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  • pharmacokinetics  (417)
  • Ultrastructure  (348)
  • Springer  (765)
  • American Association for the Advancement of Science (AAAS)
  • American Institute of Physics (AIP)
  • 1980-1984  (765)
  • 1960-1964
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  • Springer  (765)
  • American Association for the Advancement of Science (AAAS)
  • American Institute of Physics (AIP)
  • Wiley-Blackwell  (1)
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  • 101
    Electronic Resource
    Electronic Resource
    A tubular configuration of the granular endoplasmic reticulum forming a raft-like parallel array in the pinealocytes of two species of Japanese moles (Mogera kobeae and M. wogura) (1984)
    Springer
    Cell & tissue research 236 (1984), S. 15-18 
    Details
    ISSN: 1432-0878
    Keywords: Granular endoplasmic reticulum ; Ultrastructure ; Pinealocyte ; Mole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ten or more straight tubules, each of which consists of a double unit membrane of granular endoplasmic reticulum with a cylindrical profile, are joined side by side in a raft-like configuration in the cytoplasm of the pinealocytes of Japanese moles. They measure about 60 nm and 100 nm in their inner and outer diameters, respectively, and are often partially connected to unspecialized granular endoplasmic reticulum. Cisterns held between the inner and outer unit membranes with cylindrical profiles vary from 15 nm to 30 nm in width. Ensheathed portions of the cytoplasm are contiguous with cytoplasm outside the tubular units. The inner unit membranes of the tubules bear fewer ribosomal particles than the outer ones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216507
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  • 102
    Electronic Resource
    Electronic Resource
    Satellite cells in the tail muscles of the urodelan larvae during development (1984)
    Springer
    Cell & tissue research 236 (1984), S. 431-438 
    Details
    ISSN: 1432-0878
    Keywords: Satellite cells ; Satellite fibres ; Tail muscle ; Urodela ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The incidence and ultrastructure of satellite cells in the tail muscles of urodelan larvae were examined during development during which the number of satellite cells is gradually reduced. They are found more frequently in red than in the white fibres in all four stages examined (stage 53, 64, 66+ and juvenile). As development proceeds, intercellular space between satellite cell and muscle fibre is in general gradually extended and is mostly filled with basal lamina. Small muscle cells, satellite fibres, which are situated under the basal lamina of the parent fibre, are morphologically similar to satellite cells but contain a small amount of myofibrils. Three types of satellite fibres are distinguishable on the basis of differences in K2-EDTA-treated ATPase activity, width of Z line, and parent fibre type. Neuromuscular junctions are visible in satellite fibres.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00214247
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  • 103
    Electronic Resource
    Electronic Resource
    Morphometric analysis of loading-induced changes in collagen-fibril populations in young tendons (1984)
    Springer
    Cell & tissue research 236 (1984), S. 465-470 
    Details
    ISSN: 1432-0878
    Keywords: Tendon ; Collagen fibrils ; Morphometry ; Ultrastructure ; Loading ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary This study was designed to gain more detailed morphological information on skeletal tendons in the course of adaptation to physical loading. The effect on collagen fibrils was investigated in 6-week-old mice by means of electron microscopy. Physical loading was performed on a treadmill 5 days a week for 1, 3, 5, 7 and 10 weeks. Morphometric analysis of collagen fibrils revealed the mean diameter, the diameter distribution, the number and the cross-sectional area. The principal observations included: 1. After one week of physical loading an increase in mean fibril diameter (30%, p≦0.01), in number (15%, p≦ 0.05), and in cross-sectional area (15%, p≦0.05), as well as a change in mean fibril diameter distribution. 2. From the third to the seventh week a fall under the level of the controls in mean diameter (26%, p≦0.01), in number (26%, p≦0.01), and a reduced cross-sectional area (17%, p≦0.01), accompanied by signs of splitting of individual collagen fibrils. 3. In the long-term study an increase in fibril number (29%, p≦0.01), a fall in mean diameter from 189 nm in the controls to 179 nm (p≦0.05) but no statistically significant change in the relative cross-sectional area (32%) per unit in comparison to unloaded tendons. The possible physiological implications of the findings are discussed in the light of several regulatory mechanisms known to appear during the course of physical loading in connective tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00214251
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  • 104
    Electronic Resource
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    Changes in metabolism and hepatic ultrastructure induced by estradiol and testosterone in immature female Epinephelus akaara (Teleostei, Serranidae) (1984)
    Springer
    Cell & tissue research 236 (1984), S. 651-659 
    Details
    ISSN: 1432-0878
    Keywords: Steroids ; Vitellogenesis ; Metabolism ; Ultrastructure ; Teleosts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Estradiol injections increase serum level of calcium, amino acid, glucose, protein, ammonia and creatinine in immature Epinephelus akaara, and also increase levels of total lipid, cholesterol, phospholipid and esterified fatty acids. Hepatic protein, glycogen and lipid concentrations also rise after estradiol treatment, and some hepatic enzymes participating in the metabolism of nitrogen, lipid and carbohydrate, show increased activity. Serum vitellogenin levels are increased. Testosterone treatment increases serum protein, total lipid, cholesterol, amino acid and ammonia levels, and also hepatic glycogen content, but in contrast to estradiol treatment, testosterone does not change serum vitellogenin, glucose, calcium, phospholipid, esterified fatty acid and creatinine levels, nor the hepatic lipid and protein content. A small number of hepatic enzymes shows an increased activity. Vitellogenic fish show biochemical changes similar to that of estradiol-treated fish, but are different from those of immature fish. Estradiol treatment induces ultrastructural changes in the hepatocytes of immature fish that are similar to those found in vitellogenic fish. These include a proliferation of rough endoplasmic reticulum and Golgi apparatus, and an increase in glycogen and lipid, all indicative of enhanced metabolic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217235
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  • 105
    Electronic Resource
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    Synaptic organization of a multifunctional interneuron in the central nervous system of Helix pomatia L. (1984)
    Springer
    Cell & tissue research 236 (1984), S. 677-683 
    Details
    ISSN: 1432-0878
    Keywords: Interneuron ; Synaptology ; Ultrastructure ; Horseradish peroxidase ; Helix pomatia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphology, axonal arborization and ultrastructure of synaptic connections of the V21 giant neuron in the visceral ganglion of the snail Helix pomatia has been investigated following intracellular labelling with horseradish peroxidase. The V21 neuron establishes several afferent and efferent axo-axonic connections, mainly along the first half of the primary axon. Collaterals of 200–300 μm length originate from the primary axon, which shows further arborization, and both afferent and efferent synaptic contacts are formed on these fine axon profiles. Afferent and efferent contacts of the cell occur within very short distances of a few micrometers. On the basis of ultrastructure and vesicle and granule content, several afferent terminals can be distinguished on V21 labelled axon profiles. The majority of these afferent terminals resembles peptidergic-(neurosecretory)-like terminals. This finding supports the possible transmitter role of neuropeptides in the central nervous system of gastropods. Our results are consistent with and provide morphological evidence for recent electrophysiological observations suggesting that, in addition to integrating input, the V21 neuron functions as an interneuron in Helix central nervous system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217238
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  • 106
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    Interactions between immature porcine Leydig and Sertoli cells in vitro (1984)
    Springer
    Cell & tissue research 237 (1984), S. 357-362 
    Details
    ISSN: 1432-0878
    Keywords: Leydig-Sertoli cell interaction ; FSH stimulation ; Ultrastructure ; Pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Interactions between Leydig and Sertoli cells, as well as a stimulatory effect of FSH on Leydig cell activity, have been reported in many studies. In order to investigate these interactions, the ultrastructure of immature pig Leydig cells under different culture conditions has been studied. When cultured alone in a chemically defined medium, there is a marked regression of the Leydig cell smooth endoplasmic reticulum and a swelling of the mitochondria. Addition of FSH or hCG does not prevent these phenomena. Co-culturing of Leydig cells with Sertoli cells from the same animal maintains the smooth endoplasmic reticulum at the level seen in vivo and in freshly isolated Leydig cells. The addition of FSH to the co-culture stimulates its development and increases Leydig cell activity, as assessed by an increase in hCG binding sites and an increased steroidogenic response to hCG. These results suggest that Sertoli cells exert a trophic effect on Leydig cells, and that the stimulatory effect of FSH on Leydig cell function is mediated via the Sertoli cells. These results reinforce the concept of a local regulatory control of Leydig cell steroidogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217157
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  • 107
    Electronic Resource
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    Restoration of fast muscle characteristics following cessation of chronic stimulation (1984)
    Springer
    Cell & tissue research 238 (1984), S. 221-230 
    Details
    ISSN: 1432-0878
    Keywords: Fiber type ; Ultrastructure ; Stereology ; Stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary When fast-twitch skeletal muscles of the adult rabbit are subjected to continuous low-frequency activity by electrical stimulation of the corresponding motor nerves, the fibers undergo an ultrastructural transformation, so that after 6 weeks they have acquired an appearance typical of slow-twitch fibers. In the present study, stimulation was discontinued at this stage in order to follow the reverse transformation, in which the fibers recovered their original morphological characteristics under conditions of normal endogenous activity. Stereological techniques were used to assess the time course of this process over a period of 20 weeks in terms of fiber cross-sectional area, extent of T-system, thickness of the Z-band, and volume fraction of mitochondria in the fiber core. Fibers of transformed muscles were smaller than those of control muscles, but the differences were no longer evident after 9 weeks of recovery. After 2 weeks the T-system was still of limited extent, as is characteristic of slow-twitch fibers; it increased toward the amount typical of fast-twitch fibers between 2 and 4 weeks, and had reached its full extent by 12 weeks. The wide Z-bands characteristic of slow-twitch fibers were retained for 4 weeks, but the thickness had begun to decrease by 8 weeks and recovery was complete by 12 weeks. The mitochondrial volume did not increase during recovery, in contrast to the large increases which had been observed to take place between 2 and 6 weeks during the fast-to-slow transformation. Overall, the recovery of fast-twitch ultrastructural characteristics was complete, but followed a more extended time course, and involved less myofibrillar disruption at an intermediate stage, than the original fast-to-slow transformation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217292
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  • 108
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    Development and ultrastructural autoradiographic studies of nucleolus-like bodies (nuages) in oocytes of a viviparous teleost (Xiphophorus helleri) (1984)
    Springer
    Cell & tissue research 238 (1984), S. 121-128 
    Details
    ISSN: 1432-0878
    Keywords: Ultrastructure ; Autoradiography ; Oocytes ; Nucleolus-like bodies ; Teleost
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cytoplasmic granulo-fibrillar masses, usually termed nucleolus-like bodies (NLB) or nuages, have been described in several different cell types. They are sometimes associated with a mitochondrial arrangement, this association often being marked during certain phases of the oocyte cycle. In Xiphophorus helleri, NLB consist of fibrillar and granular material that gradually becomes more granular during meiotic prophase I, and is associated with mitochondrial arrangements during diplotene and dictyate of meiosis. Autoradiographic studies of uridine incorporation into the nucleolus and subsequently into NLB suggest that the latter represent a reserve of ribonucleoproteins that is later used in ribosomal maturation during vitellogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00215152
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  • 109
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    Ultrastructure of the eyes of the grass shrimp, Palaemonetes pugio (1984)
    Springer
    Cell & tissue research 238 (1984), S. 271-288 
    Details
    ISSN: 1432-0878
    Keywords: Compound eye ; Ultrastructure ; Grass shrimp, Palaemonetes pugio ; Light adaptation ; Dark adaptation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cone cells and corneagenous cells possess extensive networks of smooth tubular endoplasmic reticulum that may be involved in optical reflectance and light-adaptational responses, respectively. The extracellular basal lamina of the basement membrane is confluent with glial cell capillary walls and may prove to be a viaduct for the transmission of hemolymph-borne substances to the retina or of retinal degradation products to the hemolymph. In addition to dense pigment granules, the distal pigment cells are shown for the first time to contain migratory reflecting platelets that are usually polymorphic in light-adapted eyes but are rectangular in dark-adapted eyes. In the latter these plates become aligned against the crystalline cones and presumably contribute to the reflection superposition optics of the grass shrimp. Dark-adapted retinular cells possess well-developed perirhabdomal cisternae, oblong or ovoid mitochondria, generally vesicular rough endoplasmic reticulum, and occasional, spherical, calcium-like intrarhabdomal inclusions. Light-adapted retinular cells possess poorly developed perirhabdomal cisternae, lamelliform rough endoplasmic reticulum, and condensed mitochondria frequently associated with lipid droplets and pigment granules. The cytoplasmic boundaries of the reflecting pigment cells expand into the extracellular spaces between individual ommatidial retinular cells during dark adaptation and recede to the interommatidial extracellular spaces during light adaptation. Cytoplasmic microfilament bundles found only at the bases of partially light-adapted rhabdomeric microvilli may be involved in microvillar shortening.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217299
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  • 110
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    Fine structure of submandibular glands of mice with testicular feminization (Tfm/Y) (1984)
