cell occurs under the influence of the germinal centre reaction. The germinal centre reaction originates by tingible body macrophages (TBM).
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    URL: http://dx.doi.org/10.1007/BF00231019
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    Morphological changes in the esophageal epithelium of the eel, Anguilla japonica, during adaptation to seawater (1978)
    Springer
    Cell & tissue research 192 (1978), S. 25-38 
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    ISSN: 1432-0878
    Keywords: Esophageal epithelium ; Eel ; Seawater adaptation ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The esophageal epithelium of the Japanese eel, Anguilla japonica, was studied by light and electron microscopy. In freshwater-adapted eels, longitudinal folds of the mucosal surface are simple in form and lined by a stratified epithelium composed of mucous cells, filament and ribosome-rich cells. Mucous cells are numerous. The filament-rich cells form the outermost and the basal layers of the stratified epithelium and are scattered in the middle zone among the mucous cells. They are firmly bound to one another by many desmosomes and prominent interdigitations of plasma membrane. The distal free surface of the filament-rich cell has a fingerprint-like pattern of microridges. A small number of columnar cells occur at the apices of the folds. They are rich in mitochondria and their distal surfaces bear short microvilli. In seawater-adapted eels, irregularly meandering folds increase the surface area of the mucosa. The stratified epithelium is extensively replaced by a simple columnar epithelium free of mucous cells. The columnar cells resemble in many respects those found in freshwater-adapted eels. They are rich in mitochondria and their distal free surface were provided with short microvilli. However, prominent lateral intercellular spaces and elaborate interdigitations of cytoplasmic processes in the distal zone distinguish the former from the latter. Results are considered in connection with the changes in ion and water permeability of the epithelium after seawater adaptation.
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    URL: http://dx.doi.org/10.1007/BF00231020
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    Ultrastructure of capillaries in the conduction system of the heart in various mammals (1978)
    Springer
    Cell & tissue research 192 (1978), S. 77-87 
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    ISSN: 1432-0878
    Keywords: AV-node ; AV-bundle ; Fenestrated capillary endothelium ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The capillaries in the atrioventricular node and atrioventricular bundle of the heart (mammals) were investigated by thin sections and freezeetch replicas. Fenestrated endothelial cells were found to occur in all mammals examined in this study. These fenestrations (500±50 Å diameter) are bridged by a diaphragm and occur in relatively small sieve areas. In contrast to the AV-node and AV-bundle, the non-specialized myocardium is supplied by continuous capillaries. The presence of the fenestrated capillary in the conduction system of the heart may serve to increase both permeability and passive transport capacity.
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    URL: http://dx.doi.org/10.1007/BF00231024
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    A stereological ultrastructural study of peritoneal macrophages from germ-free and conventionally-reared mice (1978)
    Springer
    Cell & tissue research 192 (1978), S. 157-166 
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    ISSN: 1432-0878
    Keywords: Germ-free mice ; Macrophages ; Peritoneum ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The reported work is the first direct ultrastructural comparison of resident peritoneal macrophages from germ-free and conventional animals. Three groups of mice were studied: germ-free (GF), conventionally-reared under isolation conditions (IC), and conventionally-reared in an open environment (OC). The macrophages from the three groups of animals are closely similar morphologically. Particularly noteworthy are the electron-dense, lysosome-like granules which are numerous in the macrophages of germfree mice and which provide a structural foundation for the presumed microbicidal capability of the phagocytes. Morphometric estimates showed that the “average macrophage” from GF mice is smaller and possesses a smaller, rounder nucleus, a smaller volume fraction of mitochondria and more lysosome-like granules per unit of cytoplasmic volume than the “average macrophage” from conventional mice. Moreover, granules and mitochondria are smaller, on average, in the GF phagocytes than in macrophages from conventional mice. The results suggest that peritoneal macrophages from the germ-free mouse represent, more truly than those from the conventional mouse, the nature of the fully differentiated but as yet unstimulated mononuclear phagocyte.
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    URL: http://dx.doi.org/10.1007/BF00231030
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    Ultrastructural analysis of the action of reserpine on the brain neuroendocrine system of the wax moth, Galleria mellonella L., Lepidoptera (1978)
    Springer
    Cell & tissue research 192 (1978), S. 143-155 
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    ISSN: 1432-0878
    Keywords: Neuroendocrine system ; Galleria ; Ultrastructure ; Reserpine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This study concerns the influence of reserpine on the fine structure of peptidergic neurosecretory cells in the pars intercerebralis of Galleria mellonella, and of neurons containing smaller dense-cored vesicles (presumed to be aminergic) localized in the same area of the brain. The drug, administered in doses of 125 μm and 250 μg per g of insect body weight, reduces both the amount and the electron opacity of the dense-cored vesicles with a diameter of 60–80 nm in the neuronal perikarya as well as their terminals. Simultaneously, this treatment evokes an abnormal accumulation of secretory granules within the perikarya of peptidergic neurosecretory cells belonging to three types. This accumulation of secretory material is followed by some changes in the fine structure of these cells. One (fourth) type of neurosecretory cells seems to be insensitive to reserpine action. Participation of the aminergic system in the regulation of the secretory activity of some populations of peptidergic neurosecretory neurons of the insect brain is postulated.
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    Structure of the adenohypophysis in parturient female and neonate harp seals, Pagophilus groenlandicus (1978)
    Springer
    Cell & tissue research 192 (1978), S. 341-357 
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    ISSN: 1432-0878
    Keywords: Adenohypophysis ; Cell types ; Neonate ; Parturient ; Harp seal, Phagophilus groenlandicus ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The pars distalis of parturient harp seals (Pagophilus groenlandicus) is divisible into three distinct zones based on the major cellular components of the different regions. A clear zonation is lacking in neonate seals, the medial “basophilic wedge” and the anterior gonadotrophic were small and difficult to identify. Five cell types were identified based on cytological characteristics: somatotrophs, mammotrophs, thyrotrophs, gonadotrophs and stellate cells; corticotrophs could not be identified, with any certainty, in any of the preparations, nor could the gonadotrophs be classified into LH, FSH, and ICSH cells. The pars intermedia enlarged during the early post-partum period and was large in the parturient females.
