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  • 1990-1994  (22,121)
  • 1985-1989  (17,345)
  • 1975-1979  (14,077)
  • Polymer and Materials Science  (50,929)
  • pharmacokinetics  (1,358)
  • Electron microscopy
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Year
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  • 1
    Electronic Resource
    Electronic Resource
    Widespread aluminium deposition in extracerebral organ systems of patients with dialysis-associated encephalopathy (1994)
    Springer
    Virchows Archiv 424 (1994), S. 105-112 
    Details
    ISSN: 1432-2307
    Keywords: Silver staining ; Aluminium ; Laser microprobe ; Electron microscopy ; Dialysis-associated encephalopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have described new silver-staining methods for the demonstration of lesions in senile dementia of the Alzheimer type. The same procedure was used to visualize characteristic aluminium (Al)-containing inclusions in choroid epithelium, glia and neurons of the central nervous system in dialysis-associated encephalopathy (DAE). Here we describe the patterns and degree of Al deposition in extracerebral tissues of 12 DAE autopsy cases. Light microscopy of silver-stained paraffin sections demonstrated autonomic ganglion cells filled with numerous intracytoplasmic black-stained fine granular inclusions, which were also seen in endocrine tissues (pituitary, parathyroid and adrenal) and in Leydig cells. Heart, liver cells and the testicular tubules were involved, but decalcified bones, haematopoetic elements, hyperplastic epithelium and one case of malignant epithelium lacked inclusions. Laser microprobe mass analysis revealed prominent Al-related mass signals within the en-bloc silver-stained inclusions which were seen at low intensity in adjacent non-stained structures. Electron microscopy demonstrated accumulations of small electron-dense granules intermingling with lipopigments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00197400
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  • 2
    Electronic Resource
    Electronic Resource
    Sarcoma of the pulmonary artery: report of four cases with electron microscopic and immunohistochemical examinations, and review of the literature (1994)
    Springer
    Virchows Archiv 424 (1994), S. 217-224 
    Details
    ISSN: 1432-2307
    Keywords: Pulmonary artery ; Neoplasm ; Sarcoma ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Herein we report the clinicopathological features of four cases of pulmonary artery sarcoma that appeared at our institution during a period of 30 years. The patients, 2 males and 2 females, were 50–62 years old. Tumour was found in the pulmonary trunk and right pulmonary artery in all cases, in the pulmonary valve and left pulmonary artery in three of the four cases, and in the right ventricular outflow tract in one case. There was direct extension or metastases to the lungs in two cases, the heart in one case, mediastinum or lymph nodes in two cases and the pleura in one case. Ultrastructural examination in one case revealed cells with features of smooth muscle cells and myofibroblasts. Immunohistochemical examination of three cases gave the following results: vimentin and smooth muscle specific actin was positive in all three cases, desmin in one case and cytokeratin in one case. No positivity was found for Factor VIII. This and other studies indicate that histologically most pulmonary artery sarcomas are leiomyosarcomas or “undifferentiated spindle cell sarcomas”. Immunohistochemical and ultrastructural examinations favour an origin from myofibroblasts, probably derived from multipotent (undifferentiated) cells in the wall of the vessel. Most lesions show extensive intrathoracic growth although they rarely metastasize outside the thoracic cavity. They have a poor prognosis although some cases are currently being diagnosed during life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193503
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  • 3
    Electronic Resource
    Electronic Resource
    Ultrastructural localization of tissue factor on monocyte-derived macrophages and macrophage foam cells associated with atherosclerotic lesions (1994)
    Springer
    Virchows Archiv 425 (1994), S. 49-54 
    Details
    ISSN: 1432-2307
    Keywords: Thromboplastin ; Atherosclerosis ; Electron microscopy ; Cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of tissue factor (TF) antigen by circulating monocytes, cultured macrophages, and macrophages associated with atherosclerotic lesions was ultrastructurally analysed using immunogold labeling. A subpopulation of macrophages associated with the intimal surface overlying lesions had a significant TF expression. Macrophages and macrophage foam cells that projected from the intima into the arterial lumen also expressed a high level of TF (14-fold increase over control). In contrast, circulating monocytes and macrophages in culture did not express TF above background control levels. This TF expression by macrophages in vivo but not by macrophages cultured from either normal or hypercholesterolemic animals suggests that monocyte activation and macrophage transition, as measured by TF expression, is lesion-dependent and not stimulated solely by intimal attachment, surface migration, or hypercholesterolemia. These results further suggest that macrophages and foam cells associated with early lesions of atherosclerosis can initiate fibrin formation, which could contribute to lesion complications and transition to a fibromuscular stage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193948
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  • 4
    Electronic Resource
    Electronic Resource
    Uptake and phototoxic effects of aluminum-chlorophthalocyanine (AISPc) in hurnan bladder carcinoma cells (1994)
    Springer
    Urological research 22 (1994), S. 79-83 
    Details
    ISSN: 1434-0879
    Keywords: Phototoxicity ; Aluminum-chlorophtalocyanine ; Electron microscopy ; DAB staining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vitro experiments were performed on human bladder carcinoma cells to evaluate the uptake of aluminum-chlorophthalocyanine (AlSPc) and the subcellular target of phototoxicity. In order to quantify the correlation of intracellular uptake and incubation time and to identify the primary subcellular target of phototoxicity, fluorescence and absorption measurements have been carried out as well as electron microscopic studies. Absorption and fluorescence measurements showed the largest value after 24 h of incubation time. Fluorescence microscopic studies suggested the sensitizer to be located in a brighter patch within cytoplasm. Electron microscopic studies using DAB (3,3′ diaminobenzidine) staining showed that the mitochondria are the primary target of phototoxic activity of AlSPc and that the majority of vacuoles of treated cells were originally mitochondria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00310996
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  • 5
    Electronic Resource
    Electronic Resource
    Madin-Darby canine kidney cells are injured by exposure to oxalate and to calcium oxalate crystals (1994)
    Springer
    Urological research 22 (1994), S. 197-203 
    Details
    ISSN: 1434-0879
    Keywords: MDCK ; Calcium oxalate ; Oxalate ; Scanning ; Electron microscopy ; Trypan blue ; Adenine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reaction of Madin-Darby canine kidney cells (MDCK) to potassium oxalate (KOx), calcium oxalate monohydrate (COM) crystals, or a combination of the two was studied. The most noticeable effect of exposure of the cells to either KOx or COM crystals was loss of cells from the monolayer ranging from 20% to 30%, depending upon the particular treatment. Cellular enzyme values in the media were elevated significantly by 12h of exposure, although in specific instances, elevated levels occurred at earlier time periods. As regards the monolayer, trypan blue exclusion was decreased significantly, although amounting to only a 4–5% reduction. Specific tritiated release occurred at 4 and 12 h after exposure to KOx and at 12 h after exposure to crystals. Structurally, COM-cell interactions were complex and extensive endocytosis was noted. Cells were released from culture either as cellcrystal complexes or from the intercellular spaces after exocytosis. When treatment were combined the effects were only slightly additive, but the two treatments potentiated each other: all media enzyme levels (with one exception) were elevated at 2 h, tritiated adenine release was present at 4 h, and there was more extensive cell loss from the culture monolayer. These data suggest that both KOx and COM crystals damage MDCK cells when applied alone, and in concert they act synergistically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541892
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  • 6
    Electronic Resource
    Electronic Resource
    Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate) (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 511-519 
    Details
    ISSN: 1432-0533
    Keywords: Vacuolization ; Neurotoxicity ; Neuropathology ; Electron microscopy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-d-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60–70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296487
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  • 7
    Electronic Resource
    Electronic Resource
    Cytoplasmic inclusions of astrocytic elements of glial tumors: special reference to round granulated body and eosinophilic hyaline droplets (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 501-510 
    Details
    ISSN: 1432-0533
    Keywords: Key words Round granulated body ; Eosinophilic ; hyaline droplets ; Astrocytic tumors ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Round granulated body (RGB) and eosinophilic hyaline droplets (EHDs) have been described as cytoplasmic inclusions of certain astrocytic tumors. In the previous literature, however, these inclusions have been described using various terms or regarded as nosologically the same entity. Light microscopically, RGB appeared as a round discrete body filled with fine uniform granules, while EHDs demonstrated a cluster of bright eosinophilic, round objects of various size. They could be clearly distinguished even by conventional histochemical staining such as the Masson trichrome stain and the phosphotungstic acid hematoxylin preparation. Both RGB and EHDs expressed positive immunoreactions for glial fibrillary acidic protein, several lysosomal markers, and some stress-response proteins. The ultrastructural appearances of these inclusions were distinct, however, one common feature was that they consisted of aggregations of numerous membrane-bound electron-dense bodies. Thus, both inclusions appear to be produced by neoplastic astrocytes and are possibly related to the lysosomal system. We examined the presence of RGB and EHDs in 138 astrocytic tumors. Both inclusions occurred most frequently in pleomorphic xanthoastrocytomas, followed by gangliogliomas and pilocytic astrocytomas. Subependymal giant cell astrocytomas exhibited only RGBs. RGBs and EHDs were not seen in any abundance in glioblastomas, gliosarcomas, fibrillary astrocytomas, protoplasmic astrocytomas, or oligo-astrocytomas. Some glioblastomas, however, showed only EHDs in small numbers. Several anaplastic astrocytomas were associated with a large number of RGBs and/or EHDs, and they revealed only rare mitosis despite marked cellular pleomorphism. Although RGB and EHDs have different morphological features, the presence of these inclusions in abundance may represent either a degenerative change, a long-standing lesion, or an indolent growth of the astrocytic tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296486
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  • 8
    Electronic Resource
    Electronic Resource
    Neomyogenesis in neonatally de-efferented and postnatally denervated rat muscle spindles (1994)
    Springer
    Acta neuropathologica 89 (1994), S. 85-95 
    Details
    ISSN: 1432-0533
    Keywords: Key words     Neonatal de-efferentation ; Sensory denervation ; Electron microscopy ; Intrafusal muscle fibre types ; Postnatal myogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract      The ultrastructure of muscle spindles de-efferented by the extirpation of the lumbosacral spinal cord at the age of 2 days and subsequently deprived of their sensory innervation by the section of the sciatic nerve at 3–4 weeks of age was studied in serial sections of 2-month-old rat hindlimb muscles. De-efferentation leaves the primary sensory neurons and their peripheral axons intact and capable of inducing the muscle spindle morphogenesis during the critical period of their development. In de-efferented and subsequently denervated muscle spindles, new supernumerary intrafusal muscle profiles (SIPs) appeared in the muscle spindle A region. They were formed in intimate spatial relation with the original intrafusal muscle fibres (IMFs) predominantly from activated satellite cells derived from both nuclear bag (larger diameter) and nuclear chain fibres. SIPs, however, lacked the typical nuclear accumulations, as well as other ultrastructural distinctions present in control IMFs. The majority of differentiated SIPs separated from original IMFs, whereas the less differentiated SIPs were usually closely apposed to the surface of the parent IMFs and both were covered by the common basal lamina. In some spindles, the original IMFs and/or new SIPs at different stages of their differentiation were found together and they formed clusters of variable shape and composition. In the majority of clusters, all profiles seemed to be isolated along their entire length, although in few clusters, occasional cytoplasmic connections of variable length between intrafusal profiles were found. This result is important for the interpretation of the forthcoming study of expression of muscle spindle-specific myosin heavy chain isoforms in denervated SIPs in rat muscle spindles gradually deprived of their motor and sensory innervation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050219
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  • 9
    Electronic Resource
    Electronic Resource
    Ontogeny of the endocrine cells of the stomach of sea bass (Dicentrarchus labrax L.): an ultrastructural study (1994)
    Springer
    Anatomy and embryology 190 (1994), S. 507-514 
    Details
    ISSN: 1432-0568
    Keywords: Endocrine cells ; Gut ; Ontogeny ; Electron microscopy ; Dicentrarchus labrax (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The endocrine cells present in the developing stomach of sea bass larvae have been characterized ultrastructurally. Only one endocrine cell type (type I) was found in the presumptive stomach of 9- and 12-day-old larvae, one (type II) and five (types III, IV, V, VI and VII) in the aglandular stomach of 32-, and of 39- to 46-day-old larvae, respectively, and five (types III, VIII, IX, X and XI) in the differentiated stomach of 55- and 60-day-old larvae. A maturation process was established for some of these cells. Types I, II and III and types IV and X were thought to be different maturational stages of the same endocrine cell type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235499
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  • 10
    Electronic Resource
    Electronic Resource
    Ontogeny of the endocrine cells of the intestine and rectum of sea bass (Dicentrarchus labrax L.): an ultrastructural study (1994)
    Springer
    Anatomy and embryology 190 (1994), S. 529-539 
    Details
    ISSN: 1432-0568
    Keywords: Endocrine cells ; Gut ; Ontogeny ; Electron microscopy ; Dicentrarchus labrax (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several endocrine cell types were ultrastructurally characterized during the differentiation of the intestine and rectum of sea bass (Dicentrarchus labrax L.) larvae. Only one cell type (type I) was found in the posterior region of the undifferentiated gut of 5-day-old larvae (phase I). Types V and VI were found in both the intestine and rectum, types II, III and IV in the intestine, and types VII and VIII in the rectum of 9- and 12-day-old larvae (phase II), the rectum alone showing signs of functional differentiation. In phase III larvae, in which both the intestine and rectum were differentiated, types IX, X, XI, XII, XIII, XIV and XV were found in the intestine, only types X, XI and XII being seen in the rectum. Besides these, a new cell type, XVI, was observed in the intestine of 55- and 60-day-old larvae (phase IV), in which the digestive tract was completely differentiated. The endocrine cells appearing in phases I and II showed very scarce secretory granules and the ultrastructural features of undifferentiated cells. Some endocrine cell types in the earliest developmental stages were related to some of those found later. A maturational process of the endocrine cell types paralleled the differentiation of the intestine and rectum, with an apparent increase in the number of secretory granules accompanying organelle development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00190103
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  • 11
    Electronic Resource
    Electronic Resource
    Immunocytochemical and ultrastructural studies of the motor cortex in amyotrophic lateral sclerosis (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 578-585 
    Details
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Motor cortex ; Betz cells ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report concerns an immunocytochemical and ultrastructural study of the motor cortices of 11 patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 normal individuals served as controls. Antibodies against phosphorylated neurofilament (PNF; 200 kDa), ubiquitin, glial fibrillary acidic protein (GFAP) and phosphorylated tau protein were used. The pyramidal cells of layer III of all ALS patients were stained, with varying intensities, by the antibody to PNF. By contrast, Betz cells reacted less frequently with this antibody. Staining for GFAP was noted in numerous astrocytes in layer III and at the transition between white matter and motor cortex of most patients. Ubiquitin-positive inclusions were only occasionally seen in Betz cell and pyramidal cell of layer V. These observations indicate that alterations of the motor cortex occur first in the pyramidal cells of layer III rather than in Betz cells. Pyramidal cells and Betz cells were not stained by the antibody to phosphorylated tau protein. In controls, pyramidal cells and Betz cells were less frequently stained with the anti-neurofilament antibody than those from ALS patients. Immunoreactivity of GFAP in layer III and at the junction of white matter and motor cortex was observed in only one patient. Ultrastructural examination revealed that the Betz cells of some ALS patients had Bunina bodies (BB), Lewy body-like inclusions (LBI) and skein-like inclusions (SI), as well as bundles of filaments that were thicker than neurofilaments; some of these filaments appeared to be constricted. The incidence of these inclusions was lower than that seen in anterior horn neurons. Cytoplasmic inclusions such as BB, LBI, and SI were not observed in any of the controls. Our findings suggest that the cytopathology of upper motor neurons is similar to that of lower motor neurons and that the changes seen in Betz cells appear to be a reflection of the lower motor neuron alterations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293318