    Springer
    Cell & tissue research 235 (1984), S. 295-301 
    Details
    ISSN: 1432-0878
    Keywords: Tfm/Y mouse ; Submandibular gland ; Sexual ; dimorphism ; Androgens ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the submandibular gland of the mouse with testicular feminization (Tfm/Y) was studied by light and electron microscopy. The architecture of the Tfm/Y gland proved to be rather similar to that of the normal female mouse in both tubular ratio and structure. Granular convoluted tubular cells in Tfm/Y mice characteristically had fewer secretory granules and increased cytoplasmic vacuoles than normal littermates, suggesting an altered synthesis of secretory granules in this cell type of the Tfm/Y mouse. Moreover, there were differences in the ultrastructure of submandibular glands between Tfm/Y and normal female mice. In the gland of the Tfm/Y mouse, basal striations of the striated secretory tubular cells were not so developed and granular intercalated duct cells were less than those of normal females. These findings support the evidence that the secretory tubule of the mouse submandibular gland responds to androgens, resulting in accentuated development in the male, while also suggesting the possibility that the mouse submandibular gland is regulated by other factors which lead to the prominent sexual dimorphism observed in this gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217853
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  • 111
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    Invaginated apical vacuoles in the cells of the proximal convoluted tubule in the rat kidney (1984)
    Springer
    Cell & tissue research 235 (1984), S. 463-466 
    Details
    ISSN: 1432-0878
    Keywords: Endocytosis ; Kidney (rat) ; Proximal tubule ; Apical vacuoles ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Following perfusion fixation of the rat kidney with glutaraldehyde the proximal tubule cells display small apical vacuoles, large apical vacuoles, and apical vacuoles in which a part of the limiting membrane is invaginated into the vacuole. These invaginated apical vacuoles occur more frequently in proximal convoluted tubules than in proximal straight tubules. One tubular cell may contain apical vacuoles of different sizes and stages of invagination, ranging from larger vacuoles with a wide lumen and a small area of invaginated membrane to smaller elements with no apparent lumen and a large area of invaginated membrane. Invaginated apical vacuoles lie either singly in the cytoplasm or close to the membranes of other apical vacuoles, but never in contact with the cell membrane or the membranes of lysosomes, endoplasmic reticulum, Golgi apparatus, mitochondria and peroxisomes. These findings suggest that the invaginated apical vacuoles are not fixation artifacts, but rather develop in living state in cells of the proximal tubule from spherical endocytotic elements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217875
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  • 112
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    The ecdysis of hair mechanoreceptors in crayfish (1984)
    Springer
    Cell & tissue research 236 (1984), S. 339-343 
    Details
    ISSN: 1432-0878
    Keywords: Moulting ; Mechanosensory hair ; Chordotonal organ ; Ultrastructure ; Crustacea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of hair mechanoreceptors in crayfish during moulting was investigated with special attention to the interface apparatus between cuticular hairs and sensory cells: the chorda. The chordae are lost with old exuviae at every moulting. They are drawn out from a moulting canal at the tip of the new hair. The chordae are regenerated from a material secreted by sheath cells after moulting. Therefore, the chorda is an inward projection of the cuticular exoskeleton, and it has direct contact with the sensory element, the scolopidium. The scolopidium has been found in both hair mechanoreceptors and subcuticular chordotonal organs in crustaceans, and is thought to be a primitive type of mechano-sensory transducing element. The present observation gives additional evidence for the homology of two sensory elements in arthropods, i.e., the cuticular hair sensilla and subcuticular chordotonal organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00214236
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  • 113
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    In vivo shedding of apical plasma membrane in the thyroid follicle cells of the mouse (1984)
    Springer
    Cell & tissue research 236 (1984), S. 87-97 
    Details
    ISSN: 1432-0878
    Keywords: Iodination ; Membrane shedding ; Peroxidase ; Thyroid follicle cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Clusters of luminal dense bodies, limited by a triple-layered membrane, were found in all follicle lumina in thyroid glands of mice. After thyroxine treatment the number of luminal dense bodies increased, especially in the periphery of the lumen, where the intraluminal bodies often displayed a striking resemblance to microvilli. In hyperplastic goiters, obtained by feeding mice with propylthiouracil, luminal dense bodies were replaced by intraluminal vesicles. During goiter involution the vesicles were gradually replaced by luminal dense bodies; the presence of intermediate forms suggests that vesicles and dense bodies are basically the same formations. Luminal dense bodies were observed in colloid droplets indicating their removal by endocytosis. As demonstrated by electron-microscopic cytochemistry, luminal dense bodies contain a membranebound peroxidase, and electron-microscopic autoradiography after administration of 125I indicate that they possess an iodinating capacity. Our observations on mouse thyroid glands suggest that the luminal dense bodies, which appear as vesicles in hyperplastic glands, are formed by shedding of the apical plasma membrane of the follicle cell. The shedding process might be of importance for the turnover of plasma-membrane material.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216517
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  • 114
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    Immunocytochemistry and ultrastructure of the neuropil located ventral to the rat supraoptic nucleus (1984)
    Springer
    Cell & tissue research 236 (1984), S. 171-180 
    Details
    ISSN: 1432-0878
    Keywords: Immunocytochemistry ; Ultrastructure ; Supraoptic nucleus ; Neuropil ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The neuropil located ventral to the SON was investigated by the use of immunoperoxidase staining for neurophysins, oxytocin and vasopressin, and electron miroscopy. The study was performed in six groups of rats: 1) control; 2) infusion of isotonic saline into the CSF; 3) infusion of hypertonic saline into the CSF; 4) drinking hypertonic saline for 4 days; 5) same as group 4 but injection of colchicine into the CSF on second day of dehydration; 6) salt loading for 3 months. In the control rats the ventral neuropil contained a few immunoreactive processes, the general morphology of which was completely different from that of the neurosecretory axons emerging from the SON at its dorsal aspect. In rats of groups 3 to 6 the ventral processes (VP) became loaded with neurosecretory granules, whereas the perikarya and axons were depleted. Based on their general morphology and reactivity pattern it is suggested that the VP are dendrites. Most of these “dendrites” were embedded in a glial cushion formed by the processes of a particular type of marginal glia. Some of these “dendrites” enveloped an arteriole penetrating the optic tract. All VP were rich in synaptic contacts. The possibility that the VP of neurosecretory cells may be functionally related to the subarachnoid CSF and the arteriolar blood flow is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216528
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  • 115
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    Peripolar cell hypertrophy in the renal juxtaglomerular region of newborn sheep (1984)
    Springer
    Cell & tissue research 236 (1984), S. 197-202 
    Details
    ISSN: 1432-0878
    Keywords: Peripolar cells ; Juxtaglomerular apparatus ; Newborn sheep ; Dexamethasone ; Ultrastructure ; Cytoplasmic granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the renal juxtaglomerular region of newborn sheep, it was found that glomerular peripolar cells and their granules were very much larger than those found in fetal lambs or adult sheep. Similar peripolar cell hypertrophy was triggered in fetal lambs treated in utero with intraperitoneal injections of dexamethasone. Ultrastructurally, granules of peripolar cells from newborn lambs resembled closely the enlarged zymogen granules described in the pancreas of newborn rats. Such peripolar cell hypertrophy may reflect a functional adaptation of the kidney to immediate postnatal life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216531
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  • 116
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    Proliferation and differentiation of intestinal epithelial cells during development of Barbus conchonius (Teleostei, Cyprinidae) (1984)
    Springer
    Cell & tissue research 236 (1984), S. 207-216 
    Details
    ISSN: 1432-0878
    Keywords: Development ; Enterocytes ; Fish ; Mitosis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The processes of proliferation, cell division and differentiation of intestinal epithelial cells have been studied during development of the fish, Barbus conchonius. On the 3rd day, nearly all cells of the presumptive gut proliferate. Once the intestinal epithelium begins to differentiate, a decreasing percentage of proliferative cells can be found. On the 7th day, when intestinal folds start to develop, the proliferative cells become restricted to the future basal parts of the folds. Ultrastructural examination of 3H-thymidine-labeled cells and mitotic cells of 6-day-old larvae shows that functional enterocytes are proliferative. The same feature is suggested for older fish. Proliferating undifferentiated “dark” cells, characterized by many free ribosomes and a few organelles, are also present in the intestinal epithelium of larval fish; they are considered to be stem cells, mainly for goblet cells. Proliferating goblet cells and enteroendocrine cells were not observed. The latter cell type is scarce and has a long turnover time. A common feature of all these dividing cells is the presence of isolated spherical to cylindrical lamellar structures which may have lost contact with the cell membrane during prophase; they probably regain this contact by fusion with the cell membrane at the end of mitosis.
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    URL: http://dx.doi.org/10.1007/BF00216533
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  • 117
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    Morphometric and fine-structural studies of rat pancreatic acinar cells during early postnatal life (1984)
    Springer
    Cell & tissue research 237 (1984), S. 123-129 
    Details
    ISSN: 1432-0878
    Keywords: Pancreas, exocrine (rat) ; Ultrastructure ; Morphometry ; Development, ontogenetic ; Zymogen granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Pancreatic acinar cells of rats obtained at 1,2, 3, 5, 7 and 14 days of age were examined using fine structural and morphometric techniques. From 5 days of age onwards, the acinar cells were analysed twice per day, at 20.00 h and 08.00 h. The present study demonstrates changes in the average volume of the cell, nucleus and cytoplasm, and volume densities of various cytoplasmic organelles during the first two weeks after birth. During early postnatal life, the volume density of rER increases, whereas that of zymogen granules decreases. From 5 days of age onwards, the volume densities of these two organelles differ significantly at 20.00 h and 08.00 h. During the first 2–3 days after birth, inclusion body-like structures appear in the cytoplasm of acinar cells; they contain aggregated zymogen granules and, sometimes, amorphous structures or cytoplasmic organelles. These structures also occur in interstitial cells and cells located in the intercalated region between acinar and ductal epithelial cells. Serum level of α-amylase activity is high at birth, compared with other stages during the first three weeks. Degenerating acinar cells and cell debris can be seen in the acinar and ductal lumina during these stages, a feature suggesting holocrine secretion. Cellular polarity appears to be incomplete during the first two or three days after birth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229207
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  • 118
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    Morphological and pharmacological basis for pulmonary ventilation in Amphiuma tridactylum (1984)
    Springer
    Cell & tissue research 238 (1984), S. 1-12 
    Details
    ISSN: 1432-0878
    Keywords: Lung ; Amphibia ; Ultrastructure ; Smooth muscle ; Extracellular matrix
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The lung of the giant salamander, Amphiuma tridactylum, is divided into respiratory alveoli by muscular septa that increase the surface area of the lung as well as provide a mechanism for its almost complete collapse during exhalation. The epithelium of the internal surface is of two types: respiratory, composed of a single layer of pneumocytes overlying anastomosing capillaries, and non-respiratory, composed of ciliated cells and mucus-secreting goblet cells. Non-respiratory epithelium covers the apical edges of the septa, whereas the respiratory epithelium lines the alveoli. The smooth muscle of the septa and walls of the lung was studied in preparations of uninflated and acetylcholine-contracted lung. The muscle cells are ultrastructurally similar to other types of smooth muscle but are surrounded by extraordinary amounts of extracellular matrix, containing collagen and elastic fibers and numerous fine fibrils of unknown composition. Smooth muscle in isolated lung strips contracted in a dose-dependent manner when treated with acetylcholine or methacholine; contraction was blocked by atropine. Responses of lung strips to adrenergic agents were limited; only high doses of adrenalin caused slight relaxation of previously contracted muscle. These observations support the hypothesis that contraction of pulmonary smooth muscle is responsible for the ventilatory efficiency of the lung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00215138
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  • 119
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    Morphological evidence for the presence of two cell types in the ependyma of the subcommissural organ of the snake, Natrix maura (1984)
    Springer
    Cell & tissue research 238 (1984), S. 407-409 
    Details
    ISSN: 1432-0878
    Keywords: Subcommissural organ ; Secretory granules ; Secretory process ; Ultrastructure ; Natrix maura (Reptilia, Ophidia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two different types of ependymal cells were found in the subcommissural organ (SCO) of Natrix maura. Most secretory cells showed morphological features resembling the general structure and ultrastructure of cells in the SCO of other vertebrates. This report describes a second population of cells lining a portion of the dorsal groove of the SCO. These cells were not selectively stained by chromalum-hematoxylin and, under the electron microscope, they were characterized by scarce surface differentiations, sparse apical cytoplasm and short basal processes. Flat, parallel cisternae of the rough endoplasmic reticulum produced vesicles that appeared to be transported to the well-developed Golgi apparatus. Dense secretory granules about 200 nm in diameter were found in the Golgi region. Similar granules were seen in the vicinity of the apical plasma membrane; some of them opened toward the ventricle. All these characteristics clearly differentiate this cell group from the other secretory cells lining the SCO laterally and ventrally.
