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  • 2000-2004
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Materialart
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  • 2000-2004
  • 1980-1984
  • 1975-1979  (1.208)
  • 1840-1849
Jahr
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  • 1
    Digitale Medien
    Digitale Medien
    Das Anastomosengeschwür am operierten Magen (1977)
    Springer
    Langenbeck's archives of surgery 343 (1977), S. 133-151 
    Details
    ISSN: 1435-2451
    Schlagwort(e): Peptic ulcer ; Anastomosis ; Duodenogastric reflux ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die vorliegende Studie gilt dem Anastomosengeschwür am operierten Magen. Diese schwerwiegende Komplikation entsteht nahezu ausschließlich nach Resektionsverfahren mit duodenaler Exklusion (Billroth II; Verlegung des Duodenum in den Nebenschluß). - An 54 männlichen Wistarratten wurden verschiedene Formen der duodenalen Exklusion mit und ohne duodenogastrischen Reflux durchgeführt. Die Ergebnisse unserer Untersuchungen zeigen, daß nach duodenaler Exklusionmit Reflux gesetzmäßig peptische Anastomosengeschwüre entstehen. Der kontinuierliche Reflux von Galle und Pankreassekret ist der ausschlaggebende ätiologische Faktor für die Ulcusentstehung im Grenzgebiet der Anastomose von Magen und Dünndarm. Stase im ausgeschalteten Zwölffingerdarm (Syndrom der zuführenden Schlinge) fördert die lcerogene Refluxwirkung. Fehlt der Pylorus, so potenzieren sich Reflux und Stase zur größten Ulcusfrequenz (〉 90%). Bei erhaltenem Pylorus ist die Geschwürsincidenz wesentlich geringer. Der duodenogastrische Reflux hemmt die meßbare Salzsäuresekretion signifikant (P 〈 0,01); Salzsäure spielt demnach für die Entstehung des experimentellen Anastomosengeschwürs der Ratte keine wesentliche Rolle. - Im Hinblick auf die Prophylaxe des Anastomosengeschwürs führen diese Erkenntnisse zu der Forderung, auf Operationsverfahren mit duodenaler Exklusion und Reflux (Billroth II) zu verzichten und das Operationsziel bei der Magenresektion auf die Wiederherstellung der orthograden MagenDarm-Passage zu richten.
    Notizen: Summary Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of ref lux and stasis potentiate, resulting in a high frequency of ulcer (〉 90 %). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (P 〈 0.01); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. - In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01262005
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  • 2
    Digitale Medien
    Digitale Medien
    Microridge cells in the larynx of the male white rat. Investigations by reflection scanning electron microscopy (1977)
    Springer
    European archives of oto-rhino-laryngology and head & neck 215 (1977), S. 1-9 
    Details
    ISSN: 1434-4726
    Schlagwort(e): Respiratory epithelium ; Larynx ; Microridge cells ; Rat ; Scanning electron microscopy ; Respiratorisches Epithel ; Kehlkopf ; Mikroleistenzelle ; Ratte ; Rasterelektronenmikroskopie
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Das Kehlkopfepithel ausgewachsener männlicher Albinoratten wird rasterelektronenmikroskopisch untersucht. Zusätzlich zu den zilientragenden und zu den Mikrovillizellen, zu den Bürsten- und Becherzellen, welche insgesamt für das respiratorische Epithel charakteristisch sind, werden in bestimmten Abschnitten des Larynx die Mikroleisten- oder Labyrinthzellen beschrieben. Die freie Oberfläche typischer Labyrinthzellen ist durch ein System von sich verzweigenden Mikroleisten gekennzeichnet, die miteinander durch Querbrücken verbunden sind und in der Zellperipherie eine bevorzugte Parallelausrichtung zur Zellgrenze zeigen können. Der Durchmesser der Mikroleisten beträgt ca. 0,05–0,15 μm. Die Querverbindungen zwischen den Mikroleisten haben einen Durchmesser von ca. 0,01 μm. Der Raum zwischen zwei benachbarten Querbrücken variiert. Labyrinthzellen können außer Mikroleisten auch Mikrovilli zeigen und es gibt Übergänge zwischen den Mikroridge- und den Mikrovillizellen. Die bevorzugte Lokalisation der Mikroleistenzellen im Bereich der Glottis und des Aditus laryngis wird belegt. Die mögliche Funktion dieser Zellen und ihre Bedeutung für die Diagnostik pathologischer Schleimhautveränderungen wird diskutiert.
    Notizen: Summary The laryngeal epithelium of male white rats is studied by reflection scanning electron microscopy (SEM). In addition to ciliated cells, microvilli cells, brush cells and goblet cells that are characteristic for normal respiratory epithelium the microridge or labyrinth cell can be seen in particular regions of the larynx. The apical surface of a typical labyrinth cell is characterized by a system of narrow standing microridges of about 0.05–0.15 μm in diameter and interconnecting microridges with a diameter of about 0.01 μm. The microridge system of a labyrinth cell originates from the fusion of densely standing microvilli. Between microridge cells and microvilli cells all transition forms can be observed. The preferable localiziation of the microridge cell in the larynx and its possible function is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00463186
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  • 3
    Digitale Medien
    Digitale Medien
    Rasterelektronenmikroskopische Studien zur Feinstruktur des Epiglottisepithels von Ratten (1977)
    Springer
    European archives of oto-rhino-laryngology and head & neck 217 (1977), S. 41-51 
    Details
    ISSN: 1434-4726
    Schlagwort(e): Respiratory epithelium ; Epiglottis ; Rat ; Scanning electron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The epithelial surface of the epiglottis in adult male and female albino rats is studied by scanning electron microscopy. Prominent differences exist between the surface morphology as observed in the males and that observed in the females sacrificed in the estrus phase of the ovarial cycle. The differences are most pronounced in respect to the amount of secretory vesicles, microvilli- and microridge-cells and in respect to the observable number of desquamating cells. The existence and the importance of the microridge-cells are discussed. Special attention is also paid to the results indicating that at least some parts of the extrapulmonary airway epithelia act as possible target organs for sex hormones. Finally the importance of the observed differences is discussed for the correct interpretation of pathomorphological alterations in the extrapulmonary airway epithelia that have been observed under experimental conditions and during infections.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00453889
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  • 4
    Digitale Medien
    Digitale Medien
    Cyclic nucleotide phosphodiesterases of human and rat gastric mucosa (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1977), S. 187-190 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Cyclic nucleotide phosphodiesterase ; Gastric mucosa ; Human ; Rat ; Inhibitors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Cyclic adenosine-3′,5′-monophosphate (cAMP) phosphodiesterases (PDE) were partially purified from human and rat gastric mucosa. Drugs known to affect the cyclic nucleotide system and/or gastric secretion were tested for effects on the PDE-activities from both species. In rat gastric mucosa PDE-activity can be detected in the 100 000×g sediment (K m =8.3 μM; V max=3.2 nmoles cAMP hydrolyzed/mg protein x min) and the cytoplasma (K m =5.6 μM; V max=2.6 nmoles cAMP hydrolyzed/mg protein x min). The most effective inhibitors of the particle-bound activity are papaverine (K i =4 μM, non-competitive) and 3-isobutyl-1-methylxanthine (K i=14 μM, competitive). There was only a modest competitive inhibition by theophylline (K i =495 μM). PDE-activity in the cytoplasma was inhibited competitively by these three drugs (papaverine: K i =6.5 μM; 3-isobutyl-1-methylxanthine: K i =37 μM; theophylline: K i =152 μM. In human gastric mucosa PDE-activity can be detected in the particular fraction (K m =23.9 μM; V max=1.2 nmoles cAMP hydrolyzed/mg protein x min), and the soluble fraction (K m =12.1 μM; V max=2.4 nmoles cAMP hydrolyzed/mg protein x min). PDE-activity in the 100 000×g sediment was inhibited by papaverine (K i =5.6 μM, non-competitive), 3-isobutyl-1-methylxanthine (K i =16 μM, non-competitive), theophylline (K i =165 μM, non-competitive), and N6-2′-O-dibutyryl-cAMP (K i =746 μM, competitive). Inhibition in the 100 000×g supernatant was noncompetitive with 3-isobutyl-1-methylxanthine (K i =7.1 μM and papaverine (K i =8.5 μM), but competitive with N6-2′-O-dibutyryl-cAMP (K i =170 μM), and theophylline (K i =225 μM). This study indicates that PDE-activities of the two species are qualitatively similar, but quantitative differences exist.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00508473
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  • 5
    Digitale Medien
    Digitale Medien
    Cortical bone remodeling in normal rat (1977)
    Springer
    Calcified tissue international 23 (1977), S. 161-170 
    Details
    ISSN: 1432-0827
    Schlagwort(e): Bone ; Growth ; Rat ; Remodeling ; Tetracyclines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Cortical bone remodeling along the femur diaphysis was determined in normal female rats (Sprague-Dawley) with the tetracycline technique. Three segments on the cortical bone circumference (the anterolateral, the medial, and the posterior) were found to be most suitable for the study of the remodeling process. Oxytetracycline was administered at age 60 and 75 days, and groups of animals were killed at age 75, 85, 95, and 105 days. The accumulated endosteal growth during age 60 to 75 days in the anterolateral segment was found to increase uniformly in the distal direction along the femur diaphysis. A method is described where this accumulated endosteal growth is used. This method eliminates the use of calipers to determine the section level and makes it possible to study comparable sections even after varying periods of time. The proximal part of the diaphysis showed periosteal apposition in all three segments. The periosteal apposition turned into resorption in the distal part of the diaphysis in the anterolateral and medial segments, whereas the periosteal appsition increased in the posterior segment. The endosteal growth increased in the distal direction in the anterolateral and medial segments. Irregular OTC bands made measurements of endosteal remodeling in the posterior segment impossible. The cortical width decreased in the distal direction along the femoral shaft. Comparison between the different age groups is described and also the relation between the accumulated endosteal growth and the diameter of the medullary cavity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02012782
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  • 6
    Digitale Medien
    Digitale Medien
    An analysis of response properties of spinal cord dorsal horn neurones to nonnoxious and noxious stimuli in the spinal rat (1977)
    Springer
    Experimental brain research 27 (1977), S. 15-33 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Spinal cord ; Dorsal horn interneurones ; Pain mechanisms ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Electrophysiological properties of neurones in the spinal cord dorsal horn were studied in decerebrated, immobilized spinal rats. Extracellular recordings were performed at the thoraco-lumbar junction level. Each track was systematically located by extracellular injection of pontamine sky blue. According to their responses to mechanical peripheral stimuli, cells were classified in four classes: Class 1 cells: Cells activated only by nonnoxious stimuli. They were divided into — 1A: hair movement and/or touch and 1B: hair movement and/or touch and pressure or pressure only. Class 2 cells: Cells driven by both nonnoxious and noxious stimuli, divided into — 2A: hair movement and/or touch, pressure, pinch and/or pin-prick, and 2B: pressure, pinch and/or pin-prick. Class 3 cells: Cells only activated by noxious stimuli (pinch and/or pin-prick). Class 4 cells: Cells responding to joint movement or pressure on deep tissues. Peripheral transcutaneous or sural nerve stimulation clearly showed that class 1 cells were activated only by A fiber input while 68% of classes 2 and 3 cells received A and C input. Histological examination indicated that cells driven only by noxious input were located either in the deepest part or in the marginal zone (lamina I) of the dorsal horn. Nevertheless, some lamina I cells were also driven by both nonnoxious and noxious stimuli. In addition, there is a great deal of overlap between class 1 and class 2 cells. This fact was confirmed by considering the wide distribution in the dorsal horn of cells receiving A and C input. However, spinal organization of the different classes of cells consists of a preferential distribution rather than a strict lamination. This study indicates that properties of dorsal horn interneurones in the rat have a high degree of similarity with those previously described in other species (cat and monkey).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00234822
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  • 7
    Digitale Medien
    Digitale Medien
    The influence of the amygdala on the basal septum and preoptic area of the rat (1977)
    Springer
    Experimental brain research 29 (1977), S. 249-263 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Preoptic area ; Basal septum ; Amygdala ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Extracellular microelectrode recordings were made from single neurones in the medial preoptic area and basal septum of normal female rats anaesthetised with urethane and the effects of stimulation of the ipsilateral amygdala (AMY) was tested. 1. Quiescent cells were excited with latencies between 4 and 〉 40 msec with the majority being between 10 and 27 msec. Variable latency, changing latency and recruitment were observed and suggest that many pathways are oligo- or polysynaptic. 2. A minority of spontaneously active units (20.6%) were excited with latencies between 5 and 36 msec. The predominant initial response was inhibition (67.1%). The remaining 12.3% of neurones did not respond. 3. A predominantly positive complex field potential was associated with excitation, particularly of quiescent neurones. 4. Inhibitory responses were classified according to duration (short: 20–60 msec; long: 100–400 msec). All responses contained an inhibitory component. Responses were further described on the basis of presence and rhythmicity of post-inhibitory excitation. 5. The majority of action potentials evoked from quiescent neurones were of small amplitude (80–150 μV) and occurred in small groups. These characteristics and their occurrence at the onset of inhibition are consistent with the view that all or a proportion of them may be generated by inhibitory interneurones. 6. Only minor differences were observed between response characteristics evoked by stimulation of the corticomedial or basolateral AMY indicating that differential effects of these regions on adenohypophysial hormone secretion are determined at the septopreoptic level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237045
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  • 8
    Digitale Medien
    Digitale Medien
    A cerebellar projection onto the pontine nuclei in the albino rat (1977)
    Springer
    Experimental brain research 30 (1977), S. 149-154 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Dentate and interpositus nuclei ; Pontine gray ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Following removal of a significant part of the dentate nucleus and most of the interpositus nucleus in the rat cerebellum degenerated cerebellopontine fibres are shown to end in three fairly restricted regions in the contralateral pontine gray: in the paramedian position, in the middle and in the lateral third. The three regions are arranged in rostro-caudal longitudinal columns in the caudal three-quarters of the pons and these columns are continuous with one another by regions of scattered degeneration. The fibres appear to end in relation to distal dendrites of the pontine cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237866
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  • 9
    Digitale Medien
    Digitale Medien
    Ultrastructural responses of the hypoglossal nucleus to the presence in the tongue of botulinum toxin, a quantitative study (1977)
    Springer
    Experimental brain research 30 (1977), S. 313-321 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Hypoglossal nucleus ; Botulinum toxin ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The ultrastructural effects of local injection of botulinum toxin into the left half of the tongue of the rat, were studied quantitatively 35 days postoperatively in the left hypoglossal nucleus. The results showed (1) a decrease in somatic and neuropil bouton numbers because of loss of boutons with symmetrical synapses and clear spherical synaptic vesicles, (2) a decrease in the numbers of dendrite profiles in the neuropil, (3) an increase in the proportion of dendrites and boutons with unusual inclusions, suggestive of profile retraction, (4) an increase in the proportion of profiles which were unusually electron-dense, (5) an increase in the amount of astrocyte, and a growth of astrocyte sheaths around bouton-free neurone surfaces, (6) the presence of occasional microglia, and (7) subastrocytic subsurface cisterns. Control rats injected with boiled toxin had no responses except (3) and (4) above, and then only to a modest extent, possibly due to mechanical damage of a few axons or terminals at the time of injection, or to insufficient inactivation of the toxin by boiling. The results were compared with those at 35 days after axotomy, and it was concluded that botulinum toxin, which interrupts neuromuscular transmission, elicits the same responses in the hypoglossal neurones, as does transection of the hypoglossal nerve, even though earlier studies had discovered no glial replication after botulinum toxin, in contrast to axotomy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237258
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  • 10
    Digitale Medien
    Digitale Medien
    Cholinergic transmission in subcortical and cortical visual centers of rats: No evidence for the involvement of primary optic system (1977)
    Springer
    Experimental brain research 27 (1977), S. 211-219 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Visual system ; Degeneration ; AChE ; Choline acetyltransferase ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effect of unilateral enucleation, ablation of the visual cortex or coagulation of the lateral geniculate nucleus (LGN) upon the activity of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) in different structures of the visual system of albino rats was studied. The localization and extent of the degeneration pattern were followed up by histological silver degeneration methods. Afferents from the retina project mainly contralaterally to the dorsal and ventral LGN, the pretectal region and the superior colliculus. Afferent fibres from the dorsal LGN enter the visual cortex in area 17 only. Neurons of this area project back ipsilaterally to the LGN and the superior colliculus (SC). No significant decrease in the activity of the cholinergic marker enzyme choline acetyltransferase could be observed under any of the experimental conditions; there was rather a tendency to increased activity in the subcortical centres. AChE as a less specific marker also exhibited no gross changes in activity in the lesioned animals. The results add more direct proof to pharmacological and physiological evidence that ACh is not involved in the synaptic transmission of the direct optic projections in rats, either at the subcortical or at the cortical level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237699