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    Studies on the ultrastructure and permeability of the hemotrichorial placenta (1978)
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    Cell & tissue research 192 (1978), S. 391-407 
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    ISSN: 1432-0878
    Keywords: Placenta (rat) ; Permeability ; Tracer ; Intercellular junctions ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of lanthanum chloride and horseradish peroxidase within the full-term chorioallantoic placenta of the rat was investigated 1 to 20 min after administration of these tracers into the maternal blood circulation. Both tracers rapidly penetrate trophoblastic layer I and diffuse into the interspace between layers I and II. They are localized in extensive infoldings and caveolae of the outer surface of layer II. The syncytial character of layer II is confirmed at this developmental stage of the placenta. There is no vesicular uptake or penetration beyond layer II until 20 min after tracer administration. Our results indicate that trophoblastic layer II is the main barrier in the chorioallantoic rat placenta preventing the permeation of macromolecules from maternal to fetal compartments. With freeze-fracturing, particulate structures of variable arrangement and size are found between adjacent cells of layer I. With goniometric analysis small gaps between the appositions of the membrane are observed. These structures are interpreted as tight and/or gap junctions during stages of assembly or disassembly.
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    Studies on the ultrastructure and permeability of the hemotrichorial placenta (1978)
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    Cell & tissue research 192 (1978), S. 409-422 
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    ISSN: 1432-0878
    Keywords: Placenta (rat) ; Capillary ; Permeability ; Tracer ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of horseradish peroxidase and lanthanum chloride within the full term chorioallantoic placenta of the rat was examined after administration of these tracers into the umbilical artery. Both tracers rapidly traverse the capillary endothelium. Transendothelial channels, fenestrations and micropinocytotic vesicles provide the main pathways. Intercellular clefts which are either patent or interrupted by leaky intercellular junctions, also contribute to a rapid passage of low and high molecular weight substances. Deep channel-like invaginations, effecting an increase of the exchange area of layer III, are freely accessible to the tracers from the interspace between the capillary endothelium and trophoblastic layer III. The invaginations, however, are not in continuity with the interspace between layers II and III, verifying the syncytial character of layer III. Neither an uptake of the tracers nor a passage across layer III is observed. The main permeability barrier to feto-maternal transfer within the chorioallantoic placenta is localized in the syncytiotrophoblastic layer III. This layer controls the passage of low molecular weight substances and restricts the penetration of high molecular weight substances.
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    Control of the pars intermedia of the lizard, Anolis carolinensis (1978)
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    Cell & tissue research 186 (1978), S. 241-258 
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    ISSN: 1432-0878
    Keywords: Neural lobe ; Anolis carolinensis ; Ultrastructure ; Intermediate lobe control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the neural lobe of the lizard, Anolis carolinensis, was studied after fixation in a threefold aldehyde solution. The neural lobe appeared as narrow vertical diverticula separated from one another and from the pars intermedia by a continuous vascular septum. No nerves passed through this septum. The ependymal, fibrous and external layers were readily recognized. Peptidergic fibres were the main component of the fibrous layer. The peptidergic endings were in intimate contact with the ependymal cells, suggesting that the ependyma mediates the release of neural lobe peptides. The external layer contained ependymal end-feet and numerous aminergic terminals, ending directly on the perivascular basal lamina and/or on the ependymal end-feet. The functional aspects are discussed in terms of intermediate lobe control. The findings suggest that aminergic substances take part in the control of the intermedia, but do not exclude the involvement of peptide hormones.
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    Ultrastructure and lipid content of the liver of the zebrafish, Brachydanio rerio, related to vitellogenin synthesis (1978)
    Springer
    Cell & tissue research 186 (1978), S. 297-308 
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    ISSN: 1432-0878
    Keywords: Liver ; Teleost ; Ultrastructure ; Lipid ; Vitellogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The female zebrafish is capable of producing mature eggs on the fifth day of each reproductive cycle. During this five-day period the ultrastructure of hepatocytes undergoes several changes. The number of nuclear pores increases rapidly during spawning, followed by a proliferation of RER within 24 h. Two days after spawning, glycogen has disappeared and the liver contains large amounts of lipids. The lipid droplets are closely surrounded by elongated mitochondria. Golgi complexes are abundant, secreting dense bodies. Four days after spawning the hepatocytes tend to regain their pre-spawning appearance. It is suggested that the changes in the hepatocytes, which coincide with special phases of ovarian activity, are related to vitellogenin synthesis. Steroids, especially estradiol-17β, may trigger this process in the liver.
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    URL: http://dx.doi.org/10.1007/BF00225539
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    An ultrastructural study of the larval integument of the midge, Chironomus riparius meigen (Diptera: Chironomidae) (1978)
    Springer
    Cell & tissue research 186 (1978), S. 327-335 
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    ISSN: 1432-0878
    Keywords: Cuticle ; Epidermis ; Chironomus ; Respiration ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The larval integument of the midge, Chironomus riparius Mg., is unusually thin although it conforms with the normal insect pattern. The cuticle of the post-cephalic segments is about 3 μm thick and overlies an epidermis which has an irregular basal plasma membrane resulting in spaces occurring between it and the basement membrane. The ventral tubuli have a similar epidermis but the cuticle is somewhat thinner. The anal papillae have the thinnest cuticular covering with a uniquely folded epicuticle of variable thickness, and their epidermis has the characteristics of a transporting epithelium. No evidence of pore canals could be found in the cuticle of any part except the head capsule which has a remarkably smooth epicuticle and a distinct layer which may represent the exocuticle. There are no spaces between the basement membrane and basal plasma membrane of the epidermis in the head. Ultrastructural evidence would suggest that gaseous exchange can occur across most of the post-cephalic integument.
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    URL: http://dx.doi.org/10.1007/BF00225541
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    Effects of systemic administration of 6-hydroxydopamine on the circumventricular organs in nonhuman primates (1978)
    Springer
    Cell & tissue research 187 (1978), S. 115-127 
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    ISSN: 1432-0878
    Keywords: Area postrema ; 6-Hydroxydopamine ; Degenerative changes ; Ultrastructure ; Cynomolgus and squirrel monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 6-Hydroxydopamine (6-OH-DA) has been shown to produce degenerative changes in noradrenergic nerve terminals and preterminals in the CNS following intracisternal, intraventricular or direct injection into the brain parenchyma. Systemic injection of 6-OH-DA is known to result in degenerative changes in noradrenergic terminals in the peripheral nervous system. However, only a few studies have been carried out on the effects of systemic injections of 6 OH-DA on noradrenergic terminals in the CNS. In the present study cynomolgus and squirrel monkeys were injected intravenously on two successive days with total doses of 350mg/kg and 150 mg/kg of 6-OH-DA, respectively, and sacrificed at 2 and 24 h following the second injection. Degenerative changes in the area postrema (AP) neurons in all injected animals were characterized by a generalized increase in electron density of cytoplasmic elements in axonal terminals and preterminals. Multilamellar bodies, clusters of clear and dense core vesicles, increased numbers of secondary lysosomes, and an increase in the number of glycogen granules were observed in these structures. In astrocytes the amount of glycogen increased markedly in injected animals, but no other glial alterations were observed. The number of mast cells in the AP was greater in injected than in noninjected animals, both in the perivascular spaces (PVS) and in parenchymal locations. Cell processes in the PVS were occasionally observed to contain electron dense bodies, and degenerative changes were seen in supraependymal processes in some injected animals.