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  • 12
    Electronic Resource
    Electronic Resource
    Astrocytic straight tubules in the brain of a patient with Pick's disease (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 587-591 
    Details
    ISSN: 1432-0533
    Keywords: Astrocytes ; Electron microscopy ; Immunocytochemistry ; Pick's disease ; Straight tubules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report concerns an immunohistochemical and ultrastructural study of cerebral astrocytes in a patient with Pick's disease of 20 years' duration. The autopsied brain was prominently small (710 g) with marked fronto-temporal lobar atrophy. Histological examination demonstrated profound neuronal loss and spongy changes with tau-positive Pick bodies in the frontal and temporal cortex. In addition, many glial cells in the temporal lobe white matter contained round to oval, argentophilic and slightly hematoxinophilic cytoplasmic inclusions that were also immunolabeled with the anti-tau antibody. On electron microscopy, the glial inclusions were observed in the perikarya of astrocytes that were recognized as such from intracytoplasmic glial filaments and the presence of gap junctions. The inclusions were free in the cytoplasm, without a limiting membrane, and mainly comprised irregular aggregations of bundles of about 15-nm straight tubules, which were indistinguishable from those of intraneuronal Pick bodies. Furthermore, various patterns of accumulation of the same straight tubules were frequently noted in perivascular astrocytic processes carrying a basal lamina. These findings indicate that in Pick's disease astrocytes are also affected by a similar insult to that which affects neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296498
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  • 13
    Electronic Resource
    Electronic Resource
    Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N -methyl-D-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate) (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 511-519 
    Details
    ISSN: 1432-0533
    Keywords: Key words Vacuolization ; Neurotoxicity ; Neuropathology ; Electron microscopy ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-D-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60 – 70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296487
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  • 14
    Electronic Resource
    Electronic Resource
    An ultrastructural analysis of human post-infectious (allergic) encephalomyelitis (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 541-544 
    Details
    ISSN: 1432-0533
    Keywords: Allergic Encephalomyelitis ; Astrocytes ; Demyelination ; Electron microscopy ; Multiple sclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old boy developed post-infectious encephalomyelitis and underwent a brain biopsy (10 days after the onset of neurologic symptoms). Electron microscopic analysis of brain showed demyelinated axons, thinly myelinated axons, aberrant remyelination, and numerous phagocytes containing myelin debris. Physical stripping of myeling by pseudopodial extensions of macrophages, as reported in experimental allergic encephalomyelitis, was noted. Hypertrophic and hyperplastic astrocytes were prominent among the phagocytic cells and played an unexpectedly active role in demyelination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294183
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  • 15
    Electronic Resource
    Electronic Resource
    Immunocytochemical and ultrastructural studies of the motor cortex in amyotrophic lateral sclerosis (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 578-585 
    Details
    ISSN: 1432-0533
    Keywords: KeyWordsAmyotrophic lateral sclerosis ; Motor cortex Betz cells ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report concerns an immunocytochemical and ultrastructural study of the motor cortices of 11 patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 normal individuals served as con- trols. Antibodies against phosphorylated neurofilament (PNF; 200 kDa), ubiquitin, glial fibrillary acidic protein (GFAP) and phosphorylated tau protein were used. The pyramidal cells of layer III of all ALS patients were stained, with varying intensities, by the antibody to PNF. By contrast, Betz cells reacted less frequently with this antibody. Staining for GFAP was noted in numerous astrocytes in layer III and at the transition between white matter and motor cortex of most patients. Ubiquitin-positive inclusions were only occasionally seen in Betz cell and pyramidal cell of layer V. These observations indicate that alterations of the motor cortex occur first in the pyramidal cells of layer III rather than in Betz cells. Pyramidal cells and Betz cells were not stained by the antibody to phosphorylated tau protein. In controls, pyramidal cells and Betz cells were less frequently stained with the anti-neurofilament antibody than those from ALS patients. Immunoreactivity of GFAP in layer III and at the junction of white matter and motor cortex was observed in only one patient. Ultrastructural examination revealed that the Betz cells of some ALS patients had Bunina bodies (BB), Lewy body-like inclusions (LBI) and skein-like inclusions (SI), as well as bundles of filaments that were thicker than neurofilaments; some of these filaments appeared to be constricted. The incidence of these inclusions was lower than that seen in anterior horn neurons. Cytoplasmic inclusions such as BB, LBI, and SI were not observed in any of the controls. Our findings suggest that the cytopathology of upper motor neurons is similar to that of lower motor neurons and that the changes seen in Betz cells appear to be a reflection of the lower motor neuron alterations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293318
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  • 16
    Electronic Resource
    Electronic Resource
    Generalised nuclear and cytoplasmic inclusion disease: a rare case investigated by microscopy and immunohistochemistry (1994)
    Springer
    Acta neuropathologica 87 (1994), S. 648-654 
    Details
    ISSN: 1432-0533
    Keywords: Inclusion body disease ; Electron microscopy ; Immunohistochemistry ; Viral infection ; Primary metabolic disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Caucasian female who was noted to be mildly microcephalic at birth was diagnosed as having cerebral palsy at the age of 1 year. Her development was delayed and she never walked or talked. She appeared relatively stable neurologically until the age of 17 years when she had an illness with fever thought to be due to a virus. She was noted to deteriorate from this time on until her death at the age of 19 years. Autopsy revealed intranuclear and cytoplasmic inclusions widespread throughout the brain and visceral organs. There was no evidence of inflammation. Immunohistochemistry revealed strong immunoreactivity for tau protein and neurofilament protein. Electron microscopy revealed the inclusions to be composed of homogeneous finely granular material. Scattered with the granular material in the cytoplasmic bodies were crystalline structures with a honeycomb appearance. The possibility of these changes representing an old viral infection or a primary metabolic disorder are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293327
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  • 17
    Electronic Resource
    Electronic Resource
    Light and electron microscopic study of omental milky spots in New Zealand Black mice, with special reference to the extramedullary hematopoiesis (1994)
    Springer
    Anatomy and embryology 189 (1994), S. 215-226 
    Details
    ISSN: 1432-0568
    Keywords: Omental milky spot ; Megakaryocyte ; Myelopoiesis ; Electron microscopy ; New Zealand Black mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Omental milky spots are especially large and numerous in New Zealand Black (NZB) mice, which are known to develop spontaneous autoimmune diseases. We investigated omental milky spots in NZB mice by light and electron microscopy. The milky spots were composed of abundant lymphocytes/plasma cells with macrophages, neutrophils, eosinophils, megakaryocytes, and various stromal cells. In addition, clustered neutrophils in various maturation stages with occasional mitotic figures were frequently present in the milky spots: apparent neutrophilic myelopoiesis was present. The presence of megakaryocytes was sporadic. Considering the giant size of megakaryocytes, their direct migration into the milky spots from the bone marrow or spleen seems improbable. Thus, the presence of megakaryocytes was interpreted as probable megakaryopoiesis. Erythroblasts were not contained in the milky spots. These findings seem to indicate that the milky spots in NZB mice represent a special type of lymphoid tissue with active neutrophilic myelopoiesis and probable megakaryopoiesis. Reticulum cells in the milky spots in NZB mice had well-developed dense bodies consisting of clustered parallel tubules that showed a hexagonal array. However, the biological significance of these cells remains unknown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00239009
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  • 18
    Electronic Resource
    Electronic Resource
    Fiber composition of the lateral plantar and superficial peroneal nerves in the rat foot (1994)
    Springer
    Anatomy and embryology 189 (1994), S. 393-399 
    Details
    ISSN: 1432-0568
    Keywords: Rat ; Myelinated axons ; C-fibers ; Skin ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examines the fiber composition of two nerves projecting to the rat hindpaw: the lateral plantar nerve (LPN), which innervates plantar glabrous skin and some plantar muscles, and the foot branch of the superficial peroneal nerve (fSPN), which projects to dorsal hairy skin. The LPN contains 872 (33%) myelinated axons with a size range of 1–7 μm and a peak at 4 μm. Some 200 of the myelinated axons are muscle efferents. There are 1,969 (67%) C-fibers. After neonatal capsaicin treatment, the number of C-fibers in the LPN is 61% below the normal level, but it is not significantly different from control levels after chemical sympathectomy with guanethidine. The fSPN is composed of 470 (20%) myelinated axons with a size range similar to that in the LPN. Virtually all myelinated fibers are sensory. There are 1,791 (80%) C-fibers. In neonatally capsaicin-treated animals, the occurrence of C-fibers is 65% below control levels. In chemically sympathectomized animals, the number of C-fibers in the fSPN is normal. This description of the fiber composition of the LPN and the fSPN in the rat provides a basis for future experimental studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00185434
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  • 19
    Electronic Resource
    Electronic Resource
    Astrocytic straight tubules in the brain of a patient with Pick's disease (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 587-591 
    Details
    ISSN: 1432-0533
    Keywords: Key words Astrocytes ; Electron microscopy ; Immunocytochemistry ; Pick's disease ; Straight tubules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report concerns an immunohistochemical and ultrastructural study of cerebral astrocytes in a patient with Pick's disease of 20 years' duration. The autopsied brain was prominently small (710   g) with marked fronto-temporal lobar atrophy. Histological examination demonstrated profound neuronal loss and spongy changes with tau-positive Pick bodies in the frontal and temporal cortex. In addition, many glial cells in the temporal lobe white matter contained round to oval, argentophilic and slightly hematoxinophilic cytoplasmic inclusions that were also immunolabeled with the anti-tau antibody. On electron microscopy, the glial inclusions were observed in the perikarya of astrocytes that were recognized as such from intracytoplasmic glial filaments and the presence of gap junctions. The inclusions were free in the cytoplasm, without a limiting membrane, and mainly comprised irregular aggregations of bundles of about 15-nm straight tubules, which were indistinguishable from those of intraneuronal Pick bodies. Furthermore, various patterns of accumulation of the same straight tubules were frequently noted in perivascular astrocytic processes carrying a basal lamina. These findings indicate that in Pick's disease astrocytes are also affected by a similar insult to that which affects neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296498
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  • 20
    Electronic Resource
    Electronic Resource
    Cytoplasmic inclusions of astrocytic elements of glial tumors: special reference to round granulated body and eosinophilic hyaline droplets (1994)
    Springer
    Acta neuropathologica 88 (1994), S. 501-510 
    Details
    ISSN: 1432-0533
    Keywords: Round granulated body ; Eosinophilic hyaline droplets ; Astrocytic tumors ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Round granulated body (RGB) and eosinophilic hyaline droplets (EHDs) have been described as cytoplasmic inclusions of certain astrocytic tumors. In the previous literature, however, these inclusions have been described using various terms or regarded as nosologically the same entity. Light microscopically, RGB apeared as a round discrete body filled with fine uniform granules, while EHDs demonstrated a cluster of bright eosinophilic, round objects of various size. They could be clearly distinguished even by conventional histochemical staining such as the Masson trichrome stain and the phosphotungstic acid hematoxylin preparation. Both RGB and EHDs expressed positive immunoreactions for glial fibrillary acidic protein, several lysosomal markers, and some stress-response proteins. The ultrastructural appearances of these inclusions were distinct, however, one common feature was that they consisted of aggregations of numerous membrane-bound electron-dense bodies. Thus, both inclusions appear to be produced by neoplastic astrocytes and are possibly related to the lysosomal system. We examined the presence of RGB and EHDs in 138 astrocytic tumors. Both inclusions occurred most frequently in pleomorphic xanthoastrocytomas, followed by gangliogliomas and pilocytic astrocytomas. Subependymal giant cell astrocytomas exhibited only RGBs. RGBs and EHDs were not seen in any abundance in glioblastomas, gliosarcomas, fibrillary astrocytomas, protoplasmic astrocytomas, or oligo-astrocytomas. Some glioblastomas, however, showed only EHDs in small numbers. Several anaplastic astrocytomas were associated with a large number of RGBs and/or EHDs, and they revealed only rare mitosis despite marked cellular pleomorphism. Although RGB and EHDs have different morphological features, the presence of these inclusions in abundance may represent either a degenerative change, a long-standing lesion, or an indolent growth of the astrocytic tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296486
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  • 21
    Electronic Resource
    Electronic Resource
    Fine structure of the retinal pigment epithelium in the Port Jackson shark (Heterodontus phillipi) (1994)
    Springer
    Anatomy and embryology 190 (1994), S. 501-506 
    Details
    ISSN: 1432-0568
    Keywords: Retinal pigment epithelium (RPE) ; Electron microscopy ; Elasmobranch ; Heteterodontus phillipi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the Port Jackson shark (Heterodontus phillipi). In this elasmobranch the RPE consists of a single layer of low cuboidal cells which show basal (scleral) infoldings and apical (vitreal) processes that enclose photoreceptor outer segments. Laterally these epithelial cells are joined by a series of apically located tight junctions. The RPE cells display a large vesicular nucleus, abundant smooth endoplasmic reticulum as well as numerous polysomes and mitochondria. Phagosomes are present, rough endoplasmic reticulum is scarce and myeloid bodies were not observed. Melanosomes are absent over the choroidally located tapetum lucidum, but are not abundant even in extratapetal areas. This paucity of melanosomes probably makes retinomotor movements unimportant. Bruch's membrane or complexus basalis is a pentalaminate structure. The endothelium of the choriocapillaris is thin but minimally fenestrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235498
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  • 22
    Electronic Resource
    Electronic Resource
    Fine structure of the choroidal tapetum lucidum in the Port Jackson shark (Heterodontus phillipi) (1994)
    Springer
    Anatomy and embryology 190 (1994), S. 591-596 
    Details
    ISSN: 1432-0568
    Keywords: Tapetum lucidum ; Electron microscopy ; Elasmobranch ; Heterodontus phillipi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The choroidally located tapetum lucidum of the Port Jackson shark (Heterodontus phillipi) was examined by light and electron microscopy in light-adapted specimens. In this species the tapetum consists of a single layer of overlapping cells oriented at an angle of about 30° to the incoming light and situated immediately external to the choriocapillaris. These tapetal cells alternate with and are separated from one another by melanocytes which extend beyond the tapetal cells to intervene between the tapetal cells and the incoming light. The tapetal cells and the melanocytes are flattened plate-like cells with their widest dimension facing the retina. Internally the tapetal cells display a peripherally located vesicular nucleus with most organelles in a paranuclear location. The bulk of a tapetal cell is packed with regularly spaced crystals reported to be guanine. The size and spacing of these reflective crystals is commensurate with the principles of constructive interference. In light adaptation, the melanosomes of the intervening melanocytes are widely dispersed and for the most part block the passage of light to the tapetal cells. Although dark-adapted specimens were not available, it seems reasonable to assume that in dark adaptation these melanosomes will retreat to unmask the tapetum and allow it to function as a known reflective layer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00190109