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  • 11
    Digitale Medien
    Digitale Medien
    Responses in the hypoglossal nucleus to delayed regeneration of the transected hypoglossal nerve, a quantitative ultrastructural study (1977)
    Springer
    Experimental brain research 29 (1977), S. 219-231 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Rat ; Hypoglossal nucleus ; Delayed regeneration ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Electron micrographs of the left hypoglossal nucleus of adult male albino rats were quantitatively analyzed from 9–70 days after allowing the transected left hypoglossal nerve to regenerate after an 84 day delay. Delay was achieved by implanting the proximal stump into already innervated sternomastoid muscle, where no regeneration occurred. Regeneration was then allowed by denervating the sternomastoid. During the regenerative period the initially high number of abnormally electron dense perikarya and dendrites decreased to almost normal values, but no cell removal was seen. This suggested that the degenerate appearance of many profiles after prolonged prevention of regeneration, was reversible. The neuropil bouton and dendrite counts, and the numbers of synapsing boutons per dendrite, increased steadily to normal values from the low values of suppressed regeneration. Somatic bouton frequencies, even though already low, decreased further at 32 days, and later increased but not to normal values. The decrease at 32 days coincided with the loss of many subsurface cisterns, and dispersion of Nissl substance, all suggestive of chromatolysis. Later the subsurface cisterns and Nissl substance returned. It was suggested that the delay of complete recovery of somatic bouton frequencies might be because of lack of sensory information from the denervated muscle into which the hypoglossal nerve was regenerating, or because of abnormally low starting values for the recovery phase. Astrocyte (or, occasionally microglial) sheaths persisted along boutonfree perikaryal surfaces.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00237043
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  • 12
    Digitale Medien
    Digitale Medien
    Cell death in the optic tectum of the developing rat (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 29-34 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Optic tectum ; Rat ; Cell death
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The death of cells was studied by light microscopy in the optic tectum of normal, developing rats. Normal cell death in the tectum during development has previously been described in chickens but not in a mammal. The total period of cell death was from the 20th embryonic day through the 11th postnatal day. During this period the number of dying cells was comparatively small for the first 2 days, reached a peak at birth and then decreased over the next 11 days. In comparison to the number of surviving cells the number of dead cells in each section was small. The dead cells appeared to be randomly distributed in all layers of the optic tectum.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315295
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  • 13
    Digitale Medien
    Digitale Medien
    The postnatal development of rat dentate gyrus and the effect of early thyroid hormone treatment (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 335-339 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Autoradiography ; Hippocampus ; Neurogenesis ; Rat ; Thyroid hormone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The postnatal development of the dentate gyrus and the effect of 5 μg/day triiodothyronine treatment was examined by means of tritiated thymidine autoradiography. The polymorph layer of the dentate gyrus is a secondary germinal layer and forms cells for the granular layer. The cell formation in the dentate gyrus was found to be nearly completed on the 21st day, but development ended only in adulthood. Thyroid-hormone treatment did not affect significantly the postnatal cell formation of the dentate gyrus, but resulted in the appearance of a great number of pycnotic cells in the granular layer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318935
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  • 14
    Digitale Medien
    Digitale Medien
    The surface ultrastructure of the habenular complex of the rat (1977)
    Springer
    Anatomy and embryology 152 (1977), S. 43-64 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Habenula ; Ependyma ; Supraependymal cells ; Supraependymal axons ; Electron microscopy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The surface features of the ependymal lining of the habenular complex in rats, aged between three weeks and nine months, were studied by means of scanning and transmission electron microscopy. The ependyma of the medial habenular nucleus is heavily ciliated, the cilia obscuring underlying substructure in SEM — preparations. On the habenular commissure most cilia are arranged in tufts. Cilia are provided with segmental indentations and occasional apical thickenings. Vesicular protrusions of the ependymal cytoplasm into the ventricular lumen and the frequent occurrence of homogeneous supraependymal globules were interpreted as signs of ependymosecretory activity of nucl. hab. med. Supraependymal cells are most numerous on the anterior and superior surface of the habenular commissure. Cells presenting features identical to Kolmer (epiplexus) cells were identified on the ventricular surface of nucl. hab. med. in one specimen showing degenerative changes of undetermined aetiology in the habenular nuclei. It is therefore suggested that such cells need not necessarily be restricted to the choroid plexus. Supraependymal unmyelinated axons are particularly numerous on both nucl. hab. med. and commiss. hab. They make desmosome contacts (maculae adherentes) with the ependymal plasmalemma. Contacts presenting all features of typical synapses were not encountered. The vesicle population of the axonal profiles mainly comprises 35–50 nm translucent round vesicles besides small numbers of 60–100 nm dense-cored vesicles and large pleiomorphic vesicles. Most probably the axons belong to the well-established dense population of serotonergic axons in the dorsal part of the third ventricle.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00341434
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  • 15
    Digitale Medien
    Digitale Medien
    Absorption of horseradish peroxidase by the principal cells of the large intestines of postnatal developing rats (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 53-62 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Large intestine ; Intestinal absorption ; Postnatal development ; Rat ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The absorption of horseradish peroxidase in the rat large intestine during the postnatal developing period was investigated by cytochemical and ultrastructural methods. In the ceca and ascending colons from 4-, and 5-day-old rats, intraluminaly injected peroxidase became localised on microvilli, in the intracytoplasmic network of the apical tubules and small vacuoles (tubulo-vacuolar system), in the large supranuclear vacuole, in the Golgi apparatus, on the lateral and basal cell membranes of the surface principal cells, and also in the lumen of blood capillaries in the subjacent propria. On the other hand, the protein tracer was not seen in the large intestinal epithelial cells that lack tubulo-vacuolar systems and large supranuclear vacuoles within their cytoplasm. In the descending colons of rats of any postnatal age, the epithelial principal cells are devoid of these membrane systems, and exogenous peroxidase was not detected in the cytoplasm of the principal cells. It is assumed that at least the proximal portion of the large intestine in neonatal animals has the capacity to absorb macromolecular protein through those surface principal cells that have specialized intracellular membrane systems.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315297
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  • 16
    Digitale Medien
    Digitale Medien
    Influence of adrenalectomy on “Gomori-positive” substances in the hypothalamo-neurohypophysial system of rats heterozygous and homozygous for hypothalamic diabetes insipidus (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 81-89 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Neurosecretion ; Adrenalectomy ; Diabetes insipidus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of adrenalectomy on the amount of “Gomori-positive” neurosecretory material in the outer layer of the median eminence and in the supraoptico-hypophysial system was studied in normal Long-Evans rats and in Long-Evans rats heterozygous and homozygous for hypothalamic diabetes insipidus. In all non-adrenalectomized rats very few “Gomori-positive” granules were found in the outer median eminence layer. After adrenalectomy the amount of the granules increased markedly in normal Long-Evans rats and only slightly in Long-Evans rats heterozygous for diabetes insipidus. However, no augmentation of the granules occurred in homozygous diabetes insipidus rats. The amount of “Gomori-positive” substances demonstrable in the supraoptic and paraventricular nuclei, in the inner layer of the median eminence, and in the neural lobe of the hypophysis was less in rats heterozygous for diabetes insipidus than in normal Long-Evans rats and the smallest in homozygous diabetes insipidus rats. No differences in the amounts of the substances were observed between adrenalectomized and non-adrenalectomized animals. The findings suggest that the “Gomori-positive” granules occurring in the outer layer of the median eminence of adrenalectomized rats are of similar origin as those of the supraoptico-hypophysial system and represent a vasopressin-neurophysin-complex. The results support the concept that vasopressin is involved in the regulation of ACTH release.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315300
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  • 17
    Digitale Medien
    Digitale Medien
    The fine structure of the ependymal surface of the recessus infundibularis in the rat (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 241-265 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Scanning E.M. ; Third ventricle ; Neurohypophysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The surface of the recessus infundibularis of the third ventricle has been studied with the scanning and transmission technique in normal and experimental material. Surface specializations such as microvilli, craters and areas of discontinuous lining are described. Supraependymal cells and fibres have been found; some of these cells form wide-meshed networks. The supraependymal fibres may be regular or varicose; the former seem to perforate the ependyma. With the transmission electron microscope the supraependymal cells are divided into three categories: nerve cells, lymphocytes and “dense cells”. Two fibre populations are distinguished: thin profiles (nerve fibres) and thick profiles (nerve terminals). Axosomatic and axoaxonic synapses are described. Synapses between supraependymal fibres and ependyma cells have also been found.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318929
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  • 18
    Digitale Medien
    Digitale Medien
    The accessory phrenic nerve in the rat (1977)
    Springer
    Anatomy and embryology 151 (1977), S. 63-69 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Rat ; Phrenic nerve ; Accessory phrenic nerve ; Diaphragmatic myotomes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Reinnervation studies of the diaphragm led us to reinvestigate the normal anatomy of the phrenic nerve of the rat. The phrenic nerve originates from the cervical nerve roots C4 and C5. In 16 out of 19 normal rats an accessory phrenic nerve was observed receiving its segmental fibres from C6. The number of myelinated axons of the accessory phrenic nerve varied from 41 to 101 (mean: 64.3, i.e. about 15% of the average number of axons in the common phrenic nerve). The accessory phrenic nerve innervates the dorsal part of the costal and the lateral part of the crural region, whereas the remaining parts of the hemidiaphragm are supplied by the segments C4 and C5. There is no evidence for any additional contribution to the motor innervation of the diaphragm from intercostal nerves.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315298
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  • 19
    Digitale Medien
    Digitale Medien
    The influence of protein-calorie malnutrition on the development of paranodal regions in spinal roots (1977)
    Springer
    Acta neuropathologica 40 (1977), S. 253-257 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Protein-calorie malnutrition ; Rat ; Spinal root ; Paranodal region ; OTAN method
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary During the early postnatal development of spinal roots in rats paranodal regions were often found, containing OTAN-positive inclusions in the Schwann cell cytoplasm. The presence of OTAN-positive paranodal regions showed variations in time, which were synchronous for ventral and dorsal roots. Dorsal roots, however, showed a more marked presence during development than ventral roots. Spinal roots of animals submitted to a 50% food restriction, were shown to contain more OTAN-positive paranodal regions than controls. This was true for ventral as well as dorsal roots. It is suggested that crowding of internodal segments could be one factor, determining the presence of paranodal, OTAN-positive material.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00691963
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  • 20
    Digitale Medien
    Digitale Medien
    Paranodal myelin retraction in protein deficient and normal rats (1977)
    Springer
    Acta neuropathologica 40 (1977), S. 249-252 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Low-protein diet ; Rat ; Peripheral nerve ; Paranodal area ; Morphometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Young rats, submitted to severe protein restriction were studied concerning the width of intermyelin gaps at the nodes of Ranvier in peripheral nerve fibres. The results gave no proof of increased paranodal myelin retraction in lumbar spinal roots or the sciatic nerves of low-protein rats. Malnourished rats as well as controls showed great interindividual differences as to the presence of nodes with wide inter-myelin gaps.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00691962
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  • 21
    Digitale Medien
    Digitale Medien
    Plasma fluoride and enamel fluorosis (1977)
    Springer
    Calcified tissue international 22 (1977), S. 77-84 
    Details
    ISSN: 1432-0827
    Schlagwort(e): Fluoride ; Blood plasma ; Enamel mineralization ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Abstract It is postulated that tissue fluid F concentrations are the primary determinants of fluoride effects on bones and developing teeth and that these concentrations are dependent on, or mirrored by, blood plasma F. It has earlier been shown that the plasma F levels are dependent on the dietary F supply as well as on skeletal F concentration. Fasting and post-ingestion or postinjection plasma F levels have been determined in rats on F doses that cause different degrees of enamel fluorosis. The results indicate that temporary peak values rather than elevated fasting values are responsible for the occurrence of enamel fluorosis and that the peak values must approach about 10 μM in order to block enamel formation by the ameloblasts. The diagnostic and prognostic importance of plasma F determinations is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02010348
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  • 22
    Digitale Medien
    Digitale Medien
    Lamellar organisation in the rat hippocampus (1977)
    Springer
    Experimental brain research 28 (1977), S. 335-344 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Hippocampus ; Rat ; Lamellae
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A series of experiments was conducted in the urethane anaesthetised rat to determine the organisation of some hippocampal pathways in this species, using stimulating and recording microelectrodes to elicit and record population spikes. It was found that the mossy fibres, alvear fibres and perforant path were clearly arranged in a lamellar fashion. Lamellar organisation could not be demonstrated for the afferents in the stratum radiatum which include the Schaffer collaterals. It was concluded that hippocampal organisation in this species essentially resembles that in the rabbit and cat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00235715
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  • 23
    Digitale Medien
    Digitale Medien
    An automated method for studying exploratory and stereotyped behaviour in rats (1977)
    Springer
    Psychopharmacology 52 (1977), S. 271-277 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Rat ; Exploratory behaviour ; Stereotyped behaviour ; Hole-board ; dl-Amphetamine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A technique is described for studying exploratory as well as stereotyped behaviour in rats using an automated hole-board. Both visual and automated recordings can be employed using the technique. Hole dipping is monitored automatically using an infra-red detector system. Repetitive patterns of hole-dipping are used as parameters of stereotyped behaviour while the more random patterns of hole-dipping are used as parameters of exploration. There was a high significant correlation between the records of hole-dipping behaviour as recorded visually and automatically. There was also a high significant correlation between the measures of repetitiveness/randomness of hole-dipping behaviour from automatic and visual recordings. The pattern and levels of hole-dipping conformed with expectations both as regards changes with time and with increasing doses of dl-amphetamine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00426711
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  • 24
    Digitale Medien
    Digitale Medien
    Naloxone-induced or postwithdrawal abstinence signs in Δ9-Tetrahydrocannabinol-Tolerant rats (1977)
    Springer