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    URL: http://dx.doi.org/10.1007/BF00217314
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    On the nature of the opaque and translucent enamel regions of some macropodinae (Macropus giganteus, Wallabia bicolor and Peradorcas concinna) (1984)
    Springer
    Cell & tissue research 238 (1984), S. 329-337 
    Details
    ISSN: 1432-0878
    Keywords: Teeth (Macropodinae) ; Enamel (opaque, translucent) ; Ultrastructure ; Enamel hardness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Teeth of three macropod species, M. giganteus, W. bicolor and P. concinna, have been studied using the techniques of light microscopy, scanning- and transmission-electron microscopy and hardness measurement. Light microscope observations showed that the teeth of these species had a translucent enamel region close to the dentine and an outer opaque enamel region at the tooth's surface. These regions were not related to the presence or absence of tubules which are a characteristic feature of marsupial enamel. Hardness tests showed that the opaque enamel was softer than the translucent enamel. Scanning electron microscope observations revealed that there was no correlation between any particular prism packing or orientation and the opaque and translucent enamel regions. Transmission electron microscope observations showed that the translucent enamel region consisted of well defined prisms and well packed, lath-like crystals, whereas the opaque enamel was disrupted by voids (which ranged in size from enlarged micropores to about 2 μm in diameter in extreme cases) between crystals and some randomly oriented, loosely packed crystals. This disruption within the opaque enamel region was more common at prism boundaries but pockets of disrupted enamel were also found within prisms and interprismatic regions. The opacity of the enamel was caused by scattering of light from the voids. The ultrastructure of the opaque enamel region indicated that this region was hypomineralized; hardness tests and polarized light microscope observations were consistent with these results.
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    URL: http://dx.doi.org/10.1007/BF00217305
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    Organ culture of the goldfish pineal body (1984)
    Springer
    Cell & tissue research 238 (1984), S. 565-575 
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    ISSN: 1432-0878
    Keywords: Pineal organ teleost ; Tissue culture ; Ultrastructure ; Indoles ; High performance liquid chromatography (HPLC)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure and biochemistry of the goldfish pineal organ were examined in expiants cultured for 1, 3, and 6 days. All four cell types (photoreceptor, supportive, ganglion, phagocytic) were identified; they exhibited many of the characteristics of these cells in vivo. Exceptions included a gradual disorganization of the outer segments and reduction of synaptic ribbons in photoreceptors with time in culture. In addition, there was a marked proliferation of endoplasmic reticulum in both photoreceptor and supportive cells. The indoles 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, 5-methoxytryptophol, and melatonin were separated in expiants by high performance liquid chromatography using electrochemical detection. Serotonin levels could be depleted by p-chlorophenylalanine and elevated by nialamide or by adding 5-hydroxytryptophan to the culture medium. These findings suggest that organ culture may be a useful model for study of regulatory processes related to the photoneuroendocrine functions of the teleost pineal organ.
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    URL: http://dx.doi.org/10.1007/BF00219873
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    Electron-microscopic study of innervation of smooth muscle cells surrounding collecting tubules of the fish kidney (1984)
    Springer
    Cell & tissue research 238 (1984), S. 307-312 
    Details
    ISSN: 1432-0878
    Keywords: Innervation ; Smooth muscle ; Fish ; Kidney ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the collecting tubules of the trout and killifish kidney was studied. These tubules are surrounded by layers of smooth muscle cells which are commonly innervated. The nerve terminals contain synaptic vesicles and, occasionally, a few dense-cored granules as well. Capillaries occur in the connective tissue space between these smooth muscle cells and the collecting tubule. Epithelial cells of the collecting tubules contain abundant mitochondria and a well developed membrane system displaying parallel arrays, and were considered to be actively involved in the transport of materials. In the trout, the collecting tubules contain peculiar cells in addition to regular tubule cells. The fine structure of these peculiar cells is highly reminiscent of that of gill chloride cells. The significance of these findings may be summarized as follows: If the smooth muscles around the collecting tubule contract under neural influence, intratubular pressure may be increased and, thus affect glomerular filtration rate. The contraction of these muscles may also cause the collapse of peritubular capillaries, affecting the transport activity of tubule cells.
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    URL: http://dx.doi.org/10.1007/BF00217302
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    Ultrastructural identification of catecholaminergic fibers in the goldfish pituitary (1984)
    Springer
    Cell & tissue research 238 (1984), S. 621-626 
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    ISSN: 1432-0878
    Keywords: Catecholamines ; Pituitary innervation ; Radioautography ; Ultrastructure ; Goldfish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The monoaminergic innervation of the goldfish pituitary gland was studied by means of light- and electronmicroscopic radioautography after in vitro administration of 3H-dopamine. The tracer was specifically incorporated and retained by part of the type-B fibers innervating the different lobes of the pituitary. In the rostral pars distalis labeled fibers were most frequently observed in contact with the basement membrane separating the neurohypophysis and the adenohypophysis. In the proximal pars distalis and the pars intermedia, labeled profiles were detected in the neural tissue and in direct contact with the different types of secretory cells. According to the previous data concerning the uptake and retention of tritiated catecholamines in the central nervous system, it is assumed that the labeled fibers are mainly catecholaminergic (principally dopaminergic). This study provides morphological evidence for a neuroendocrine function of catecholamines in the goldfish.
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    URL: http://dx.doi.org/10.1007/BF00219880
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    Peroxidase-positive endothelial cells in rat liver (1984)
    Springer
    Cell & tissue research 238 (1984), S. 635-642 
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    ISSN: 1432-0878
    Keywords: Liver ; Endothelium ; Kupffer cells ; Peroxidase ; Cytochemistry ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat liver fixed by perfusion with low glutaraldehyde concentrations was incubated in diaminobenzidine-containing medium to stain for peroxidase. Endogenous peroxidatic activity was found not only in Kupffer cells but also in the endothelial cells lining the sinusoids and central veins. The reaction product was localized in the nuclear envelope and endoplasmic reticulum. The peroxidatic activity in endothelial cells showed a concentration-dependent sensitivity to glutaraldehyde: in liver samples fixed with 0.25% glutaraldehyde, approx. 23% of the sinusoidal endothelial cells and 65% of central vein endothelium were peroxidase-positive; with 0.5% glutaraldehyde, only approx. 8% of the sinusoidal endothelial cells contained detectable amounts of the reaction product; with 1.5% glutaraldehyde all endothelial cells were consistently peroxidase-negative. No peroxidatic activity could be found in liver endothelial cells following isolation by centrifugal elutriation. Endothelial cell peroxidase may possibly be involved in defense responses of liver and/or, as a part of prostaglandin synthase system, in prostanoid production.
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    URL: http://dx.doi.org/10.1007/BF00219882
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    Ultrastructure of the flagellar apparatus in the green flagellateSpermatozopsis similis (1984)
    Springer
    Plant systematics and evolution 146 (1984), S. 145-162 
    Details
    ISSN: 1615-6110
    Keywords: Chlorophyceae ; Spermatozopsis similis ; Ultrastructure ; green flagellate ; flagellar apparatus ; function ; phylogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The ultrastructure of the flagellar apparatus of the naked, biflagellate green algaSpermatozopsis similis Preisig & Melkonian has been studied in detail using an absolute configuration analysis. The two basal bodies are displaced by 350 nm in the 1/7 o'clock direction and do not overlap proximally. They are interconnected by a principal distal connecting fibre consisting of a bundle of 5–8 nm filaments and possibly two proximal striated connecting fibres. The flagellar root system is cruciate (5-2-5-2 or 4-2-4-2 system) and contains a prominent continuous system I fibre overlying the two opposite two-stranded roots. A system II fibre is absent. Pronounced structural differences have been observed in the flagellar apparatus ultrastructure at two types of flagella orientation: During backward swimming basal bodies are parallel, the distal connecting fibre is extremely contracted; during forward swimming basal bodies assume various angles (from 20° to 180°) and the connecting fibre is about five times longer compared to the contracted state. The function of the connecting fibre as a contractile organelle and the mechanism of its contraction are discussed. On the basis of the flagellar apparatus ultrastructure,Spermatozopsis similis is related toChlamydomonas-type green algae.
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    URL: http://dx.doi.org/10.1007/BF00989542
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    Zur Ultrastruktur und Funktion pollenverbindender Fäden beiEricaceae und anderen Angiospermenfamilien (1984)
    Springer
    Plant systematics and evolution 147 (1984), S. 189-203 
    Details
    ISSN: 1615-6110
    Keywords: Angiosperms ; Ericaceae ; Onagraceae ; Mimosaceae ; Musaceae ; Ultrastructure ; function of pollen connecting threads and viscin threads ; palynology ; pollination ecology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Viscin threads and other pollen connecting threads of some angiosperm families were investigated, especially those ofEricaceae. According to the definition adopted, viscin threads are ± long exinous processes which consist of exinous material and connect pollen grains or tetrads. Such viscin threads are found within theOnagraceae, Caesalpiniaceae, Ericaceae, andMimosaceae only. While they differ in structure and composition, they always consist of sporopollenin and exhibit a very strong stickiness, even after all viscid substances have been removed by acetolysis. In contrast, the pollen connecting scleroprotein threads ofOrchidaceae and the cellular threads ofStrelitzia reginae Aiton. (Musaceae) are not connected with the exine surface, are destroyed by acetolysis, and thus do not correspond to viscin threads.
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    URL: http://dx.doi.org/10.1007/BF00989383
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    The influence of cold acclimation on the behavior of the plasma membrane following osmotic contraction of isolated protoplasts (1984)
    Springer
    Protoplasma 123 (1984), S. 161-173 
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    ISSN: 1615-6102
    Keywords: Cold acclimation ; Exocytotic extrusions ; Freeze-fracture ; Isolated rye protoplasts ; Lipid bodies ; Osmotic contraction ; Plasma membrane ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Osmotic contraction of protoplasts isolated from cold acclimated leaves ofSecale cereale L. cv. Puma results in the formation of exocytotic extrusions of the plasma membrane. Numerous knobs or polyps were observed on the surface of the protoplasts with scanning electron microscopy. In thin sections, the extrusions were bounded by the plasma membrane with a densely osmiophilic interior. Cross-fracturing of the extrusions revealed aparticulate bodies within, a further indication that the interior of the extrusions was predominantly lipid material. Freeze-fracture of the plasma membrane suggests a possible source of this lipid material. Following osmotic contraction, the particle density on the plasma membrane protoplasmic face (PFp) increased, being reflected in both a substantial increase in paracrystalline arrays and an increase in the particle density in non-crystalline regions. This increase in particle density indicates that lipid material is preferentially lost from the plasma membrane during contraction. The density on the exoplasmic face (EFp) did not change. Together, these findings suggest that during hypertonic contraction of acclimated protoplasts, lipid material is preferentially subducted from the plasma membrane and sequestered into lipid bodies (the osmiophilic regions). The formation of lipid bodies and extrusions was readily reversible. Following osmotic expansion of acclimated protoplasts, the extrusions were retracted back into the plane of the plasma membrane.
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    URL: http://dx.doi.org/10.1007/BF01281163
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    Relationships among membranes in plastids of the red algaNitophyllum punctatum (Stackh.) Grev. (1984)
    Springer
    Protoplasma 119 (1984), S. 55-61 
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    ISSN: 1615-6102
    Keywords: Rhodophyta ; Nitophyllum ; Membranous body ; Plastid ; Red algae ; Thylakoidal origin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fine structure of plastids in the early stages of differentiation has been studied during the carposporogenesis of the red algaNitophyllum punctatum (Stackh.) Grev. A membranous body has been found in the plastidial matrix, which shows connections either with thylakoids, or with the plastidial genophore. More than one membranous body may be present and in some instances they show a morphological relationship also with the plastidial limiting membranes. The presence of such bodies has been observed also in fully differentiated plastids in a number of other red algae currently under study. It has been shown that the plastidial envelope may release in the matrix vesicles that give rise to the single thylakoids typical of the red algal plastids.