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  • 23
    Electronic Resource
    Electronic Resource
    Distribution of apoptosis-mediating Fas antigen in human skin and effects of anti-Fas monoclonal antibody on human epidermal keratinocyte and squamous cell carcinoma cell lines (1994)
    Springer
    Archives of dermatological research 286 (1994), S. 396-407 
    Details
    ISSN: 1432-069X
    Keywords: Fas antigen ; Immunohistochemical ; Skin disease ; Keratinocytes ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fast antigen is a cell surface protein that mediates apoptosis. Using immunohistological, flow cytometry and electron microscopic analyses, we investigated the expression of Fas antigen on various skin tissues, and on cultured SV40-transformed human epidermal keratinocyte cell line KJD and human skin squamous cell carcinoma cell line HSC. The Fas antigen was widely distributed in skin components such as the keratinocytes in the lower portion of the epidermis, epidermal dendritic cells, endothelial cells, fibroblasts, apocrine glands, eccrine sweat glands, sebaceous glands, some normal melanocytes and infiltrating lymphoid cells. It was also strongly expressed on the keratinocytes of lichenoid eruptions seen in lupus erythematosus and lichen planus, and on the spongiotic or acanthotic epidermis seen in chronic eczema, adult T-cell leukaemia/lymphoma (ATLL) and atopic dermatitis. Its expression was closely correlated with lymphoid infiltrating cells and it was strongly expressed in lymphoid neoplastic cells, particularly ATLL cells, and fibroblasts seen in dermatofibroma. However, the antigen was not detected on basal cell epithelioma cells, some malignant melanomas or any junctional naevi. The cell lines KJD and HSC strongly expressed the Fas antigen, and crosslinking of the Fas antigen by an anti-Fas monoclonal antibody induced apoptosis of these cell lines. These results indicate that the apoptosis-mediating Fas antigen may play an important role in normal skin turnover and cell differentiation, in immune regulation of skin tumours, and in the pathogenesis of various skin diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00371800
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  • 24
    Electronic Resource
    Electronic Resource
    Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects (1994)
    Springer
    Diabetologia 37 (1994), S. 377-380 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; pharmacokinetics ; insulin absorption ; metabolic control ; skin temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Subcutaneous insulin absorption kinetics were assessed in 50 healthy study subjects (21 female, 29 male; age 26±3 years, BMI 22.5±1.8 kg/m2; mean±SD) during 45 min after periumbilical injection of soluble human U40- or U100-insulin (0.15 IU/kg). Subcutaneous fat thickness was measured by ultrasound, and skin temperature at the injection site was registered. Serum insulin concentrations increased within 30 min from basal values of 37±15 to 140±46 pmol/l after U40-insulin and from 36±10 to 116±37 pmol/l after U100-insulin (p〈0.001). After 45 min serum insulin concentrations were 164±43 pmol/l with U40-insulin and 128±35 pmol/l with U100-insulin (p〈0.001). Decline in blood glucose levels and suppression of C-peptide were comparable. The serum insulin levels reached 30 and 45 min after U40- and U100-insulin injection were positively correlated with skin temperature (p〈0.0008), and negatively correlated with subcutaneous fat thickness (p〈0.009). In conclusion, the lower insulin concentration of U40-insulin, higher skin temperature, and a thinner subcutaneous fat tissue at the injection site are associated with accelerated and enhanced subcutaneous insulin absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408474
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  • 25
    Electronic Resource
    Electronic Resource
    Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AG-EE 623 ZW, during euglycaemic clamp in healthy subjects (1994)
    Springer
    Diabetologia 37 (1994), S. 703-707 
    Details
    ISSN: 1432-0428
    Keywords: Glibenclamide ; glyburide ; sulphonylurea ; compounds ; AG-EE 623 ZW ; dose-response ; time-action profiles ; pharmacokinetics ; glucose clamp technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3–3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25–40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per μmol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417695
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  • 26
    Electronic Resource
    Electronic Resource
    Once daily dosing of netilmicin in neonatal and pediatric intensive care (1994)
    Springer
    Intensive care medicine 20 (1994), S. 365-367 
    Details
    ISSN: 1432-1238
    Keywords: Netilmicin ; Once daily dosing ; Neonatal/pediatric intensive medicine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. Design and setting Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5–6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. Results All peak levels (n=28) were clearly above 12 μmol/l (mean 22, range 13–41 μmol/l). Eighty-nine trough levels were within desired limits (〈4 μmol/l) and 11 (11%) above 4 μmol/l, mostly in conjunction with impaired renal function. Conclusions Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01720910
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  • 27
    Electronic Resource
    Electronic Resource
    Plasma levels of oxybutynine chloride in children (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 83-85 
    Details
    ISSN: 1432-1041
    Keywords: Enuresis ; Oxybutynine chloride ; children ; pharmacokinetics ; adverse effects ; anticholinergic actions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg · kg−1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg · kg−1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195921
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  • 28
    Electronic Resource
    Electronic Resource
    Plasma concentrations and effect on testosterone metabolism after single doses of MK-0434, a steroid 5 alpha-reductase inhibitor, in healthy subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 123-126 
    Details
    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199874
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  • 29
    Electronic Resource
    Electronic Resource
    Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 261-265 
    Details
    ISSN: 1432-1041
    Keywords: Cystic fibrosis ; Cyclosporin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg·kg−1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg·kg−1). The mean maximum blood concentration of CsA for the oral dose was 776 ng·ml−1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng·ml−1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192559
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  • 30
    Electronic Resource
    Electronic Resource
    Esmolol, an ultrashort-acting, selective β1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 399-404 
    Details
    ISSN: 1432-1041
    Keywords: Esmolol ; β1-Adrenoceptor antagonist ; tricresylphosphate ; pharmacokinetics ; effect kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of esmolol at different rates of infusion (100, 250 and 500 μg·kg−1 BW·min−1) were compared with β-adrenoceptor occupancy (β1 and β2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 μg·kg−1 BW·min−1 there was a maximal β1-receptor occupancy of 84.7% while β2-receptor occupancy was below the detection limit; confirming the β1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 μg·kg−1 BW · min−1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 μg·ml−1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 μg·kg−1 BW·min−1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191900
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  • 31
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 545-550 
    Details
    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196113
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  • 32
    Electronic Resource
    Electronic Resource
    On the relation between standard deviation and arithmetic mean in pharmacokinetic studies (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 573-574 
    Details
    ISSN: 1432-1041
    Keywords: Standard deviation ; Arithmetic mean ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196120
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  • 33
    Electronic Resource
    Electronic Resource
    Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 565-567 
    Details
    ISSN: 1432-1041
    Keywords: Phenytoin ; Saliva ; therapeutic drug monitoring ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196118
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  • 34
    Electronic Resource
    Electronic Resource
    Cyclosporine pharmacokinetics in nephrotic and kidney-transplanted children (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 61-65 
    Details
    ISSN: 1432-1041
    Keywords: Cyclosporine A ; kidney transplant ; nephrotic syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39 %, blood clearance was 0.55 l · h-1 · kg-1 and volume of distribution at steady-stade was 2.77 l · kg-1. The absorption profile was monophasic (67 %), biphasic (29 %) or poor (4 %). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng · ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l · h-1 · kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193480
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  • 35
    Electronic Resource
    Electronic Resource
    Differences in the bioavailability of dihydrotachysterol preparations (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 81-84 
    Details
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193484
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  • 36
    Electronic Resource
    Electronic Resource
    Doxycycline carrageenate — an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 143-146 
    Details
    ISSN: 1432-1041
    Keywords: Doxycycline ; bioavailability ; pH dependent absorption ; pharmacokinetics ; carrageenate ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199878
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  • 37
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 163-166 
    Details
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199882
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  • 38
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dosage recommendations of teicoplanin in patients treated by continuous veno-venous haemodialysis (CVVHD) (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 179-180 
    Details
    ISSN: 1432-1041
    Keywords: Teicoplanin ; haemodialysis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199886
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  • 39
    Electronic Resource
    Electronic Resource
    Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 237-242 
    Details
    ISSN: 1432-1041
    Keywords: Metoprolol ; bioavailability ; bioequivalence ; receptor binding assay ; pharmacokinetics ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its β1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung β1-and rat reticulocyte β2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml−1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml−1, (n=6); the AUC0–24 h-values for the formulations were 700 and 310 ng·h·ml−1, respectively. The Cmax for the β1-adrenoceptor binding component of metoprolol was 180 ng·ml−1 (n=7) after administration of the conventional, and 74 ng·ml−1 after administration of the sustained-release formulation. The corresponding AUC0–24 h-values for the receptor binding component were 920 and 470 ng·h·ml−1 (n=7). Thus, the kinetic differences between R,S-metoprolol and the β1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage β1- and β2-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average β1-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average β2-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant. The results demonstrate that plasma concentration-kinetics were more discriminating than β-adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192555
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  • 40
    Electronic Resource
    Electronic Resource
    Changes in clearance create pharmacokinetic pitfalls as illustrated by studies on tiopronin (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 575-575 
    Details
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196121
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  • 41
    Electronic Resource
    Electronic Resource
    Conventional and controlled release diltiazem (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 75-79 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; Angina pectoris ; controlled release formulation ; metoprolol ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmcokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in antianginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193483
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  • 42
    Electronic Resource
    Electronic Resource
    The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 161-167 
    Details
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194967
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  • 43
    Electronic Resource
    Electronic Resource
    Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 41-47 
    Details
    ISSN: 1432-1041
    Keywords: Buspirone ; pharmacokinetics ; renal impairment ; hepatic impairment ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The single dose and steady-state pharmacokinetics of buspirone and its metabolite 1-pyrimidinyl piperazine (1-PP) have been evaluated in normal volunteers and patients with renal or hepatic impairment, using a parallel group design, with assignment of patients to study group on the basis of the degree of renal (mild, moderate, severe) or hepatic (compensated or decompensated) impairment. Each healthy volunteer or patient received a single dose of 10 mg buspirone on Day 1 of the study, and starting 36 h after the first dose, healthy volunteers and patients received 10 mg doses of buspirone every 12 hours for 9 days. On the morning of Day 10 they received the last dose. Serial blood samples were collected on Days 1, 5 and 10 and plasma was analysed for buspirone and 1-PP. The plasma concentrations of buspirone and 1-PP were highly variable regardless of the renal or hepatic function. The peak concentrations (Cmax) and area under the curves (AUC) of buspirone and 1-PP on Days D 5 and 10 were higher than on Day D 1. The trough levels (Cmin) and AUCs (D 5 and 10) of buspirone and 1-PP indicated, that, regardless of renal or hepatic function, steady state was reached after 3 to 5 days of dosing. At steady-state, patients with renal or hepatic impairment had significantly higher Cmax and AUC values of buspirone than in normal volunteers. However, the intensity and frequency of adverse experiences in patients with renal or hepatic impairment were not significantly different from those observed in normal volunteers. There was no correlation between the average plasma concentrations of buspirone ( $$\bar C$$ ) and the degree of renal impairment judged by creatinine clearance. An excellent correlation was observed between $$\bar C$$ of buspirone and serum albumin (r=0.862, and P〈0.0001) as well as between $$\bar C$$ and bromsulphalein clearance (r=0.678, P〈0.0003). In view of high intra-and inter-subject variability in buspirone concentrations, definitive dosing recommendations for patients with compromised renal or hepatic function could not be made, but such patients should initially be dosed cautiously with buspirone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195914
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  • 44
    Electronic Resource
    Electronic Resource
    Availability of synthetic salmon calcitonin in tissue fluid after a single intravenous dose (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 371-373 
    Details
    ISSN: 1432-1041
    Keywords: Salmon calcitonin ; Skin blister fluid concentration ; synthetic ; plasma concentration ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To obtain further information about the availability of salmon calcitonin in the biophase compartment that surrounds the receptor site, salmon calcitonin concentrations in plasma and skin blister fluid (SBF) after a single IV dose of 100 IU synthetic salmon calcitonin were compared in 15 healthy volunteers. Serial blood and SBF samples were collected before and up to 8 h after administration and calcitonin was determined by a specific RIA. The maximum concentration in plasma was 225 pg·ml-1 (in the first sample at 15 min), whereas in SBF the mean peak of 84 pg·ml-1 was reached after about 30 min. The distribution of salmon calcitonin into SBF, defined as the ratio of the AUCs in SBF and plasma, was 1.5. The kinetic profiles of salmon calcitonin in plasma and interstitial fluid were different. Calcitonin in plasma peaked and then levelled out, while in SBF it persisted longer than in plasma. This is the first report of the distribution of salmon calcitonin into blister fluid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194408
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  • 45
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of torasemide and its metabolites in end-stage renal disease (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 157-159 
    Details
    ISSN: 1432-1041
    Keywords: Torasemide ; metabolites ; end-stage renal disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of torasemide, a new loop diuretic, as well as its active metabolites M1 and M3, and its inactive main metabolite, M5, were studied in 12 patients with end-stage renal failure during single i.v. (n=6) or single oral (n=6) dosing of 200 mg torasemide, and during chronic oral treatment for 9 days (n=12). The elimination half-life (t1/2) of torasemide was unchanged in renal failure, whereas t1/2 of the torasemide metabolites M1, M3, and M5 were markedly prolonged. However t1/2 as well as the area under the plasma level time curve of torasemide and its metabolites were unchanged during chronic compared to acute administration. The results of this study suggest that despite the increased half-life of torasemide metabolites M1, M3 and M5 in end-stage renal failure patients, no accumulation of the parent drug torasemide and its metabolites during chronic dosing is demonstrable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194966