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    URL: http://dx.doi.org/10.1007/BF00220623
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    Osteodentine and vascular osteodentine of Anarhichas lupus (L.) (1978)
    Springer
    Cell & tissue research 187 (1978), S. 135-146 
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    ISSN: 1432-0878
    Keywords: Osteodentine ; Anarhichas lupus ; Ultrastructure ; X-ray diffraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Le tissu dentinaire d'Anarhichas lupus s'est révélé être une ostéodentine vasculaire. Les études en MET, MEB et diffraction X montrent l'hétérogénéité de ce tissu. L'aspect désordonné des fibres de collagène, incomplètement minéralisées (leur striation est encore bien visible), explique la complexité de la répartition des cristaux puisqu' elles en déterminent l'ordonnance. La minéralisation imparfaite du tissu, dont témoignait déjà la striation visible du collagène, est confirmée par l'analyse des poudres en diffraction X (la cristallinité de l'ostéodentine vasculaire est nettement inférieure à celle de la couche de tissu dentaire périphérique) et par l'examen en MET de haute résolution, aucun réseau cristallin n'ayant pu être mis en évidence. L'ostéodentine, l'os basal et l'os profond ont en commun une phase minérale, avec une organisation plus ou moins bonne, différente du système des apatites.
    Notes: Summary TEM, SEM and X-ray diffraction analysis demonstrate the heterogeneity of the dentinal tissue of Anarhichas lupus, a vascular osteodentine. The disordered aspect of collagen fibres, incompletely mineralized (the periodical striation being still visible), explains the scattered distribution of crystallites since they are responsible for their arrangement. The low degree of mineralization revealed by the visible collagen striation is confirmed by X-ray diffraction analysis (the crystallinity of vascular osteodentine being much lower than that of the peripheral dental tissue) as well as by high resolution TEM, since no lattice planes could be observed. Osteodentine, supporting bone and proper bone have in common a mineral phase, more or less organized, different from the apatite system.
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    The ultrastructure and renewal of the intestinal epithelium of the juvenile grasscarp, Ctenopharyngodon idella (Val.) (1978)
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    Cell & tissue research 187 (1978), S. 181-200 
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    ISSN: 1432-0878
    Keywords: Intestine ; Teleost ; Epithelium ; Renewal ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The intestinal absorptive epithelium of starved and fed fish has been studied electron microscopically. After feeding, cells of the proximal segment of the intestine show morphological characteristics of lipid absorption. Absorptive cells in the middle segment contain many pinocytotic vesicles in both fasted and fed specimens. Absorption of protein macromolecules is supposed to be one of the main functions of this part of the gut. In the most caudal part of the intestine, absorptive cells carry relatively few and short microvilli. The proximal and distal segments show structural indications of a function in osmoregulation. The renewal of the epithelium has been studied with light microscopic autoradiography, using tritiated thymidine. The intestinal mucosal fold epithelium represents a cell renewal system. The cells proliferate at the base of the fold and migrate towards the apex in 10–15 days at 20° C. The functional absorptive cells proved to be generally present in the intestinal epithelium, including the proliferative area. Undifferentiated cells have not been identified. The results will be compared with data on absorption of lipid and protein macromolecules in teleostean and mammalian intestines and with descriptions of the cell renewal system in the mammalian intestine.
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    The ultrastructure of the non-neurosecretory components in the brain of the midge, Chironomus riparius Mg. (Diptera: Nematocera) (1978)
    Springer
    Cell & tissue research 187 (1978), S. 355-366 
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    ISSN: 1432-0878
    Keywords: Neuron ; Glial ; (Insect, Chironomus riparius) ; Extracellular space ; Perineurium ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the neural sheath, glial cells and neurons in the brain of the neoimaginal male Chironomus riparius is described. The neural sheath comprises a neural lamella and underlying perineurium. The neural lamella consists of an amorphous matrix in which fine fibrils occur. The perineurium is composed of two cell types forming a continuous layer around the brain. The subjacent cortical layer, composed of the cell bodies of neurons and glial cells, varies considerably in thickness and surrounds the centrally located neuropiles. Three types of glial cells are distinguished on the basis of their positions and appearances. Five types of neurons are described which differ in size and relative frequency of organelles. Four types of axons, including those of neurosecretory cells, are distinguished by their size and content.
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    The posterior pituitary of the garden dormouse (Eliomys quercinus L.) (1978)
    Springer
    Cell & tissue research 188 (1978), S. 189-204 
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    ISSN: 1432-0878
    Keywords: Neural lobe of hypophysis ; Hibernating mammals ; Ultrastructure ; Neurosecretory granules ; Whorls
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé L'ultrastructure de la posthypophyse du Lérot a été examinée à différents stades du cycle annuel de ce rongeur hibernant. Il n'a pas été observé de différences évidentes entre les stades étudiés, et sont donc présentées ici les caractéristiques générales retrouvées chez tous les animaux. Les axones neurosécréteurs et leurs terminaisons peuvent être divisés en deux catégories suivant l'aspect des grains de neurosécrétat et des microvésicules présents. Le premier type contient des grains arrondis, à contenu d'apparence homogène, avec des microvésicules rondes. Dans les autres axones, les grains sont de forme variable, souvent allongés, et leur contenu présente deux sortes d'organisations cristallines; les microvésicules y sont en majorité aplaties. Considérant comme improbable que cette dualité résulte seulement d'un artefact, trois hypothèses sont envisagées. La dualité d'aspect des grains peut être liée à leur contenu en hormone (ocytocine ou vasopressine); ou bien l'aspect des grains peut correspondre à leur degré de maturation. Il est possible aussi que ces explications soient toutes deux valables. Par ailleurs, les pituicytes du Lérot contiennent fréquemment un réticulum endoplasmique organisé en lamelles concentriques (whorls). La signification de ces formations reste pour l'instant obscure.
    Notes: Summary Ultrastructural examination of the posterior pituitary of the garden dormouse (Eliomys quercinus L.) was carried out at different times in the annual cycle of this hibernating rodent. Obvious differences between experimental groups have not been observed, and the results presented here must be considered as general features of the garden dormouse posterior pituitary. Neurosecretory axons and endings can be divided into two types, according to different aspects of neurosecretory granules (NSG) and microvesicles (MV). One type contains spherical NSG with homogeneous cores and round MV. In the other type, NSG have various, often elongated, shapes. Their content shows two types of crystalline structures and most of the MV have flattened aspects. As it is very unlikely that this duality in NSG is a result of an artefact of fixation, three hypotheses are presented as explanation. The duality of NSG might be related either to their hormonal content (oxytocin or vasopressin) or to their degree of maturation. Moreover, both explanations may be valid. In the species studied, pituicytes often contain concentric lamellar structures of the endoplasmic reticulum (whorls), the significance of which remains obscure.