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    URL: http://dx.doi.org/10.1007/BF01287817
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    Etioplast-chloroplast transformation in maize leaves: Effects of tissue age and light intensity (1984)
    Springer
    Protoplasma 119 (1984), S. 110-120 
    Details
    ISSN: 1615-6102
    Keywords: Plastid greening ; Zea mays ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effects of light intensity and cell age on the greening of etioplasts were studied in seedlings of maize. We could see that in the youngest tissues examined by us the etioplast greening is very fast and occurs according to a particular pattern which is characterized by the contemporary presence of grana and large non crystalline prolamellar bodies. On the contrary, in the oldest examined tissues the etioplast greening is slow and the formation of grana appears to be delayed and subsequent to the using up of the prolamellar bodies. In the young tissues the intensity of the light mainly affects the duration of the lag-phase preceding the chlorophyll accumulation, while in the old tissues it also affects the total amount of chlorophyllous pigments, the restraining effect of the light appearing amplified by a concomitant restraining effect of cell age.
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    URL: http://dx.doi.org/10.1007/BF01287823
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    Ultrastructure of mitosis in the aphid-pathogenic fungusErynia neoaphidis (1984)
    Springer
    Protoplasma 120 (1984), S. 72-83 
    Details
    ISSN: 1615-6102
    Keywords: Fungus ; Mitosis ; Entomophthoraceae ; Erynia neoaphidis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An account of mitosis in the aphid-pathogenic, entomophthoraceous fungusErynia neoaphidis is presented. The mitotic apparatus is characterized by a closed, intranuclear, polarized spindle. Chromosomes are permanently attached by kinetochore microtubules (kcMTs) to the poles during mitosis. The spindle develops as the spindle pole bodies migrate and separate. At metaphase the eccentric spindle contains only kcMTs and is located in a relatively chromatinfree zone. Paired sister kinetochores are arranged in a broad metaphase plate. During anaphase kcMTs shorten, astral and nonchromosomal microtubules develop and elongate and the interpolar distance increases.
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    URL: http://dx.doi.org/10.1007/BF01287619
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    The taxonomic significance of the mitotic spindle and nucleus-associated organelle ofEntomophaga aulicae (1984)
    Springer
    Protoplasma 120 (1984), S. 84-90 
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    ISSN: 1615-6102
    Keywords: Entomophaga aulicae ; Fungi ; Mitosis ; Nucleus associated organelle ; Taxonomy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Nuclei in protoplasts ofEntomophaga aulicae contain abundant condensed chromatin and a large central nucleolus. The metaphase spindle occupies a small eccentric area of the nucleus while the remainder of the nucleus is filled with condensed chromatin. Small portions of condensed chromatin are aligned along a broad metaphase plate and connected to the spindle poles by kinetochore microtubules. The nucleus associated organelle (NAO) is a solid barlike structure which lies at the spindle poles and is closely associated with the outer membrane of the nuclear envelope. Comparison of the nuclear characteristics ofE. aulicae with those of other members of theEntomophthorales supports the separation of theEntomophthoraceae from theBasidiobolaceae andAncylistaceae. Further comparison of details of nuclear division in theEntomophthoraceae, specifically NAO morphology, may be useful in helping to delineate evolutionary lines within the family.
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    URL: http://dx.doi.org/10.1007/BF01287620
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    The behavior of the plasma membrane following osmotic contraction of isolated protoplasts: Implications in freezing injury (1984)
    Springer
    Protoplasma 123 (1984), S. 83-94 
    Details
    ISSN: 1615-6102
    Keywords: Freeze-fracture ; Isolated rye protoplasts ; Osmotic contraction ; Plasma membrane-derived vesicles ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Following osmotic contraction of isolated rye protoplast (Secale cereale L. cv. Puma) that results in nearly a 50% reduction in volume, the plasma membrane was smooth, with no folding or pleating. Instead, deletion of plasma membrane occurred and numerous cytoplasmic vesicles were observed. As a result, the area of the plasma membrane was reduced by approximately 40%. Thin sections revealed that the cytoplasmic vesicles were membrane bound and not merely voids in the cytoplasm. High resolution video microscopy revealed the extent of vesiculation showing large clusters of cytoplasmic vesicles following osmotic contraction. Labeling the plasma membrane with fluorescein-Con-A prior to hypertonic contraction suggested that the cytoplasmic vesicles were derived from the plasma membrane. Freeze-fracture particle density on both the protoplasmic (PFp) and exoplasmic face (EFp) of the plasma membrane remained unchanged following contraction, which is consistent with a unit-membrane deletion into cytoplasmic vesicles. Upon partial re-expansion of the protoplasts, thin sections showed that the vesicles remained in the cytoplasm. These results using osmotic manipulation confirm earlier observations of isolated protoplasts at the light microscope level. Upon contraction plasma membrane is deleted into cytoplasmic vesicles, which are not readily reincorporated into the plasma membrane upon expansion. Lysis occurs before the original volume and surface area are regained.
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    URL: http://dx.doi.org/10.1007/BF01283579
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    Ultrastructure and behaviour of the spindle pole body of the aphid-pathogenic fungusErynia neoaphidis (1984)
    Springer
    Protoplasma 120 (1984), S. 61-71 
    Details
    ISSN: 1615-6102
    Keywords: Fungus ; Spindle pole body ; Entomophthoraceae ; Erynia neoaphidis ; Ultrastructure ; Replication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A detailed account of the ultrastructure and behaviour of the spindle pole body (SPB) of the entomophthoraceous fungusErynia neoaphidis is presented for the first time. The SPB consists of extranuclear (ENC) and intranuclear (INC) components. The ENC is a “saucepan-shaped” structure which lies in a pocket of the nuclear envelope. It is composed of a forked, fibrillar “handle” and a shallow, cylindrical “pan”. The “pan” has a wall of two layers, both of which are thickened with a regular periodicity so that they appear to be “beaded”. It is postulated that the “pan“ is formed from rough endoplasmic reticulum and that it synthesizes the amorphous, electron-dense material coating the ENC. The INC is a “saucer-shaped”, electron-dense plaque in which the ends of the spindle microtubules terminate. During metaphase, a “clear zone” separates the INC from the nuclear envelope and persists until telophase. The roles of the amorphous, electron-dense material and the “clear zone” as well as the method of SPB replication are discussed.
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    URL: http://dx.doi.org/10.1007/BF01287618
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    Gametogenesis inCoelomomyces dodgei Couch (Blastocladiales, Chytridiomycetes) (1984)
    Springer
    Protoplasma 121 (1984), S. 65-76 
    Details
    ISSN: 1615-6102
    Keywords: Blastocladiales ; Chytridiomycetes ; Coelomomyces ; Cytoplasmic cleavage ; Gametogenesis ; Mosquito-copepodpathogen ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The ultrastructure of gametogenesis was studied inCoelomomyces dodgei Couch (Blastocladiales, Chytridiomycetes), an obligate parasite of anopheline mosquito larvae and the copepod,Acanthocyclops vernalis. In infected copepods reared under a 16/8 hours light/dark photoperiod at 25 +2 °C., the gametophyte develops over a period of approximately seven days, and gametogenesis is triggered by the onset of the dark period during the last day of development. The initial step of gametogenesis is the elongation of the centriole to form the kinetosome, and measuring time from the onset of the final dark period (0 hours), this occurs prior to the beginning of the light period (8 hours). Subsequently, small vesicles that appear to originate from elements of the rough endoplasmic reticulum (rER) fuse at the distal end of the kinetosome forming the flagellar vesicle into which the axonemal microtubules elongate to form the flagellum (8–12 hours). Similar small vesicles apparently also derived from rER align in planes and fuse to form cleavage furrows which delineate the gamete initials (12–14 hours). As the gamete initials begin forming, the mitochondria within each initial fuse to form a single mitochondrion that associates with the lipid globules and microbodies forming the microbody-lipid globule complex (12–16 hours). The time elapsed between the formation of the flagellar vesicle to the release of mature gametes from the copepod host is about 8.5 hours. No differences were observed in the processes or timing of gametogenesis in male and female gametophytes.
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    Ultrastructure of the gametes ofCoelomomyces dodgei Couch (Blastocladiales, Chytridiomycetes) (1984)
    Springer
    Protoplasma 121 (1984), S. 77-86 
    Details
    ISSN: 1615-6102
    Keywords: Blastocladiales ; Coelomomyces ; Gametes ; Mosquitocopepod pathogen ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary As part of an investigation on the developmental biology ofCoelomomyces dodgei Couch (Blastocladiales, Chytridiomycetes), the ultrastructure of the male and female gametes was studied. The nucleus is central and conical in shape except for a basal spur that curves back towards the large plate-like mitochondrion. A nuclear cap of ribosomes sits on the flat anterior end of the nucleus. Approximately seven lipid globules are partially embedded in the mitochondrion and are interconnected by membrane cisternae. The lipid globules are covered by a single fenestrated microbody and a backing membrane lies between the microbody and the gamete plasma membrane. The kinetosome is at the base of the nucleus and is connected to a single, posterior, whiplash flagellum. A nonkinetosomal centriole is absent. In the peripheral cytoplasm of both mating types there is a paracrystalline body of unknown composition and function. No significant ultrastructural differences were found between the male and female gametes.
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    The fine structure of granular amoebocytes from the gonads of the sea anemoneActinia fragacea (Cnidaria: Anthozoa) (1984)
    Springer
    Protoplasma 122 (1984), S. 203-221 
    Details
    ISSN: 1615-6102
    Keywords: Actinia fragacea ; Granular amoebocytes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The structure of granular amoebocytes of the intertidal sea anemoneActinia fragacea (Cnidaria: Anthozoa) has been investigated using the electron microscope. Cells from the gonads of large, intact individuals were studied in most detail, but other regions of the anemone were also examined. The amoebocytes are cells of variable appearance which are widely distributed both in the mesogloea and in the epithelial cell layers. They contain numbers of characteristic dense granules, which may enclose spherical cores of greater or lesser electron density. They also contain rough endoplasmic reticulum, Golgi apparatus and a range of inclusions, some of which may have lysosomal origins. They may contain extensive deposits of glycogen, and usually smaller quantities of lipid droplets. They may take on a variety of forms, depending partly on their location within the various types of mesogloea and epithelia. The amoebocytes appear to be motile and phagocytic, and may also be involved in the storage and transport of glycogen. They are involved with gametogenesis, both during the development of the oocytes and spermatogenic cysts and during the resorption of degenerating gametes. Their possible role in the secretion or maintenance of the mesogloea remains uncertain. No evidence of amoebocytes differentiating into other cell types was obtained.
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    URL: http://dx.doi.org/10.1007/BF01281698
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    The nucleolar cycle in karyomeres ofTetranychus urticae Koch (Acari, Tetranichidae) in relation to replication of fragments of holokinetic chromosomes (1984)
    Springer
    Protoplasma 123 (1984), S. 78-82 
    Details
    ISSN: 1615-6102
    Keywords: Chromosome fragments ; Holokinetic chromosomes ; Karyomeres ; Nucleolar material ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Chromosomes and nucleoli in the karyomeres of cleavage eggs of the arrhenotokous spidermiteTetranychus urticae Koch were treated with a silver-staining procedure for nucleolar material to establish the number of nucleoli and of the chromosomes that produce them. Each of the three holokinetic chromosomes of the haploid chromosome complement produces nucleolar material. This is confirmed by observations on the ultrastructure of karyomeres in serial sections of interphase cleavage divisions. These findings are thought to be in agreement with facts from previous radiation research and may help to explain the fate of induced fragments in holokinetic chromosomes.
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    URL: http://dx.doi.org/10.1007/BF01283184
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    Cell division in baeocyte producing cyanobacteria (1984)
    Springer
    Protoplasma 123 (1984), S. 104-115 
    Details
    ISSN: 1615-6102
    Keywords: Constrictive binary fission ; Cyanobacteria ; Development ; Multiple fission ; Septate binary fission ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An ultrastructural examination of cell division in two baeocyte producing cyanobacteria,Pleurocapsa minor andDermocarpa violaceae, reveals two distinct patterns of binary (transverse) fission. Septate binary fission, inPleurocapsa minor, involves centripetal synthesis and deposition of the mucopolymer cell wall layer (L 2). The ingrowth of the cytoplasmic membrane and L 1 cell wall layer, along with the synthesis of the L 2 cell wall layer, results in the formation of a prominent septum. Partitioning of the cell occurs by the constriction of the outer cell wall layers (L 3 and L 4) through the septum. InDermocarpa violaceae, constrictive binary fission occurs by the simultaneous ingrowth or constriction of the cytoplasmic membrane and all cell wall layers (L1, L2, L3, L4). Septate and constrictive binary fission may proceed symmetrically (medially) or asymmetrically (nonmedially). Multiple fission occurs regularly inDermocarpa violaceae and provides for a rapid means of reproduction when compared to binary fission. Successive radial and tangential divisions of the protoplast result in formation of many small daughter cells (baeocytes). The process of multiple fission is similar to septate binary fission with reduced septa being formed. However, constriction of the outer cell wall layers, through the septa, proceeds concurrently with septum formation.