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  • 46
    Electronic Resource
    Electronic Resource
    Weighted serum pools in comparison to the trapezoidal rule for estimating AUCs for ethinyl estradiol (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 77-81 
    Details
    ISSN: 1432-1041
    Keywords: Trapezoidal rule ; Ethinyl estradiol ; variance components ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The concept of a weighted pool for estimating the area under the curve (AUC) is presented and set in relationship to the trapezoidal rule. An example from a pharmacokinetic study on ethinyl estradiol is used to demonstrate the use of variance component analysis for relating the intraindividual variance of the AUC, trapezoidal rule and weighted pool to the variance of the determination process. Depending on the sampling times, the theoretical variance of the weighted pool is greater than the theoretical variance of the trapezoidal rule. In the example presented, it was shown that this difference is of no importance in relation to the interindividual variance of the AUC, which dominates the total variance. In the example study, routine quality control samples were also determined in each assay, which allowed independent confirmation of the discussed results on the intraindividual variance of the AUCs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195920
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  • 47
    Electronic Resource
    Electronic Resource
    Kinetic interaction between theophylline and a newly developed anti-allergic drug, pemirolast potassium (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 55-58 
    Details
    ISSN: 1432-1041
    Keywords: Pemirolast ; Asthma ; theophylline ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of a newly developed anti-allergic drug, pemirolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in seven healthy male volunteers. A sustained-release theophylline formulation (100 mg twice daily at 12 h intervals) was given as monotherapy and coadministered with TBX (10 mg twice daily at 12 h). Plasma concentration-time curves and the urinary excretion of theophylline and its major metabolites after administration of theophylline alone and after coadministration with TBX were compared. No significant adverse effects from this study were observed. There were no significant differences in the total body clearance, renal clearance and maximum concentration of theophylline between the two treatments, although coadministration of TBX significantly delayed the time to reach maximum concentration of theophylline. In the case of urinary excretion, no significant changes in the fraction of urinary excretion of theophylline and its metabolites were observed. These results indicate that TBX has little or no effect on the pharmacokinetics and metabolism of theophylline and suggest that TBX is safe for asthma patients receiving theophylline therapy for treatment of chronic obstructive airway diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195916
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  • 48
    Electronic Resource
    Electronic Resource
    Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 151-157 
    Details
    ISSN: 1432-1041
    Keywords: Entacapone ; catechol-O-methyltransferase ; pharmacokinetics ; healthy volunteers ; adverse effects ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The inhibition of soluble catechol-O-methyltransferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5–800 mg) and IV (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. Oral entacapone dose-dependently decreased the activity of S-COMT in RBCs with a maximum inhibition of 82% after the highest dose (800 mg). The inhibition of S-COMT in RBCs was reversible and the activity recovered within 4–8 h. Entacapone showed linear pharmacokinetics over the dose range studied: Cmax and AUC were correlated with the dose of the drug. Oral absorption of entacapone was fast, with a tmax ranging from 0.4 to 0.9 h, depending on the dose. Systemic availability of entacapone varied between 30 and 46%. Entacapone was rapidly eliminated by metabolism with a half-life of 0.27–0.30 h after oral doses of 5 to 50 mg. After doses from 100 to 800 mg the disposition was best described by two phases with a t1/2α of 0.27–0.37 h and t1/2β of 1.59–3.44 h. Over the dose range studied, the single oral and IV doses of entacapone were well tolerated. No haematological, biochemical or haemodynamic adverse effects were seen. The results show that entacapone is an orally effective and reversible COMT inhibitor in man and has simple, linear pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199880
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  • 49
    Electronic Resource
    Electronic Resource
    A comparative study of the steady-state pharmacokinetics of immediate-release and controlled-release diltiazem tablets (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 243-247 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; immediate-release tablet ; controlled-release tablet ; steady state ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the controlled-release properties and relative systemic availabilities of two dosages of the same controlled-release (CR) diltiazem tablet formulation by comparing them at steady state with those of an immediate-release formulation. We measured 24-hour plasma concentration profiles during 4-day treatments with diltiazem 90 mg CR tablet bd diltiazem 120 mg CR tablet bd, and conventional diltiazem 60 mg immediate-release (IR) tablet tid. The study had a randomized, three-way crossover design. Twelve healthy men (38–52 y) participated. Trough plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the last morning dose on day 4 of each period. The following steady-state pharmacokinetic values were calculated: the minimum plasma concentration (Cmin), the maximum plasma concentration (Cmax), the time interval during which the plasma concentration exceeded 75% of Cmax (t75), the area under the plasma concentration-time curve (AUC72–96), the peak-to-trough fluctuation (PTF), and the area-under-the-curve fluctuation (AUCF). Steady state was achieved on day 3. The pharmacokinetics were comparable. For diltiazem CR 90 mg and diltiazem CR 120 mg, AUC84–96 (night) was approximately 75% of AUC72–84 (daytime). The diltiazem plasma concentration increased slowly from about 6 h after the evening dose of both CR tablets, resulting in relatively high plasma concentrations in the early morning hours. Only during treatment with diltiazem CR 120 mg were the plasma concentrations of diltiazem maintained above the minimum therapeutic plasma concentration of 50 μg·1−1 throughout the full 24 h. In conclusion, twice-daily treatment with diltiazem CR tablets can replace thrice-daily treatment with the conventional diltiazem IR tablet. The early morning rise of the diltiazem plasma concentration, which might lead to a lower incidence of ischaemic events, may be an important clinical advantage of both CR tablets. Because of the minimum therapeutic plasma concentration of 50 μg·1−1, twice-daily administration of the 120 mg CR tablet may be preferred from a therapeutic point of view. Diltiazem, a benzothiazepine, is a calcium antagonist used in the treatment of angina pectoris and hypertension. The anti-ischaemic mechanism of diltiazem seems to result from an increase of myocardial oxygen supply and a reduction in myocardial oxygen demand, respectively by coronary artery dilatation and/or direct and indirect haemodynamic effects, such as afterload reduction and heart rate decrease (Braunwald 1982). Its therapeutic effect is evident at daily dosages between 180 and 360 mg (Low et al. 1981). After oral administration it is almost completely absorbed from the gastrointestinal tract, but owing to extensive first-pass metabolism, its systemic availability is approximately 40–50% (Echizen and Eichelbaum 1986). The time to maximum plasma concentrations after oral administration of immediate-release formulations is approximately 3 to 4 h. The elimination half-life of diltiazem is 3.5–7 h, implying that frequent dosing is required to maintain effective plasma concentrations. Therefore, a controlled-release formulation of diltiazem, designed to be taken twice daily, has been developed. The aim of this crossover study was to compare the systemic availability and steady-state pharmacokinetics of a controlled-release diltiazem tablet formulation (90 and 120 mg) with those of a conventional diltiazem immediate-release tablet in healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192556
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  • 50
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of factor IX in patients with haemophilia B (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 325-332 
    Details
    ISSN: 1432-1041
    Keywords: Factor IX ; Haemophilia B ; macromolecules ; pharmacokinetics ; methodological study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aims of this study were to investigate the influence of total blood sampling time on the estimated pharmacokinetic parameters of Factor IX procoagulant activity (FIX:C) and to relate the pharmacokinetics of FIX:C to the putative physiological disposition of Factor IX (FIX). Six patients with severe haemophilia B each received 2 infusions of FIX and on both occasions blood samples were collected for 104 h. Each FIX:C decay curve was processed with successive deletion of the last (remaining) datapoint. The fitted terminal half-life (t1/2β) and the calculated model-independent mean residence time (MRTMI), elimination clearance (CLMI) and volume of distribution at steady state (Vss) stabilised close to their final values when FIX:C data corresponding to at least 56 h of sampling were used. The final mean values were t1/2β=34 h, MRTMI=37 h, CLMI=4.0 ml · h-1 · kg-1 and Vss=0.15 l · kg-1. The disposition of FIX could be characterised by a two-compartment pharmacokinetic model. On average, FIX molecules spent 44% of their total MRT in the second (or “extravascular”) compartment. The distribution clearance was comparable to estimated total lymph flow. The volume of the central compartment was twice the estimated plasma volume, which may reflect the rapid and reversible binding of FIX to vascular endothelium. This explains the common clinical finding that the peak activity of FIX:C is less than the injected dose divided by the estimated plasma volume of the patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194400
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  • 51
    Electronic Resource
    Electronic Resource
    Dose proportionality of iopromide pharmacokinetics and tolerability after IV injection in healthy volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 339-343 
    Details
    ISSN: 1432-1041
    Keywords: Iopromide ; X-ray contrast medium ; pharmacokinetics ; tolerability ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Twelve healthy male volunteers participated in a single-blind, randomised, placebo-controlled cross-over study of IV iopromide in doses of 15 g iodine or 80 g iodine infused over a period of 15 min. The volunteers were observed for three days during which time blood samples, urine and faeces were collected. The terminal disposition phase half-life of iopromide was 2 h and 1.9 h, and the total clearance was 110 and 103 ml·min-1 at the lower and at the higher dose levels, respectively. The steady state volume of distribution was 16 and 17 l, indicating predominantly extracellular distribution of iopromide. Statistical analysis (one-sided t-test) showed that all the target parameters (AUC, half-life and urinary excretion) were equivalent at both dose levels, indicating dose proportionate, first order kinetics of iopromide over the large dose range tested. Iopromide was well tolerated after both doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194402
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    Electronic Resource
    Pharmacokinetics of ganciclovir in a patient undergoing chronic haemodialysis (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 379-381 
    Details
    ISSN: 1432-1041
    Keywords: Ganciclovir ; Renal failure ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of ganciclovir was evaluated in a 73-year old anuric, haemodialyzed patient given 1.25 mg·kg-1 at the end of each haemodialysis session, three times per week. A biexponential decrease in plasma ganciclovir was observed, with a peak concentration of 3.7 mg·1-1 followed by a steady state value of 2.6 mg·1-1 for almost 40 h. The total plasma clearance was 0.05 ml·min-1·kg-1, the volume of distribution at steady state was 0.61·kg-1, the elimination half life was 132 h, the area under curve was 372 μg·h·ml-1, the mean residence time was 190 h, and the percentage of ganciclovir cleared from plasma after a 5 h haemodialysis session was 52.1%. The simulated pharmacokinetics over one month, following the same scheme of administration, did not suggest marked accumulation of ganciclovir. These results were obtained after a reduction of 58% in the recommended dose in patients with impaired renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194410
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  • 53
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    Electronic Resource
    Population approaches in drug development (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 389-391 
    Details
    ISSN: 1432-1041
    Keywords: Population approach ; Drug development ; software ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract An expert meeting to discuss population pharmacokinetic/pharmacodynamic software was held in Brussels in November 1993 under the auspices of the European Co-operation in Science and Technology (COST), Medicine (B1) programme. Recently developed statistical methods offer the possibility of gaining integrated information on pharmacokinetics and response from relatively sparse observational data obtained directly in patients who are being treated with the drug under development. These methods can minimize the need to exclude patient groups and also allow analysis of a variety of unbalanced designs that frequently arise in the evaluation of the relationships between dose or concentration on the one hand and efficacy or safety on the other relationships that do not readily lend themselves to other forms of statistical analysis. The purpose of the Brussels meeting was to evaluate the state of both existing software and software under development, and to specify the needs and wishes of potential users of such software. It was apparent from the meeting that software development for population data analysis is currently a very active area of investigation and that several very good packages are already available, with more in development. The general consensus of the meeting was that well validated, easy to use software was essential to the implementation of the population approach to drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191898
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  • 54
    Electronic Resource
    Electronic Resource
    Paracetamol pharmacokinetics during the first trimester of human pregnancy (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 451-454 
    Details
    ISSN: 1432-1041
    Keywords: Pregnancy ; Paracetamol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Paracetamol pharmacokinetics was evaluated in groups of pregnant (8–12 weeks) and non pregnant women given the standard oral dose of 650 mg. The mean half-life was significantly lower and oral clearance was significantly higher in the first trimester group compared to the control group. The AUC was lower in the first trimester but the difference was not significant. The maximum serum concentration (Cmax) was reached 48 min after administration in both groups, and the mean maximal serum concentration was similar in the pregnant and non-pregnant women (11.16 and 11.58 μg·ml−1). A correlation of r=0.85 was found between Cmax and the weight of the pregnant women (P〈0.01) but not with the weight of the control women, this suggests that weight gain might be used to determine the women in whom dosage adjustment is needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191910
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  • 55
    Electronic Resource
    Electronic Resource
    The quinolone, flumequine, has no effect on theophylline pharmacokinetics (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 477-478 
    Details
    ISSN: 1432-1041
    Keywords: Theophylline ; flumequine ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The kinetics of a single i. v. dose of theophylline given either alone or with flumequine was studied in eight healthy volunteers. No statistically significant differences were observed in the pharmacokinetic parameters of theophylline (volume of distribution, elimination half-life, AUC, plasma clearance) following the two treatments. Pretreatment for 5 days with oral flumequine (400 mg, three times daily) had no significant effect on the disposition of a single i. v. dose of theophylline in healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191915
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  • 56
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    Electronic Resource
    Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 537-543 
    Details
    ISSN: 1432-1041
    Keywords: Lisinopril ; Dose adjustment ; ACE inhibitors ; pharmacokinetics ; pharmacodynamics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e. g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n=8; endogenous creatinine clearance [CLCR]: 18 ml·min−1·1.73m−2) and in healthy subjects with normal renal function (n=16; CLCR: 107 ml·min−1·1.73m−2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1–2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (C max) in patients was lower than in volunteers (30.7 vs 40.7 ng·ml−1, while the mean area under the concentration-time curve (AUC 0–24 h) was higher (525 vs 473 ng·h−1·ml−1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9–2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose. Despite substantial dose reduction, blood pressure and proteinuria decreases were observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196112
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  • 57
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    Electronic Resource
    Protein binding of 2-chloro 2′-deoxyadenosine (cladribine) in healthy subjects and in patients with leukaemia (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 563-564 
    Details
    ISSN: 1432-1041