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    URL: http://dx.doi.org/10.1007/BF00222630
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    Ovarian follicles of normal NMRI mice and homozygous “Nude” mice (1978)
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    Cell & tissue research 188 (1978), S. 409-426 
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    ISSN: 1432-0878
    Keywords: Ovary ; “Nude” mouse ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ovarian follicles of juvenile (15-day and 21-day old), pubescent (28-day old) and sexually mature (45-day old) “Nude” mice have been compared to those from normal NMRI mice of the same age and breeding groups. At the electron microscopical level, some differences were observed in both follicular cells and oocytes. In the follicular cells, the following alterations could be seen in the “Nude” ovaries: (1) the differentiation between clear and dark cells, normally not occurring before the age of 21 days, was already present in the 15-day old “Nude” mice and (2) the follicular intercellular spaces were frequently dilated, possibly because of a contraction of the cells, even in the small growing follicles of the bilaminar type in the athymic animals. The “Nude” oocytes could be characterized by (1) a precocious appearance and an early disappearance of the nuage material, (2) a nearly complete absence of micropapillae on the oolemma, (3) a dense and disseminated aspect of their Golgi complexes, (4) the presence of a large amount of multivesicular bodies and (5) of tiny (about 30 nm) dense membrane-bounded particles in their ooplasm. These differences are discussed in relation to the possible interference of congenital athymia with the development of the hypothalamo-pituitary-gonadal axis. However, the influence of the reduced immunological responsiveness of the “Nude” mice on their ovarian development cannot be excluded for animals raised in a normal — and consequently infected — environment.
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    URL: http://dx.doi.org/10.1007/BF00219781
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    Histological and cytological studies on the fat body of the cockroach Nauphoeta cinerea during the first reproductive cycle (1978)
    Springer
    Cell & tissue research 188 (1978), S. 481-490 
    Details
    ISSN: 1432-0878
    Keywords: Fat body ; Cockroach ; Reproductive cycle ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The central fat body of the ovoviviparous cockroach Nauphoeta cinerea was studied during the first reproductive cycle of the female by means of light microscopy, autoradiography and electron microscopy. Comparative studies in larval stages were also undertaken. The fat body of Nauphoeta contains a large amount of lipid droplets and the remaining cytoplasm is very scarce. The cytological cyclicity of the fat body is consistent with the known biochemical rhythms of vitellogenin production. The proteosynthetic apparatus appears about 3 days after imaginal ecdysis, along with vitellogenin. The ribosomal endoplasmic reticulum (RER) shows a tremendous increase by the 7th day of the first cycle. The most active period of vitellogenin production lasts from day 7 to day 12. The proteosynthetic apparatus then returns to an inactive stage and disappears. This inactive condition lasts to the end of the gestation period. The autoradiographic results are consistent with the cytological features.
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    URL: http://dx.doi.org/10.1007/BF00219785
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    The ultrastructure and function of follicle cells in Foucartia squamulata (Herbst) (Curculionidae) (1978)
    Springer
    Cell & tissue research 189 (1978), S. 347-353 
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    ISSN: 1432-0878
    Keywords: Vitelline membrane ; Chorion ; Ultrastructure ; Curculionidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The follicle cells of Foucartia squamulata are involved in the formation of both vitelline membrane and chorion. Precursors for these egg coverings are synthesized by the rough endoplasmic reticulum and condensed within dictyosomes. The vitelline membrane and the chorion appear on the oocyte surface simultaneously, which is an unusual phenomenon for insects. The follicular epithelium has not been found to contribute to vitellogenesis in the species under study.
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    URL: http://dx.doi.org/10.1007/BF00209282
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    Oogenesis in Acerentomon gallicum Jonescu (Protura) (1978)
    Springer
    Cell & tissue research 189 (1978), S. 365-374 
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    ISSN: 1432-0878
    Keywords: Previtellogenesis ; Oocyte ; Ultrastructure ; Acerentomon gallicum ; Protura
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary At the onset of previtellogenesis, the oocytes of Acerentomon gallicum begin to grow and increase their content of organelles. The nuage material in the oocytes at first increases in amount, then declines gradually to disappear completely from oocytes that have attained 50 μm in diameter. During the growth period, new dictyosomes, mitochondria and ribosomes appear. Numerous vesicles become detached from the cell membrane and subsequently fuse into cisternae, thus forming extensive complexes of the rough endoplasmic reticulum. In oocytes with diameters between 50 and 100 μm the Golgi complexes show a considerable increase in activity, and many lamellar bodies arise from mitochondria that have undergone specific transformation.
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    URL: http://dx.doi.org/10.1007/BF00209284
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    Tormogen cell and receptor-lymph space in insect olfactory sensilla (1978)
    Springer
    Cell & tissue research 189 (1978), S. 549-554 
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    ISSN: 1432-0878
    Keywords: Tormogen cell ; Receptor-lymph space ; Chemoreceptor ; Ultrastructure ; Histochemistry ; Calliphora (Insects)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary (1) The basiconic sensilla on the antennae of Calliphora resemble other insect epidermal sensilla; one or several bipolar sense cells are surrounded by three non-neural cells. (2) The apical cell membrane of the tormogen cell(one of the three accessory cells) forms microvilli coated internally with particles. (3) In the (extracellular) outer receptor-lymph space hyaluronic acid can be demonstrated histochemically. (4) Demonstration of non-specific alkaline phosphatase, Mg2+-activated ATPase, and the presence of mitochondria in the apical part of the tormogen cell suggest active transport processes through these cells into the outer receptor-lymph space.