    Psychopharmacology 55 (1977), S. 243-249 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Abstinence syndrome ; Tolerance ; Physical dependence ; Rat ; THC ; Morphine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ten rats were injected s.c. with THC twice daily for 5 weeks in increasing doses. In the last 3 weeks they received 40 mg/kg THC in each administration. Ten control rats received the same amount of vehicle by the same route for the same period. The comparison of rectal temperatures of the first and fifteenth days showed that a very pronounced tolerance developed to the hypothermic effect of THC. The administration of naloxone on the 22nd and 31st days precipitated an opiatelike abstinence syndrome. The termination of the drug administration on the 35th day also produced a similar withdrawal syndrome. The most common signs of abstinence syndrome in THC-treated animals were teeth chattering, defecation, urination, dyspnea, and complete palpebral closure. Although the frequency of the incidence of the following signs were not high, they have been observed only in THC-treated animals: chewing, tremors on the face, escape behavior, jumping, eating of objects, biting of fingers, and sniffing. During abstinence, an increased locomotor activity was recorded by an activity-meter. Similarly, the total amount of excreted feces and urine was higher in the THC group than in the controls. Both abstinence scores and increased motility exhibited the peak in the 48th h of withdrawal. Some similarities between the effects of THC and morphine have been reviewed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00497855
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  • 25
    Digitale Medien
    Digitale Medien
    On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas (1977)
    Springer
    Pflügers Archiv 372 (1977), S. 69-76 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Dibutyryl cyclic AMP ; Pancreas ; Rat ; Secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary DbcAMP≥0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-d-glucose andl-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neuro-transmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00582208
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  • 26
    Digitale Medien
    Digitale Medien
    Relative organ blood flow in rats exposed to intermittent high altitude hypoxia (1977)
    Springer
    Pflügers Archiv 368 (1977), S. 111-115 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Altitude ; Myocardium ; Regional blood flow ; Blood volume ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Circulating blood volume, cardiac output and relative organ perfusion changes were studied, using the Sapirstein method of86Rb tissue uptake, in male 75-day-old rats exposed to intermittent high altitude hypoxia (gradually up to 7000 m, 4 h daily, 5 days a week; the total number of exposures was 24). Intermittent hypobaric exposure caused a significant rise of the erythrocyte volume, whereas the plasma volume remained unchanged. The relative perfusion of the left and particularly of the right ventricular myocardium, as well as of the spleen, liver, lung, small intestine and skeletal muscle, was significantly higher. The cardiac output determined in other experimental animals similarly treated was significantly higher after 24 exposures to the intermittent high altitude hypoxia. We suggest that these changes are triggered by tissue hypoxia and a greater blood flow demand.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01063462
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  • 27
    Digitale Medien
    Digitale Medien
    Fever in rats after intravenousE. coli endotoxin administration (1977)
    Springer
    Pflügers Archiv 368 (1977), S. 125-128 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Endotoxin ; Rat ; Fever ; Anti-endotoxin system
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In conscious unrestrained rats, at an ambient temperature of 22°C, oesophageal temperature was measured and temperature effect of single and repeated intravenous injection ofE. coli endotoxin was examined. The first injection of endotoxin in a dose of 10.0 μg/rat did not change the rat body temperature. The second injection of this dose in the same animals repeated after 48 h produced fever. With following injections the fevers observed were less pronounced. The absence of fever after a single injection of endotoxin was accompanied by the rapid loss of pyretic activity of the rat plasma samples (bioassayed in rabbits). When fever was observed (48 h interval between endotoxin injections) the pyretic activity of the rat plasma remained unchanged for 90 min following endotoxin injection. It was concluded that after a single injection endotoxin is rapidly detoxified in the rat circulation while this process does not take place after the second endotoxin injection (48 h interval). The process of endotoxin detoxification can be depressed by the pretreatment with nitrogen mustard. Analysis of changes of skin temperature following endotoxin injections and the influence of aspirin on endotoxin-induced fever suggest that the fever observed was of central origin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01063464
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  • 28
    Digitale Medien
    Digitale Medien
    Plasma level of chlormethiazole and two metabolites after oral administration to young and aged human subjects (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 137-145 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlormethiazole ; pharmacokinetics ; metabolites ; oral administration ; young and elderly human subjects ; quantitative gas chromatographymass spectrometry ; whole blood distribution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration of chlormethiazole and two of its metabolites has been measured in three young and three aged human subjects following administration of a single oral dose of chlormethiazole. A sensitive analytical method based on gas chromatography-mass spectrometry using the selective ion monitoring mode of operation was developed to permit quantitation of the plasma levels. The time course of the plasma concentration of chlormethiazole and metabolites showed wide inter-subject variation, particularly between the young and elderly subjects. Absorption of chlormethiazole was rapid in the subjects of both groups as assessed by the time taken to reach the peak plasma concentration. The mean peak plasma level of chlormethiazole was more than five times greater in the elderly (2.90±1.56 µg/ml) than in the young (0.55±0.58 µg/ml) subjects. The plasma level of chlormethiazole was consistently higher in the aged subjects and this was reflected by the larger area under the plasma curve in aged (7.62±5.37 µg.h/ml) than in young (0.94±0.66 µg.h/ml) individuals. Decreased pre-systemic elimination by the liver has been suggested as an important factor contributing to the higher plasma level in the elderly. Estimates of absolute systemic availability, calculated by reference to previous intravenous studies, were greater for the elderly subjects. The distribution of chlormethiazole in whole blood from six young and six elderly human subjects was investigated in vitro. The unbound fraction of chlormethiazole in plasma increased significantly from 0.308±0.035 in young subjects to 0.403±0.067 in the elderly. Distribution of the drug in whole blood was different for the two age groups; the fraction of drug distributed to plasma water was significantly greater and the fraction in blood cells was significantly less in the aged.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00645135
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  • 29
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tolamolol in the treatment of hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 171-174 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609855
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  • 30
    Digitale Medien
    Digitale Medien
    Comparison of the pharmacodynamic effects of furosemide and BAY g 2821 and correlation of the pharmacodynamics and pharmacokinetics of BAY g 2821 (muzolimine) (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 341-344 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Muzolimine ; pharmacodynamics ; pharmacokinetics ; furosemide ; saluresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first two hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562448
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  • 31
    Digitale Medien
    Digitale Medien
    Disposition of valproic acid in man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 125-132 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Valproic acid ; pharmacokinetics ; saliva concentration ; urinary excretion ; serum protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of valproic acid (VPA) have been studied in 6 healthy subjects following a single 600 mg dose, and after multiple doses over 12 days (1200 mg daily) of enteric-coated sodium valproate. A time lag before absorption of 1 to 2 h was observed in each subject, and then absorption was rapid, peak concentrations being recorded 3 to 4 h after administration of the dose. The plasma level decline was biphasic with a terminal half-life of 15.9±2.6 h in the single dose and 17.3±3.0 h in the multiple dose experiments. There was no evidence of dose dependent kinetics or autoinduction. Total plasma clearance was 0.0064±0.0011 l/kg×h. The apparent volume of distribution was small at 0.15±0.2 l/kg. The mean steady state plasma concentration (Css) reached after 4 days was 81.3±13.0 µg/ml. Css observed was lower than Css predicted (99.2±14.7 µg/ml) from single dose kinetics (p〈0.001). The difference was probably due to a reduction in plasma protein binding at higher concentrations. VPA concentration in saliva was between 0.4 and 4.5% of the total plasma concentration and was not equal to the concentration of unbound drug in plasma (6.7±0.8% unbound). 3.2% of the dose was excreted in urine as the parent drug and 21.2% as conjugated metabolites.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00645133
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  • 32
    Digitale Medien
    Digitale Medien
    Effect of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 367-373 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Sulphamethizole ; tetracycline ; doxycycline ; rest ; exercise ; pharmacokinetics ; excretion ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The serum level and urinary excretion of sulphamethizole, tetracycline and doxycycline were studied in healthy volunteers subjected to intensive exercise and bed rest in a cross-over trial. Each group consisted of 7–8 subjects. The exercise or bed rest began 15 min before oral administration of the drug and was continued for the following 4 hours. During exercise serum drug concentration and the area under the serum concentration-time curve for each agent was significantly higher (p〈0.05) than the corresponding values at rest. Exercise greatly suppressed the renal excretion of tetracycline and doxycycline, but the decrease alone appeared insufficient to account for the pronounced increase in serum drug concentration. Total drug excretion in urine was unchanged. Thus, it seemed most unlikely that overall absorption from the gastrointestinal tract had been altered by exercise. However, the rate of absorption appeared to be more rapid in the exercise than in the rest period. Marked haemoconcentration was not produced by the exercise. In addition to changes in absorption and elimination rates, alteration in the volume of distribution might contribute to the higher serum drug concentration during exercise. Therefore, the level of physical activity should be considered in the interpretation of pharmacokinetic data both in clinical practice and in pharmacokinetic studies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562453
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  • 33
    Digitale Medien
    Digitale Medien
    Fluorometric determination of hydroflumethiazide in human plasma and urine after its oral administration (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 149-154 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Hydroflumethiazide ; spectrofluorometry ; pharmacokinetics ; plasma half life ; renal excretion ; renal disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A spectrofluorometric method for determination of hydroflumethiazide in human plasma and urine has been developed. The limit of detection was 10 ng/ml plasma and 100 ng/ml urine. The plasma concentration of hydroflumethiazide was determined for 9–11 hours and excretion in urine for 24–37 hrs after oral administration of about 1 mg/kg body weight to 7 subjects. Plasma half life in healthy subjects was 1.9–2.1 h, and 2.7–8.6 h in patients during the period 4–9 hrs after dosing. Cumulative excretion in urine was 67–79% of the dose during 31–37 hrs in 6 subjects; one patient with renal disease was found to excrete only 25.8% of dose during 24 hours. Renal clearance of hydroflumethiazide was higher in the healthy subjects (0.29–0.44 1 h−1 kg−1) than in the patients (0.040–0.15 l h−1 kg−1). Plasma half life of hydroflumethiazide was not closely correlated with renal clearance of the drug, which suggests that other factors may play a role in determining plasma half life.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562907
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  • 34
    Digitale Medien
    Digitale Medien
    Transfer of nitrazepam across the human placenta (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 355-357 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nitrazepam ; placental transfer ; pharmacokinetics ; plasma levels ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six women from 14 to 17 weeks pregnant, and 12 woman from 36 to 40 weeks pregnant, were given nitrazepam 5 mg orally about 12 h before legal abortion by hysterotomy in the former group and elective caesarean section in the latter group. The concentration of nitrazepam was determined by gas-liquid chromatography. Binding to plasma proteins was evaluated by separation of the protein-free fraction by ultracentrifugation. In the first group (early pregnancy) the level of nitrazepam was found to be lower in the fetal than in the maternal circulation. The concentration in amniotic fluid was still lower. In the latter group (late pregnancy) the concentration both of unbound and total nitrazepam in maternal and fetal plasma were in equilibrium, which indicated an increase in transplacental transfer in late pregnancy. The percentage of unbound nitrazepam in both cases was 12%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562451
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  • 35
    Digitale Medien
    Digitale Medien
    Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 383-386 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562455
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  • 36
    Digitale Medien
    Digitale Medien
    Overall pharmacokinetics during prolonged treatment of healthy volunteers with digoxin andβ-methyldigoxin (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 387-392 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; β-methyldigoxin ; prolonged administration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy volunteers received digoxin 0.4 mg or β-methyldigoxin 0.4 mg i. v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and β-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54±0.31 days was significantly shorter than the half life of 2.29±0.34 days for β-methyldigoxin. The distribution volume of 807±187 liters for digoxin was not significantly larger than the 735±227 liters for β-methyldigoxin. Renal digoxin clearance of 191±25 ml/min was significantly higher than both the renal clearance of β-methyldigoxin of 111±23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of β-methyldigoxin injected once a day, which was significantly higher than the 1.8-fold accumulation of digoxin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562456
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  • 37
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of carbamazepine (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 451-456 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bioavailability ; carbamazepine ; elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following values were obtained for various pharmacokinetic parameters:k abs =0.176±0.209 h−1;k=0.0203±0.0055 h−1; T1/2=37.5±13.1 h; VD=0.825±0.1041 · kg−1; Clearance=0.0163±0.0061 l · kg−1. The elimination rate constant showed a statistically significant increase with increasing drug dose. This may help explain the clinical observation that the rate of rise of steady state plasma carbamazepine concentrations tends to decrease with dose increase in patients taking carbamazepine alone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561065
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  • 38
    Digitale Medien
    Digitale Medien
    Biochemical and morphological changes in some organs of rats in nickel intoxication (1977)
    Springer
    Archives of toxicology 37 (1977), S. 159-164 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Nickel ; Rat ; Toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Zu verschiedenen Zeiten nach täglicher Zufuhr von Nickelsulfat an Ratten wurden Leber, Niere, Hoden und Herzmuskel auf biochemische und histologische Änderungen untersucht. Während sich in der Initialphase noch keine signifikanten Veränderungen nachweisen ließen, traten nach längerer Exposition deutliche enzymatische und histopathologische Veränderungen in allen vier untersuchten Organen auf. Das Ausmaß der Organläsionen zeigte einen direkten Zusammenhang mit der Behandlungsdauer.
    Notizen: Abstract Biochemical and histological alterations in liver, kidney, testis and myocardium of albino rats were investigated at various intervals after daily administration of nickel sulphate. No significant changes were observed during the initial periods of the treatment, but longer exposures produced marked enzymatic and histopathological alterations in all the four organs examined. The severity of the histological lesions was found to be directly related to the duration of the treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00293867
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  • 39
    Digitale Medien
    Digitale Medien
    Levels of sulfhydryls and sulfhydryl-containing enzymes in brain, liver and testis of manganese treated rats (1977)
    Springer
    Archives of toxicology 37 (1977), S. 319-325 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Sulfhydryls ; Enzymes ; Brain ; Liver ; Testis ; Manganese ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die Wirkung von Mangan auf Sulfhydrylgruppen und SH-enthaltende Enzyme in Gehirn, Leber und Hoden von Ratten wurde untersucht. Mangan verminderte den Gehalt an Nicht-Eiweiß-SH und hemmte die Glucose-6-phosphatdehydrogenase sowie die Glutathionreduktase in diesen Geweben. In Gehirn, Leber und Hoden der Mn-behandelten Tiere war der Mn-Gehalt signifikant erhöht.