    Keywords: 2-Chloro-2′-deoxyadenosine (CdA) ; Protein binding ; Cladribine ; pharmacokinetics ; leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The plasma protein binding of 2-chloro-2′-deoxyadenosine (CdA) at 37°;C was studied by ultrafiltration in 5 healthy volunteers, in 11 patients with haematological malignancies and in purified protein preparations. In the patients, the binding of CdA to plasma proteins was 25.0% and in healthy subjects it was 21.1%. In a solution of human serum albumin (40 g·1−1), 24.3% CdA was bound, but less than 5% was bound in a solution of α1-acid-glycoprotein (0.7 g·1−1). No dependence of binding on the concentration of CdA was found within a range 25–1000 nmol·1−1. In conclusion, due to its limited binding to plasma proteins, any change in the binding of CdA is unlikely to have a major influence on its pharmacological effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196117
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  • 58
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    Electronic Resource
    Azithromycin does not alter the effects of oral midazolam on human performance (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 49-52 
    Details
    ISSN: 1432-1041
    Keywords: Azithromycin ; Erythromycin ; Midazolam ; drug interaction ; healthy volunteers ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Since macrolide antibiotics inhibit the oxidative hepatic metabolism of various drugs, including midazolam, the present double blind studies were conducted to find out if azithromycin, a new macrolide of the azalide type, would inhibit the metabolism of midazolam and enhance the effects of midazolam on human performance. In Study I, 64 healthy medical students, divided in four parallel groups received placebo, midazolam (10 mg or 15 mg), and midazolam 10 mg combined with azithromycin (500mg+250mg). In Study II, three males received oral midazolam 10 mg in combination with placebo, azithromycin or erythromycin 750 mg (as a positive control) in a cross-over trial. Objective and subjective tests were done before the intake of midazolam and 30 and 90 min after it, and venous blood was sampled for the assay of midazolam. In the placebo group in Study I, the mean numbers of letters cancelled (LC) at baseline, 30 min and 90 min were 21, 20 and 20, respectively, and the corresponding mean numbers of correct digit symbol substitutions (DSS) were 126, 137 and 140, indicating a practice effect. Midazolam 10 mg impaired these performances (21, 13 and 12 for LC, and 127, 113 and 111 for DSS). Either dose of midazolam produced clumsiness, mental slowness and poor subjective performance, midazolam 15 mg being slightly more active. The corresponding, scores in the azithromycin + midazolam group were 21, 16, 16 for LC, and 132, 121 and 119 for DSS, the only significant difference from placebo being the impairment of DSS at 90 min. The combination differed from midazolam 15 mg in producing less drowsiness and mental slowness. In Study II, mean plasma midazolam concentrations (μg·1-1) after erythromycin + midazolam 10 mg were 0 (baseline), 168 (30 min) and 113 (90 min), which were higher than the values (0, 79 and 41) after placebo + midazolam. The corresponding concentrations (μg·1-1) after azithromycin + midazolam (0, 85 and 46) were similar to those found after placebo + midazolam. Erythromycin but not azithromycin enhanced the objective and subjective effects of midazolam. Our results suggest that as azithromycin, unlike erythromycin, does not interfere with midazolam metabolism, it also does not enhance the effects of midazolam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193477
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  • 59
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    Electronic Resource
    The effect of hyperglycaemia on the absorption of glibenclamide in patients with non-insulin-dependent diabetes mellitus (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 53-55 
    Details
    ISSN: 1432-1041
    Keywords: Glibenclamide ; Diabetes ; NIDDM ; absorption ; hyperglycaemia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the absorption of glibenclamide 10 mg as a single morning dose in 7 patients with non-insulin-dependent diabetes mellitus, comparing normoglycaemic and hyperglycaemic states. The maximal glibenclamide plasma concentrations were significantly higher in the normoglycaemic than in the hyperglycaemic state (448 vs 228 mg·1-1) and these peak concentrations were attained faster in normoglycaemia than in hyperglycaemia (3.7 vs 5 h). We conclude that the absorption of glibenclamide in the two states is different.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193478
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  • 60
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    Electronic Resource
    The effects of age and sex on the systemic (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 57-60 
    Details
    ISSN: 1432-1041
    Keywords: Butorphanol ; transdermal ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effects of age and sex on the pharmacokinetics and the systemic availability of transnasal butorphanol in a randomized, two-way, crossover study of 48 subjects: young men and women, and elderly men and women. Each subject took a single 1 mg dose of intravenous and transnasal butorphanol tartrate on separate occasions with a one-week washout period. Blood samples were collected over 16 hours. Plasma butorphanol concentrations were determined using radioimmunoassay. The AUC of plasma butorphanol concentrations after an intravenous injection were higher in the elderly women than in the other groups. However, there were no significant differences in Cmax and AUC between the groups after transnasal administration. The mean systemic availability of transnasal butorphanol was about 70 %, except for the elderly women (48 %). After intravenous and transnasal administration, the half-life and mean residence time were greater in the elderly than the young. Clearance was lower in women than men. Apparent volume of distribution was higher for elderly men than the others. The age- and sex-related changes in the pharmacokinetics of transnasal butorphanol are not large enough to necessitate dosage differences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193479
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  • 61
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    The effect of food on the interaction of ofloxacin with sucralfate in healthy volunteers (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 67-69 
    Details
    ISSN: 1432-1041
    Keywords: Ofloxacin ; sucralfate ; food ; drug interaction ; absorption ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of food on the interaction of ofloxacin with sucralfate. Six healthy men took a single oral dose of ofloxacin (200 mg) on 4 occasions: alone after overnight fasting or after breakfast (non-fasting), and with sucralfate fasting or non-fasting. There were no significant differences in the plasma concentration-time profiles of ofloxacin after ofloxacin alone between fasting and non-fasting conditions. On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61 % compared with ofloxacin alone; the changes non-fasting were 39 and 31 % respectively. The interaction of ofloxacin with sucralfate was markedly reduced by food, but still could not be disregarded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193481
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  • 62
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    Electronic Resource
    Whole blood concentrations of mefloquine enantiomers in healthy Thai volunteers (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 85-87 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; Enantiomers ; pharmacokinetics ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We studied the pharmacokinetics of the enantiomers of mefloquine in whole blood in healthy Thai volunteers after administration of a single oral dose of 750 mg of the racemic mixture. Mefloquine pharmacokinetics were stereoselective. The peak concentrations and areas under the curve of the (−) enantiomer were significantly higher than those of its antipode (0.79 versus 0.46 μg · ml-1 and 402 versus 94 μg · h · ml-1). The half-lives of (−)MQ were significantly longer than those of (+)MQ (531 versus 206 h). No stereoselectivity was observed for tmax values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193485
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  • 63
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    Pharmacokinetic analysis of sparse in vivo NMR spectroscopy data using relative parameters and the population approach (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 187-193 
    Details
    ISSN: 1432-1041
    Keywords: NMR spectroscopy in vivo ; drug tissue concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract NMR spectroscopy in vivo when applied to studying drugs and their metabolites usually measures relative concentration in a tissue over time. Only ratios of clearance and volume parameters can be estimated from these data. Low drug dosages (relative to the sensitivity of in vivo NMR) or rapid drug elimination create the additional problem of data sparsity where a pharmacokinetic model cannot be fitted individually. We have investigated whether relative and absolute pharmacokinetic parameters can be estimated from such data by applying a population model. The data analysed were relative concentractions of 5-fluorouracil (FU) and of the sum of its catabolits α-fluoro-β-ureido-propanoic acid (FUPA) and α-fluoro-β-alanine (FBAL) in te liver, as monitored in 16 cancer patients by [19F]-NMP spectroscopy during and after a 10-min intravenous infusion of 650 mg FU·m−2. The “structural” part of the population model was a non-linear, two-compartment model featuring one FU compartment with volume V FU , a saturable clearance of FU by conversion into the catabolites where CL=v max /(k M +C FU ), a catabolite compartment with volume V cat , and a concentration-independent clearance of the catabolites, CL cat . The parameters actually fitted were: γ, v max , k M ·V FU , V cat /V FU , and CL cat /V cat where γ is a proportionality factor relating the NMR signal intensity of FU to the amount of FU in the body and, therefore, has no purely pharmacokinetic interpretation. All parameters were checked for random interindividual variation; γ and v max were also tested for inter-occasion variation. The program system NONMEM was used for model fitting. The estimated mean population parameters were: v max =121 μmol·min−1, k M ·V FU =2590 μmol, V cat /V FU =0.0648, CL cat /V cat =0.0555·min−1. The proportionality factor γ was found to depend on body weight and, in addition, to have an inter-occasion random variation (within patients, between examinations). No other random variation of a kinetic parameter could be identified. The estimated v max is similar to a reported estimate of 2.02 μmol·min−1·kg−1 derived from FU plasma kinetics. This study shows that sparse relative concentration data can be analysed by using relative parameters in a population model. Only one parameter has no unequivocal pharmacokinetic meaning due to the lack of absolute concentration information. Any contribution of the measuring procedure to the inter-occasion variation of in vivo NMP spectroscopy measurements should be minimized in order to allow the detection of possible inter-individual variances of the pharmacokinetic parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194971
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  • 64
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    Electronic Resource
    Comparative pharmacokinetics of bismuth from ranitidine bismuth citrate (GR122311X), a novel anti-ulcerant and tripotassium dicitrato bismuthate (TDB) (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 177-180 
    Details
    ISSN: 1432-1041
    Keywords: Ranitidine bismuth citrate ; Tripotassium dicitrato bismuthate ; Duodenal ulcer ; bismuth ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract GR122311X (ranitidine bismuth citrate, Glaxo Group Research Ltd.) is a salt of ranitidine with a complex of bismuth and citric acid which is being developed for the treatment of peptic ulceration. In this study, 4 groups of 12 healthy male subjects were dosed for 10 days with either GR122311X 500 mg bid (301 mg bismuth per day), GR122311X 1.0 g bid (602 mg bismuth per day), tripotassium dicitrato bismuthate (TDB, DeNoltab, Gist Brocades Ltd., Weybridge, England) 240 mg bid (431 mg bismuth per day) or placebo. After the last dose the geometric mean for Cmax for 500 mg bid of GR122311X was 5 ng·g−1, for 1.0 g bid GR122311X it was 12 ng·g−1 and it was 21 ng·g−1 for 240 mg TDB bid. The corresponding trough plasma levels were 2 ng·g−1, 4 ng·g−1 and 4 ng·g−1, respectively. The AUC over a dosing interval after the last dose (AUCτ) were 34 ng·h·g−1, 71 ng·h·g−1 and 79 ng·h·g−1, respectively. The bismuth urinary recoveries over the last dosing interval (Aeτ) were 97 μg, 227 μg and 309 μg, respectively, which is less than 1 % of the administered doses. The renal clearance of bismuth was less than the glomerular filtration rate. After adjustment for bismuth dose, the Cmax for GR122311X 500 mg was 35 % that of TDB, while for GR122311X 1.0 g the Cmax was 42 % that of TDB. Similar differences were observed for Aeτ. In conclusion bismuth pharmacokinetics after oral administration of GR1223311X exhibited lower Aeτ and Cmax, with a much narrower Cmax range than those observed for TDB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194969
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  • 65
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    Electronic Resource
    Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus (1994)
    Springer
    Experimental brain research 101 (1994), S. 353-364 
    Details
    ISSN: 1432-1106
    Keywords: Transplantation ; Serotonin neurons ; Hypothalamus ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227329
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  • 66
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    Electronic Resource
    Ammonium-excreting Azospirillum sp. become intracellularly established in maize (Zea mays) para-nodules (1994)
    Springer
    Biology and fertility of soils 17 (1994), S. 1-8 
    Details
    ISSN: 1432-0789
    Keywords: Ammonium excretion ; Azospirillum brasilense ; Auxine ; 2,4-Dichlor-phenoxy-acetic acid ; Nitrogen fixation ; Paranodulation ; Maize ; Zea mays ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Maize seedlings develop nodule-like tumour knots (para-nodules) along primary roots when treated with the auxin 2,4-dichlor-phenoxy-acetic acid (2,4-D). Inoculated NH 4 + -excreting Azospirillum brasilense cells were shown to colonize these tumours, mostly intracellularly, promoting a high level of N2 fixation when microaerophilic conditions were imposed. The nitrogenase activity inside the para-nodules was less sensitive to free O2 than in non-para-nodulating roots. Both light and electron microscopy showed a dense bacterial population inside intact tumour cells, with the major part of the cell infection along a central tumour tissue. The bacteria colonized the cytoplasm with a close attachment to inner cell membranes. In an auxin-free growth medium, young 2,4-D-induced para-nodules grew further to become mature differentiated root organs in which introduced bacteria survived with a stable population. These results provide evidence that gramineous plants are potentially able to create a symbiosis with diazotrophic bacteria in which the NH 4 + -excreting symbiont will colonize para-nodule tissue intracellularly, thus becoming well protected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418663
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  • 67
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    Electronic Resource
    Influence of input rates on (±)-isradipine haemodynamics and concentration-effect relationship in healthy volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 29-33 
    Details
    ISSN: 1432-1041
    Keywords: Israpidine ; haemodynamics ; pharmacokinetics ; healthy volunteers ; drug input rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Since the magnitude of the response to a drug may depend upon the drug input rate, the concentration-effect relationship of the new dihydropyridine (±)-isradipine was investigated using different administration modalities. Ten normotensive healthy volunteers were given, double-blind and in a crossover fashion, isradipine as a 1 mg iv infusion, 5 mg oral solution, 5 mg standard tablet, 10 mg slow release formulation, and a placebo. Blood pressure, heart rate, and plasma isradipine concentrations were recorded for 24 h. The maximal fall in diastolic blood pressure was similar after the infusion (-11.40 mmHg), the oral solution (-15.20 mmHg), and the standard tablet (-12.50 mmHg). In healthy volunteers the slow release form had no significant effect on blood pressure. The concentration-effect plots showed an increasing slope in the order infusion, solution, and tablet, and anticlockwise hysteresis. This was partly due to marked heart rate counter-regulation, the corresponding mean maximal heart rate increases being 24, 19, and 17 beats·min−1. The pronounced counter-regulation of the heart rate implies that a slow isradipine input rate would be more effective in decreasing blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195912
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  • 68
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    The pharmacokinetics of recombinant human erythropoietin after subcutaneous injection at different sites (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 333-337 
    Details
    ISSN: 1432-1041
    Keywords: Erythropoietin ; recombinant human erthropoietin ; pharmacokinetics ; subcutaneous ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of recombinant human erythropoietin (RhEPO) were investigated after subcutaneous (s.c.) injection in the thigh and in the abdominal wall. Eleven healthy subjects, age 24.4 years (median), were studied. Each subject received two s.c. injections of 100 U·kg-1 RhEPO dissolved in 1 ml water: one injection in the thigh and another in the abdomen. Serum erythropoietin was measured regularly by radioimmunoassay until 144 h after each injection. The mean residence time was significantly longer after injection in the thigh than in the abdomen (32.7 vs 26.2 h). The estimated half-life of absorption was significantly longer after injection in the thigh than after abdominal application (14.9 vs 12.3 h). The estimated half-life of elimination was not significantly different (4.4 vs 4.8 h). The relative difference in the area under the curve between injection in the abdomen and the thigh in the same subject ranged from -36% to +68% but there was no significant difference in bioavailability. The peak concentration was not significantly different and appeared at around 10 h (Cmax thigh, 175 U·l-1 vs Cmax abdomen, 216 U·l-1). A twin-peak configuration of the concentration vs time curve with a significant second peak at 24 h was found after injection in the thigh but not after abdominal injection. In conclusion, the mean residence time was longer after administration in the thigh, probably due to delayed absorption, but bioavailability was not significantly different. Following injection in the thigh the concentration curve had two peaks. The differences may be due to regional variations in lymph flow and to physical activity. The overall differences in pharmacokinetics appeared to be too small to recommend a general preference of the injection site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194401