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    URL: http://dx.doi.org/10.1007/BF00209140
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    Kinetics of functional and morphological changes during decoupling and recoupling induced by glycerol in isolated muscle fibres of the crayfish (1978)
    Springer
    Cell & tissue research 192 (1978), S. 167-185 
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    ISSN: 1432-0878
    Keywords: T-system tubules ; Glycerol procedure ; Structure-activity relationship ; Ultrastructure ; Astacus fluviatilis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of ultrastructural changes in the T-system of isolated muscle fibres of the crayfish by the glycerol procedure is described in correlation with the dissociation of excitation-contraction (E-C) coupling as well as with recoupling of the E-C link. The sequence of events in the process of disconnection of the tubules is as follows: dilation of the T-system tubules, disconnection of the constricted tubular segments from the surface membrane and from the T-system vesicle, disappearance of the lumen and its disintegration. The decoupled state is characterised by the presence of round vesicles uniformly distributed in the entire volume of the fibre. The volume of vesicles accounts well for the residual postglycerol volume increase (15%) of the muscle fibres. Functional and structural recovery can be induced by reapplication of glycerol to fibres decoupled and vesiculated with concentrations of glycerol≦300mmol · l-1 in crayfish saline. The restitution starts with the organisation of the material of the disintegrated connecting segment of the T-system tubule into small vesicles which coalesce to form the tubule from the vesicular site. At the same time the surface membrane is invaginated toward the vesicle, thus forming the tubule from the surface membrane site. Recovery starts already in the first minute after application of glycerol and is completed within approximately 15min.
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    URL: http://dx.doi.org/10.1007/BF00231031
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    Separation and maturation of gonadotrophs from 2A8 clonal cells in vitro (1978)
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    Cell & tissue research 189 (1978), S. 31-40 
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    ISSN: 1432-0878
    Keywords: Pituitary cell clone ; LHRH-Sepharose ; Gonadotrophs ; Hypertrophy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 2A8 clonal cells derived from the epithelium of Rathke's pouch of fetal rats were cultured in growth medium supplemented with fresh rat serum, median-eminence extract and l-thyroxine. Then, in order to isolate gonadotrophs, cyanogen bromide-activated Sepharose which was conjugated with LHRH (LHRH-Sepharose) was added to the culture medium. Fourteen days after incubation of 2A8 cells with LHRH-Sepharose, agranular and granular cells were rapidly bound to LHRH-Sepharose when fresh serum had previously been added in the medium. The cytoplasm of granular cells that were bound to LHRH-Sepharose contained spherical secretory granules (200–250 nm in diameter). These cells were similar in morphology to the FSH and LH gonadotrophs described by Kurosumi (1968). Moreover, many of them appeared as hypertrophied cells that resembled “castration” cells. These results demonstrate that LHRH conjugated to Sepharose can be used to separate gonadotrophs from other 2A8 cells, and it is suggested that the hypertrophy of some cells might be due to persistent stimulation by LHRH which is likely bound to receptors on the cell membrane.
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    URL: http://dx.doi.org/10.1007/BF00223119
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    The ultrastructure of the herring bodies in rats subjected to different experimental conditions (1978)
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    Cell & tissue research 189 (1978), S. 41-51 
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    ISSN: 1432-0878
    Keywords: Herring bodies (rat) ; Colchicine ; Cold ; Neurosecretion ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A study of the morphology of Herring bodies of the posterior pituitary lobe of rats treated with colchicine and/or exposed to low temperatures has been performed. After treatment with colchicine (20 μg in distilled water injected intracisternally) a predominance of Herring bodies with a large number of small “synaptic-like” vesicles surrounded by neurosecretory granules is found. Exposures to low temperature (4–6° C) result in an increase in the neurosecretory material and the Herring bodies show many neurosecretory granules of different densities. After treatment with colchicine and subsequent exposure to low temperatures, the Herring bodies are characterized by having a great number of autophagic bodies which become more numerous as the length of the exposure is increased; later autophagic vacuoles and lamellar bodies become evident.
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    URL: http://dx.doi.org/10.1007/BF00223120
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    The ultrastructure and histochemistry of the mesenteric connective tissue of the cockroach Periplaneta americana L. (Insecta, Dictyoptera) (1978)
    Springer
    Cell & tissue research 189 (1978), S. 91-107 
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    ISSN: 1432-0878
    Keywords: Connective tissue sheath ; Periplaneta ; Ultrastructure ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé La gaine conjonctive épaisse entourant l'intestin moyen de la Blatte Periplaneta americana a été étudiée en faisant appel à la microscopie photonique, électronique et l'histochimie. Cette couche conjonctive, reliée à l'épithélium mésentérique par une lame basale, traversée par des faisceaux musculaires, des trachées et des nerfs, contient de très nombreuses fibrilles de collagène, des fibrilles élastiques, des fibroblastes et des hémocytes. Au cours des premiers stades le matériel conjonctif est élaboré par des fibroblastes. Différentes réactions, en particulier le bleu alcian, la métachromasie et les digestions enzymatiques ont montré la présence de glycosaminoglycanes. La présence d'acide hyaluronique à tous les stades, l'apparition et l'augmentation des composés sulphatés ainsi que la présence de glycoprotéines ont été mises en évidence.
    Notes: Summary The thick layer of collagenous connective tissue around the mesenteron of the cockroach Periplaneta americana has been examined by light microscopy, electron microscopy and histochemical techniques. This sheath, connected to the mesenteric epithelium by a basal lamina and traversed by longitudinal and circular musculature, tracheae and nerves, contains numerous collagen fibrils, elastic fibers, fibroblasts and rare hemocytes. Development starts during the first instars with the production of connective tissue material by fibroblasts. Glycosaminoglycans have been observed with the use of various histochemical reactions, in particular alcian blue staining, metachromasia and enzymatic digestion. The reactions indicate the presence of hyaluronic acid in the various instars, the appearance and increase of sulphated components during development, and the presence of neutral glycoproteins.
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    An ultrastructural study of periderm granules in the regenerating feather of the jungle fowl (1978)
    Springer
    Cell & tissue research 192 (1978), S. 319-326 
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    ISSN: 1432-0878
    Keywords: Periderm granules ; Regenerating feather ; Ultrastructure ; Jungle fowl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Periderm granules in the support cells of regenerating feathers of mature male Jungle Fowls were studied ultrastructurally and histochemically. Histochemical results showed the absence of carbohydrate and lipid, and the presence of protein in the periderm granules. The periderm granules were measured at successive levels of feather regeneration. The mean size of the periderm granules increased significantly as the regenerating feather matured, and this observation was suggestive of a storage function, perhaps of surplus or waste protein. The cells in which the periderm granules are found also contain glycogen. There are numerous desmosomal junctions on their interdigitating plasma membranes. These transient cells may collect waste, provide nutrition, and serve as a protective barrier for the definitive cells of the regenerating feather.
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    URL: http://dx.doi.org/10.1007/BF00220749
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    A further type of transient cytoplasmic organelle in human spermatids (1978)
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    Cell & tissue research 192 (1978), S. 359-361 
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    ISSN: 1432-0878
    Keywords: Spermatids ; Human ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Osmiophilic granules with surrounding vesicles resembling flower-like structures occur transiently during the differentiation of human spermatids. These organelles are incorporated into the residual bodies when mature spermatids are released from the germinal epithelium.