    Notizen: Abstract The effect of manganese on sulfhydryls and sulfhydryl-containing enzymes in brain, liver and testis of rats was investigated. Manganese produced lowering in the contents of non-protein sulfhydryl groups and inhibited the activity of glucose-6-phosphate dehydrogenase and glutathione reductase in these tissues. The contents of the metal increased significantly in brain, liver and testis of manganese administered rats. The significance of these findings is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00330824
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  • 40
    Digitale Medien
    Digitale Medien
    Zur Toxikologie von Carbromal (1977)
    Springer
    Archives of toxicology 37 (1977), S. 275-288 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Carbromal ; Bromoethylbutyramide ; Ethylbutyrylurea ; Rat ; Pharmacokinetics ; Smooth muscle ; Carbromal ; Carbromid ; Äthylbutyrylharnstoff ; Ratte ; Pharmakokinetik ; glatter Muskel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Oral verabreichtes Carbromal und Carbromid wurden bei Ratten in Dosen unter 20 mg/kg rasch aus dem Magen-Darmtrakt aufgenommen, aus dem Dünndarm 5–8mal rascher als aus dem Magen. Die enterale Resorption von Carbromaldosen größer als 20 mg/kg verlief wesentlich langsamer. Dies ist hauptsächlich auf eine verzögerte Magenentleerung zurückzuführen. Sowohl Carbromal als auch Carbromid hemmten in vitro den Tonus und die durch Acetylcholin induzierte Kontraktion glatter Muskeln des Magenfundus. Carbromal und Carbromid fanden sich im Organismus in gleicher Konzentration in Serum, Gehirn und Skelettmuskulatur. Im Fettgewebe wurden dreimal höhere Werte gemessen. Die Konzentrationen beider Stoffe fallen in den untersuchten vier Organen mit der gleichen Geschwindigkeit wieder ab. Es lassen sich daher mit Hilfe der leicht zu messenden Serumkonzentrationen rasch die im Organismus verteilten Mengen beider Substanzen ermitteln. Intraperitoneal injizieŕtes Carbromal und Carbromid verlassen Serum und Gehirn mit einer Halbwertzeit von 3–4 h, Äthylbutyrylharnstoff mit einer Halbwertzeit von 5–7 h. Carbromal, Carbromid und Äthylbutyrylharnstoff werden von der Ratte rasch und nahezu vollständig metabolisiert. In Urin und Kot erschienen nur Spuren dieser Substanzen. Für eine Sekretion von Carbromal und seinen beiden Metaboliten in den Magen ergab sich kein Anhalt. Die Ergebnisse werden im Hinblick auf die akute Carbromalvergiftung beim Menschen diskutiert.
    Notizen: Abstract Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5–8-fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with a half-life of 3–4 h and 5–7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00330819
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  • 41
    Digitale Medien
    Digitale Medien
    The effect of mercuric chloride on the excretion of two urinary enzymes in the rat (1977)
    Springer
    Archives of toxicology 37 (1977), S. 219-225 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Inorganic mercury ; Renal enzyme excretion ; Chelating agents ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die Wirkung von intravenös verabreichtem HgCl2 auf die renale Ausscheidung von alkalischer Phosphatase (AP) und Leucinaminopeptidase (LAP) wurde an Ratten untersucht. Am ersten Tag nach Hg-Injektion erfolgte ein Anstieg der Enzymausscheidung, der von einem Schwellenwert von 0.44 mg Hg/kg ausgehend eine lineare Abhängigkeit von der Hg-Dosis aufwies. Am zweiten Tag wurde ein statistisch signifikanter Effekt bereits nach 0.25 mg Hg/kg beobachtet. Nach Dosen von 0.75 mg Hg/kg oder mehr fand ein Abfall der Enzymaktivität unter die Kontrollwerte statt, der mehr als 4 Tage anhielt. Behandlung mit 2,3-Dimercaptopropansulfonat (DMPS) bewirkte eine Normalisierung der AP-Ausscheidung. Eine Wirkung auf die LAP-Exkretion wurde nur bei baldiger Verabreichung von DMPS beobachtet. Das gleiche gilt für den Effekt von DMPS auf die Hg-induzierte Letalität. Die Nützlichkeit einer LAP-Bestimmung im Urin zur Abschätzung einer Hg-Inkorporation wird diskutiert.
    Notizen: Abstract The effect of intravenous injections of HgCl2 on the renal excretion of alkaline phosphatase (AP) and leucine aminopeptidase (LAP) was investigated in rats. On the first day after Hg enzyme excretion showed a linear rise with the Hg dose from a threshold value of 0.44 mg Hg/kg. On the second day a statistically significant effect was seen already after 0.25 mg Hg/kg. After doses of 0.75 mg/kg or more a decrease of enzyme activity below control values occurred which persisted for more than 4 days. Treatment with 2,3-dimercaptopropansulfonate (DMPS) brought about a normalization of AP excretion. An effect on LAP excretion was observed only with early treatment. The same holds for the effect of DMPS on Hg-induced lethality. The usefulness of a measurement of LAP excretion for estimating the exposure to inorganic mercury is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00355490
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  • 42
    Digitale Medien
    Digitale Medien
    Neurobehavioral and systemic effects of longterm blood lead-elevation in rats (1977)
    Springer
    Archives of toxicology 37 (1977), S. 247-263 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Lead in blood ; Longterm exposure ; Learning deficit ; Overreaction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Zur Erfassung neuropsychologischer Störungen nach ontogenetisch früher Bleiexposition wurde bei männlichen Wistar-Ratten pränatal über deren Mütter, neonatal über die Muttermilch und postnatal über Bleiazetathaltiges Futter (745 mg Pb/kg Futter) chronisch ein erhöhter Blutbleispiegel (PbB) eingestellt. In der Trächtigkeits-und Säugezeit stieg der PbB-Spiegel der Mütter von 24.2 auf 31.2 μg-% an, während derjenige der Nachkommen im Alter von ca. 16 Tagen 26.6 μg-% und im Alter von ca. 190 Tagen 28.5 μg-% betrug. PbB altersgleicher Kontrollen war stets 〈 6 μg-%. Im Alter zwischen 100 und 200 Tagen wurden 20 Bleitiere und 20 Kontrollen blind verschiedenen Verhaltensprüfungen unterzogen, und zwar einem Open Field-Test und einer visuellen Unterscheidungs-Lernaufgabe. Zwei Lernprobleme unterschiedlicher Schwierigkeit, Richtungs- und Größenunterscheidung, wurden benutzt. Im Open Field-Test waren die Bleitiere im Vergleich mit den Kontrollen signifikant unruhiger: Lokomotorische Aktivität, Aufrichten und Putzverhalten waren gesteigert. Die schwierige Größenunterscheidung erlernten nur die Kontrollen, während das leichte Problem, nämlich die Richtungsunterscheidung, von Kontroll- und Bleitieren gleich schnell erlernt wurde. Die beobachteten Bleiwirkungen, gesteigerte motorische Unruhe und Lernleistungshemmung, lassen sich als Indikatoren einer funktionellen Hirnschädigung deuten. Sie legen den Schluß nahe, daß die „Wirkschwelle” für neuropsychologische Störungen nach ontogenetisch frühzeitiger Bleieinwirkung bei der Ratte als unterhalb 35 μg/100 ml liegend angenommen werden muß.
    Notizen: Abstract In order to assess neurobehavioral deficit subsequent to early low-level lead-exposure, Wistar-rats were prenatally Pb-exposed via their mothers, neonatally via their dams' milk, and later on via their diet containing lead acetate (745 mg Pb/kg diet). Blood-lead levels (PbB) of dams increased from 24.2–31.2 μg-% during pregnancy and suckling-periods, those of offsprings were 26.6 μg-% at about 16 days of age and 28.5 μg-% at about 190 days of age. Between 100 and 200 days of age 40 male offsprings were subjected to behavioral testing, namely an open field-test and a visual discrimination-learning task. Two learning-tasks of different complexity, i.e. orientation-and size-discrimination, were used. Data of 20 lead-treated animals were compared with those of 20 age-matched controls. In the open-field test lead-fed animals were significantly more restless than controls; an increase of ambulation, rearing and grooming was observed. In the difficult learning-task, i.e. size discrimination, only the controls did learn the problem, whereas only one of the lead-group did; there was, however, no difference between lead-and control-animals for the easy task, i.e. orientation-discrimination. The observed effects, namely overreaction in the open field and a deficit of visual discrimination learning, may be interpreted in terms of lead-induced CNS-dysfunction. They clearly suggest that the “no-response level” for neurobehavioral damage in the rat, subsequent to early lead-exposure, must be assumed to be lower than 35 μg/100ml.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00330817
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  • 43
    Digitale Medien
    Digitale Medien
    Behaviour of glibenclamide on repeated administration to diabetic patients (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 19-25 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes mellitus ; sulfonylurea ; glibenclamide ; pharmacokinetics ; repeated administration ; deep compartment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating “deep” compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561783
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  • 44
    Digitale Medien
    Digitale Medien
    Model independent derivation of general equations for the “first-pass” effect and extra-hepatic drug elimination (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 57-64 
    Details
    ISSN: 1432-1041
    Schlagwort(e): General equation ; pharmacokinetics ; first pass effect ; extra-hepatic drug elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A general expression for the ratio of areas below the blood concentration-time curves after intravenous and oral drug administration is derived. This derivation does not require the assumption of a specific compartmental model to describe drug distribution within the body. Similarly an expression for the amount of drug metabolised in the liver is derived. The latter expression is used to estimate the extent of extra-hepatic drug elimination from the body.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561789
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  • 45
    Digitale Medien
    Digitale Medien
    Pharmacokinetic aspects of protriptyline plasma levels (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 51-56 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Antidepressive agent ; protriptyline ; plasma concentration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma levels of protriptyline have been determined in 30 depressed female patients undergoing antidepressant therapy. After 3 1/2 weeks treatment at dosage levels of 40 mg/day, protriptyline plasma levels ranged from 430 to 1430 nmol/l. During this period only two-thirds of the subjects had definitely achieved asymptotic concentrations. Single dose studies in 5 volunteers suggest that the volume of distribution of protriptyline shows little intersubject variation. The half life of the drug, however, may vary appreciably from subject to subject, ranging from 54 to 198 h. The effects of two sedatives on mean protriptyline plasma levels have been determined. Mean plasma levels for nitrazepam recipients are indistinguishable from those for patients receiving no night sedation. The mean plasma levels for a group of patients receiving sodium amylobarbitone were significantly reduced. The problem of choice and early adjustment of dosages in order to achieve satisfactory plasma levels is discussed. For practical purposes it is suggested that early values may be of predictive significance in allowing early dosage adjustments to be made.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561788
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  • 46
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of salicylate and indomethacin in coeliac disease (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 473-477 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Salicylate ; aspirin ; indomethacin ; pharmacokinetics ; coeliac disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of salicylate and indomethacin were measured after a single oral dose of aspirin (600 mg) and indomethacin (50 mg) in twelve starved normal subjects and twelve adult patients with coeliac disease. The absorption of salicylate in the coeliac patients was faster than in the normal subjects. The plasma concentration/time curve of indomethacin in both groups was similar during the absorption phase, but there were significant differences between the groups in its elimination. The abnormal absorption pattern of salicylate in coeliac disease does not appear to be related to its pKa. Possible causes of the difference in salicylate absorption include changes in gastric emptying or altered small intestinal permeability.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562942
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  • 47
    Digitale Medien
    Digitale Medien
    Human experience of cetiedil, a new vasodilator with anticholinergic properties (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 205-208 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cetiedil ; vasodilator ; anticholinergic drug ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cetiedil, a new vasodilating drug with anticholinergic properties, was shown to be metabolised very rapidly in man after intravenous and oral administration of the14C-compound. Higher concentrations of labelled compound after oral than after intravenous administration at the same sampling time, and proportional differences in urinary excretion, suggest that metabolic handling of the drug differs depending on the route of administration. Experiments in which inhibition of saliva secretion was measured indicated that (an) active metabolite(s) probably was (were) responsible for the action of the drug. As an anticholinergic drug, cetiedil is at least 400 times weaker than atropine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609862
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  • 48
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of cefuroxime after intravenous injection (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 221-227 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cefuroxime ; cephalosporin antibiotics ; intravenous injection ; pharmacokinetics ; volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cefuroxime, a new cephalosporin antibiotic which is stable to most β-lactamases produced by Gram-negative bacteria, was given by bolus intravenous injection to six volunteers in doses of 500 mg and 750 mg. The concentrations of cefuroxime in serum and urine were measured at pre-determined times after injection and the data analysed by a two-compartment open system model. A serum concentration of 8 µg/ml was exceeded for 100.3 min (±18.3) after a 500 mg dose and for 144.5 min (±19.8) after 750 mg. The ultimate serum half-life was 1.1 h. Excretion of cefuroxime in the urine was almost complete in 24 h, the clearance being 150 ml/min/1.73 m2. About 45% was excreted through the renal tubules. The injections were well tolerated and no changes in haematological or biochemical values were seen. The resulting data are compared with those published for some other cephalosporins. It is concluded that the favourable pharmacokinetics, especially the high concentrations of unbound cefuroxime in the serum, are likely to aid effective therapy of human infection caused by sensitive bacteria.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609865
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  • 49
    Digitale Medien
    Digitale Medien
    Antiarrhythmic and electrocardiographic effects of single oral doses of disopyramide (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 91-99 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Disopyramide ; plasma concentration ; cardiodepressant drugs ; ventricular arrhythmia ; ventricular tachycardia ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten patients with various heart diseases and ventricular arrhythmia received a single oral dose of disopyramide (DE) 200 mg. The ECG was recorded continuously for about 50 h from 2–4 h before drug administration. A statistically significant reduction in the number of ventricular ectopic beats (VEBs) was seen 1.0–3.5 h after drug intake; the average number of VEBs per 30 min decreased from 317 during the control period to 92 by 1.0–3.5 h after treatment and if one patient who did not respond is excluded, the corresponding figures were 272 and 14, respectively. Consecutive VEBs were seen in seven patients before DE was given and decreased significantly (p〈0.05) 1.5–5.5 h after drug administration. There was no change in the PQ interval, the QRS interval showed a slight increase, whereas the QT interval was prolonged 0.5–4 h after administration of DE. A specific gas chromatographic method was used for DE assay in plasma and urine. Absorption was rapid in all patients. Urinary excretion during the first 48 h after drug intake varied between 35 and 75%. The lowest effective antiarrhythmic concentration estimated in six patients ranged from 1.4 to 7.0 µg/ml. β-Phase half-life in five patients was between 10.3 and 22.1 h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562898
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  • 50
    Digitale Medien
    Digitale Medien
    Dose-dependence of the pharmacokinetics of quinidine (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 73-76 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Quinidine ; pharmacokinetics ; non-linearity ; dose-dependent pharmacokinetics ; steady state plasma level ; oral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Quinidine was administrated orally to five healthy male volunteers. Doses of 0.2 g t. i. d., 0.3 g t. i. d. and 0.4 g t. i. d. were given for five days with at least four weeks between each test period. The plasma concentration of quinidine was measured before the morning dose on Days 2–5 of treatment, and 1, 2, 4 and 8 h after the morning dose on the 5th day. There was not a linear relationship between the increase in dose and the increase in plasma concentration of quinidine. A dose increase of 50% from 0.6 to 0.9 g quinidine sulphate per day resulted in an increase in steady state concentration of 94%. A further 33% increase in dose, from 0.9 to 1.2 g daily, resulted in a 55% increase in the steady stae concentration of quinidine. The results demonstrate dose-dependent pharmacokinetics for quinidine. Possible explanations for the nonlinear pharmacokinetics are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561409
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  • 51
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of methyldopa in healthy man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 117-123 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Methyldopa ; radioactive label ; pharmacokinetics ; metabolism ; healthy volunteers ; intravenous and oral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of 2-14C-L-α-methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined α-methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of α-methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00645132
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  • 52
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 283-286 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Paracetamol ; Acetaminophen ; pharmacokinetics ; first-pass elimination ; intravenous administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352±40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63±0.02 after 500 mg, to 0.89±0.04 and 0.87±0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607678
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  • 53
    Digitale Medien
    Digitale Medien
    Distribution and elimination of digoxin in infants (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 329-335 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; pharmacokinetics ; two-compartment model ; radioimmunoassay ; neonates ; infants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The distribution and elimination of intravenous digoxin were investigated in seven neonates and infants with heart failure. Serum digoxin concentrations during a 24 h period were determined by radioimmunoassay, using125I as tracer. The serum values declined biexponentially after the injection and could be fitted to a two-compartment open model by non-linear least-squares regression. The calculated mean half-lives of the distribution (alpha) phase in neonates and infants were 37 and 28 min, respectively. The mean half-life of the elimination (beta) phase in neonates was 44 h, as compared to 19 h in infants. The mean volume of the central compartment and the mean volume of distribution at steady-state were calculated to be 1.3 and 9.9 l/kg, respectively; no significant differences between neonates and infants were found. The relation between these volumes indicates that digoxin is extensively distributed in tissues. The steady-state distribution volumes of digoxin in neonates and infants exceed those reported in adults. The larger volume of distribution might explain in part why infants with cardiac insufficiency require larger doses of digoxin than adults (on a mg/kg body weight basis) to obtain the same serum concentrations. Elimination of digoxin from the body was slower in neonates than in infants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00566529