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    URL: http://dx.doi.org/10.1007/BF01283581
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    The occurrence of calyx nodules inPsychotria spp. (Rubiaceae) (1984)
    Springer
    Protoplasma 121 (1984), S. 199-208 
    Details
    ISSN: 1615-6102
    Keywords: Psychotria ; Leaf nodules ; Calyx nodules ; Symbiosis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The occurrence and structure of calyx nodules in the flowers of two leaf nodulated rubiaceous speciesPsychotria punctata Vatke andPsychotria kirkii Hiern. has been described for the first time at the ultrastructural level. Bacteria, resident in colleter-secreted mucilage in the space between calyx and corolla, invade stomatal pores which develop on the calyx protoderm. The bacteria proliferate in the substomatal cavity and then invade the calyx mesophyll. This invasion is most pronounced inP. punctata where the bacteria even penetrate and enter the cells of the vascular tissue. Although no sheath forms around the calyx nodules, the calyx mesophyll cells surrounded by the bacteria become identical in shape, size and secretory function to the invasive mesophyll cells of leaf nodules. The functional and evolutionary significance of calyx nodulation is discussed.
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    URL: http://dx.doi.org/10.1007/BF01282313
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    Experimental toxicology of ASTA Z 7557 (INN mafosfamide) (1984)
    Springer
    Investigational new drugs 2 (1984), S. 201-206 
    Details
    ISSN: 1573-0646
    Keywords: ASTA Z 7557 ; acute toxicity in mice and rats ; myelotoxicity ; immunosuppression ; urotoxicity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The LD 50 of Z 7557 in mice was between 500 and 625 mg/kg after i.v. and around 2310 mg/kg after oral administration. The corresponding LD 10 was around 435 mg/kg (i.v.) or 1100–1250 mg/kg (p.o.), respectively. The LD 50 values in rats were in the range of 250–310 mg/kg after i.v. administration and around 1000–1250 mg/kg if given orally. With repeated daily i.v. injections only 70% of the daily dose contributed to lethality. A second administration of Z 7557 to rats after reversal of all toxic signs from the first administration induced the same symptoms and degree of toxicity as the initial injection. Reversible myelosuppression was the predominant feature of toxicity in mice and rats, but at equimolar doses this myelotoxicity was less than half that of cyclophosphamide (CP). First signs of immunosuppression were seen only at 100 mg/kg i.v. No severe urotoxicity was observed in rats with single i.v. doses up to 192 mg/kg. This might be due to the fast and complete renal excretion of the thiol moiety of Z 7557, whereas the activated oxazaphosphorine component occurred in the urine only to a much smaller amount, as could be shown by a pilot pharmacokinetic study. In conclusion, Z 7557 appeared to have an overall tolerance in rats and mice similar to cyclophosphamide but was clearly less toxic with respect to the bone marrow, the immune system and the urinary tract.
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    URL: http://dx.doi.org/10.1007/BF00232352
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    The deterministic identifiability of nonlinear pharmacokinetic models (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 177-191 
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    ISSN: 1573-8744
    Keywords: compartmental analysis ; identification ; Michaelis-Menten kinetics ; nonlinear systems ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper deals with the deterministic identifiability of nonlinear pharmacokinetic models, namely, whether the model parameters can be identified with perfect data. It is shown that the most familiar method for analyzing the deterministic identifiability of linear models, in which the Laplace transform of the observation is examined, does not work for nonlinear models. An alternative method, in which the observation is expanded as a Taylor series about t=0,is described and is illustrated with some examples of nonlinear models familiar in the pharmacokinetics literature, in which an elimination rate is assumed capacity limited, with Michaelis-Menten kinetics.
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    Pharmacokinetic-pharmacodynamic analysis of unbound disopyramide directly measured in serial plasma samples in man (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 559-573 
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    ISSN: 1573-8744
    Keywords: disopyramide ; pharmacokinetics ; pharmacodynamics ; electrophysiology ; protein binding ; modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of the antiarrhythmic drug, disopyramide, were investigated in 12 volunteers who took 300 mg doses of 3 different capsule preparations and an aqueous oral solution of the drug at 1-week intervals. Concentrations of drug unbound to plasma proteins were measured by a sensitive immunoenzyme assay after ultrafiltration of plasma samples taken serially after dosing. QT interval was measured on serial ECG recordings with correction for changes in heart rate. Unbound concentrations of disopyramide were modelled by an open one-compartment pharmacokinetic model with a zero-order absorption rate and a lag time. There was no significant difference in parameter estimates between the four preparations, except for the lag time, which was significantly shorter for the solution preparation. The saturable protein binding of disopyramide was described by a hyperbolic model including a specific binding site and additional nonspecific binding. The pharmacodynamic relationship between unbound drug concentration and QT prolongation was fit by a simple linear model. This fit was better using unbound concentration of the drug than using total concentrations.
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    Concentration andpH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 597-610 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; steady-state volume of distribution ; methotrexate pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effects of plasma concentration and pH on the steady-state volume of distribution, Vss,of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100μg/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the Vss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p〈0.05) concentration and plasma pHdependent Vss of MTX were observed. Concentration dependence of Vss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in Vss at 1 μg/ ml relative to the two higher concentrations (20 and 100 μg/ ml) for dogs treated with ammonium and sodium chloride, respectively. However, Vss of MTX at the targeted concentrations of 20 and 100 μg/ml was relatively constant. Plasma pHdependence of Vss was observed only at the plasma concentration of 1 μg/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher Vss,respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.
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    Analytical approximations of sensitivities of steady state predictions to errors in parameter estimation: II. Michaelis-Menten kinetics (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 525-534 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; Michaelis-Menten model ; steady state predictions ; sensitivity analysis ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Linear sensitivity theory is used to estimate the reliability of predictions of the minimum and maximum concentrations at steady state in the Michaelis-Menten model with i.v. bolus. The dependence of the relative errors in the predictions on the errors in the pharmacokinetic parameters is derived in an analytical form. It is shown that the quality of the predictions is not equally sensitive to all errors in parameters, and that the sensitivity factors vary with the degree of saturation of the system. An example of application for a drug, such as phenytoin, is discussed. It is suggested that sensitivity analysis may be useful in design of pharmacokinetic experiments aimed at the control of steady state levels for drugs with Michaelis-Menten kinetics.
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    Absence of a significant pharmacokinetic interaction between hydrochlorothiazide and triamterene when coadministered (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 575-586 
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    ISSN: 1573-8744
    Keywords: hydrochlorothiazide ; triamterene ; hydroxytriamterene sulfate ; pharmacokinetics ; bioavailability ; renal clearance ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate were monitored in the plasma and urine of 24 healthy young men taking single doses of a liquid preparation containing both hydrochlorothiazide and triameterene, liquid preparations containing either of these drugs alone, and a combination tablet recently formulated with a dose ratio of hydrochlorothiazide: triamterene (1∶1,5) found to give optimal potassium-sparing effect. In contradiction to a recent publication, no interaction between the drugs affecting the bioavailability or renal clearance of either could be demonstrated. The previous report of drug-drug interaction probably arose from formulationrelated problems with bioavailability from the two capsule and two tablet products which had been studied. A well-formulated hydrochlorothiazide-triamterene combination tablet promotes plasma concentrations and urinary excretion of hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate which are virtually identical to those seen after either a combination liquid dosage form or simple liquid forms containing only one of the two drugs.
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    Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and14C-disopyramide (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 289-313 
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    ISSN: 1573-8744
    Keywords: protein binding ; pharmacokinetics ; bioavailability ; disopyramide ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10−7M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7X105 M−1 and 4.4X10 5 M−1, respectively (p 〈 0.05). The unbound clearance of disopyramide averaged 277ml/min and 209 ml/min in normal subjects and in patients (p 〈 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p 〈 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.
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    Quantitative relationships between structure and pharmacokinetics of beta-adrenoceptor blocking agents in man (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 263-287 
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    ISSN: 1573-8744
    Keywords: beta-adrenoceptor blocking agents ; pharmacokinetics ; structure ; lipophilicity ; octanol/water partition coefficient
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The structure and pharmacokinetics relationship of 14-beta-adrenoceptor antagonists was investigated in humans. Statistically significant linear and parabolic correlations were found to exist between standard and derived mean pharmacokinetic parameters and the apparent octanol/buffer (pH7.4) partition coefficient of the compounds. The lipophilic/hydrophilic properties were the primary determinants for the pharmacokinetic behavior of the compounds. Most of the pharmacokinetic parameters were also significantly correlated with the plasma protein/plasma water partition coefficient for the compounds. When the values of the pharmacokinetic parameters of the individual compounds were predicted from the regressions on the apparent partition coefficients in octanol/buffer (pH 7.4) and in plasma protein/plasma water, the error was on average 60%.
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    A physiological model for the pharmacokinetics of methylene chloride in B6C3F1 mice following i.v. administrations (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 413-436 
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    ISSN: 1573-8744
    Keywords: methylene chloride ; pharmacokinetics ; physiological model ; hybrid model ; I.V. administrations ; mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A physiologic mathematical model was developed to describe the time course of14C-methylene chloride (14CH2Cl2) distribution and elimination in mice following single i.v. administrations of 10 and 50mg/kg. A whole-body model was used to simulate14CH2Cl2 concentrations in blood and tissues, pulmonary clearance of unchanged14CH2Cl2, and metabolic conversion to14CO2 and14CO as monitored by the appearances of these metabolites in expired breath. This diffusion-limited model was identified via a sequential optimization scheme using hybrid models for each compartment. Pulmonary elimination of unchanged14CH2Cl2 was modeled as a linear process while hepatic metabolism of14CH2Cl2 to the compounds14CO2and14CO was described by a saturable metabolic rate term. The model adequately described the dose dependence in methylene chloride distribution and metabolism when simulations were compared to experimental data.
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    Two-compartment model for plasma pharmacokinetics in individual blood vessels (1984)
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 451-461 
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    ISSN: 1573-8744
    Keywords: rabbit ear chamber ; granulation tissue ; serum albumin ; sodium fluorescein ; Stokes-Einstein radius ; fluorescence ; photometric analysis ; vascular permeability ; renal clearance ; erythrocyte-free plasma layer ; two-compartment model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma pharmacokinetics of sodium fluorescein, fluorescein isothiocyanate conjugated bovine serum albumin, and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber. The data obtained were fitted with a two-compartment open model to obtain an effective permeability and an effective clearance. Both parameters decreased with increasing molecular radius for dextrans. Values for albumin were considerably less than expected on the basis of molecular radius, presumably due to the configuration, charge, and binding characteristics of albumin.
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    The design of pharmacokinetic experiments for model discrimination (1984)
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 351-365 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; model discrimination ; experiment design ; information theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The need for objective design of pharmacokinetic experiments aimed at model discrimination is argued. A sequential design strategy based on information theory is outlined. The characteristics of this strategy and its applicability to pharmacokinetic experiments is examined by means of computer simulated experiments. The limitations of the technique are discussed and alternative approaches outlined.
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    Pharmacokinetics of teicoplanin in man after intravenous administration (1984)
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 119-128 
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    ISSN: 1573-8744
    Keywords: teicoplanin ; pharmacokinetics ; three-compartment model ; noncompartmental analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of teicoplanin, a new glycopeptide antibiotic active against gram-positive aerobic and anaerobic bacteria, was studied in adult male volunteers given 2- and 3- mg/ kg doses by a constant-rate 0.5-hr infusion. Serum and urine samples were collected up to 96 hr. Mean peak serum levels after the two doses were 15.7 and 22.4 μg/ml. Postinfusion serum teicoplanin levels showed triexponential decay. A three-compartment body model gave close values for pharmacokinetic parameters after the two doses. The mean half-life of the λ1 phase was 20.3 min, that of the λ2 phase was 2.9 hr, and the half-life of the estimated λ3 phase was 40.5 hr, in good agreement with that of the λZ phase (45.9 hr) calculated from the last urine data. The mean volume of distribution of the central compartment was 0.09 liter/kg and the steady-state volume of distribution using noncompartmental analysis was 0.84 liter/kg. Total clearance averaged 16.05 ml/hr/kg, with renal clearance arbout half this (9.51 ml/hr/kg), calculated by two different methods. The average total recovery of active teicoplanin in urine over 4 days was 52%, suggesting that both renal and nonrenal mechanisms are involved in elimination of the drug. The concentrations of teicoplanin in serum and urine exceeded the MIC (ranging from 0.02 to 2 μg/ml) on many pathogenic organisms for at least 1 day after administration.