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    URL: http://dx.doi.org/10.1007/BF00220752
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    Ultrastructural changes in the fat body of adult female Aedes aegypti in relationship to vitellogenin synthesis (1978)
    Springer
    Cell & tissue research 186 (1978), S. 499-506 
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    ISSN: 1432-0878
    Keywords: Fat body ; Aedes aegypti ; Vitellogenin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the fat body of Aedes aegypti was followed from emergence through a blood meal. Changes in the volume of protein granules and lipid droplets were also examined. The relationship of these events to the known endocrinology of vitellogenin synthesis in mosquitoes is discussed.
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    URL: http://dx.doi.org/10.1007/BF00224938
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    Leptomeric fibrils and T-tubule desmosomes in the Z-band region of the mouse heart papillary muscle (1978)
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    Cell & tissue research 188 (1978), S. 205-215 
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    ISSN: 1432-0878
    Keywords: Myocardium ; Mouse ; Ultrastructure ; Leptofibrils ; Desmosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The papillary muscle of the heart of adult white mice is investigated. Intrafibrillarly located leptomeric fibrils, frequently encountered in the Z-band region of the myofibrils. The leptomeric fibrils are always running in a transverse direction and often in close proximity to the transverse tubules (which are also located at this level). There seems to be a close connection between the dense striae of the leptofibrils and the Z-bands of ordinary myofibrils. The leptomeric fibrils are spindle-shaped and have a length varying between 0.6 and 1.2 μm. The banding periodicity of the fibrils is approximately 0.16 μm. Occasionally desmosomes are observed in the T-tubule system.
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    URL: http://dx.doi.org/10.1007/BF00222631
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    Evolution d'une garrigue de quercus coccifera L. soumise a divers traitements: Quelques resultats des cinq premieres annees (1978)
    Springer
    Plant ecology 38 (1978), S. 135-142 
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    ISSN: 1573-5052
    Keywords: Evolution ; Expériences ; Garrigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In 1969, several experiments were carried out in a Quercus coccifera garrigue, in order to clear up the role of man's action. Two of these experiments are described here: - one based on the repeated action of fire with two controlled factors (period of fire setting and fire frequency). - the other simulating rational grazing after mechanical scrub-clearing, with two controlled factors (fertilization and cutting period). The experimental results presented here are those obtained from 1969 to 1974, by observation along lines. They concern the species number and the behaviour of certain species; it appears from these results: - Whatever the experiment and the treatment, the number of species increases from 1969 to 1974. - The number of species is higher with ‘autumn fire’ than with ‘spring fire’, and with ‘fire every six years’ than with other fire frequencies (two and three years). - The number of species is the highest with mean fertilization and the latest cutting time. - The number of species in a reference line varies very much year after year, it follows that only the increase of the number of species with mean fertilization and the latest cutting time is higher than that of the reference ones. The stability of the original flora is noteworthy but the species frequency is modified. A few species appear, these ones are rare in the Quercus coccifera garrigue or come from the surrounding vegetation. The experiment ‘fire’ has not yet allowed to obtain by succession, the Brachypodium ramosum sward-hypothesis currently supported — the experiment ‘cutting’ has led towards a formation in which the grasses predominate. These experiments are now in progress.
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    Evolutionary trends in Mediterranean flora and vegetation (1978)
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    Plant ecology 37 (1978), S. 175-185 
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    ISSN: 1573-5052
    Keywords: Ecosystems ; Evolution ; Mediterrannean flora ; Mediterranean vegetation ; Paleoecology ; Technological impact ; Vegetational systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Die Vegetation der Mittelmeerländer bestand ursprünglich aus immergrünen Hartlaubwäldern; während des Pleistozäns breiteten sich sommergrüne Laubwälder aus, besonders in den gebirgigen Teilen. Die dichtere menschliche Besiedlung nach der Steinzeit bewirkte eine Einschränkung des Waldgürtels der zum Grossteil durch anthropogene Vegetationstypen (Macchie, Garigue, Unkrautgemeinschaften) ersetzt wurde. Die Spuren dieses Prozesses spiegeln sich in den Polyploidieverhältnissen. Bis zu diesem Punkt entwickelte sich das vegetationelle System autonom. Mit dem Auftreten des Menschen beginnt eine rege Dialektik zwischen dem vegetationellen und dem sozialen System. Einige Gesetzmässigkeiten werden dargestellt und eine geeignete Terminologie wird vorgeschlagen. Während des Altertums und des Mittelalters war eine gegenscitige Kontrolle zwischen Vegetation und menschliche Einwirkung möglich (zyklisches System), und die Vegetation wurde dadurch in einem Zustand von Fliessgleichgewicht stabilisiert; durch die Technologie wurden diese Verhältnisse verändert und es entstand ein lineares System, sodass nun die Vegetation unter der Drohung einer irreversiblen Aenderung steht.
    Notes: Summary The vegetation of the Mediterranean Basin was originally composed of evergreen forests; during the Pleistocene deciduous forests expanded, chiefly in the mountains. In historical time the forest belt was strongly reduced by human activity and substituted by anthropogenous vegetation types (macchia, garigue, weed-communities). The frequency of polyploids in the present vegetation types support this interpretation. Reciprocal relationships between the vegetational system and social system are discussed and a terminology is proposed. During ancient times and the middle ages a reciprocal control of vegetation and human activity was possible (cyclic system), stabilizing the vegetation in a steady state; the technological impact modified these conditions in a linear sense, and now the vegetation is menaced by irreversible changes.
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    Pharmacokinetic interpretation of the enterohepatic recirculation and first-pass elimination of morphine in the rat (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 505-519 
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    ISSN: 1573-8744
    Keywords: morphine ; first-pass elimination ; pharmacokinetics ; enterohepatic recirculation ; availability ; routes of administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Morphine was administered to rats by oral, intraportal, and intravenous routes in a dose of 7.6 mg · kg −1.From the serum concentration data after intraportal administration it was calculated that the first-pass elimination of morphine in the liver amounts to 72±2% (sd). The first-pass fraction eliminated after oral administration was 85±7% (sd), thus yielding a contribution by the gut mucosa of 46% to the overall first-pass elimination after an oral dose. The results were obtained with a general compartmental model which included the kinetics of enterohepatic recirculation. The oral availability was also estimated with the aid of pharmacological effect data. This availability was in good agreement with the corresponding value determined from the serum concentration data. The results suggest that morphine is subjected to enterohepatic recirculation and that the slowest phase of decline of morphine concentrations in serum might be due to this physiological process.