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  • 69
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    Electronic Resource
    Pharmacokinetics and absolute bioavailability of colchicine after i. v. and oral administration in healthy human volunteers and elderly subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: Colchicine ; pharmacokinetics ; healthy volunteers ; elderly subjects ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of colchicine were studied in six healthy male and four elderly female volunteers after i. v. and oral administration. Plasma samples were collected over 72 h and assayed for colchicine by a specific and sensitive radioimmunoassay. Plasma concentration-time curves were fitted using a three-compartmental model after i. v. administration of 0.5 mg (healthy volunteers) and 1 mg (elderly group) colchicine. The first distribution half-life (t1/2 λ1) was short: 9.2 min in healthy volunteers and 3.0 min in the elderly group; the second distribution half-life (t1/2 λ2) was of the same order for both groups, 1.2 h. Plasma elimination half-lives were also in the same range: 30 h for healthy volunteers versus 34 h for the elderly subjects. Mean residence time was also in the same range in the two groups: 27 h in healthy volunteers and 21 h for elderly subjects. The volume of distribution (Vz) was 6.71·kg-1 for the healthy group and 6.31·kg-1 for the elderly group, while Vss was smaller: 4.21·kg-1 for healthy volunteers and 2.91·kg-1 for elderly subjects. Total body clearance was 10.51·h-1 for healthy and 5.51·h-1 for elderly subjects. After oral administration of 1 mg, lag-time was 14 min in healthy volunteers and 11 min in elderly subjects. Maximal plasma concentration was 5.5 ng·ml-1 at 62 min in the healthy group, while in the elderly group Cmax was 12 ng·ml-1 at 87 min. Mean absolute bioavailability of the tablet was the same in both groups, 44% for healthy volunteers and 45% for elderly subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194404
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  • 70
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    Electronic Resource
    Food-induced increase in bioavailability of 5-methoxypsoralen (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 375-377 
    Details
    ISSN: 1432-1041
    Keywords: 5-Methoxypsoralen ; Psoriasis ; food ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 5-Methoxypsoralen (5-MOP) in combination with ultraviolet light exposure is used for the treatment of psoriasis. The effect of food on the pharmacokinetics of 5-MOP was evaluated in a randomized, crossover study in nine healthy subjects. Each subject received the tablets with a standardized breakfast or under fasting conditions. The food had a dramatic effect on the bioavailability of 5-MOP. Five of the subjects showed no measurable quantities (detection limit of the analytical technique 1 ng·ml-1) of 5-MOP when the drug was given under fasting conditions. However, plasma peak concentration within the range 37–144 ng·ml-1 (median 102 ng·ml-1) was measured when the drug was taken with food. The time for the plasma peak concentration was within the range 2.0–5.1 h (median 3.0 h) under non-fasting conditions. The elimination half-life was within the range 1.4–2.7 h (median 1.9 h). We conclude that it is imperative that 5-MOP tablets are administered together with food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194409
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  • 71
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    Electronic Resource
    A pharmacokinetic interaction between roxithromycin and midazolam (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 551-555 
    Details
    ISSN: 1432-1041
    Keywords: Midazolam ; Roxithromycin ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The interaction between roxithromycin and midazolam was investigated in a double-blind, randomised crossover study of two phases. Ten healthy volunteers were given roxithromycin (300 mg) or placebo once daily for 6 days. On the sixth day they ingested 15 mg midazolam. Plasma samples were collected and psychomotor performance measured for 17 h. Roxithromycin administration significantly increased the area under the plasma midazolam concentration-time curve from 8.3 to 12.2 ώg·ml−1·min and the elimination half-lives from 1.7 to 2.2 h. In psychomotor performance only minor differences were seen between the treatments in one of the measured psychomotor parameters. Thus, in contrast to the strong interaction between erythromycin and midazolam, the interaction between roxithromycin and midazolam appears less likely to be clinically significant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196114
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  • 72
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    Electronic Resource
    Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 147-150 
    Details
    ISSN: 1432-1041
    Keywords: Fluconazole ; Itraconazole ; pharmacokinetics ; food interaction ; gastric emptying time ; pH radiocapsule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The influence of food on the pharmacokinetics of the triazole antimycotics fluconazole and itraconazole was investigated in a randomised, parallel group, single dose study in 24 healthy subjects. Each group took either a 100 mg capsule of fluconazole or a 100 mg capsule of itraconazole, pre-prandially or after a light meal or a full meal, in a three-way crossover design. Gastric and intestinal pH were measured with a co-administered radio-telemetric pH capsule, and gastric emptying time of the capsule (GET) was taken as the maximum gastric residence time of drug and food. The plasma AUC and Cmax of itraconazole were significantly different under the various conditions and the mean AUC was greatest after the full meal. The bioavailability (90% confidence intervals) of itraconazole relative to that after the full meal, was 54% (41–77%) on an empty stomach and 86% (65–102%) after a light meal. The criteria for bioequivalence were not attained. In contrast, the bioavailability (90% CI) of fluconazole relative to the full meal was 110% pre-prandially (100–115%) and 102% after the light meal (88–103%), and the criteria for bioequivalence were attained. Itraconazole absorption was promoted by low stomach pH, long gastric retention time and a high fat content of the coadministered meal, whereas the pharmacokinetics of fluconazole was relatively insensitive to physiological changes in the gastrointestinal tract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199879
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  • 73
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and tolerability of ascending intravenous doses of granisetron, a novel 5-HT3 antagonist, in healthy human subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 159-162 
    Details
    ISSN: 1432-1041
    Keywords: Granisetron ; Anti-emetic ; pharmacokinetics ; tolerance ; ascending dose ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and tolerance of granisetron, a novel 5HT3-receptor antagonist which is under development as an anti-emetic agent have been studied after administration of single 30 min intravenous infusions to three groups of 8 healthy male subjects, in a series of placebo-controlled ascending dose studies (50, 80, 100 and 130 μg·kg−1 to group 1; 150, 180, 200 and 230 μg·kg−1 to group 2 and 270 and 300 μg·kg−1 to group 3). Plasma and urine samples were analysed for granisetron by HPLC with fluorimetric detection. Administration of granisetron was well tolerated by the volunteers and there were no serious adverse effects reported. Pharmacokinetic parameters and dose-normalised plasma levels appeared to be independent of dose in the range 50 to 300 μg·kg−1, although there was extensive inter-subject variability. Granisetron was extensively distributed, with mean volumes of distribution ranging from 186–264 l at the various doses. Total plasma clearance was, in general, rapid (mean values of 37.0 to 49.9 l·h−1) and predominantly non-renal, with most subjects excreting less than 20% of the dose unchanged in urine. Mean t1/2 values ranged from 4.1 to 6.3 h and MRT from 5.2 to 8.1 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199881
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  • 74
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    Electronic Resource
    The effect of renal function on the pharmacokinetics of ranitidine (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 167-171 
    Details
    ISSN: 1432-1041
    Keywords: Ranitidine ; Renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This open study evaluated the influence of renal function on the pharmacokinetics of ranitidine (50 mg iv infusion given over 6 min). Five groups, each of 8 subjects, 1 with normal renal function and 4 with different degrees of renal impairment were studied. Renal function was assessed in each patient by 51Cr-EDTA (glomerular filtration rate, GFR), creatinine clearance (GFR) and N-methylnicotinamide clearance (reflecting glomerular and tubular function). Sixteen blood samples (5 ml) taken up to 48 h post dose from each subject were analysed for plasma ranitidine concentrations by reversed phase HPLC. Patient groups with renal impairment had significantly increased AUC∞ and t1/2 with corresponding decreases in CLp and λz when compared with normal subjects. There was also a significant increase in tmax but not in Cmax. There was a high linear correlation between the degree of renal impairment and ranitidine clearance. In patients with GFR ≤ 20 ml min−1, the AUC∞ mean ratio (compared with normal subjects) was up to 4.6 while for patients with GFR 20–50 ml min−1, the average AUC∞ ratio was 2.6. It is recommended that the dose of ranitidine is halved in patients with GFR ≤ 20 ml min−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199883
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  • 75
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intravenous omeprazole in children (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 181-185 
    Details
    ISSN: 1432-1041
    Keywords: Omeprazole ; pharmacokinetics ; children ; genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This study was undertaken to define the pharmacokinetics of omeprazole in children and included 13 patients, heterogenous in terms of age (0.3 to 19 years), underlying disease and biological constants, indication of omeprazole administration and associated therapy. The dose administered ranged from 36.9 to 139 mg·1.73 m−2. The pharmacokinetic parameters of omeprazole were: systemic clearance, 0.23 1·kg−1·h−1; volume of distribution, 0.45 1·kg−1; elimination half life 0.86 h; but were highly variable between individuals. Dosage, differences in hepatic and renal function and associated therapy may contribute to inter-individual variability. Within the range of doses administered, the pharmacokinetic parameters were similar to those reported in adults. The drug has been well tolerated in all children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194970
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  • 76
    Electronic Resource
    Electronic Resource
    A new isosorbide dinitrate extended-release formulation: pharmacokinetic and clinical parameters in patients with stable angina pectoris (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; Angina pectoris ; pharmacokinetics ; clinical efficacy ; digital photoplethysmography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In a double-blind, cross-over study the acute clinical efficacy and pharmacokinetic profile of a newly developed isosorbide dinitrate extended-release (ISDN-ER) formulation (10 mg immediate release and 60 mg slow release) were examined in eight angina patients. Exercise tests were done 1 h before and 1, 6 and 10 h after acute ISDN or placebo; similar testing was repeated after 14 days of open-labelled treatment. At 1, 6 and 10 h after administration, ISDN-ER significantly reduced the mean ST depression at highest comparable workload (HCWL) by 0.8, 0.6, and 0.6 mm, respectively. Total exercise duration increased significantly by 46, 42 and 72 s. The rate-pressure product at HCWL was not reduced significantly at any time, while digital plethysmography demonstrated a significant effect on arterial pulse curves throughout the 10 h. After 14 days of once-daily treatment, similar or somewhat attenuated clinical effects were observed. Pharmacokinetic measurements showed a first peak of ISDN at 1–2 h and a second peak at 4–5 h. The 5-isosorbide mononitrate (5-ISMN) metabolite peaked at 5–8 h and remained high at 10 h. After 14 days of treatment, the mean plasma concentrations of ISDN and 5-ISMN before drug were 0 and 69 ng·ml−, respectively. Thus, satisfactory acute clinical efficacy and low nitrate levels during the night were observed. However, long-term clinical efficacy needs to be established in larger, placebo-controlled trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191167
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  • 77
    Electronic Resource
    Electronic Resource
    Effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 361-366 
    Details
    ISSN: 1432-1041
    Keywords: Ketoprofen ; diet ; bioavailability ; pharmacokinetics ; sustained release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The indirect effect of diet on the single-and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period. On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a tendency to longer absorption-lag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUC0–24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC0–24 the differences were on average 15% (day 1) and 24% (day 5). The same tendency was observed for the amount excreted in urine over 24 h (Ae), but the difference was only significant on day 1 (14%). The elimination rate constant (Kβ) and the mean residence time were similar for the two diets, both on day 1 and on day 5. From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4 h after intake of the medication. This resulted in a greater extent of ketoprofen absorption with the LCFD than with the HCFD. The absorption rate was apparently not influenced by this acute effect. The longer gastric residence time of ketoprofen with the HCFD may be the result of a long-term indirect effect on gastric emptying rate. If the extreme difference between the diets in this study is taken into account, it seems unlikely that the observed indirect effects have implications for clinical practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191169
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  • 78
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    Electronic Resource
    Lack of interaction between ramipril and simvastatin (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 373-375 
    Details
    ISSN: 1432-1041
    Keywords: ACE-inhibitors ; Simvastatin ; ramipril ; lipid lowering drugs ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Twenty two healthy males participated in a randomised, placebo-controlled, double blind, cross-over study to investigate the influence of simvastatin on the pharmacokinetics of ramipril and its active metabolite (ramiprilat), and on the ACE-inhibiting effect of ramiprilat. During two study periods, each of 7 days, subjects received daily either simvastatin 20 mg at 19.00 h or placebo; ramipril (5 mg) was given on Day 5 of each of the periods. Plasma concentrations of ramipril and ramiprilat and ACE-activity were measured in sequential blood specimens, and ramipril and ramiprilat concentrations were measured in urine. Blood and urine collections for pharmacokinetic and pharmacodynamic assessment were made up to 72 h after the dose of ramipril. The mean AUC of ramipril for ramipril+placebo (R+P) and ramipril+simvastatin (R+S) was 22.2 and 21.3 ng.h.ml−, respectively; for ramiprilat the corresponding figures were 61.3 and 57.6 ng.h.ml−. The urinary excretion of ramipril+metabolites for (R+P) and (R+S) was 25.2 and 24.1% of dose. The maximum percentage inhibition of ACE-activity for (R+P) was 94.6%, and for (R+S) it was 94.1%. It is concluded that concomitant administration of simvastatin and ramipril has no clinically relevant effect on the pharmacokinetics or ACE-inhibition of the latter drug and its metabolites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191171
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  • 79
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    Electronic Resource
    Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 275-277 
    Details
    ISSN: 1432-1041
    Keywords: Prostaglandin E1 ; Infusion ; pharmacokinetics ; metabolism ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In a single-blind, randomized, two-way crossover study with 12 healthy male volunteers, 60 μg of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg·ml−1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg·ml−1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00192562
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  • 80
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 319-324 
    Details
    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; route of administration ; isosorbide-5-mononitrate ; finger pulse wave ; pharmacokinetics ; haemodynamic effects ; plasma nitrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers. After the sublingual spray Cmax was higher (39.0 ng·ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng·ml-1 and 13.8 min) and peroral (16.9 ng·ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray 〈 sublingual tablet 〈 peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively. The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (emax=130%) and the time to emax (temax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194399
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  • 81