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  • 54
    Digitale Medien
    Digitale Medien
    Individual variation in the response to phenprocoumon (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 351-358 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Phenprocoumon ; protein binding ; pharmacokinetics ; pharmacodynamics ; drug therapy ; myocardial infarction ; chronic disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In nine patients, the synthesis rate Rsyn of the vitamin K-dependent clotting factors was calculated from changes in prothrombin-complex activity after intravenous administration of a synthesis-blocking dose of phenprocoumon (PPC). The biological half-life of PPC was between 2.70 and 7.01 days. No correlation was found between the level of the free fraction of this strongly protein-bound drug and its biological half-life. There was a positive correlation (p〈0.01) between the size of the free fraction of PPC and the apparent volume of distribution of the drug. Four of the patients had had an acute myocardial infarction and they showed increased sensitivity to PPC. In them the plasma level of PPC sufficient to reduce Rsyn to 50% of R°syn was significantly lower, and the depression of individual vitamin K-dependent coagulation factors was more pronounced and prolonged, than in five other patients with chronic disease. The degradation rate of coagulation factors was also found to be higher in the patients with acute myocardial infarction. In four patients with chronic disease, anticoagulant therapy with PPC was continued in the out-patient clinic. The calculated oral maintenance dose of PPC, assuming complete absorption, first-order elimination kinetics and a linear relationship between the pharmacological effect and the logarithm of the PPC-plasma concentration, showed good agreement with the dose actually found to produce the desired PP% level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00566532
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  • 55
    Digitale Medien
    Digitale Medien
    Biotransformation and pharmacokinetics of acenocoumarol (Sintrom®) in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 367-375 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Acenocoumarol ; excretory balance man ; pharmacokinetics ; biotransformation ; plasma protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption, biotransformation and elimination of the anticoagulant acenocoumarol, 3-[α- (4′-nitrophenyl)-β-acetylethyl]-4-hydroxycoumarin, have been studied by oral administration of 12 mg of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and the plasma concentration of unchanged drug reached a maximum of 169 and 412 ng/ml, respectively, after 3 hours. The elimination half-life in the two subjects, calculated from the decline between 6 and 24 h, was 8.7 and 8.2 hours. A constant proportion of 98.7% of the drug was bound in vitro to serum proteins over a concentration range of 0.021–8.34 µg/ml, with little interindividual variation. The major portion of the binding was to human serum albumin (97.5%) at two classes of binding sites: association constant K1=1.04×105 l/mole (n1=1) and K2=5.55×103 l/mole (n2=4). In addition to unchanged acenocoumarol, four metabolites were determined in plasma by isotope dilution techniques: the amino-, acetamido-, alcohol1- and alcohol2-metabolites. Of them, the amino-metabolite showed the highest concentration, namely 278 ng/ml, after 6 h in Subject A, and 163 ng/ml after 10 hours in Subject B. Judged from the integrated concentrations, the compounds analyzed accounted for 76 and 89%, respectively, of the total radioactivity in plasma. All the metabolites detected in plasma showed anticoagulant activity when tested in mice. The quantities of the metabolites excreted in urine from 0–120 hours were (Subject A/Subject B): acenocoumarol 0.3/0.2%, amino-metabolite 12.3/7.7%, acetamido-metabolite 19.0/11.1%, alcohol1-metabolite 4.6/9.0%, alcohol2-metabolite 1.7/4.4%, 6-hydroxy-metabolite 6.9/18.3% and 7-hydroxy-metabolite 14.0/22.2%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00566534
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  • 56
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of hydrochlorothiazide in man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 297-303 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Hydrochlorothiazide ; pharmacokinetics ; dose/response relationship ; natriuresis ; kaliuresis ; calciuresis ; magnesiuresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Hydrochlorothiazide (hct) was administered orally in four different doses (12.5, 25, 50 and 75 mg), to eight healthy volunteers. Plasma and urine concentrations of hct were determined by GLC. Maximal plasma levels were found at 1.5–5 h, and averaged 70, 142, 260 and 376 ng × ml−1 respectively. The peak plasma levels and AUC0→9h of hct were highly correlated (p〈0.001) with the dose. The decline in the plasma curve was biphasic in those experiments in which the plasma levels of hct could be determined for at least 24 h. The half life of the slower phase lay between 5.6 and 14.8 h. The urinary recovery of hct, which represented the gastrointestinal absorption, averaged 65 to 72 per cent of the dose. The mean renal plasma clearance did not vary with the dose and averaged 319 to 345 ml × min−1. The diuresis during the 10 h after hct 12.5 mg exceeded that after placebo by a mean of 800 ml. The diureses was not increased further after higher doses of hct. The maximal natriuretic effect (+ 100 mmol), too, was found after the 12.5 mg dose. The excretion of potassium, however, rose with increasing doses; the maximal increment, after 75 mg hct, averaged 25 mmol. The excretion of calcium was significantly increased after 50 mg hct (+ 0.6 mmol). The maximal effect on magnesium excretion occurred after 25 mg hct (+ 0.5 mmol). In healthy volunteers there was no correlation between peak plasma level of hct or AUC0→9h and the renal excretion of water and electrolytes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607430
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  • 57
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of phenobarbital in childhood (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 305-310 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Phenobarbital ; pharmacokinetics ; neonates ; infancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 14 neonates 1–4 weeks old, 30 babies aged 1–12 months, and 7 infants of 1–5 years of age, the serum levels of phenobarbital were determined by a gas chromatographic micro-method after intravenous injection of phenobarbital 5–10 mg per kg body weight. It was possible to calculate the pharmacokinetic parameters using a two compartment open model. The distribution volumes within the individual age groups and the rate constants k12 and k21 showed no significant differences, but the elimination half-life was significantly longer in neonates (118.6±16.1 h) than in babies (62.9±5.2 h) or infants (68.5±3.2 h).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607431
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  • 58
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tolmetin with and without concomitant administration of antacid in man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 421-428 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tolmetin ; pharmacokinetics ; bioavailability ; antacid ; oral dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561061
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  • 59
    Digitale Medien
    Digitale Medien
    Intracellular histidine content of various tissues (brain, striated muscle and liver) in experimental chronic renal failure (1977)
    Springer
    Journal of molecular medicine 55 (1977), S. 583-585 
    Details
    ISSN: 1432-1440
    Schlagwort(e): Histidin ; Gehirn ; Skelettmuskel ; Leber ; Urämie ; Ratte ; Histidine ; Brain ; Striated muscle ; Liver ; Uremia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Intracellular histidine levels were determined in brain, striated muscle and liver of rats with chronic renal insufficiency (5/6-nephrectomy) and compared both with normal rats and food-restricted (pair-fed) animals. There was no difference in plasma histidine concentration of the three groups whereas in the brain of the uremic rats histidine was significantly increased. Since there existed no alteration of the cerebral histidine in the corresponding pair-fed group, the finding of a raised histidine level in the renal insufficient rats seems to be due to a specific uremic disorder caused by a cerebral disturbance in histidine metabolism.
    Notizen: Zusammenfassung Bei chronisch niereninsuffizienten Ratten (5/6-Nephrektomie) wurden die intrazellulären Histidin-Konzentrationen verschiedener Organe (Gehirn, Skelettmuskel und Leber) bestimmt. Als Vergleichsgruppen dienten gesunde Kontroll-Ratten sowie sog. „pair-fed“ Ratten, die entsprechend den niereninsuffizienten Tieren eine verminderte Nahrungsmenge zu sich nahmen. Während sich in den untersuchten Gruppen die Plasma-Histidin-Konzentration nicht unterschied, war Histidin im Gehirn der chronisch niereninsuffizienten Tiere signifikant erhöht. Dieser Konzentrations-Anstieg dürfte als urämie-spezifisch anzusehen sein, da die entsprechend minderernährten Kontrolltiere keine Alteration zeigten. Als Ursache ist in erster Linie eine cerebrale Störung des Histidin-Metabolismus zu diskutieren.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01490512
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  • 60
    Digitale Medien
    Digitale Medien
    Enduring effects of morphine pellets revealed by conditioned taste aversion (1977)
    Springer
    Psychopharmacology 51 (1977), S. 279-283 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Morphine ; Naloxone ; Abstinence signs ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including “wet dog shakes” and weight loss, were noted in these subjects, but not in controls given placebo pellets and/or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00431636
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  • 61
    Digitale Medien
    Digitale Medien
    Deficits in passive-avoidance learning following atropine in the developing rat (1977)
    Springer
    Psychopharmacology 54 (1977), S. 139-143 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Atropine ; Cholinergic mechanisms ; Learning ; Ontogeny ; Passive avoidance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The maturation of cholinergic inhibitory mechanisms that may be involved in passive-avoidance learning was studied in rats 14, 17, 21, 25, 28, and 34 days of age. Acquisition and extinction of the conditioned response were examined under saline and atropine sulfate (5 mg/kg). Learning was also tested following scopolamine hydrobromide injections (1, 4, 8 mg/kg) in rats 17 days of age and following α-methylatropine (5 mg/kg) in 17-and 34-day-old groups. In normal animals the rate of acquisition increased during ontogenesis, with a significant improvement between postnatal days 17 and 21, whereas the rate of extinction did not vary with age. Acquisition was impaired by atropine sulfate at all ages and even totally prevented in younger groups (14 and 17 days of age). It was also completely disrupted by scopolamine in 17-day-old rats. Extinction following acquisition under atropine was more rapid than after normal acquisition. Methyl-atropine was without effect. These results support the hypothesis of central cholinergic mechanisms involved in response suppression, already functioning in the rat 14 days of age and maturing mainly between the 17th and the 21st postnatal days.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00426769
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  • 62
    Digitale Medien
    Digitale Medien
    The effects of psychotropic drugs on exploratory and stereotyped behaviour of rats studied on a hole-board (1977)
    Springer
    Psychopharmacology 55 (1977), S. 67-74 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Rat ; Exploratory behaviour ; Stereotyped behaviour ; Hole-board ; dl-Amphetamine ; Haloperidol ; Apomorphine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Exploratory and stereotyped behaviour of Male Wistar rats was studied on a hole-board. The two forms of behaviour were differentiated according to the pattern of hole-dipping activity. Increasing doses of dl-amphetamine stimulated both forms of behaviour with stereotyped behaviour becoming predominant particularly at the higher dose levels. At the highest dose of amphetamine used (16 mg/kg) a gradual transition from exploratory to stereotyped behaviour was observed with time. As the drug wore off this transition was reversed. Haloperidol at a dosage of 0.1 and 0.05 mg/kg blocked the response to a high dose of amphetamine whereas a lower dose (0.02 mg/kg) blocked the stereotyped response to amphetamine while some exploratory behaviour still took place. Apomorphine inhibited hole-dipping but at lower doses another form of exploratory behaviour was induced, this behaviour becoming stereotyped as the dose was increased. It is concluded that there is a close relationship between exploratory and stereotyped behaviours. Monoamine systems appear to play a significant role in the regulation of both forms of behaviour.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00432819
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  • 63
    Digitale Medien
    Digitale Medien
    The effect of chronic ethanol treatment on behaviour and central monoamines in the rat (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 205-216 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Chronic ethanol treatment ; Rat ; Behaviour ; Central monoamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Rats weaned at 16 days of age were treated with various ethanol concentrations (8–24% w/v) for 270 days. The effect of the chronic ethanol treatment on the growth rate, the diurnal pattern of drinking, the open field activity, and the conditioned avoidance acquisition and retention of the rats were studied. Termination of the chronic ethanol administration caused two types of withdrawal syndromes. The first, an acute withdrawal syndrome was observed within 12 h after the discontinuation of the ethanol treatment and was characterized by extreme hyperexcitability. The second, a delayed withdrawal syndrome was characterized by a more coordinated behavioural stimulation and developed first after about 3 days after the discontinuation of the ethanol treatment. Biochemically, the latter withdrawal syndrome was accompanied by an increased rate of tyrosine hydroxylation (measured as the accumulation of dopa after inhibition of aromatic amino acid decarboxylase) in the striatum and dopamine-rich limbic structures. No differences in the accumulation of 5-hydroxytryptophan were observed. Furthermore, there was an increased level of dopamine concomitant with a decreased level of noradrenaline in the limbic areas during ongoing ethanol treatment. On the 4th day after withdrawal of ethanol the endogenous levels of dopamine and noradrenaline were statistically significantly reduced in the limbic structures. The data of the present study indicate that chronic ethanol administration induces various kinds of behavioural changes and that these changes at least partially are mediated via central catecholamine mechanisms.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00500962
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  • 64
    Digitale Medien
    Digitale Medien
    Filaments and rod-shaped tubulated bodies in the endothelia of anterior cerebral arteries in young rats (1977)
    Springer
    Cell & tissue research 182 (1977), S. 505-511 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Endothelium ; Cerebral artery ; Filaments ; Rod-shaped inclusion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Endothelia of the anterior cerebral arteries in rats aged 1 to 3 days were studied. Thin (about 50–90 Å) and thick (about 100–110 Å) filaments are present in the endothelia. Numerous spherical- or rod-shaped bodies, measuring approximately 0.07 to 0.3 μm in diameter and up to 0.6 μm in length occur in the endothelial cells. These bodies contain a tubular structure. The diameter of the individual tubules is about 200 Å. The present observations suggest that spherical- or rod-shaped inclusions are first synthesized in the rough endoplasmic reticulum and thereafter these materials are transported into the Golgi complex for maturation. A small number of the inclusions, however, may originate directly from the rough endoplasmic reticulum and not pass through the Golgi apparatus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00219832
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  • 65
    Digitale Medien
    Digitale Medien
    Transport adenosine triphosphatase activity in the rat cornea (1977)
    Springer
    Cell & tissue research 176 (1977), S. 431-443 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Cornea ; Rat ; NaK-ATPase ; K-NPPase ; Histochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The sodium-potassium activated adenosine triphosphatase (NaKATPase) activity of the rat cornea was investigated histochemically using a Pb2+-precipitation technique in which adenosine triphosphate (ATP) is used as substrate and two methods for potassium-dependent para-nitrophenyl-phosphatase (K-NPPase) activity. With all the three techniques used it was demonstrated that the sodium-potassium-activated adenosine triphosphatase (NaK-ATPase) activity is localized in the cell membranes of the endothelium whereas a much weaker activity was observed in the epithelium. When the Pb2+-technique was used, the epithelial cell membranes showed a weaker reaction in the presence of ouabain. This activity was only Mg2+-dependent and was presumably due to an Mg2+-dependent ATPase. The validity of the histochemical techniques for NaK-ATPase activity is discussed. The results emphasize the importance of the endothelium as the main site of Na+ transport in the cornea. Small amounts of the enzyme are also present in the epithelium, which seems to be rich in Mg2+-ATPase. Provided that careful controls are performed, all the methods give consistent results in the cornea.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00231400
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  • 66
    Digitale Medien
    Digitale Medien
    Ultrastructure of the rat pineal gland grafted under the kidney capsule (1977)
    Springer
    Cell & tissue research 176 (1977), S. 131-142 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Pineal gland ; Graft ; Ultrastructure ; Innervation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Pineal glands were grafted under the kidney capsule of mature male rats for periods of 20, 40, 60 and 100 days. Each grafted gland was then excised and divided into two halves. One half was processed for conventional electron microscopy and the other was fixed in aldehydes and then incubated in a zinc iodide-osmium tetroxide mixture at pH 4.4 (A-ZIO-4.4). During the forty days following the operation pinealocytes showed the typical ultrastructural features associated with cells with a high protein and/or peptide secretory activity. On the other hand, during this period, the number of granular vesicles decreased progressively. From day 40 on, the grafted pinealocytes lacked granular vesicles. During the second half of the experimental period the ultrastructure of the pinealocytes indicated that their secretory activity was considerably decreased. During the acute phase of the experimental period numerous structures regarded as the tip of growing axons as well as typical nerve fibres appeared around blood vessels and within the parenchyma of the grafted gland. In the transplanted tissue obtained 60 and 100 days after the operation the growth cones were scarce, whereas typical nerve endings became numerous. These endings contained small clear vesicles which reacted positively when the tissue was treated with A-ZIO-4.4. The secretory activity of the grafted pineal gland and the nature of the nerve fibres which innervate the graft are discussed. The authors wish to thank Mrs. E.M. Rodríguez de Calderón for her valuable help