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    On the identification of Michaelis-Menten elimination parameters from a single dose-response curve (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 193-221 
    Details
    ISSN: 1573-8744
    Keywords: compartmental analysis ; identification ; Michaelis-Menten kinetics ; nonlinear systems ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper deals with aspects of the numerical identifiability of parameters of a model with a capacity-limited elimination rate using a single dose-response curve, namely, the prospects of being able to identify model parameters with any meaning from real data. The concept of linear bounds, first proposed by Tong and Metzler, is described and it is shown that if the Michaelis-Menten constant Km is greater than all the measured concentration values, approximation by a linear model is appropriate. At the other end of the scale, if Km is small compared with measured concentration values, the nonlinear response approximates to a zero-order curve.
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    Observations on the ultrastructure ofFrankia sp. in root nodules ofDatisca cannabina L. (1984)
    Springer
    Plant and soil 79 (1984), S. 383-402 
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    ISSN: 1573-5036
    Keywords: Actinorhizae ; Datisca cannabina ; Frankia ; Nitrogen fixation ; Root nodules ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The fine structures of the microsymbiont inside the root nodules ofDatisca cannabina have been studied by light, by transmission- and by scanning-electron microscopy. The endophyte is prokaryotic and actinomycetal in nature. The hyphae are septate and branched, diameter 0.3–0.5 μm. The tips of hyphae are swollen to form electron-dense, clubshaped to filamentous vesicles, ranging in diameter: 0.4–1.4 μm. The endophyte penetrates through walls of the cortial cells. The infected zone is kidney shaped and confined to one side of the acentric stele. The orientation of infection is reversed from other actinorhizae exceptCoriaria. The hyphae are near the host cell wall and vesicles are directed towards the central vacuole. Vesicles are aseptate and no collapsing of the vesicle cell wall (void area) has been observed. Vesicle clusters structures are globular with an opening at one side of the cluster. The host cell is multinucleate or contains a lobed nucleus. Groups of mitochondria are located in between the hyphae, suggesting a strong association between the host and the endophyte for energy supply and amino acid production. The consequences of the inability to separate the mitochondria from the vesicle clusters in nodule homogenates in physiological studies have been discussed. Isolated vesicles clusters showed dehydrogenase activity, indicated by the presence of formazan crystals, after incubation with NADH and NBT. Strongest reducing activity was found within the vesicles. The possible role of filamentous vesicles in nitrogen fixation has been discussed.
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    Mycorrhizal improvement in non-leguminous nitrogen fixing associations with particular reference toHippophaë rhamnoides L. (1984)
    Springer
    Plant and soil 78 (1984), S. 189-199 
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    ISSN: 1573-5036
    Keywords: Alnus Hippophaë ; Mycorrhiza ; Myrica ; Nitrogenase ; Phosphate ; Triple symbiosis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The roots ofHippophaë rhamnoides which regularly bear actinomycete induced nodules when growing on Scottish sand dunes have also been found to support an endomycorrhizal association withGlomus fasciculatus. Ultrastructural and cytochemical studies carried out on the indigenous infections of establishedHippophaë mycorrhizal roots would support the postulate that transport is indeed occurring between the fungal symbiont and the host plant and vice versa in respect of phosphate and carbohydrate. Experiments using various inoculation regimes, demonstrated the significant improvement in the mycorrhizal/nodulated plants compared to the nodulated-only and the mycorrhizal-only plants with respect to plant growth, uptake of phosphate and nitrogenase activity, when grown in a medium poor in combined nitrogen and soluble phosphate. Preliminary work onAlnus andMyrica species growing in Central Scotland indicates that the mycorrhizae associated with these nodulated root systems exhibit a different interaction pattern which may be dependent on habitat type and associated angiosperm species.
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    Effect of aeration status of nutrient solution on microorganisms, mucilage and ultrastructure of wheat roots (1984)
    Springer
    Plant and soil 80 (1984), S. 381-390 
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    ISSN: 1573-5036
    Keywords: Aeration status ; Microorganisms ; Mucilage ; Rhizosphere ; Ultrastructure ; Wheat root
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Outer layers of wheat roots grown in aerated and unaerated nutrient solutions were studied by transmission electron microscopy. Root growth was considerably impaired in unaerated nutrient solution. In contrast to aerated roots, no mucilaginous layer but dense bacterial colonization were observed on the root caps of unaerated roots. The root cap mucilage had apparently been decomposed by the microorganisms. The peripheral root cap cells of the unaerated roots appeared to contain less cell organelles than those of the aerated roots, while the central cap cells and the meristematic cells of the root tip seemed not to be affected by lack of aeration. The bacterial population in the elongation, root hair, and lateral root zones, was also remarkably higher on roots grown in unaerated nutrient solution. In the lateral root zone of unaerated roots, even the cortical cells were invaded by bacteria.
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    The pharmacokinetics of subcutaneous bolus cytosine arabinoside in an arachis oil plus aluminium distearate suspension (1984)
    Springer
    Investigational new drugs 2 (1984), S. 271-276 
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    ISSN: 1573-0646
    Keywords: pharmacokinetics ; cytosine arabinoside ; delayed release ; arachis oil suspension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An attempt was made to create a delayed release preparation of cytosine arabinoside (araC) which could be administered subcutaneously, and would produce plasma levels similar to steady state infusion concentrations. A thixotropic suspension of araC in arachis oil and aluminium distearate was formulated. This preparation was similar to that previously used with bleomycin oil suspension and procaine penicillin. Two hundred mg/ml of araC in arachis oil containing varying amounts of aluminium distearate were administered firstly to New Zealand White rabbits and then to patients with acute myelogenous leukaemia. This preparation was well tolerated by both rabbits and patients but did not delay the release of araC from the subcutaneous tissues.
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    Comparison of brain biogenic amine level and blood ethanol kinetics in C57Bl/6 and CBA mice (1984)
    Springer
    Bulletin of experimental biology and medicine 98 (1984), S. 1183-1185 
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    ISSN: 1573-8221
    Keywords: ethanol ; pharmacokinetics ; blood ; serotonin ; dopamine ; noradrenalin ; brain ; CBA and C57Bl/6 mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00804290
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    Effect of isolation stress on the pharmacokinetics of the blood ethanol in rats (1984)
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    Bulletin of experimental biology and medicine 98 (1984), S. 1226-1227 
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    ISSN: 1573-8221
    Keywords: pharmacokinetics ; alcohol ; isolation ; stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00804306
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    Enzymatic and pharmacokinetic studies on the metabolism of branched chain α-keto acids in the rat (1983)
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    Details
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
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    URL: http://dx.doi.org/10.1007/BF02020781
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  • 160
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    Ultrastructural localization of adenylate cyclase and cAMP phosphodiesterase in the gastrulating chick embryo (1983)
    Springer
    Development genes and evolution 192 (1983), S. 42-44 
    Details
    ISSN: 1432-041X
    Keywords: Chick embryo ; Gastrulation ; Adenylate cyclase ; cAMP phosphodiesterase ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The ultrastructural localization of adenylate cyclase (E.C. 4.6.1.1.) and cAMP phosphodiesterase (PDE) (E.C. 3.1.4.17.) in the ectoderm of the developmental stage 4 chick embryo was studied. Adenylate cyclase was localized in the lateral surfaces of the ectodermal cells. In the primitive streak cells the enzymatic activity was observed on all the lateral surfaces, whereas in the periphery of the blastoderm the reaction product was localized in the apical parts of the lateral plasma membranes only. cAMP PDE localized in the apical cytoplasm of the ectodermal cells, with highest activity in the globular projections.
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    URL: http://dx.doi.org/10.1007/BF00848768
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  • 161
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    Electron microscopical study of self-differentiation potency in the chick embryonic endoderm cultured in vitro (1983)
    Springer
    Development genes and evolution 192 (1983), S. 171-178 
    Details
    ISSN: 1432-041X
    Keywords: Differentiation ; Digestive tract ; Endoderm ; Organ culture ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The self-differentiation potency of the endoderm of the chick embryo was investigated mainly by transmission electron microscopy. Endodermal fragments isolated from 4- to 6-day stomach or small intestine were cultured in the absence of mesenchyme and were able to differentiate in vitro into organ-specific epithelia. Endodermal fragments isolated from the stomach region differentiated into a pseudo-stratified epithelium with periodic acid Schiff-positive mucous granules in the apical cytoplasm, while those from the small intestinal region differentiated into a simple columnar epithelium with a striated border which was positive in alkaline phosphatase activity. These features are comparable with those of the mucous secretory epithelium of the normal embryonic stomach and the absorptive epithelium of normal embryonic small intestine, respectively. Next, the self-differentiation potencies were investigated of the upper and lower layers of the blastoderms, at stages 1–5 of Hamburger and Hamilton (H. and H.). Both stomach-type and small-intestine-type epithelia developed only when fragments of the lower layer isolated from the blastoderms older than stage 3 of H. and H. were cultured, suggesting that cells possessing the potency to differentiate into the stomach- and small-intestine-type epithelia exist in the definitive endoderm at the beginning of its formation.
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    URL: http://dx.doi.org/10.1007/BF00848687
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  • 162
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    Pharmacodynamic and pharmacokinetic evaluation in man of the new sympathomimetic amezinium (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 185-190 
    Details
    ISSN: 1432-1041
    Keywords: amezinium ; hypotension ; antihypotensive drug ; ECG ; concentration-effect relationship ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood pressure, ECG and plasma concentration were determined for up to 12h following single i.v. (10 mg) and oral (20 mg) doses of amezinium (Regulton®) in 8 healthy, male volunteers. The i.v. and oral doses were almost equi-active in significantly increasing systolic blood pressure (SBP) by 14.5 and 15.6 mmHg, respectively. The maximum SBP after the i.v. dose was reached after 45 min, and 105 min after oral administration. The heart rate fell reflexly. The increases in mean and diastolic blood pressures were not significant. Pulse pressure was enhanced after both i.v. and oral administration. The effect on systolic blood pressure lasted for about 4 h. There was a slight shortening of the QTc duration, which could not be explained as a drug effect. Other ECG time intervals were not altered. Multiple regression analysis showed a significant positive correlation between the log plasma concentration and the increase in SBP between 0.5 and 5 h after oral administration (r=0.78,p〈0.001) and between 0.75 and 5 h after i.v. administration (r=0.83,p〈0.001). 30 min after amezinium p.o. the mean SBP began to rise, when a plasma level of about 30 ng/ml was reached.
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    URL: http://dx.doi.org/10.1007/BF00613815
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  • 163
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    Plasma levels of sulfinpyrazone and of two of its metabolites after a single dose and during the steady state (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 231-235 
    Details
    ISSN: 1432-1041
    Keywords: sulfinpyrazone ; pharmacokinetics ; metabolites ; inhibition of platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulfinpyrazone, and the plasma levels of its sulfide and sulfone metabolites, have been determined after a single oral dose (400 mg) and during steady-state conditions (4×200 mg daily for 6 days) in healthy female volunteers. The plasma half-lives of sulfinpyrazone, the sulfone and the sulfide were 3.7, 3.2 and 14.7 h, respectively, during steady-state. After a single dose and during steady state conditions the half-lives of sulfinpyrazone and the sulfone did not differ significantly. The trough plasma levels of the sulfide metabolite exceeded those of the parent compound in four of the six volunteers on the last day of the study. The data suggest that in man the most likely candidate for the prolonged inhibition of platelet aggregation observed after treatment with sulfinpyrazone is its sulfide metabolite, because of its prolonged elimination.
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    URL: http://dx.doi.org/10.1007/BF00613823
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  • 164
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    Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 267-271 
    Details
    ISSN: 1432-1041
    Keywords: trimethoprim ; sulphadiazine ; urinary tract infection ; children ; pharmacokinetics ; urinary concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2–56 months. A suspension of TMP-SD (9+41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9–3.7 mg/kg/day) and SD (12.9–16.7 mg/kg/day) were also given to children of different ages. After 2–4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 µg/ml and 27 µg/ml, respectively, were found within 2–4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.
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    URL: http://dx.doi.org/10.1007/BF00613830
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    Pharmacodynamic and pharmacokinetic interactions between ketamine and diazepam (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 337-343 
    Details
    ISSN: 1432-1041
    Keywords: ketamine ; diazepam ; drug interaction ; pharmacokinetics ; premedication ; clorazepate ; drug metabolism ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Anaesthesia with continuous i.v. ketamine and 65% nitrous oxide in oxygen was given to a total of 49 patients undergoing major abdominal surgery. A control group was premedicated with atropine and other groups received in addition rectal diazepam or clorazepate i.v. Four further patients had been on oral diazepam or barbiturates for 1–14 years; as premedication they received atropine alone. The anaesthetic technique gave good operative conditions in the 4 groups of patients. The haemodynamic stimulation of ketamine was significantly reduced in patients premedicated with diazepam. Psychotomimetic side effects were not prominent in any of the groups. Patients premedicated with diazepam required a lower rate of ketamine infusion as compared to controls during the initial 30 min of anaesthesia. The patients in the other groups did not differ from the control group in this respect. There were large differences in metabolic pattern between the groups. As compared to the controls, the patients on long-term diazepam or barbiturates had high concentrations of hydroxylated metabolites, with levels higher than that of norketamine. The patients pretreated with diazepam had very low plasma levels of hydroxylated metabolites. Clorazepate premedication did not significantly affect the metabolism of ketamine. The biological half-life of ketamine was significantly increased in the diazepam-treated group, and it was shortened in those on long term treatment with barbiturates or diazepam.