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    Linear systems analysis in pharmacokinetics (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 265-282 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; linear systems analysis ; in vivo dissolution rates ; absorption rates ; metabolic rates ; bioavailability ; numerical desconvolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of certain aspects of linear systems analysis to pharmacokinetic-problems is described. Topics covered include the evaluation of in vivodissolution rates, absorption rates, and metabolic rates, and the use of pharmacological data. Relevant numerical procedures are also discussed.
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    Pharmacokinetic analysis of percutaneous absorption; evidence of parallel penetration pathways for methotrexate (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 315-325 
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    ISSN: 1573-8744
    Keywords: percutaneous penetration ; methotrexate ; compartmental models ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Compartmental models were developed to describe the penetration of a drug from a topically applied vehicle through the skin. Data for in vitro penetration of methotrexate through hairless mouse skin from vehicles varying in PH from 3.5 to 6.5 were computer- fitted to estimate model parameters. Comparison of lag time and the exponential coefficient suggested that parallel penetration pathways exist. The fraction of drug penetrating through the shunt pathway increased as vehicle pH and ionization increased. Penetration curves were quantitatively partitioned into bulk tissue and shunt contributions. At pH 6.5, flux through the shunt pathway predominated.
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    Mathematical prediction of drug distributionin vivo: Studies with doxantrazole in rats (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 521-537 
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    ISSN: 1573-8744
    Keywords: compartmental analysis ; doxantrazole ; drug distribution ; mathematical prediction ; pharmacokinetics ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic model incorporating 14 compartments and 29 transfer coefficients has been developed from experimental data obtained after intravenous administration of a single dose to describe the distribution of doxantrazole in the rat. The distribution calculated from the model agreed closely with that determined experimentally. In addition, the model was able to predict with considerable accuracy the distribution of doxantrazole after repeated dosing.
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    Chlorpromazine metabolism. IX. Pharmacokinetics of chlorpromazine following oral administration in man (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 187-196 
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    ISSN: 1573-8744
    Keywords: Chlorpromazine ; pharmacokinetics ; oral absorption ; single dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A single oral dose (120 mg/m2) of Chlorpromazine hydrochloride was administered to four healthy subjects and the blood levels of Chlorpromazine were determined with time. Appropriate equations describing the two-compartment open model with zero-order absorption and the two-compartment model with first-order absorption, both with a lag time, were fitted to the observed data using weighted nonlinear least-squares regression analysis. Fitting the two-compartment model with zero-order absorption and a lag time to the observed data resulted in a significant reduction of the weighted sum of squared deviations, i.e., better correlation between the observed and calculated data, and a closer random scatter of the observed concentration data around the calculated curve with no apparent systematic deviations from the curve. These results suggest that Chlorpromazine absorption is zero order. Chlorpromazine began to appear in the systemic circulation after a mean lag time of 0.4 hr and continued to be absorbed for approximately 2.9 hr. The mean half-lives of the distribution and elimination phases were 1.63 and 17.7 hr, respectively.
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    Statistical moments in pharmacokinetics (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 547-558 
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    ISSN: 1573-8744
    Keywords: statistical moments ; network theory ; pharmacokinetics ; bioavailability ; deconvolution ; plasma concentration-time curve ; urinary excretion rate-time curve ; compartment models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Statistical moments are parameters that describe the characteristics of the time courses of plasma concentration (area, mean residence time, and variance of residence time) and of the urinary excretion rate that follow administration of a single dose of a drug. The relationship between the moments of a time-course curve and pharmacokinetic profiles of drug disposition, i.e., absorption, distribution, metabolism, and excretion, is described. The moments are related to the extent and rate of bioavailability, and it is shown that they can be effectively applied to the deconvolution operation.
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    URL: http://dx.doi.org/10.1007/BF01062109
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    Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 539-546 
    Details
    ISSN: 1573-8744
    Keywords: trapezoidal rule ; area under the curve ; pharmacokinetics ; clearance ; bioavailability ; integration method ; sulfisoxazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n)of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n=0.5 is about 1%. The error increases to 15.5% and 57.1 % when nis increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062108
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  • 94
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    Absorption of oral tetracycline in patients with Billroth-II gastrectomy (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 295-303 
    Details
    ISSN: 1573-8744
    Keywords: tetracycline ; antibiotics ; Billroth-II gastrectomy ; gastrectomy ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of a single 250-mg oral dose of tetracycline hydroghloride was studied in seven patients following Billroth-II gastrectomy in comparison with seven control subjects matched for age and body weight. There were no significant differences between control subjects and gastrectomized patients in the apparent lag time prior to the start of absorption (23.6 vs. 22.8 min), peak serum tetracycline concentration (1.72 vs. 1.75 μg/ml), the time of attainment of peak concentrations (3.35 vs. 3.42 hr), the apparent first-order absorption half-life (1.8 vs. 1.4hr), or the apparent first-order elimination half-life (8.0 vs. 8.7hr). Completeness of tetracycline absorption, as judged by area under the 24-hr serum concentration curve, did not differ significantly between the two groups, nor did 24-hr urinary excretion of tetracycline. Thus the abnormalities of gastrointestinal structure and function produced by Billroth -II gastrectomy do not result in impairment of the rate and completeness of tetracycline absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060093
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  • 95
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    Disposition kinetics in dogs of diethyldithiocarbamate, a metabolite of disulfiram (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 369-387 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; dog ; diethyldithiocarbamate metabolite of disulfiram ; presence of methyl ester ; kinetic evaluation of prior studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Following the intravenous infusion of sodium diethyldithiocarbamate to dogs, the disposition kinetics of diethyldithiocarbamate (DDC), a metabolite of disulfiram, were assessed. Approximately 27% of the administered dose was S-methylated, this process exhibiting a mean first-order rate constant of 0. 0569 min−1 (t1/2=12.2 min), while the remainder was eliminated by other routes having a rate constant of 0.148 min−1 (t1/2=4.68 min). The methyl diethyldithiocarbamate (MeDDC) formed from DDC showed an elimination rate constant of 0.0141 min−1 (t1/2=49.2 min). These observations are discussed in the light of previous investigations where the presence of MeDDC has rarely been sought or reported. A few comparisons with prior studies, in which DDC or disulfiram was administered, are made by retrospective kinetic evaluation of published data. The results are discussed in relation to the duration of action of disulfiram in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062720