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00220349
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  • 67
    Digitale Medien
    Digitale Medien
    Further evidence for the existence of intralobular nerves in the rat liver (1977)
    Springer
    Cell & tissue research 177 (1977), S. 287-290 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Liver ; Intralobular nerves ; Rat ; Cobalt and Procion Yellow staining
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In a recent study (Skaaring and Bierring, 1976) we found cholinesterase positive nerve-like structures in the lobules of rat liver, and scanning electron microscopy revealed cords having a distribution pattern similar to that of the cholinesterase-positive structures. To obtain further evidence for an intralobular nerve supply the methods of cobalt and Procion Yellow nerve staining (Stretton and Kravitz, 1968; Iles and Mulloney, 1971; Pitman, Tweedle and Cohen, 1972) were adapted, iontophoretic introduction of the dyes being attempted through cut axonal ends in the surface of small excised blocks of rat liver.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00221089
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  • 68
    Digitale Medien
    Digitale Medien
    Regeneration of soleus muscles of rat autografted in toto as studied by electron microscopy (1977)
    Springer
    Cell & tissue research 177 (1977), S. 159-180 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Muscle transplantation ; Rat ; Electron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Rat soleus muscles were autografted from right to left legs, and regeneration following necrosis of all original myofibres was studied after 7 to 250 days. The best regenerates were from grafts replacing all calf muscles and sutured to the tendon stumps. After 30 days the size of such regenerates was equal to those from minced gastrocnemius muscles: the cross sectional area of muscle tissue was 30% (1.7 mm2) and the number of fibres was 180% (4500) of normal soleus muscles; the fibre diameters were 10 to 40 μm. To increase the number of myoblasts before grafting some muscles were injured by Ringer solution of 70° C and transplanted after 2 days. Nevertheless, this did not influence regeneration. After 7 days clusters of myotubes occurred in the periphery of the muscle. These myotubes originated from myoblasts growing like endothelial cells on the inner face of the persisting basal lamina tubes of necrotic fibres. After 30 days the muscles were vascularized. Fibres formed in a common basal lamina detached and so looked “split”. Satellite cells of new fibres came from undifferentiated cells associated with myotubes, i.e. from myoblasts. After 30 days and more regenerates contained three sorts of fibres. 1. Thin (5 to 20 μm) fibres resembling fetal muscle fibres. They were most prominent after 30 days, and probably not yet innervated. 2. Thin (10 μm) degenerating fibres as in long-time denervated muscles. 3. Thick (more than 30 μm) mature looking fibres which were innervated and revealed end-plates. Half of the grafts studied after 30 and 60 days contained unmyelinated and myelinated axons which had grown along strands of surviving Schwann cells. After 250 days, only two muscles were studied which both lacked innervation. Almost all regenerates contained muscle spindles, which, however, were not innervated. Within the persisting spindle capsules new muscle fibres had been formed from satellite cells of the former intrafusal fibres.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00221079
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  • 69
    Digitale Medien
    Digitale Medien
    The development of innervation in the rat atrioventricular node (1977)
    Springer
    Cell & tissue research 178 (1977), S. 73-82 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Atrioventricular node ; Rat ; Innervation ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The problem of development of the innervation of the rat atrioventricular node has been investigated by electron microscopy. Nerve bundles appear in relation to the node as early as the second postnatal day and vesiculated axons are seen throughout the entire node by the fourth day. Intimate contacts between nodal cells, axons and terminal varicosities are frequently observed. Use of the 5-hydroxydopamine tracer technique has enabled the identification of both cholinergic and adrenergic axons. It is concluded that the node has a dual innervation although cholinergic endings far outnumber those classified as adrenergic on the sixth postnatal day. These results are quite different to earlier findings made at the light microscope level and the discrepancies are discussed with respect to the histochemical techniques used. The suggestion that nodal differentiation is induced by nerves is considered in relation to the differences in cholinesterase activity exhibited by nodal cells during normal development and following neonatal sympathectomy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00232825
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  • 70
    Digitale Medien
    Digitale Medien
    Effects on gonadal function by lesioning tanycytes in the median eminence of the rat and Japanese quail (1977)
    Springer
    Cell & tissue research 178 (1977), S. 143-153 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Median eminence ; Tanycytes ; Gonadal function ; Rat ; Japanese quail
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The ependymal linings of the median eminence were destroyed by electric cautery or intraventricular injection of picric acid in the rat and Japanese quail. In these animals the ventricular lumen near the median eminence disappeared due to adhesion of lesioned walls on both sides of the third ventricle. Electric lesions of the ependymal layer containing tanycytes did not induce appreciable disturbance in the estrous cycles. Rats in which tanycytes were lesioned by picric acid displayed 4-day estrous cycles after prolonged diestrus (10–22 days). After destruction of tanycytes in the quail, a photostimulated gonadal growth was observed. It is concluded that the tanycyte transport of the ventricular fluid to capillaries of the portal vessels appears unnecessary for maintenance of adenohypophysial gonadotrophic activities.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00219042
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  • 71
    Digitale Medien
    Digitale Medien
    Effect of glucagon on the secretory process in the rat exocrine pancreas (1977)
    Springer
    Cell & tissue research 182 (1977), S. 193-204 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Glucagon ; Exocrine pancreas ; Secretory process ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Glucagon was infused into conscious rats in doses of 10 to 80 μg/h for periods up to 24 h. The effect on the secretory process of the exocrine pancreas was studied in vitro using isolated pancreatic lobules. A pronounced inhibition of the rate of protein synthesis and discharge of stored and newly synthesized proteins combined with increased enzyme content in the pancreas were observed after 30 min infusion. This effect was absent after longer infusion periods of up to six hours. After 12 to 24 h infusions a marked degranulation and decrease in enzyme content was observed. While the rate of protein synthesis was not significantly enhanced, both the basal and stimulated discharge of enzymes from the pancreas were increased. The results suggest a biphasic response of the pancreas to prolonged glucagon infusion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00220588
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  • 72
    Digitale Medien
    Digitale Medien
    Ultrastructural studies on the secretory cycle of the neurosecretory cells and the formation of herring bodies in the paraventricular nucleus of the rat (1977)
    Springer
    Cell & tissue research 177 (1977), S. 1-8 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Paraventricular nucleus ; Rat ; Types of neurons ; Secretory cycle ; Herring body
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The ultrastructure of the neurosecretory cells in the paraventricular nucleus of the normal male rat was studied by electron microscopy during various functional states. Four morphologically distinct types of neurosecretory cells were observed. It appears that they do not represent different classes of cells but different phases of secretory activity of a single cell type. The perikarya of the neurosecretory cells show a definite cycle of formation and transportation of secretory granules. We have designated the phases of this cycle as: (1) phase of synthesis, (2) phase of granule production, (3) phase of granule storage and (4) phase of granule transport. The neurosecretory granules appear to be moved in bulk into the axons, forming a large axonal swelling filled with granules as a result of one cycle in the neurosecretory process. Thus it may be postulated that a secretory cycle in the perikaryon of the neurosecretory cell seems to result in the formation of a Herring body in its axon, and that its content is then conveyed to the posterior pituitary.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00221114
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  • 73
    Digitale Medien
    Digitale Medien
    Curve fitting and modeling in pharmacokinetics and some practical experiences with NONLIN and a new program FUNFIT (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 513-531 
    Details
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; nonlinear regression ; curve fitting ; computer program ; time sharing ; modeling ; weighting ; least squares ; parameter estimation ; discrimination between models
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The problems of curve fitting and modeling in pharmacokinetics are discussed. A new nonlinear regression program FUNFIT, written for interactive time sharing, is presented which should be more reliable than programs based on the Gauss-Newton or other related gradient methods. The new program and the well-established program NONLIN were tested on two linear models using human plasma drug level data. FUNFIT found a substantially better solution than NONLIN in the majority of the cases.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061732
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  • 74
    Digitale Medien
    Digitale Medien
    Influence of sampling on drug kinetics in liver perfusion (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 335-358 
    Details
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; perfusion models ; sampling ; parameter estimation ; computer program ; Org GB 94 ; mianserin ; Org GC 94
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A mathematical treatment of the influence of sampling on drug kinetics in liver perfusion is presented. Based on the derived equations, a Fortran IV computer program (PERFUS) is given, by which the time course of drug concentrations can be simulated for any sampling scheme. The simulations show that the withdrawal of large samples from the reservoir, i.e., larger than 5% of the reservoir volume, results in substantially biased parameters for drugs that are rapidly distributed and/or metabolized. For the fitting of empirical data, a Fortran IV computer program is given, based on BMDX85 nonlinear least squares by Gauss-Newton iterations. This program (PERFIT) estimates model parameters corrected as if no sampling had occurred, no matter how distorted the drug disappearance curve mày be as a result of sampling or due to degeneration of the two-compartment model into a one-compartment model. The conditions under which this degeneration occurs are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061695
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  • 75
    Digitale Medien
    Digitale Medien
    Hepatic clearance of local anesthetics in man (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 111-122 
    Details
    ISSN: 1573-8744
    Schlagwort(e): hepatic clearance ; extraction ratio ; local anesthetics ; pharmacokinetics ; lidocaine ; bupivacaine ; etidocaine ; cardiovascular effects of local anesthetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Two independent methods of calculating hepatic drug clearance were applied to data from studies of the human pharmacokinetics of lidocaine, bupivacaine, and etidocaine. Within experimental limitations, agreement was good between estimates obtained by measurement of areas under blood drug concentration-time curves after rapid intravenous injection and by direct measurement of arterial and hepatic venous drug concentrations. Apparent hepatic extraction ratios of the agents followed the order etidocaine (∼0.73)/s〉lidocaine (∼0.68〉bupivacaine (∼0.37).Pharmacokinetic implications of increases in hepatic blood flow induced by the agents are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01066215
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  • 76
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide HCl in healthy subjects: Single-dose studies by the intravenous, intramuscular, and oral routes (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 3-23 
    Details
    ISSN: 1573-8744
    Schlagwort(e): chlordiazepoxide ; benzodiazepine ; two-compartment model, biopharmaceutics ; pharmacokinetics ; single dose ; routes of administration ; intravenous ; intramuscular ; oral
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Single 30- mg doses of chlordiazepoxide HCl were administered to six healthy human subjects by the intravenous, oral, and intramuscular routes. Plasma concentration- time curves following intravenous administration were satisfactorily described by a biexponential equation consistent with a two-compartment open model system. Mean values of half-lives for the so-called distribution and elimination phases were 0.252 and 9.39 hr, respectively. The mean values for the volume of the central compartment (V 1) and volume of distribution $$(V_{d_\beta } )$$ were 18.0 and 30.9% of body weight, respectively. Following oral administration, the drug was rapidly and completely absorbed. Absorption was first order (t1/2≈27 min), and three of the six subjects showed a discernible lag time of approximately 20 min. Drug absorption following intramuscular administration was comparatively slow. A two- compartment “muscle model” comprised of precipitated and solubilized drug in the muscle was found to satisfactorily characterize the absorption process following administration by this route.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01064806
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  • 77
    Digitale Medien
    Digitale Medien
    A pharmacokinetic model for high-dose methotrexate infusions in man (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 421-433 
    Details
    ISSN: 1573-8744
    Schlagwort(e): methotrexate ; pharmacokinetics ; model ; computer ; cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The infusion of high doses of methotrexate followed by folinic acid rescue is clinically useful against a variety of tumors. We studied the plasma pharmacokinetics of high-dose methotrexate infusions in patients with advanced cancer and devised a compartmental, kinetic model. our model is based on an earlier, mathematical model which describes the pharmacokinetics of moderate- to- high-dose methotrexate given as a single, intravenous injection. Mathematical equations for our model were solved on a UNIVAC1108 computer with the SAAM program. Seven compartments represent the distribution spaces for methotrexate and its metabolites. The transport of drug into and out of compartments is described by first-order differential equations. A nonlinear, concentration-dependent function is used for renal excretion with saturation of secretory and reabsorption mechanisms by methotrexate. Our model accurately depicts the pharmacokinetics of nine courses of therapy in five patients. The model can also be used to simulate the kinetics of methotrexate for patients with impaired renal function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061726
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  • 78
    Digitale Medien
    Digitale Medien
    Gentamicin disposition and tissue accumulation on multiple dosing (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 559-577 
    Details
    ISSN: 1573-8744
    Schlagwort(e): gentamicin ; tissue distribution ; pharmacokinetics ; two-compartment modeling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Gentamicin pharmacokinetics was examined in a group of 47 patients with stable renal function treated an average of 10 days for severe infection. Serum concentrations rose continually during treatment, and declined in two phases after the drug was stopped, with a mean half-life of 112hr (range 27–693 hr) in the second phase. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of drug in the tissue compartment at all times during and after treatment. Predicted tissue amounts of gentamicin rose continually on multiple dosing in all patients. In six patients who died, postmortem tissues were obtained to quantitate recovery. In all cases, the predicted amount of gentamicin in tissues was in close agreement with the amount recovered at autopsy. Tissue distribution and accumulation constitute a major reason for variability in gentamicin pharmacokinetics and explain both the rising peak and trough serum concentrations and the prolonged detection of gentamicin in serum and urine after the drug is stopped.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059684
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  • 79
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide HCl in healthy subjects: Multiple-dose oral administration (1977)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 25-39 
    Details
    ISSN: 1573-8744
    Schlagwort(e): chlordiazepoxide ; benzodiazepine ; two-compartment model ; multiple dosing ; pharmacokinetics ; biopharmaceutics ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Eight healthy male volunteers received chlordiazepoxide HCl orally at a dosage of 10 mg every 8 hr over a period of 21 days. On day 22, the regimen was changed to 30 mg every 24 hr for an additional 15 days. Plasma concentrations of chlordiazepoxide and its metabolites desmethyl-chlordiazepoxide, demoxepam, and desoxydemoxepam were measured during 14 of the 36 treatment days. Chlordiazepoxide plasma concentration- time data were consistent with first-order absorption and complete bioavailability. The harmonic mean absorption half-life was 12.3 min. Disposition of chlordiazepoxide was described by a two-compartment open model with a harmonic mean terminal exponential half-life of 10.1 hr. Average steady — state plasma levels of chlordiazepoxide, desmethylchlordiazepoxide, and demoxepam were approximately 0.75, 0.54, and 0.36 μg/ml, respectively.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01064807
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  • 80
    Digitale Medien
    Digitale Medien
    Der Einfluß des duodenogastrischen Refluxes auf das Epithel an der gastroenteralen Anastomose (1977)
    Springer
    Langenbeck's archives of surgery 344 (1977), S. 207-217 
    Details
    ISSN: 1435-2451
    Schlagwort(e): Gastroenterostomy ; Duodenal reflux ; Epithelial lesions ; Nitrosoguanidine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Der Einfluß des chronischen duodenogastrischen Refluxes auf die Magenschleimhaut des nicht resezierten Magens wurde im Hinblick auf die Disposition der gastroenteralen Anastomose für die Krebsentstehung tierexperimentell an männlichen Wistarratten untersucht. Hierzu wurden Tiere mit einer Gastroenterostomie ohne Enteroanastomose und Tiere, bei denen ein Reflux durch eine Y-Gastroenterostomie nach Roux ausgeschlossen war, mit einer zeitlich unterschwelligen Cancerogendosis (Nitrosoguanidin) exponiert. Es wird gezeigt, daß auch unabhängig von der Cancerogenexposition ein chronischer duodenogastrischer Reflux zu adenomartigen Drüsenproliferationen mit z. T. atypischen Epithelregeneraten an der Anastomose führt, die durch eine Gastroenterostomie nach Roux verhindert werden können. Anastomosencarcinome, wie in früheren Untersuchungen am resezierten Magen bei sonst gleichen Versuchsbedingungen beschrieben, konnten nicht induziert werden. Somit spielen für die Krebsentstehung an der gastroenteralen Anastomose neben dem Reflux auch die durch die Magenresektion selbst hervorgerufenen Veränderungen eine nicht unwesentlilche Rolle.