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    URL: http://dx.doi.org/10.1007/BF00610051
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    Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 485-494 
    Details
    ISSN: 1432-1041
    Keywords: amiodarone ; pharmacokinetics ; therapeutic serum level ; thyroid function ; antiarrhythmic therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 µmol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 µmol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 µmol/l. Tentatively, a therapeutic range of 1.5 to 4 µmol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.
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    URL: http://dx.doi.org/10.1007/BF00609891
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    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
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    URL: http://dx.doi.org/10.1007/BF00609896
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    Pharmacokinetics of biliary excretion in man V (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 549-556 
    Details
    ISSN: 1432-1041
    Keywords: dibromosulfophthalein ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; biliary fistula ; enterohepatic circulation ; hepatic transport test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dibromosulfophthalein (DBSP), the 3,6-dibromo analogue of BSP, was studied in 7 patients with a biliary fistula, 52 h after cholecystectomy, and in 6 gynaecological patients with an indwelling urethral catheter, following extirpation of the uterus i.e. with an intact enterohepatic circulation. Plasma protein binding determined by ultrafiltration was 98–99% up to a concentration of 700 µg/ml. After an intravenous bolus injection of DBSP 5 mg/kg, a biexponential plasma decay was found in both groups, with a rapid initial t1/2 of 2–6 min and a slow secondary phase of 33–109 min (mean 66 min) in the cholecystectomy patients, and 10–30 min (mean 19 min) in the gynaecological patients. The biliary excretion rate varied considerably between the patients and was highly correlated with bile flow. Biliary output amounted to a maximum of 86% of the dose in 24 h. The excretion rate curves showed ascending and descending phases, the mean terminal t1/2 being 65 min. Urinary excretion was 3–11% of the dose in 8 h in the gynaecological patients (mean 6%) and 6–31% in the cholecystectomy group (mean 16%). Renal clearance of unbound DBSP was about ten-times greater than the glomerular filtration rate, which indicates tubular secretion. A two compartment model with elimination from the peripheral and central compartments was selected because of these data. Analysis of the plasma-disappearance curves indicated an initial plasma clearance of 500–600 ml/min, which suggests that hepatic uptake will be very dependent on flow. Steady state (biliary) clearance was about 400 ml/min in the gynaecological group and approximately half that in the cholecystectomy patients; V1 tended to be higher and V2 to be lower in the latter group. It is concluded that biliary excretion rate of DBSP in patients with a biliary fistula is probably depressed by the postoperative bile drainage and the lack of enterohepatic cycling of bile salts.
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    Pharmacokinetics of hydrochlorothiazide in relation to renal function (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 661-665 
    Details
    ISSN: 1432-1041
    Keywords: hydrochlorothiazide ; pharmacokinetics ; renal failure ; dosage adjustment ; excretory mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.
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    URL: http://dx.doi.org/10.1007/BF00542218
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    The pharmacokinetics of subcutaneous dihydroergotamine with and without a dextran 70 infusion (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 813-818 
    Details
    ISSN: 1432-1041
    Keywords: dihydroergotamine ; dextran 70 ; pharmacokinetics ; radioimmunoassay ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of subcutaneous dihydroergotamine (DHE) with or without dextran 70 infusion was evaluated in a single- and multiple-dose study in 30 patients. Radioimmunoassay was used to measure plasma DHE and the anthrone method to determine the dextran concentration. In the single-dose study no significant interaction between DHE and dextran was noted with respect to their plasma levels. The absorption of s.c. DHE was rapid and the disappearance curve followed a biphasic pattern, t0.5 α being 1.4 and 2.0 h, t0.5 β 22 and 21 h for DHE and DHE/dextran 70, respectively. In the multi-dose study the trough level of DHE initially had a tendency to rise, in accordance with simulated plasma concentration curves. DHE trough levels were about 0.5 ng/ml and were well above the assumed minimum effective value to induce venoconstriction (0.06 ng/ml). Dextran concentrations were significantly higher when DHE was co-administered, possibly, due to changes in plasma volume. It is concluded that DHE 0.5 mg s.c. twice daily will give an adequate plasma concentration and that there was no important interaction between it and infused dextran 70.
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    Pharmacokinetics of the new analgesic, meptazinol, after oral and intravenous administration to volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: meptazinol ; pharmacokinetics ; multiple dosing ; plasma protein binding ; analgesic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of meptazinol (Meptid®) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vdβ) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean=8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.
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    Pharmacokinetics and absolute bioavailability of carteolol, a new β-adrenergic receptor blocking agent (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 95-101 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
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    Pharmacokinetics of triamterene after i.v. administration to man: Determination of bioavailability (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
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    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
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    On the pharmacokinetics of pengitoxin and its cardioactive derivative 16-acetyl-gitoxin (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 369-373 
    Details
    ISSN: 1432-1041
    Keywords: pengitoxin ; pharmacokinetics ; 16-acetylgitoxin ; absorption ; urinary excretion ; healthy subjects ; cardiac glycoside
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pengitoxin has been studied in 28 healthy subjects after intravenous and oral administration. The mean plasma concentration 24 h after 0.5 mg i.v. was 5.2 ng · ml−1. Following an open two-compartment model a mean elimination half-life of 60.5 h (24.9 to 103.5 h) and a mean volume of distribution (Vdarea) of 66.91 (31.8 to 109.61) were calculated. Absorption calculated by comparison of the AUC0-∞-values amounted to 99%. Within 4 days, 16.7% (11.7 to 21.1%) or 27.8% (18.4 to 33.7%) (0.5 mg i.v. or 1.2 mg p.o.) was excreted in urine. After pengitoxin 0.5 mg i.v. total body clearance and renal clearance were 13.3 ml · min−1 (7.0 to 18.6 ml · min−1) and 3.0 ml · min−1 (1.9 to 3.9 ml · min−1) respectively. The elimination half-life of pengitoxin is longer than that of digoxin and distinctly shorter than that of digitoxin, whilst its distribution volume and clearance are closer to those of digitoxin than of digoxin.
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    Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding I. Theoretical considerations (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 399-405 
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    ISSN: 1432-1041
    Keywords: ceftriaxone ; pharmacokinetics ; concentration-dependent binding ; volume of distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have theoretically examined the influence of plasma protein binding (specifically the fraction unbound, fp) on the pharmacokinetic parameters following rapid injection of a drug undergoing concentration-dependent binding. Particular emphasis was placed on the apparent volume of distribution terms based on both total and unbound drug concentrations. Computer simulations were performed to establish the validity and utility of such relationships. The following observations were made: a) distributional parameters based on total drug (both Vβ and the model-independent VSS) were inaccurate/invalid; b) V β based on unbound drug was misleading; c) the model-independent VSS for unbound drug accurately predicted the steady state situation. Furthermore, two new terms ( $$\bar f_P $$ and $$\bar V_{SS}^T $$ ) were introduced which provide additional insight concerning the disposition of this type of drug. The $$\bar f_P $$ is the area-weighted average fraction unbound in the plasma and $$\bar V_{SS}^T $$ is the corrected steady state distribution term for total drug levels. The present study indicates that useful distributional and clearance terms can be calculated for this type of drug, provided that the time course of unbound drug as well as total drug can be followed. Moreover, guidelines for their extrapolation to steady state conditions and their correct interpretations are discussed.
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    Rapid achievement of a serum concentration plateau of digoxin through controlled infusion (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 455-457 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; concentration plateau ; pharmacokinetics ; systolic time intervals ; optimal infusion scheme ; dose-response data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a volume-controlled infusion pump, a mean serum plateau level of digoxin of 4–5 ng/ml was rapidly achieved and maintained in 6 healthy volunteers. The infusion scheme was calculated on the basis of data published on the pharmacokinetics and pharmacodynamics of digoxin following bolus intravenous injection. The magnitude of the response (change in electromechanical systole) at the end of the plateau phase was comparable to that observed with the concentration in the therapeutic range at steady state.
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    URL: http://dx.doi.org/10.1007/BF00542110
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    Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    Details
    ISSN: 1432-1041
    Keywords: canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
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    URL: http://dx.doi.org/10.1007/BF00542109
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  • 178
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    Pharmacokinetics of methadone in methadone maintenance treatment: Characterization of therapeutic failures (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 497-501 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; pharmacokinetics ; steady state ; addiction rehabilitation ; therapeutic failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the β-phase (t1/2β), volume of distribution during the postdistributive phase (Vdβ) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vdβ and Vdss were found between the two groups. The therapeutic failures had a smaller Vdβ and Vdss 3.09±0.96 l/kg and 2.74±0.96 l/kg vs 4.56±1.00 l/kg and 4.20±0.78 l/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2β — 24.5±2.6 h in the therapeutic failures and 34.0±7.0 h (p〈0.001) in the comparison group. However, the change in t1/2β was probably a consequence of the change in Vdβ, as the body clearance of M was similar in the two groups — 104±36 ml/min vs 111±36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval. The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage interval. Alternatively, a longer-acting opiate, such as 1-α-acetylmethadol (LAAM), may be used.
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    URL: http://dx.doi.org/10.1007/BF00542117
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  • 179
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    Pharmacodynamic and pharmacokinetic study of oral and intravenous penbutolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 529-534 
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    ISSN: 1432-1041
    Keywords: penbutolol ; pharmacokinetics ; blood pressure effect ; heart rate effect ; dose response relationship ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The present study was done to establish the dose-response relationships for effects on heart rate and systolic and diastolic blood pressure, tolerance and plasma disappearance kinetics after large intravenous and oral doses of penbutolol. Twelve healthy volunteers were randomly allocated to receive penbutolol (n=8) or placebo (n=4) in this single blind, placebo-controlled investigation. The degree of beta-blockade was measured by standarized exercise tests at work loads selected to produce a heart rate of 150/min without treatment. Penbutolol was given as single i.v. doses of 3, 6 and 12 mg and as 40, 80 and 120 mg once daily for one week, measurements being made 2 and 24 h after the last dose. Penbutolol i.v. did not influence the resting heart rate but it did reduce resting systolic blood pressure in a non-dose dependent manner. Exercise heart rate and systolic pressure were lowered by all the intravenous doses. All oral doses of penbutolol lowered exercise heart rate and systolic blood pressure to the same extent. The reductions in exercise tachycardia was still present after 24 h. After i.v. administration t1/2 was approximately 1.2 h and the volume of distribution was 32–42 l. All doses were well tolerated.
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  • 180
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    Relationships between several pharmacokinetic parameters and psychometric indices of subjective effects of Δ9-tetrahydrocannabinol in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 633-637 
    Details
    ISSN: 1432-1041
    Keywords: delta-9-tetrahydrocannabinol ; mood ratings ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study explored the relationships in man between various pharmacological effect of Δ9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective “high” rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, “high”). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective “high” rating, rather than other ratings more specific for particular moods.
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    URL: http://dx.doi.org/10.1007/BF00542351
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  • 181
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    Pharmacokinetics of digoxin in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 117-121 
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    ISSN: 1432-1041
    Keywords: serum digoxin ; pregnancy ; digoxin-renal-clearance ; creatinine-clearance ; digoxin-elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Digoxin-renal-clearance, creatinine-clearance, 24-h urine elimination of digoxin and serum digoxin were studied in 15 patients in the third trimester of pregnancy and 6 to 12 weeks post-partum. There was significant fall post-partum in the first three. There was also a significant fall post-partum in serum digoxin levels. This finding was unexpected, but may be due to heightened absorption exceeding increased elimination because of the physiological status in pregnancy.
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    URL: http://dx.doi.org/10.1007/BF00544027
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  • 182
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    Pharmacokinetics of theophylline in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 89-92 
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    ISSN: 1432-1041
    Keywords: theophylline ; kwashiorkor ; marasmus ; children ; nutritional status ; pharmacokinetics ; dosage recommendation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of theophylline in Ethiopian children of differing nutritional status was studied. In 8 children of normal weight, the t1/2β (4.93 h) plasma clearance (1.22 ml/min/kg and Vd area (504 ml/kg) were similar to those of Swedish children of normal weight. In children with marasmus or kwashiorkor there was an increased volume of distribution. The increase in Vd was reflected in an increased biological half-life, in spite of a slight but not significant increase in clearance in both of these groups of children. The pharmacokinetic changes in clearance and volume of distribution found in malnutrition should counteract each other, so from a clinical point of view theophylline can be given to Ethiopian children according to the standard dosage recommendation, regardless of nutritional status.