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  • 96
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    The taxonomic status ofRhabdolichops troscheli (Kaup, 1856), and speculations on gymnotiform evolution (1978)
    Springer
    Environmental biology of fishes 3 (1978), S. 379-384 
    Details
    ISSN: 1573-5133
    Keywords: Gymnotids ; Fish taxonomy ; Tropical fishes ; Planktivore ; Evolution ; Fish ecology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Synopsis Anatomical and ecological studies of the gymnotiformRhabdolichops troscheli (Kaup 1856), one of the weakly electric fish of South America, indicate it to be unique among gymnotiforms in possessing certain characteristics found in characins. These include post-temporal fossae, well developed gillrakers, a planktivorous feeding mode, and diurnal feeding activity. We use these findings to speculate about the evolution of gymnotiform fishes, by assuming that these character states in this most primitive gymnotiform convey information about the group's evolutionary history. We suggest that the electric organs in this group of ostaryophysans have evolved primarily as a means of locating and capturing prey in river habitats of South America whose turbid waters result in low light penetration, ruling out visual sensing systems as an effective means of receiving information. Other aspects of morphology and behavior such as the absence or reduction of scales, and the nocturnal feeding activities characteristic of other gymnotiform, can be explained as consequences of food resource availability and predation pressures in these riverine environments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00000530
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  • 97
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    Development of the filiform hairs on the cerci of Gryllus bimaculatus Deg. (Saltatoria, Gryllidae) (1978)
    Springer
    Cell & tissue research 187 (1978), S. 1-24 
    Details
    ISSN: 1432-0878
    Keywords: Insect sensillum ; Mechanoreceptor ; Development ; Ultrastructure ; Gryllus bimaculatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The filiform hairs, mechanoreceptors of Gryllus, pass through six developmental stages during the last larval stage. The cytoplasm of their sense cells suggests intensive synthesis of protein for cellular metabolism and intercytoplasmic exchange of material via glial evaginations. Ultrahistochemical tests demonstrated acid phosphatase in the lysosomes as well as in components of the Golgi apparatus. There was no significant change in the appearance of the sense cell cytoplasm, indicating a maintained functional state also during molting. The new cuticular apparatus is formed after apolysis by the three enveloping cells. Formation of the replacement hairs is initiated by a cytoplasmic outgrowth of the trichogen cell. During morphogenesis of the new hair, the microtubules serve as a cytoskeleton and probably control the flow of vesicles, which contain phenol oxidase, also demonstrated in the Golgi apparatus, and are incorporated into the new cuticle. Bundles of microfibrils are involved in the surface sculpturing of the replacement hair. The trichogen cell also forms a number of structural elements, e.g. the “cup” and “strut” marked geometric peculiarities of which indicate that they are important in the spatial orientation of the dendrite and thus also in transduction. Reduction of the apical cell membrane of the tormogen cell after apolysis permits unrestricted growth of the new hair into the exuvial space. The tormogen cell participates in the formation of the joint membrane, parts of the socket and the articulation of the hair.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00220615
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  • 98
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    Early effects of prolactin on lactating rabbit mammary gland (1978)
    Springer
    Cell & tissue research 187 (1978), S. 25-43 
    Details
    ISSN: 1432-0878
    Keywords: Lactation ; Prolactin ; Secretion ; Caseins ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Les effets de la prolactine, sur la sécrétion des protéines du lait, ont été étudiés grâce à des incubations de tranches de glandes mammaires de lapines en lactation. Dès 15min après l'addition de l'hormone au milieu d'incubation, la morphologie de la cellule est modifiée: le volume relatif des vésicules et des saccules Golgiens est fortement augmenté. Lorsque la prolactine est rajoutée, immédiatement après un marquage en 〈pulse〉 des protéines (pendant 3 min par la L-leucine 3H), elle provoque, en une heure, une augmentation de la sérétion des caséines radioactives dans le milieu d'incubation. Cette augmentation de la quantité de caséines sécrétées ne provient ni d'une augmentation du transit intracellulaire des protéines néosynthétisées (étudié par autoradiographie en Microscopie Electronique), ni d'une augmentation d'incorporation des acides aminés (mesurée par l'incorporation d'acides aminés non métabolisables), ni d'une augmentation de la synthèse protéique totale, dans le délai d'une heure. Les relations possibles entre l'action de la prolactine sur l'aspect morphologique d'un organite cellulaire tel que l'appareil de Golgi et sur la sécrétion des caséines sont discutées.
    Notes: Summary Effects of prolactin on the secretion of milk proteins have been investigated by incubating mammary tissue fragments from lactating rabbits. Within 15min of adding the hormone to the incubation medium, cell morphology is modified: the relative volume occupied by the Golgi region is greatly increased. When prolactin is added immediately after a pulse labelling of proteins (3 min with 3H-L-leucine), the amount of labelled caseins secreted during one hour is significantly increased. This increase proceeds neither from an acceleration of intracellular transit of caseins (as shown by electron microscopic autoradiography) nor by an enhancement of amino acid uptake (as measured by incorporation of non-metabolizable amino acids) nor by an increase of overall protein synthesis, during the first hour. The action of prolactin on the morphology of such subcellular organelles as the Golgi apparatus and its influence on casein secretion are discussed.
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    URL: http://dx.doi.org/10.1007/BF00220616
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  • 99
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    Cytological observations on the blood and hemopoietic tissue in the crab, Callinectes sapidus (1978)
    Springer
    Cell & tissue research 187 (1978), S. 79-96 
    Details
    ISSN: 1432-0878
    Keywords: Crustacean hemocytes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A fine structural analysis of hemocytes recovered from the pericardial sinus of the blue crab (Callinectes sapidus) demonstrates that hyaline cells, intermediate cells, and granuloyctes are present in the hemolymph. A detailed consideration of their shared and differing cytological features suggests that the various blood cells represent different stages of cytogenesis along a common or single path of cellular differentiation. The potential functional complexity of the hemocytes is attested to by the occurrence within their cytoplasm of three and/or possibly four morphologically distinct types of inclusion bodies, and other membrane-bounded compartments (e.g., lysosome-like structures, autophagic vacuoles, peroxisome-like bodies) whose function is unknown. Preliminary examination of the well-developed Golgi organelle in the intermediate cells and granulocytes indicates its probable participation in the elaboration of the inclusion bodies; however, the details of its role in granulogenesis and in the known plurifunctional capacities of these cells remain obscure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00220620
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  • 100
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    Unusual mitochondrial ultrastructure in the pig adrenal cortex (1978)
    Springer
    Cell & tissue research 187 (1978), S. 129-134 
    Details
    ISSN: 1432-0878
    Keywords: Adrenal cortex (Pig) ; Mitochondria ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Unusually large mitochondria with few cristae were observed in the cells of the boundary layer between the zonae fasciculata and reticularis of the pig adrenal. These mitochondria occasionally contained parallel arrays of beaded filaments which appeared to be composed of repetitive electron opaque particles, measuring 10 to 11 nm in diameter. The possibility that these filaments are arranged in closely packed arrays of tubular structures with a central filament is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00220624
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