    Notizen: Summary The cancerogenic effect of continous duodenal reflux on the gastric mucosa has been investigated in male Wistar-rats after gastrointestinal anastomosis. Groups of animals with gastroenterostomy without enteroenteral anastomosis and with Roux-en-y-anastomosis preventing duodenal reflux were treated with lower dosages of the cancerogenic Nitrosoguanidine. Proliferative mucosal alterations near the gastroenteral anastomosis were observed. In addition the gastric mucosa was characterized by adenomatous lesions caused by duodenal reflux. The changes detected were not influenced by Nitrosoguanidine and did not appear in cases of Roux-en-y-anastomosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01254075
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  • 81
    Digitale Medien
    Digitale Medien
    Das Krebsrisiko im Resektionsmagen (1977)
    Springer
    Langenbeck's archives of surgery 344 (1977), S. 71-82 
    Details
    ISSN: 1435-2451
    Schlagwort(e): Cancer risk ; Resected stomach ; Rat ; Duodenogastric reflux ; N-methyl-N′-nitro-N-nitrosoguanidine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Es wurde die Frage geprüft, ob obligater duodenogastrischer Reflux unter Langzeitbedingungen das Wachstum von Carcinomen oder Sarkomen im resezierten Magen beeinflußt. 72 männliche Wistarratten wurden einer Magenresektion unterworfen. Die erforderliche Gastroenteroanastomose wurde bei 39 Tieren als short loop GE (Billroth II) mit obligatem Reflux von Galle und Duodenalsekret in den Restmagen angelegt. Die restlichen 33 Tiere erhielten eine Y-förmige GE (nach Roux) mit seitlicher Einmündung des Duodenum in den Dünndarm; Reflux von Galle in den resezierten Magen war dadurch unmöglich. Die Carcinominduktion erfolgte durch kontinuierliche Gabe von N-Methyl-N'-Nitro-N-Nitrosoguanidin im Trinkwasser. Bei der Sektion der Tiere mit Reflux 33 Wochen nach Carcinogengabe fand sich die Mehrzahl der malignen Tumore von Magenstumpf, Anastomose (GE) und angrenzendem Dünndarm in der Tiergruppe mit obligatem Reflux (13 von 22). Die Tiergruppe ohne Reflux (Y-Roux GE) wies demgegenüber signifikant weniger Carcinome auf (7 von 21); die Tumorincidenz dieser Gruppe entsprach derjenigen eines nicht operierten Kontrollkollektives (5 von 22). - Die Ergebnisse unserer Untersuchungen zeigen, daß die in der Technik des short loop durchgeführte Gastroenteroanastomose des Billroth 11-Magens das Krebswachstum im Anastomosengebiet in besonders ausgeprägtem Maße fördert. Ausschlaggebend für die gesteigerte Carcinominduktion ist der chronische Reflux von Galle und Duodenalsekret, der bei der short loop-GE obligat über den Magnrest fließt.
    Notizen: Summary The purpose of this study was to find whether the reflux of bile and pancreatic juices following stomach resection (duodenogastric reflux) enhances the incidence of carcinomas near the gastroenteric anastomosis. 72 male Wistar rats were subjected to stomach resection. The gastroenteric anastomosis (GE) was performed either as short loop anastomosis (Billroth II;n = 39), thus providing a continuous duodenogastric reflux, or as Y-shaped GE (according to Roux;n = 33). By the latter technique, bile and pancreatic juices are derived quantitatively into the jejunum without coming into contact with the remaining part of the stomach. During a period of 33 weeks, operated rats as well as intact animals were given the carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (NG; 120 mg/1) in the drinking water. At autopsy, 33 to 36 weeks after daily oral administration of NG, most of the tumours were found in operated rats undergoing continuous ref lux (Billroth II group). In contrast to these findings, the incidence of carcinomas was significantly lower in animals without reflux (Roux group or intact control rats).-The results of our experiments demonstrate that, in rats, the duodenogastric reflux contributes substantially to the development of carcinomas of the resected stomach.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01259380
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  • 82
    Digitale Medien
    Digitale Medien
    Bakterielle Besiedlung und Nitritbildung im Magen nach Gastroenterostomie (1977)
    Springer
    Langenbeck's archives of surgery 344 (1977), S. 109-114 
    Details
    ISSN: 1435-2451
    Schlagwort(e): Gastric carcinoma ; Gastroenterostomy ; Bacterial flora ; Nitrit ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die Anlage einer Gastroenterostomie ohne Enteroanastomose führt zu einer Veränderung der bakteriellen Magenbesiedlung, wobei besonders der Anteil nitritspaltender Bakterien erhöht ist. Dies hat ein Ansteigen der Nitrit-Konzentration im Magensaft zur Folge. Die hierdurch mögliche vermehrte Bildung carcinogener Nitrosamine wird im Hinblick auf das Entstehen eines Carcinoms im operierten Magen diskutiert. Da die beschriebenen Veränderungen durch eine Gastroenterostomie nach Roux weitgehend verhindert werden, soll dies bei der Passagewiederherstellung nach Operation am Magen berücksichtigt werden.
    Notizen: Summary A gastroenterostomy without enteroanastomosis leads to a change in the bacterial flora of the stomach, where-by in particular the proportion of nitrite-decomposing bacteria, is enhanced. This results in an increase of nitrite concentration in the gastric fluid, which may possibly be accompanied by an augmented production of carcinogenic nitrosoamine. This latter aspect is considered with respect to the origin of carcinoma in the operated stomach. Since the reported changes will be largely prevented by a Roux-Y-gastroenterostomy, this should be taken into consideration for reconstruction of the alimentary tract after gastric surgery.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01259384
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  • 83
    Digitale Medien
    Digitale Medien
    Azimine. IITeil I, siehe [1].. Synthese und thermische Fragmentierung von cis- und trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-aziminTeilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft am 8./9. Oktober 1976 in Genf und als Autoreferat veröffentlicht [2]. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 831-843 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Azimines. IITeil I, siehe [1]. . Preparation and Thermal Fragmentation of cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine Teilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft am 8./9. Oktober 1976 in Genf und als Autoreferat veröffentlicht [2].cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine (11 and 12) wer synthesized from cis-di[15N]-azobenzene (10) and phthalimido-nitrene (2), the latter generated by lead tetraacetate oxidation of N-aminophthalimide (1). Useful information was obtained from the comparison of several data of 11 and 12 with those of the unmarked diphenyl-azimines 5 and 6 (R = C6H5).The 15N- and 13C-NMR. spectra of 11 and 12 were interpreted to furnish additional evidence for the azimine structure and for the indicated configurations. The IR. spectra permitted identification of two bands in the 1200 to 1450 cm-1 region, probably characteristic for the functionality of diaryl-phthalimido-azimines. Comparison of the mass spectrum of 11/12 with that of the unmarked analogues 5/6 (R = C6H5) permitted the interpretation of the fragmentation path of 1-phthalimidoazimines. The major path may be the purely thermal decomposition to 13 and 7 (R = C6H5), respectively. Two other competing fragmentation paths are discussed.Prolonged thermolysis of 11 at 61° in solution gave 83% of N,N′-diphenyl-N N′-phthaloyl-di[15N]-hydrazine (13) of 98% isotope purity, which means that the imide nitrogen atom and N(1) of the azimine function are removed in this reaction. A mechanism passing through an intermediate cyclic tetrazene 16 is considered.Benzocyclobutenedione (14) added to trans-azobenzene (4, R = C6H5) under the influence of a high pressure lamp in a quarz apparatus to give N,N′-diphenyl-N,N′-phthaloyl-hydrazine (7, R = C6H5). This reaction was found not to take place in the dark, even after prolonged heating in trichloromethane.
    Zusätzliches Material: 2 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600313
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  • 84
    Digitale Medien
    Digitale Medien
    Azimine. I. Bildung und Stereoisomerie von 2, 3-Diaryl- und 2, 3-Dialkyl-1-phthalimido-aziminenTeilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Lausanne am 7./8. Mai 1971 und als Autoreferat veröffentlicht [1]. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 816-830 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Azimines. I. Synthesis and Stereoisomerism of 2, 3-Diaryl- and 2, 3-Dialkyl-1-phthalimido-aziminesTeilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Lausanne am 7./8. Mai 1971 und als Autoreferat veröffentlicht [1].Special examples of a new class of compounds, the open-chain azimines (1), have been prepared and their properties examined.Addition of phthalimido-nitrene (4), generated by lead tetraacetate oxidation of N-aminophthalimide (3), to cis- and trans-azobenzene (6 and 5), -azo-p-toluene (8 and 7), and to trans-azomethane (9), -azoethane (10) and -azo-α-phenylethane (11) afforded the separable cis- and trans-isomers of 2, 3-diphenyl- (12 and 13), 2, 3-di-p-toyl- (14 and 15), 2, 3-dimethyl- (16 and 17), 2, 3-diethyl- (18 and 19) and 2, 3-di-(α-phenylethyl)-1-phthalimido-azimines (20 and 21) in different ratios (see Scheme 1).The constitution of the nitrene azo compound adducts as azimines was derived from their properties, especially from the conjugation effect (visible in the UV. spectra) of the aryl-substituted compounds and from the non-equivalence (shown by the 1H-NMR. spectra) of the substituents on the two nitrogen atoms derived from the azo compounds. This evidence excluded the triaziridine 22 and an alternative azimine constitution 23 for the adducts.Of the two stereoisomers obtained for each of the azimines, the aryl-substituted examples 12/13 and 14/15 were readily interconverted by warming in solution, the cis-isomers 12 and 14 exceeding the trans-isomers 13 and 15 in the equilibrium. The dialkyl-azimines appear to be configurationally more stable, since interconversion of the dimethyl-azimines 16 and 17 was not possible under the same conditions, and also not before another thermal reaction took place (see below).The identification of the N(2)-N(3) bond as the stereogenic center, i.e. that the stereoisomerism of the azimines is due to the difference in relative position at N(2) and N(3) of the substituents derived from the azo compounds, as well as a configurational assignment was possible in the aryl-substituted examples on the basis of the UV. spectroscopic comparison of the isomeric azimines with the corresponding stereoisomeric azoxy compounds: The cis-azimines 12 and 14 showed absorptions similar to those of cis-azoxybenzene and cis-azoxy-p-toluene, and the trans-azimines 13 and 15 showed absorptions similar to those of the respective trans-azoxy compounds. With respect to the configuration of the alkyl-substituted azimines, it was observed that the isomers 17 and 19, which from their formation and chromatographic behaviour are likely to be the trans-isomers, show a visible coupling (∽ 1 Hz) between the two H (α)'s in the 1H-NMR. spectrum, whereas the dimethyl isomer 16 (cis) does not exhibit such a coupling.Thermal treatment of four azimines, namely 12, 14, 16 and 17, in solution for a longer time afforded the corresponding N, N′-disubstituted N, N′-phthaloyl-hydrazines 27, 28 and 29. The order of velocity of this fragmentation with nitrogen extrusion was 12/13 ≍ 14/15 〉 16(cis) 〉 17(trans).