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    Electronic Resource
    Pharmacokinetics and pharmacodynamics of transdermal dexmedetomidine (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 345-349 
    Details
    ISSN: 1432-1041
    Keywords: Dexmedetomidine ; transdermal ; pharmacokinetics ; α2-adrenoceptor agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Dexmedetomidine is a novel α2-adrenoceptor agonist that may provide beneficial effects as premedication for anesthesia. The pharmacokinetics and pharmacodynamics of transdermal (TD) and intravenous (IV) dexmedetomidine were studied in nine healthy male subjects in a crossover trial. The TD preparation, containing 625 μg of dexmedetomidine base, was applied on the forehead and left in place for 12 h. The IV dose (2.0 μg·kg-1 as dexmedetomidine hydrochloride) was administered as an infusion over 5 min. Dose-normalized total AUC values were used to calculate dexmedetomidine bioavailability. The bioavailability of dexmedetomidine from the TD preparation was 51%. However, the bioavailability of dexmedetomidine released from the preparation was 88%. The mean terminal half-life was 3.1 h after IV and 5.6 h after TD administration. After TD administration, the mean maximal reductions in blood pressure (systolic/diastolic) and heart rate were 28/20 mmHg and 19 beats·min-1. A sedative effect was obvious within 5 min and 1–2 h after IV and TD administration, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194403
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  • 82
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    Electronic Resource
    Ultrastructure of an extreme thermophilic hydrogen-oxidizing bacterium Calderobacterium hydrogenophilum (1994)
    Springer
    Archives of microbiology 162 (1994), S. 267-271 
    Details
    ISSN: 1432-072X
    Keywords: Key words     Extremely thermophilic eubacterium ; Calderobacterium hydrogenophilium ; Ultrastructure ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract       Calderobacterium hydrogenophilum is an extreme thermophilic, obligately chemoautotrophic, hydrogen-oxidizing bacterium. The cells were shown to be non-motile straight rods of average size 0.4 × 2.5 μm. After negative-staining of the whole cells, no flagella were observed. The multilayered cell wall was of type 1 and possessed a crystalline proteinaceous surface layer exhibiting p4 symmetry. The square unit cells had a lattice constant of approximately 11 nm. Cell division occurred by a constriction mechanism. C. hydrogenophilum differred from a similar hydrogen-oxidizing eubacterium, Hydrogenobacter thermophilus, by the absence of intracytoplasmic membrane structures in chemically fixed cells. However, an electron-dense intracytoplasmic hemispherical structure adhering to the inner membrane was frequently observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301849
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  • 83
    Electronic Resource
    Electronic Resource
    Ultrastructure of an extreme thermophilic hydrogen-oxidizing bacterium Calderobacterium hydrogenophilum (1994)
    Springer
    Archives of microbiology 162 (1994), S. 267-271 
    Details
    ISSN: 1432-072X
    Keywords: Extremely thermophilic eubacterium ; Calderobacterium hydrogenophilium ; Ultrastructure ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Calderobacterium hydrogenophilum is an extreme thermophilic, obligately chemoautotrophic, hydrogen-oxidizing bacterium. The cells were shown to be nonmotile straight rods of average size 0.4x2.5 μm. After negative-staining of the whole cells, no flagella were observed. The multilayered cell wall was of type 1 and possessed a crystalline proteinaceous surface layer exhibiting p4 symmetry. The square unit cells had a lattice constant of approximately 11 nm. Cell division occurred by a constriction mechanism. C. hydrogenophilum differred from a similar hydrogen-oxidizing eubacterium, Hydrogenobacter thermophilus, by the absence of intracytoplasmic membrane structures in chemically fixed cells. However, an electron-dense intracytoplasmic hemispherical structure adhering to the inner membrane was frequently observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301849
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  • 84
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    Electronic Resource
    Membrane topology of insulin receptors reconstituted into lipid vesicles (1994)
    Springer
    The journal of membrane biology 140 (1994), S. 215-223 
    Details
    ISSN: 1432-1424
    Keywords: Insulin receptor ; Membrane reconstitution ; Electron microscopy ; Quaternary structure ; Immunogold labeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Insulin receptors were incorporated into liposomes by two different procedures, one using dialysis and one using detergent removal by Bio-Beads. Receptor incorporation was analyzed by gradient centrifugation and electron microscopy. Reconstituted receptors projected up to 12 nm above the membrane and exhibited a T-shaped structure compatible with that previously described for the solubilized receptor. Insulin binding and autophosphorylation experiments indicated that approx. 50% of the receptors were incorporated right-side out. Such random orientation was confirmed by immunogold labeling of the α- and the β-subunit of the receptor. Immunogold labeling of the C-terminus of the β-subunit indicates that it resides about 6 nm off the membrane, while two α-subunit epitopes were labeled at about twice this distance, confirming that the α-subunit is harbored in the cross-bar of the T-structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00233710
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  • 85
    Electronic Resource
    Electronic Resource
    Astrocytes alter their polarity in organotypic slice cultures of rat visual cortex (1994)
    Springer
    Cell & tissue research 277 (1994), S. 557-564 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Slice culture ; Cerebral cortex ; Astrocytes ; Orthogonal arrays of particles - Freeze-fracture ; Electron microscopy ; Rat (Lewis)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The ultrastructure of astrocytes in an organotypic slice culture of the rat visual cortex was investigated using ultrathin sections and freeze-fracture replicas. After a culture period of 9–15 days, a glial scaffold formed that separated the bulk of the slice neuropil from the medium and the underlying plasma clot. However, the glial cells and processes did not build a dense barrier but allowed the outgrowth of neurites. A basal lamina covering the medium-oriented surface of the astrocytes was not found. In freeze-fracture replicas, orthogonal arrays of particles (OAP) were characteristic components of astrocytic membranes. The OAP density in membranes bordering the medium was 35±13 OAP/μm2, corresponding to 2.5% of this membrane area; the OAP density in membranes within the slice neuropil was 22±12 OAP/μm2, corresponding to 1.4% of this membrane area. Although the difference was significant, it was greatly reduced when comparing OAP densities in endfoot and non-endfoot membranes in vivo. Another mode of polarity was recognized in astrocytes of the organotypic slice culture. In membranes of astrocytes bordering upon the medium, the density of non-OAP intramembranous particles (IMP) was clearly higher (1130±136 IMP/μm2) than in membranes of astrocytes in the center of the slice (700±172 IMP/μm2). This pronounced IMP-related polarity was observed neither in vivo nor in cultured astrocytes. The present study suggests, together with data from the literature, that the distribution of astrocytic OAP across the cell surface is influenced by the existence of a basal lamina and neuronal activity, and that astrocytes possess a more remarkable plasticity of membrane structure than previously suspected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00300229
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  • 86
    Electronic Resource
    Electronic Resource
    Organization of the endoplasmic reticulum in renal cell lines MDCK and LLC-PK1 (1994)
    Springer
    Cell & tissue research 277 (1994), S. 297-307 
    Details
    ISSN: 1432-0878
    Keywords: Endoplasmic reticulum ; Cellular transport ; Mitochondria ; Electron microscopy ; Contocal microscopy ; MDCK cells ; LLC-PK1 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The spatial organization of the endoplasmic reticulum has been studied in two renal cell lines, MDCK and LLC-PK1, which originate from the distal and proximal portions of the mammalian nephron, respectively, and which form a polarized epithelium when they reach confluence in tissue culture. The two renal cell lines, grown to confluence on either solid or permeable supports, were investigated by fluorescence microscopy, confocal microscopy, and transmission electron microscopy. Fluorescence labeling of the endoplasmic reticulum was achieved using the cationic fluorescent dye DIOC6 (3). In order to differentiate fluorescent labeling of the endoplasmic reticulum from that of the mitochondria, cells were also labeled with rhodamine 123. For electron microscopy, the spatial organization of the endoplasmic reticulum was examined in thick sections using the long-duration osmium impregnation technique or the ferrocyanide/osmium technique. In both cell lines, the endoplasmic reticulum formed an abundant tubular network of canaliculi that frequently abutted the basolateral domain of the plasma membrane and occasionally the apical membrane. Elements of the endoplasmic reticulum were also found in close proximity to mitochondria that, as in the nephron, formed branched structures. Canaliculi appeared circular or flattened and had an inner diameter of 10–70 nm for MDCK cells and 20–90 nm for LLC-PK1 cells. Such a three-dimensional organization might facilitate the translocation of defined lipid species between the endoplasmic reticulum and the plasma membrane, and between the endoplasmic reticulum and mitochondria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00327777
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  • 87
    Electronic Resource
    Electronic Resource
    Organization of the endoplasmic reticulum in renal cell lines MDCK and LLC-PK1 (1994)
    Springer
    Cell & tissue research 277 (1994), S. 297-307 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Endoplasmic reticulum ; Cellular transport ; Mitochondria ; Electron microscopy ; Confocal microscopy ; MDCK cells ; LLC-PK1 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The spatial organization of the endoplasmic reticulum has been studied in two renal cell lines, MDCK and LLC-PK1, which originate from the distal and proximal portions of the mammalian nephron, respectively, and which form a polarized epithelium when they reach confluence in tissue culture. The two renal cell lines, grown to confluence on either solid or permeable supports, were investigated by fluorescence microscopy, confocal microscopy, and transmission electron microscopy. Fluorescence labeling of the endoplasmic reticulum was achieved using the cationic fluorescent dye DIOC6 (3). In order to differentiate fluorescent labeling of the endoplasmic reticulum from that of the mitochondria, cells were also labeled with rhodamine 123. For electron microscopy, the spatial organization of the endoplasmic reticulum was examined in thick sections using the long-duration osmium impregnation technique or the ferrocyanide/osmium technique. In both cell lines, the endoplasmic reticulum formed an abundant tubular network of canaliculi that frequently abutted the basolateral domain of the plasma membrane and occasionally the apical membrane. Elements of the endoplasmic reticulum were also found in close proximity to mitochondria that, as in the nephron, formed branched structures. Canaliculi appeared circular or flattened and had an inner diameter of 10–70 nm for MDCK cells and 20–90 nm for LLC-PK1 cells. Such a three-dimensional organization might facilitate the translocation of defined lipid species between the endoplasmic reticulum and the plasma membrane, and between the endoplasmic reticulum and mitochondria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050156
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  • 88
    Electronic Resource
    Electronic Resource
    Progressive reorganization of the myenteric plexus during one year following reanastomosis of the ileum of the guinea pig (1994)
    Springer
    Cell & tissue research 277 (1994), S. 259-272 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Ileum ; Transection ; Reanastomosis ; Myenteric plexus ; NADH diaphorase histochemistry ; Neuron-specific enolase ; Electron microscopy ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The enteric nervous system appears to play a pivotal role in the functional recovery of the gastrointestinal tract after partial resection and reanastomosis, but the structural changes following surgery are not fully understood. The present study was designed to clarify the processes of myenteric plexus regeneration up to one year after transection and reanastomosis of the ileum of the guinea pig. The following techniques were used: nicotinamide adenine dinucleotide (NADH) diaphorase histochemistry, immunostaining of neuron-specific enolase (NSE) in whole-mount preparations, and transmission electron microscopy. Two months after transection and reanastomosis, myenteric ganglion cells with NADH diaphorase reactions were scarce in the center of the lesion, and were less numerous in adjacent areas (3 mm in width) than in the control ileum. In the areas adjacent to the lesion, a few large extraganglionic neurons that did not completely compensate for the loss of ganglion neurons were observed. The remaining ileum showed no changes in NADH diaphorase staining pattern at this stage. Two to 12 months after transection and reanastomosis, ectopic large neurons gradually increased in number not only in the areas adjacent to the lesion but also in part of the remaining ileum, up to 10 cm from the lesion. Concomitantly, large ganglion neurons decreased in number in these areas. In other ileal regions (more than 10 cm distant from the site of transection), no obvious changes in NADH diaphorase staining were noted throughout the observation period. The outgrowth of NSE-containing nerve fibers from the severed stumps was seen two weeks after transection. Six weeks later, numerous bundles of fine nerve fibers with NSE were shown to interconnect the oral and anal cut ends of the myenteric plexus, but they exhibited no subsequent alterations. Transmission electron microscopy revealed that regenerating nerve fiber bundles appeared initially among irregularly arranged smooth muscle cells eight weeks after the operation, as expected from light-microscopic observations. These findings suggest that myenteric ganglion cell bodies, unlike myenteric nerve fibers, require a longer term of reconstruction than previously believed after transection and reanastomosis of the ileum of the guinea pig.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050153
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  • 89
    Electronic Resource
    Electronic Resource
    Progressive reorganization of the myenteric plexus during one year following reanastomosis of the ileum of the guinea pig (1994)
    Springer
    Cell & tissue research 277 (1994), S. 259-272 
    Details
    ISSN: 1432-0878
    Keywords: Ileum ; Transection ; Reanastomosis ; Myenteric plexus ; NADH diaphorase histochemistry ; Neuron-specific enolase ; Electron microscopy ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The enteric nervous system appears to play a pivotal role in the functional recovery of the gastrointestinal tract after partial resection and reanastomosis, but the structural changes following surgery are not fully understood. The present study was designed to clarify the processes of myenteric plexus regeneration up to one year after transection and reanastomosis of the ileum of the guinea pig. The following techniques were used: nicotinamide adenine dinucleotide (NADH) diaphorase histochemistry, immunostaining of neuron-specific enolase (NSE) in whole-mount preparations, and transmission electron microscopy. Two months after transection and reanastomosis, myenteric ganglion cells with NADH diaphorase reactions were scarce in the center of the lesion, and were less numerous in adjacent areas (3 mm in width) than in the control ileum. In the areas adjacent to the lesion, a few large extraganglionic neurons that did not completely compensate for the loss of ganglion neurons were observed. The remaining ileum showed no changes in NADH diaphorase staining pattern at this stage. Two to 12 months after transection and reanastomosis, ectopic large neurons gradually increased in number not only in the areas adjacent to the lesion but also in part of the remaining ileum, up to 10 cm from the lesion. Concomitantly, large ganglion neurons decreased in number in these areas. In other ileal regions (more than 10 cm distant from the site of transection), no obvious changes in NADH diaphorase staining were noted throughout the observation period. The outgrowth of NSE-containing nerve fibers from the severed stumps was seen two weeks after transection. Six weeks later, numerous bundles of fine nerve fibers with NSE were shown to interconnect the oral and anal cut ends of the myenteric plexus, but they exhibited no subsequent alterations. Transmission electron microscopy revealed that regenerating nerve fiber bundles appeared initially among irregularly arranged smooth muscle cells eight weeks after the operation, as expected from light-microscopic observations. These findings suggest that myenteric ganglion cell bodies, unlike myenteric nerve fibers, require a longer term of reconstruction than previously believed after transection and reanastomosis of the ileum of the guinea pig.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00327773
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  • 90
    Electronic Resource
    Electronic Resource
    Astrocytes alter their polarity in organotypic slice cultures of rat visual cortex (1994)
    Springer
    Cell & tissue research 277 (1994), S. 557-564 
    Details
    ISSN: 1432-0878