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    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
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    URL: http://dx.doi.org/10.1007/BF00613931
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    Bioavailability of oral dexamethasone during high dose steroid therapy in neurological patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
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    ISSN: 1432-1041
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
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    URL: http://dx.doi.org/10.1007/BF00613935
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    Elimination of cefroxadine (CGP-9000) from patients undergoing dialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 109-112 
    Details
    ISSN: 1432-1041
    Keywords: cefroxadine ; haemodialysis ; pharmacokinetics ; terminal renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions. The antibiotic was administered as a single oral dose of 500 mg. Cefroxadine followed a single compartment open kinetic model. During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 µg/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function. The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions. The average extraction coefficient was 0.249. It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h.
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    Pharmacokinetics of levonorgestrel in Indian women (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 255-259 
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    ISSN: 1432-1041
    Keywords: levonorgestrel ; nutritional status ; combination pill ; pharmacokinetics ; indian women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A low dose combination pill containing levonorgestrel 150 µg and ethynylestradiol 50 µg was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The π t1/2 was lower in Group A women and the α-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (β t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.
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    Doxorubicin and 5-fluorouracil plasma concentrations and detectability in parotid saliva (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 261-266 
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    ISSN: 1432-1041
    Keywords: doxorubicin ; 5-fluorouracil ; pharmacokinetics ; parotid saliva ; plasma concentration ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50–90 mg doxorubicin or 600–1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.
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    The pharmacokinetics of melphalan in patients with multiple myeloma: An intravenous/oral study using a conventional dose regimen (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 283-285 
    Details
    ISSN: 1432-1041
    Keywords: melphalan ; myeloma ; pharmacokinetics ; i.v. dosing ; oral dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of melphalan have been studied after intravenous and oral dosing (10 mg) in 6 patients with multiple myeloma. After intravenous administration, mean plasma t0.5α was 8.0±2.3 min, t0,5β was 63.3±8.7 min, and total systemic clearance was 510.4±57.9 ml/min. After oral administration, the drug was rapidly absorbed (lagtime=18.4±3.7 min, absorption rate constant=0.0547±0.0166 min−1, Tmax=59.3±6.6 min), but there was considerable variation in its bioavailability (61.5−102.0% mean 78.3±6.3%). Variability in drug absorption may be responsible, at least in part, for variation in response to this drug.
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    Pharmacokinetics of oxmetidine, a new histamine H2-receptor antagonist, after single oral and intravenous doses (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 353-356 
    Details
    ISSN: 1432-1041
    Keywords: oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
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    Analytical model of some pharmacokinetic and pharmacodynamic properties of fazadinium in man (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 407-413 
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    ISSN: 1432-1041
    Keywords: neuromuscular blockade ; fazadinium ; pharmacokinetics ; pharmacodynamics ; predictive model ; receptor occupation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The neuromuscular blocking characteristics and plasma concentration decay of fazadinium bromide, a short acting, non-depolarizing muscular relaxant, were simultaneously observed under standardised conditions in 6 healthy, anaesthetized, adult patients. The results were analyzed by a new pharmacodynamic model, which takes into account certain relationships describing the binding of non-depolarizing neuromuscular blocking agents and the postsynaptic receptor occupation ratio. According to the simulations performed, the pharmacodynamic parameters determined: KB-apparent value of equilibrium constant of fazadinium — receptors exchange (mean ± SEM) 0.404+0.045 µmol/l, and the value of postsynaptic occupation ratio for 50% paralysis of 0.89±0.004 were in agreement with values reported in the literature for mammalian neuromuscular junctions in vitro. The apparent validity of the pharmacodynamic model and its value in simulating dose/effect relationships of non-depolarizing neuromuscular blocking agents are discussed and illustrated.
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    Pharmacokinetics of bredinin in renal transplant patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 457-461 
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    ISSN: 1432-1041
    Keywords: bredinin ; immunosupressive agent ; pharmacokinetics ; renal transplant patients ; renal function ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A pharmacokinetic study of bredinin, a new immunosupressive agent, was carried out in 28 renal transplant patients. Serum bredinin concentration-time curves were analyzed using a one-compartment open model with a first order absorption process. The peak serum bredinin level appeared 2.4 h after oral administration of bredinin 50–200 mg. The calculated mean peak serum level was 0.852 µg/ml/mg/kg, when the dose was adjusted to the body weight of the patient. In the dosage range used of 0.85–4.46 mg/kg, a linear relationship was observed between the dose and the peak serum bredinin level. The elimination rate of bredinin from serum was dependent on kidney function, and the elimination rate constant was well correlated with the endogenous creatinine clearance. No circadian rhythm was apparent in the elimination rate constant. The absorption rate of bredinin from the gastrointestinal (GI) tract was affected by GI diseases. The need for dosage adjustment based on the renal function of the transplant patient is suggested.
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    Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 503-507 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; pharmacokinetics ; renal failure ; antiarrhythmic drug ; haemodialysis ; cirrhosis ; acetyldigoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3±4.8 h (±SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5±4.6 h, which was calculated to correspond to removal of 25±14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10–55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2±4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.
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    Pharmacokinetics of prenalterol after single and multiple administration of controlled release tablets to patients with congestive heart failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 495-502 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; pharmacokinetics ; food ; congestive heart failure ; plasma levels ; urinary excretion ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prenalterol, a partial β-adrenoceptor agonist, has been studied in 12 patients with congestive heart failure, following single and repeated oral doses of 40 mg b.i.d. as controlled release tablets. A tracer dose of3H-labelled drug was given i.v. on 2 occasions to establish the variability of the pharmacokinetic parameters. Plasma levels and urinary excretion of prenalterol were measured after the oral and intravenous doses, and in addition, total radioactive metabolites were determined after the i.v. administration. Only small differences in the pharmacokinetics were observed when the i.v. tracer dose was given with the single oral dose or with the oral maintenance dose at steady state. The mean plasma elimination half-life was 2.4 h, the apparent volume of distribution 2.61/kg and the total body clearance about 800 ml/min. About 90% of the dose was excreted in urine, of which 30% was the parent drug. The remaining fraction comprised three metabolites, which were quantified by HPLC. Plasma levels of prenalterol close to steady state were obtained within 2 days and were maintained on a b.i.d. dosage regimen with controlled release tablets. The levels were independent of whether the tablets were taken fasting or with a standardized light meal. An average of 14% of the oral dose was recovered as prenalterol in urine after a single dose and 16% after a maintenance dose at steady state. Thus, about 45–55% of prenalterol reached the systemic circulation. The pharmacokinetic parameters in patients with congestive heart failure differed slightly from those in healthy subjects, but not sufficiently to require a change in the oral dosage regimen.
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    Pharmacokinetics of gentamicin in very low birth weight preterm infants (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 649-653 
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    ISSN: 1432-1041
    Keywords: gentamicin ; preterm infants ; pharmacokinetics ; low birth weight ; dosage regimens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Low birth weight preterm infants with suspected infection were administered gentamicin intramuscularly every 18 h (2.5 mg/kg) or 24 h (3.0 mg/kg). For both dosage regimens plasma gentamicin levels were monitored during a dosage interval on three separate occasions over a 10 day period. Both regimens gave satisfactory plasma concentrations and there was no important statistically significant difference between the two. The body clearance of gentamicin correlated with gestational age (r=0.76, p〈0.01). The results indicate either regimen may be useful in the clinical situation but from a practical standpoint administration every 24 h may be easier to comply with then every 18 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542216
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    Systemic availability of acetylsalicylic acid in normal men and women and its effect on in vitro platelet aggregability (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 679-682 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; salicylic acid ; platelets ; pharmacokinetics ; sex difference ; platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3±2.0% and 16.9±3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5±1.4 and 18.1±1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9±2.9 µg/ml in females and 22.5±2.7 µg/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5±5.1 µg/ml in females (p〈0.02) and to 29.5±3.8 µg/ml in males (p〈0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542222
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  • 196
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    Aspirin pharmacokinetics in migraine. The effect of metoclopramide (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 777-785 
    Details
    ISSN: 1432-1041
    Keywords: aspirin ; migraine ; salicylic acid ; metoclopramide ; drug absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of aspirin (ASA) in acute migraine attacks, and the influence of metoclopramide on ASA disposition, were studied in 32 attacks in 30 patients. An intergroup comparison was made between normal volunteers, and the migraineurs, who were assigned at random to one of three treatment groups: a) oral ASA only (900 mg); b) 10 mg oral metoclopramide + oral ASA 900 mg; c) 10 mg i. m. metoclopramide + oral ASA 900 mg. Plasma ASA and SA levels were measured serially over 2 h, and the resultant data evaluated pharmacokinetically. Metoclopramide plasma levels were also determined over 2 h, and the results compared with a second group of normal volunteers. The rates of oral ASA absorption and elimination were unaffected by migraine. Mean absorption rate constants of 14.15±9.48 h−1 (normals), 7.91±3.42 h−1 (ASA only), 6.74±3.26 h−1 (ASA + oral metoclopramide) and 8.12±2.82 h−1 (ASA + i. m. metoclopramide) were calculated. Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1, and did not differ significantly between controls and migrainous patients. Values for absorption lag time, however, were higher in migraine patients treated with ASA alone than in any other group. The amount of ASA absorbed unhydrolysed was also lower in this group. SA levels appeared unaffected either by the migraine attack, or by metoclopramide administration, over the period of study. Metoclopramide plasma levels were significantly lower during migraine attacks, and the amount of drug absorbed up to 2 h from dosing was also reduced, as compared with non-migrainous subjects. It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites, probably as a result of gastric stasis, and may have decreased the amount of ASA absorbed. The prior administration of metoclopramide, either orally or intramuscularly, reduced the absorption lag time, and thus promoted the early absorption of ASA, probably by restoring alimentary tract motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607087
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    Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 819-823 
    Details
    ISSN: 1432-1041
    Keywords: chloramphenicol ; children ; pharmacokinetics ; oral dose ; absorption ; i.v. dose ; kwashiorkor ; marasmus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/min/kg). In consequence the mean half-life was prolonged (3.76 h versus 2.85 h) and this led to somewhat higher plasma levels in the kwashiorkor children. The influence of the pathophysiological changes offset one another so that plasma concentrations within the therapeutic range were obtained in children with kwashiorkor given recommended standard i.v. doses. The absorption of chloramphenicol after oral administration in severely malnourished children was erratic, which suggests that this route should be avoided in such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607094
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    Tizanidine — Initial pharmacokinetic studies in patients with spasticity (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 65-67 
    Details
    ISSN: 1432-1041
    Keywords: tizanidine ; pharmacokinetics ; spasticity ; multiple sclerosis ; haematological parameters ; electromyogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of plasma concentrations of the antispasticity agent tizanidine were measured by a specific radioimmune-assay in six adults who had severe spasticity due to multiple sclerosis. The drug was given as a single oral 4 mg dose to each subject. The drug had a mean absorption half-life of 0.30±0.155 h following a mean lagtime of 0.361±0.118 h, and a mean terminal elimination half-life of 4.16±2.06 h. Only 2.65±0.82% of the dose was excreted unchanged in urine in 2 h. Calculated values of clearance and apparent volume of distribution were almost certainly overestimates as it seems probable that the orally-administered drug undergoes significant presystemic elimination (its bioavailability was not determined in the investigation here reported). Relief of spasticity, from the dosage used, was relatively slight and appeared greatest at the time of peak plasma levels of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544016
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    Effect of ethanol intake on disopyramide elimination by healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 103-105 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; ethanol ; pharmacokinetics ; interaction ; metabolic clearance ; renal clearance ; diuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of ethanol intake on disopyramide elimination was examined in an open cross-over study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the urine (p〈0.05) as well as the relative metabolic clearance of disopyramide (p〈0.05). The renal clearance of disopyramide was increased by 19±16% (p〈0.05) in subjects in whom ethanol caused a diuresis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544024
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  • 200
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    Cimetidine disposition in patients with Laennec's cirrhosis during multiple dosing therapy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 223-229 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; alcoholic cirrhosis ; multiple dosing ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of cimetidine after oral and intravenous administration during multiple dosing was studied in 11 patients with Laennec's cirrhosis. The average metabolic clearance of cimetidine in these patients was 151/h, similar to values reported for normal subjects. However, in 4 subjects with plasma prothrombin times above normal, the metabolic clearance was significantly decreased and ranged between 4.3 and 13.01/h. The renal clearance of cimetidine was proportional to the creatinine clearance in all subjects, regardless of the severity of the liver disease. The clearance of cimetidine in patients with Laennec's cirrhosis, therefore, appears to be predictabable from creatinine clearance and prothrombin time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543795
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