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600312
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  • 85
    Digitale Medien
    Digitale Medien
    Photochemistry of Chlorinated 2-Cycloalkenones (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 874-881 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The 6-chloro-2-cyclohexenones 3, 6 and 11, and the 5-chloro-2-cyclopentenone 15 were newly synthesized. The results obtained with compounds 3 and 15 in photocycloadditions to olefins show that the oxetane vs. cyclobutane product ratio is reduced by the substitution of florine by chlorine in the α′ -position of the enone. No oxetanes are formed in the intramolecular photocycloaddition of 6. Compound 11 does not photoadd to olefins. The newly synthesized 2-chloro-3-cyclohexenones 8 and 9 are also photostable towards light of λ=366 nm, but π-π*-excitation (λ=254 nm) in pentane leads to the formation of 4,4-dimethylcyclohexanone (29).
    Zusätzliches Material: 4 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600316
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  • 86
    Digitale Medien
    Digitale Medien
    Mehrkernige Kobaltkomplexe. II. Herstellung und Struktur von [(tren) (NH3)Co(O2)Co(NH3) (tren)](SCN)4 · 2H2OI: siehe [1]. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 867-873 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Polynuclear Cobalt Complexes. II. Preparation and Structure of [(tren) (NH3)Co(O2)Co(NH3) (tren)](SCN)4 · 2H2OThe title compound is obtained on oxygenation of [Co(tren)(H2O)2]2+ in 6M aqueous ammonia or by ligand exchange starting from [(NH3)5Co(O2)Co(NH3)5]-(NO3)4. An X-ray structure determination was made. The substance forms monoclinic crystals, space group P21/c, lattice constants a=10,135, b=8,473, c=19,484 Å, β=108,58°, with two formula units in the cell. The final R is 0,066. The binuclear cation has a center of symmetry, so the Co—O—O—Co unit is planar; the Co—O—O angle is 111,5°. The tertiary nitrogen atoms of both chelate groups are cis to the O2 bridge, as found in doubly bridged [(tren)Co(O2,OH)Co(tren)](ClO4)3 · 3H2O.On acidification in solution, the singly bridged cation [(tren) (NH3)CoO2Co(NH3)(tren)]4+ (a) loses the bound O2 completely. But unlike the doubly bridged cation b, the rate of dissociation of a is independent of pH (Fig. 5). At higher pH (8-10) bridging a→b (Fig. 2) occurs. Both reactions must have the same rate determining step, the first order rate constants being of the order of 2 · 10-3 s-1 (25°, 0,35M KCl).
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600315
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  • 87
    Digitale Medien
    Digitale Medien
    Isolation and Identification of Three Major Metabolites of Retinoic Acid from Rat Feces (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 881-887 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Following the intraperitoneal administration of high doses of 14C- and 3H- labelled retinoic acid (1) to rats, three major metabolites and the intact compound were isolated from the feces in microgram amounts by use of column, thin-layer and high-pressure liquid chromatography. Their structures were elucidated by mass spectrometry and Fourier Transform 1H-NMR. spectroscopy as 2 (all-trans-4-oxoretinoic acid), 3 (7-trans-9-cis-11-trans-13-trans-5′-hydroxy-retinoic acid).Hydroxylation of the 5-methyl group of the cyclohexene ring, oxidation of the cyclohexene ring in position 4 and cis-trans isomerisation of the nonatetraenoic acid side chain were the reactions, which produced these products from retinoic acid. The metabolites 2 and 4 each accounted for about 4% of the radioactivity administered. The metabolite 3 and the parent compound accounted for about 16% and 17% of the dose, respectively.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600317
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  • 88
    Digitale Medien
    Digitale Medien
    Nouveaux types de sucres acétyléniques. Communication préliminaireUne communication plus détaillée paraîtra ultérieurement. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 892-895 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Novel types of acetylenic sugarsThe coupling, following Cadiot's procedure, of a 6-bromo-5,6-dideoxy-1,2-O-isopropylidène-3-O-methyl-α-D-xylo-hex-5-yno-1, 4-furanose (1) with phenylacetylene, 2-propyn-1-ol or terminal acetylenic sugars gave with excellent yields the expected diynes (an enediyne when the terminal acetylene was the 3,5, 6-trideoxy-1,2-O-isopropylidene-α-D-glycero-hex-3-en-5-yno-1,4-furanose 7). The chloro analogue 8 of 1 on treatment with lithium thiophenate gave the corresponding phenylthio-acetylenic sugar 9. An acetylene was also formed by reacting the gem-difluoro-olefinic sugar 10 with butyllithium whereas the same olefinic sugar and its 3-O-benzyl analogue 11 gave only a gem-fluoro-arylthio-olefinic sugar (13-15) as a mixture of the Z and E isomers (Z/E 〉 4) when treated with the conjugate base of an arylmercaptan.
    Zusätzliches Material: 1 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600319
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  • 89
    Digitale Medien
    Digitale Medien
    Nouveaux exemples de radicaux libres stables de dérivés hétérocycliques de sucresDérivés C-glycosyliques XXXIV. Pour la 33c communication v. [1].. Communication préliminaireUne communication plus détaillée paraîtra ultérieurement. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 888-891 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Some more examples of stable free radicals of carbohydrate heterocyclic derivatives2-Glycosyl-4,4,5,5-tetramethylimidazoline- 3-oxide-1-oxyls and 2-glycosyl-4,4,5,5-tetramethylimidazoline 1-oxyls have been prepared in nine carbohydrate series, which proves the generality of the method. The hyperfine coupling constant between the free electron and the α-proton of the glycosyl group is never very large (0-2.3 G) but a correlation between its value and the structure of the aglycone has been noted. Free radicals of that type, stable in aqueous solutions, are potentially interesting for biological studies.
    Zusätzliches Material: 2 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600318
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  • 90
    Digitale Medien
    Digitale Medien
    The Structure of the Antibiotic Hedamycin. I. Chemical, Physical and Spectral PropertiesPresented in part at the fall meeting on the Swiss Chemical Society in Aarau, October 4, 1975. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 896-906 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Interpretation of the chemical and spectral (IR., UV., 1H- and 13C-NMR.) properties of the antitumor antibiotic hedamycin (C41H50N2O11) suggests that the molecule contains a methyl substituted 1-hydroxyanthraquinone nucleus, an α, β-unsaturated ketone, two sugar-like tetrahydropyran rings (4 and 8) and an aliphatic chain 2, presumably with an epoxy group (see the Scheme).
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600320
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  • 91
    Digitale Medien
    Digitale Medien
    Halogenierte Pyridine und 1,8-Naphthyridine. VI (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 907-921 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Halogenated pyridines and 1,8-naphthyridines. VI.The principle of the synthesis of 3-halomethyl-2,6-dichloro-pyridines has been extended to compounds with side chains of more than one carbon atom in the 3-position. Feasible synthetic routes are outlined starting from cheap, commercially available α-methylideneglutaronitrile and trichloroalkyl functional compounds which yield the intermediate 1,3,5-trisubstituted alkanes. These are cyclized by aqueous mineral acid or by hydrogen bromide in an organic solvent to 2-substituted glutarimids or hexahydronaphthyridinones, depending on the mode of cyclization. The final aromatization provides a simple route to pyridines or 1, 8-naphthyridines.
    Zusätzliches Material: 4 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600321
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  • 92
    Digitale Medien
    Digitale Medien
    Über Pterinchemie. 62. Mitteilung. Protonenkatalysierte [1,2]-H-Verschiebung bei der Umlagerung von 6,7-Diphenyl-5,6-dihydropterin zu 6,7-Diphenyl-7,8-dihydropterin (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 922-924 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Proton catalysed [1,2]-H-shift in the rearrangement of 6,7-diphenyl-5,6-dihydropterine (I) to 6,7-diphenyl-7,8-dihydropterine (III)The arrangement from I to the thermodynamically more stable III undergoes through a acid catalysed [1,2]-H-shift (intramolecular 6,7-hydride rearrangement) (see Scheme 1).
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600322
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  • 93
    Digitale Medien
    Digitale Medien
    Reactions of 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5] octane-2,6-diols and their 4,4,8,8-Tetrachloro- and 4,8-Dichloro-Derivatives with Diphosphorus TetraiodideFrom the planned dissertation of R. A. Dyllick-Brenzinger, ETH Zürich. (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 1403-1415 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Reaktionen von 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]octan-2,6-diolen und deren 4,4,8,8-Tetrachlor- und 4,8-Dichlorderivaten mit DiphosphortetrajodidEs wurden die P2I4-Reaktionen mit 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]-octan-2,6-diolen (3/6), mit dem 4,8-Dichlorderivat 4 und mit den 4,4,8,8-Tetrachlorderivaten 5/7 untersucht. Dabei entstanden die Styrolderivate 9 und 12, die anti-Bishomobenzolderivate 8 und 11, ein Homotropylidenderivat 10, ein Cyclo-octatetraenderivat 13 und ein 9-Oxabicyclo[4.2.1]nona-2,4,7-trienderivat 15. Die Ausbeuten lagen zwischen 1 und 10%. Die Bildung aller dieser Produkte liess sich unter der Annahme der primären Umwandlung einer oder beider Hydroxylgruppen in Abgangsgruppen X oder X und Y (wahrscheinlich X=Y=I) mechanistisch deuten. Die Reaktion der Deschlorderivate 3/6 lieferte nach Substitution beider Hydroxyl-gruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 9 (Schema 2) und (b) unter Abspaltung von XY das Homotropylidenderivat 10 (Schema 3a) und das Bishomobenzolderivat 8 (Schema 3b). Die Reaktion des 4,8-Dichlor-derivates 4 lieferte nach Substitution beider Hydroxylgruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 12 (Schema 2), und (b) unter Abspaltung von XY das Bishomobenzolderivat 11 (Schema 3b). Die Reaktion mit den 4,4,8,8-Tetrachlorderivaten 5/7 lieferte: (a) nach Substitution beider Hydroxyl-gruppen durch X und Y unter Abspaltung von XCl und YCl das Cyclooctatetraen-derivat 13 (Schema 4), und (b) nach Substitution nur einer Hydroxylgruppe durch X unter Abspaltung von XCl und HCl das bicyclische Derivat 15 (Schema 5). Alle diese Reaktionen sind zusätzlich zu den angegebenen Fragmentierungen und Eliminierungen noch teilweise von Umlagerungen des Kohlenstoffgerüstes begleitet.Die thermische Umlagerung von 1,5-Dichlor-2,4,6,8-tetramethyl-cycloocta-1,3,5,7-tetraen (13) in das Styrolderivat 12 wurde in Abhängigkeit der Lösungs-mittelpolarität untersucht und mit der analogen thermischen Umlagerung von Brom-cyclooctatetraen und Chlor-cyclooctatetraen verglichen.
    Zusätzliches Material: 1 Tab.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600432
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  • 94
    Digitale Medien
    Digitale Medien
    Diterpenoide Drüsenfarbstoffe: Coleone S und T aus Plectranthus caninus ROTH(Labiatae), ein neues Diosphenol/trans-A/B-6,7-Diketon-Paar aus der Abietanreihe (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 1443-1447 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Leaf-gland Pigments: Coleons S and T from Plectranthus caninus ROTH (Labiatae), New Hydroquinones of the Abietane Series with a Diosphenol/trans-A/B-6,7-Diketone Structure.Coleons S and T were isolated from the more polar fractions from extracts of the above mentioned plant. Coleon S, C20H26O6, has been shown to have structure 1a, and coleon T, C20H26O6, structure 2.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600436
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  • 95
    Digitale Medien
    Digitale Medien
    Über eine Synthese des angulären Di(cyclobuteno)benzols (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 1452-1455 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: On a Synthesis of the angular Di(cyclobuteno)benzolIn the course of our studies aimed at better understanding the Mills-Nixon effect, we have also prepared the angular di(cyclobuteno)benzene (1), the synthesis of which has been recently described by another group [3]. Our completely different and essentially simpler synthetic approach will be pointed out. A special pyrolysis apparatus is designed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600438
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  • 96
    Digitale Medien
    Digitale Medien
    Erratum (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 1455-1455 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600439
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  • 97
    Digitale Medien
    Digitale Medien
    Mitteilungen (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 1456-1458 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600440
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  • 98
    Digitale Medien
    Digitale Medien
    Masthead (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977) 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600501
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  • 99
    Digitale Medien
    Digitale Medien
    Iron Carbonyl Induced Reactions of Norbornene Derivatives with Substituted Acetylenes (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 2160-2170 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Photochemical reactions of norbornadiene with substituted acetylenes in the presence of Fe(CO)5 gave various products of different types, depending on the nature of the acetylene. The results are summarized in Table 1. The cyclopentanone 1 was always formed in these reactions. In the reaction of disubstituted acetylenes such as dimethyl acetylenedicarboxylate and ethyl phenylpropiolate, the cyclopentenones 2 and 5 were formed, respectively. By contrast, propiolic esters produced the cyclohexenones 3 and 4, in which the ester group was attached on the β carbon with respect to the keto group. Plausible mechanisms for the formation of these products are shown in Schemes 7 and 8. The reaction of diphenylacetylene gave the cyclohexendione 7 as well as the cyclopentenone 6. Two enedione products 8 and 9 were obtained from the reaction of phenylacetylene. Compound 9 was converted to the aromatic diacetate 13 by heating with acetic anhydride in pyridine. On irradiation in the presence of Fe(CO)5 norbornene reacted similarly with dimethyl acetylenedicarboxylate and phenylacetylene to give the cyclopentenone 14 and the cyclohexenone 15, respectively. Compound 15, upon heating, isomerized to hydroquinone 16, which on acetylation gave the diacetate 17.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600708
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  • 100
    Digitale Medien
    Digitale Medien
    Application of the Equivalent Bond Orbital Model to the C2s-Ionization Energies of Saturated Hydrocarbons (1977)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 60 (1977), S. 2234-2247 
    Details
    ISSN: 0018-019X
    Schlagwort(e): Chemistry ; Organic Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: It is shown that the ab initio STO-3G treatment applied to simple saturated linear, branched and cyclic hydrocarbons, assuming standard geometries, yields orbital energies ∊jSTO-3G for their canonical orbital ϕj which correlate perfectly with the observed C2s ionization energies Ijm, if Koopmans' approximation is accepted.Applying the Foster-Boys localization procedure to these canonical orbitals ϕj leads to localized orbitals λμ and their corresponding Hartree-Fock matrix Fλ = (Fλ,μv). An examination of the matrix elements Fλ,μv, i.e. of the self-energies Aμ = Fλ,μμ of the localized CC- and CH-orbitals λμ and of the cross terms Fλ, μv (μ ≠ v) between them, leads to the conclusion that a satisfactory approximation should be obtained by setting Aμ = A for all μ, Fλ,μv = B if λμ and λv are vicinal and neglecting all other cross terms. The resulting model is nothing but the well-known equivalent bond orbital model of Lennard-Jones & Hall, which however can now be calibrated using the known C2s-ionization energies of hydrocarbons. Due to the discrete structure and the wider range (∽ 8 eV) of the C2s band systems in the photoelectron spectra of these molecules this leads to a more satisfactory parametrization than using the narrower and badly resolved C2p band system.Comparison of calculated band positions using the calibrated model with observed C2s-band ionization energies for a series of hydrocarbons reveals that the simple equivalent bond orbital model is better than one might have expected.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/hlca.19770600715
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