    Keywords: Slice culture ; Cerebral cortex ; Astrocytes ; Orthogonal arrays of particles ; Freeze-fracture ; Electron microscopy ; Rat (Lewis)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The ultrastructure of astrocytes in an organotypic slice culture of the rat visual cortex was investigated using ultrathin sections and freeze-fracture replicas. After a culture period of 9–15 days, a glial scaffold formed that separated the bulk of the slice neuropil from the medium and the underlying plasma clot. However, the glial cells and processes did not build a dense barrier but allowed the outgrowth of neurites. A basal lamina covering the medium-oriented surface of the astrocytes was not found. In freeze-fracture replicas, orthogonal arrays of particles (OAP) were characteristic components of astrocytic membranes. The OAP density in membranes bordering the medium was 35±13 OAP/μm2, corresponding to 2.5% of this membrane area; the OAP density in membranes within the slice neuropil was 22±12 OAP/μ2, corresponding to 1.4% of this membrane area. Although the difference was significant, it was greatly reduced when comparing OAP densities in endfoot and non-endfoot membranes in vivo. Another mode of polarity was recognized in astrocytes of the organotypic slice culture. In membranes of astrocytes bordering upon the medium, the density of non-OAP intramembranous particles (IMP) was clearly higher (1130±136 IMP/ μm2) than in membranes of astrocytes in the center of the slice (700±172 IMP/μm2). This pronounced IMP-related polarity was observed neither in vivo nor in cultured astrocytes. The present study suggests, together with data from the literature, that the distribution of astrocytic OAP across the cell surface is influenced by the existence of a basal lamina and neuronal activity, and that astrocytes possess a more remarkable plasticity of membrane structure than previously suspected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00300229
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  • 91
    Electronic Resource
    Electronic Resource
    Fine structure and lectin histochemistry of the apical surface of the free neuromast of Lampetra japonica (1994)
    Springer
    Cell & tissue research 276 (1994), S. 245-252 
    Details
    ISSN: 1432-0878
    Keywords: Neuromast ; Hair cells ; Surface coat ; Electron microscopy ; Lectin histochemistry ; Lampetra japonica (Cyclostomata)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The surface coat, ciliary process, and microvilli of the lamprey neuromast were examined with electron microscopy after tannic acid prefixation and lectin histochemistry. The neuromast was found to exist in the form of a dermal mound with a furrow in the middle. On the bottom of the furrow, the hair cell was characterized by a kinocilium and 15–20 stereocilia, arranged along the longitudinal axis of the furrow. Spanning structures were demonstrated between the kinocilium and stereocilia as well as between stereocilia. The surface coat, enhanced by tannic acid prefixation, was particularly rich over the surface of the supporting cell; by contrast, it was thin over the hair cell. Some lectins (PNA, GS-I, SBA, WGA) showed affinity to the surface coat of the supporting cell as well as the hair cell, and the others (RCA-I, MPA, ConA) showed affinity only to the supporting cell. These differences in the structure and affinities of the surface coat suggest an extracellular milieu highly specialized for the hair cell in this particular form of the mechanoreceptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00306110
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  • 92
    Electronic Resource
    Electronic Resource
    Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study (1994)
    Springer
    Cell & tissue research 278 (1994), S. 21-28 
    Details
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat, transgenic (mRen2) 27
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess and increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305774
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  • 93
    Electronic Resource
    Electronic Resource
    Morphological studies by light and electron microscopy of pancreatic acinar cells under the effect of Tityus serrulatus venom (1994)
    Springer
    Cell & tissue research 278 (1994), S. 255-264 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Scorpion venom ; Exocrine pancreas ; Secretagogue ; Electron microscopy ; Pancreatitis ; cis-Golgi aggregates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. We studied in vivo and in vitro morphological aspects of pancreatic acinar cells after treatment with Tityus serrulatus venom (TSV). After three hours in an in vitro system, positive secretagogue effects of the venom were identifiable both at the light-microscopic (LM) and the electron-microscopic (EM) levels. At 1 μg/ml TSV, maximal secretion (as measured in a concomitant radiolabeling dose-response experiment) of exocrine proteins at 58% was manifest as a discharge of most zymogen granules (ZG) and consequent appearance of secretory material in acinar lumina. At the supramaximal dose of 10 μg/ml TSV, exocytotic images were often observed also with secretory contents previously discharged. The lowest dose of venom at 0.01 μg/ml caused no stimulation of zymogen discharge above resting secretion levels; however, morphological changes were observed. At high doses of TSV, both in vivo and in vitro, large aggregates associated with the cis-Golgi develop between this region and the endoplasmic reticulum (ER). Since Tityus venoms have been associated with causation of pancreatitis, we were interested in comparisons of our experimental tissue with parameters attributed to development of the disease. Our studies have demonstrated considerable evidence that large intracellular vacuoles, discharged ZG, effaced acinar lumina with disappearance of microvilli and other manifestations of possible early events in pancreatitis are indeed frequently observed both in pancreatic lobules in vitro and in whole pancreas in vivo when exposed to TSV.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00414168
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  • 94
    Electronic Resource
    Electronic Resource
    Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study (1994)
    Springer
    Cell & tissue research 278 (1994), S. 21-28 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat ; transgenic (mRen2) 27
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305774
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  • 95
    Electronic Resource
    Electronic Resource
    Immunocytochemical localization of a growth-associated protein (GAP-43) in rat adrenal gland (1994)
    Springer
    Cell & tissue research 275 (1994), S. 555-566 
    Details
    ISSN: 1432-0878
    Keywords: Adrenal ; Autonomic nervous system ; Schwann cells ; Tyrosine hydroxylase ; GAP-43 ; Electron microscopy ; Immunohistochemistry ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have localized at light and electron-microscopic level the growth-associated protein GAP-43 in adrenal gland using single and double labelling immunocytochemistry. Clusters of GAP-43-immunofluorescent chromaffin cells and many immunofluorescent fibres were observed in the medulla. GAP-43-immunoreactive fibres also formed a plexus under the capsule, crossed the cortex and ramified in the zona reticulata. Double labelled sections showed the coexpression of GAP-43 with a subpopulation of tyrosine hydroxylase-and of dopamine-β-hydroxylase-immunoreactive chromaffin cells. Dual colour immunofluorescence for GAP-43 and calcitonin gene-related peptide (CGRP) revealed that some of the GAP-43-immunoreactive fibres also express CGRP. Pre-embedding electron microscopy showed GAP-43 immunoreactivity associated with the plasma membranes and cytoplasm of noradrenaline-producing chromaffin cells, and with processes of nonmyelin-forming Schwann cells. Immunoreactive unmyelinated axons and terminals were also observed. The immunostained terminals made symmetrical synaptic contacts with chromaffin cells. Immunoreactive unmyelinated fibres and small terminals were present in the cortex. Our results show that GAP-43 is expressed in noradrenergic chromaffin cells and in various types of nerve fibres that innervate the adrenal. Likely origins for these fibres include preganglionic sympathetic fibres which innervate chromaffin cells, postganglionic sympathetic fibres in the cortex, and CGRP containing sensory fibres.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318824
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  • 96
    Electronic Resource
    Electronic Resource
    Light- and electron-microscopic study of electrophysiologically characterized neurons in the mediolateral part of the lateral septum of the guinea-pig (1994)
    Springer
    Cell & tissue research 275 (1994), S. 543-553 
    Details
    ISSN: 1432-0878
    Keywords: Lateral septum ; Intracellular injections ; Electron microscopy ; Somatie spines ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In slices of guinea-pig brains, 36 neurons located in the mediolateral part of the lateral septum were stained intracellularly with horseradish peroxidase (n=28) or biocytin (n=8) after electrophysiological characterization. These neurons belonged to class A neurons (n=23), which generated pronounced Ca++-dependent high-threshold spikes in control medium, or to class C neurons (n=9), which were recognized by the occurrence of small-amplitude sodic spikes followed by slower larger calcic spikes. The present results demonstrate that, despite the variety of individual cell types, the major morphological population (30/36 cells) was composed of a homogeneous class of large-sized neurons that displayed thick primary dendrites and abundant dendritic appendages. The remaining 6 cells were small-sized, poorly-spiny neurons. Somatic spines were observed on 5 out of the 30 large cells and on one out of the six smaller cells. Labeled axons were mainly oriented to the anterior commissure. The axons of nine cells richly collateralized near the perikaryon. Ultrastructural examination of 3 horseradish peroxidase-injected cells showed indented nuclei, classic organelles and somatic spines. Terminal boutons established symmetric synapses with the injected cells. These results describe the morphological features of electrophysiologically identified neurons and indicate that class A and class C neurons are distributed among morphological populations differing in perikaryal size. This suggests that the different electrical properties of class A and class C neurons reflect recordings from different parts of the neuron rather than from neurons of different types. Furthermore, the present findings demonstrate that, in the guinea-pig, electrical and morphological characteristics of somatospiny neurons are comparable with those of non-somatospiny neurons. Somatospiny neurons have a recognized integrative role in the hippocampo-septo-hypothalamic complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318823
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  • 97
    Electronic Resource
    Electronic Resource
    Quantitative analysis of rod-cored vesicles and dense granules of large granular lymphocytes in the liver, spleen, and peripheral blood of rats (1994)
    Springer
    Cell & tissue research 276 (1994), S. 187-195 
    Details
    ISSN: 1432-0878
    Keywords: Rod-coredvesicles ; Granules ; Lymphocytes ; Liver ; Electron microscopy ; Rat (Fischer F344/NCR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Large granular lymphocytes (LGL) comprise a natural defense system in the liver and exert an inhibitory effect on tumor cell metastasis. In order to demonstrate the maturation of LGL in the liver from the morphological aspect, we evaluated electron-microscopically the frequency of 0.2 μm vesicles (rod-cored and “empty” vesicles) and dense granules in LGL from the liver, spleen, and peripheral blood of the rat. Both of these cell organelles are characteristic to LGL and may relate to natural killer-mediated cytolysis. On the average, there were 12.7 of the 0.2 μm vesicles and 4.3 rod-cored vesicles (RCV) per cell section in the liver, 6.6 0.2 μm vesicles and 1.6 RCV in the spleen, and 8.6 0.2 μm vesicles and 0.9 RCV in the peripheral blood. The number of 0.2 μm vesicles per cell section ranged from 0 to 19 with the exception of a few higher instances. Therefore, LGL were divided into vesicle-rich(〉9 0.2 μm vesicles per cell section) and vesicle-poor (〈8 per cell section) populations. Hepatic LGL consisted mainly of a vesicle-rich population while splenic LGL consisted mainly of a vesicle-poor population, and peripheral blood contained equal proportions of both populations. In addition to diversity with regard to the number of 0.2 μm vesicles, LGL obtained from various organs also displayed heterogeneity in the number and size of dense granules. Since the number of dense granules per cell section usually ranged from 1 to 13, LGL were diveded into 2 populations, i.e., LGL with many (〉7 per cell section) granules and those with a few(〈6 per cell section) granules. Specifically, splenic LGL had a few small (average diameter, less than 400 nm) dense granules, while sections of LGL from the liver and peripheral blood displayed many small dense granules and a few large (〉400 nm) ones, respectively, in addition to the populations seen in the spleen. Thus, the present study has demonstrateda difference in the distribution of 0.2 μm vesicles in LGL based on the tissue of origin. The present study has revealed the difference in the distribution of 0.2 μm vesicles of LGL by tissue and indicated that immature LGL are predominant in the spleen, while hepatic LGL are generally more mature as defined by the number of vesicles. These data suggest that the microenvironment of the liver may contribute to the increased expression of these vesicles in LGL.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00354799
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  • 98
    Electronic Resource
    Electronic Resource
    Localization of GABAA receptors in the rabbit retina (1994)
    Springer
    Cell & tissue research 276 (1994), S. 295-307 
    Details
    ISSN: 1432-0878
    Keywords: GABAA receptors ; Light microscopy ; Electron microscopy ; α1 subunit ; β2/3 subunit ; γ2 subunit ; Immunocytochemistry ; Rabbit (New Zealand)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution of gamma-aminobutyric acidA (GABAA) receptors in the rabbit retina is investigated and compared with the distribution of GABAergic neurons using immunocytochemical methods. Antibodies against the α1, β2/3, and γ2 subunits of the GABAA receptor label subpopulations of bipolar, amacrine and ganglion cells. Double labeling experiments show that the γ2 subunit is colocalized with the α1 and the β2/3 subunits in bipolar, amacrine and ganglion cells. Electron microscopy reveals that in the outer plexiform layer, GABAA receptor immunoreactivity is present on dendrites of cone bipolar cells adjacent to the cone pedicles. Bipolar cell dendrites are also receptor-positive at synapses from interplexiform cells. Some receptor immunoreactivity is found intracellularly in processes of horizontal cells. In the inner plexiform layer, GABAA receptor immunoreactivity is present on both rod bipolar and cone bipolar axon terminals at putative GABAergic input sites. Amacrine and ganglion cell processes in sublamina a and b are also labeled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00306115
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  • 99
    Electronic Resource
    Electronic Resource
    Negatively-stained polysomes on rough microsome vesicles viewed by electron microscopy: further evidence regarding the orientation of attached ribosomes (1994)
    Springer
    Cell & tissue research 276 (1994), S. 439-444 
    Details
    ISSN: 1432-0878
    Keywords: Polysomes ; Ribosomes ; Subunits ; Liver ; Electron microscopy ; Negative stain ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Rough microsomes, derived from rough endoplasmic reticulum of rat liver, were studied by electron microscopy after negative staining, to seek further information about the orientation of ribosomal small and large subunits in bound polysomes. Rough microsomal vesicles were fixed with 2% formaldehyde, centrifuged onto electron-microscopic grid membranes, and were then negatively-stained with 2% phosphotungstic acid. In these preparations, viewed with the electron microscope, flattened rough microsomal vesicles with bound polysomes were sometimes discernible, and the individual ribosomes in the polysomes occasionally showed small and large subunits. The small subunits were uniformly oriented toward the inside of the polysomal curve. The large and small subunits appeared to be alongside one another on the membrane, consistent with the orientation that has been described by Unwin and his co-workers. The boundary between the small and large subunits occurred at approximately the same level in the ribosome where inter-ribosomal strands have been described previously in surface views of bound polysomes in positively-stained electron-microscopic tissue sections. This further confirms the identity of the strands as messenger RNA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00343942
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    Electronic Resource
    Morphological studies by light and electron microscopy of pancreatic acinar cells under the effect of Tityus serrulatus venom (1994)
    Springer
    Cell & tissue research 278 (1994), S. 255-264 
    Details
    ISSN: 1432-0878
    Keywords: Scorpion venom ; Exocrine pancreas ; Secretagogue ; Electron microscopy ; Pancreatitis ; cis-Golgi aggregates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We studied in vivo and in vitro morphological aspects of pancreatic acinar cells after treatment with Tityus serrulatus venom (TSV). After three hours in an in vitro system, positive secretagogue effects of the venom were identifiable both at the light-microscopic (LM) and the electron-microscopic (EM) levels. At 1 μg/ml TSV, maximal secretion (as measured in a concomitant radiolabeling dose-response experiment) of exocrine proteins at 58% was manifest as a discharge of most zymogen granules (ZG) and consequent appearance of secretory material in acinar lumina. At the supramaximal dose of 10 μg/ml TSV, exocytotic images were often observed also with secretory contents previously discharged. The lowest dose of venom at 0.01 μg/ml caused no stimulation of zymogen discharge above resting secretion levels; however, morphological changes were observed. At high doses of TSV, both in vivo and in vitro, large aggregates associated with the cis-Golgi develop between this region and the endoplasmic reticulum (ER). Since Tityus venoms have been associated with causation of pancreatitis, we were interested in comparisons of our experimental tissue with parameters attributed to development of the disease. Our studies have demonstrated considerable evidence that large intracellular vacuoles, discharged ZG, effaced acinar lumina with disappearance of microvilli and other manifestations of possible early events in pancreatitis are indeed frequently observed both in pancreatic lobules in vitro and in whole pancreas in vivo when exposed to TSV.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00414168
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