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  • 1990-1994  (2.730)
  • 1980-1984
  • 1960-1964
  • 1991  (2.730)
  • Cell & Developmental Biology  (1.482)
  • General Chemistry  (1.091)
  • Industrial Chemistry
  • Nuclear reactions
  • Ultrastructure
  • pharmacokinetics
Datenquelle
Materialart
Erscheinungszeitraum
  • 1990-1994  (2.730)
  • 1980-1984
  • 1960-1964
Jahr
Schlagwörter
  • 1
    Digitale Medien
    Digitale Medien
    Diethylene glycol (DEG)-associated myocardial changes: A pilot investigation of chronic intoxication in guinea-pigs (1991)
    Springer
    International journal of legal medicine 104 (1991), S. 93-97 
    Details
    ISSN: 1437-1596
    Schlagwort(e): Diethylene glycol ; Intoxication ; Myocardium ; Myocytolysis ; Ultrastructure ; Mitochondria ; Guinea pig ; Diethylenglycol ; Intoxikation ; Myokard ; Myozytolyse ; Ultrastruktur ; Mitochondrien ; Meerschweinchen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Das Myokard von Meerschweinchen, welche mit subletalen Mengen von Diethylenglycol über eine Zeitdauer von 2–11 Tagen gefüttert worden waren, wurde mikroskopisch und elektronenmikroskopisch untersucht. Eine Koagulationsmyozytolyse und Verlust von Myofibrillen war fleckförmig verstreut über das Myokard. Diese Veränderungen waren in den Kontrollen nicht zu beobachten. Die begleitenden ultrastrukturellen Veränderungen bestanden in Schwellung, Pleomorphie, Hyperplasie von Mitochondrien, begleitet von einer Erweiterung der interfibrillären Räume und Verlagerung, Verzerrung und Ruptur angrenzender Fibrillen.
    Notizen: Summary The myocardium of guinea pigs fed on sublethal doses of diethylene glycol (DEG) over a period of 2–11 days was examined for microscopical and ultrastructural changes. Coagulative myocytolysis and loss of myofibrils, not observed in the controls, was patchily distributed throughout the myocardium. The accompanying ultrastructural features included swelling, pleomorphism and hyperplasia of mitochondria with an associated distension of the interfibrillary spaces and a displacement, distortion and rupture of adjacent myofibrils.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01626038
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  • 2
    Digitale Medien
    Digitale Medien
    Effect of dopamine agonist medication on prolactin producing pituitary adenomas (1991)
    Springer
    Virchows Archiv 418 (1991), S. 439-446 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Bromocriptine ; Pituitary neoplasm ; Prolactin ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Conventional light microscopy, immunocyto-chemistry, electron microscopy and in situ hybridization were used to evaluate the effect of dopamine agonists (bromocriptine-LAR and bromocriptine) on the morphology of surgically removed prolactin (PRL)-producing pituitary adenomas. Dopamine agonist therapy resulted in decrease of serum PRL, clinical improvement and tumour shrinkage. Using light and electron microscopy cellular atrophy, interstitial and perivascular fibrosis were noted; in several tumours connective tissue accumulation was pronounced. The cellular response was not uniform. In some adenomas populations of large cells and small cells were distinguished. The large cells contained immunoreactive PRL and expressed the PRL gene indicating resistance to dopamine agonists. It appears that these cells retained the potential to secrete PRL and proliferate despite exposure to dopamine agonists. In the small cells, PRL immunoreactivity and PRL gene expression decreased providing evidence that both PRL release and synthesis were blocked. Small cells can persist in tumours after discontinuation of dopamine agonist medication suggesting these small cells are irreversibly suppressed and are not capable of regaining their endocrine function and proliferative capability. The formation of irreversibly suppressed PRL cells may explain why some PRL-producing adenomas do not recur after withdrawal of dopamine agonists.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01605931
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  • 3
    Digitale Medien
    Digitale Medien
    Immunohistochemical characterization of HLA-DR-antigen positive dendritic cells in phaeochromocytomas and paragangliomas as a prognostic marker (1991)
    Springer
    Virchows Archiv 418 (1991), S. 33-39 
    Details
    ISSN: 1432-2307
    Schlagwort(e): HLA-DR ; Phaeochromocytomas ; Paragangliomas ; Immunohistochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Twelve cases of phaeochromocytoma (PCC) and four cases of paraganglioma (PGG) were studied by immunohistochemistry and immunoelectron microscopy in order to demonstrate HLA-DR (Ia)-antigen-positive dendritic cells (IaDCs). Dense infiltration of IaDCs was detected in the majority of PCCs revealing high urinary or serum catecholamine levels, but in aggressively growing PCCs, a familial PCC and all PGGs, few IaDCs were demonstrated. Interestingly, these IaDCs were negative for S-100 protein. Although S-100-protein-positive sustentacular-like cells (SCs), morphologically similar to IaDCs, were also present, these were clearly distinguished from IaDCs by our double immunostaining method. Ultrastructurally, IaDCs had smooth or slightly indented nuclei and contained a moderate amount of endoplasmic reticulum, small mitochondria and vacuoles, extending elongated cytoplasmic processes. These results suggest that determination of the quantity of IaDCs is a highly effective method of assessing the character of PCCs, in particular, their prognosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01600242
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  • 4
    Digitale Medien
    Digitale Medien
    Cell-mediated cytotoxicity in acute rat cardiac allograft rejection: An immunological and ultrastructural study (1991)
    Springer
    Virchows Archiv 418 (1991), S. 41-50 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Cell-mediated cardiocyte injury ; Acute cardiac allograft rejection ; Mononuclear cellular infiltration ; Immunohistochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To clarify the immune mechanism of cytotoxicity in acute cardiac allograft rejection, we observed interactions between cardiocytes and mononuclear cells using immunohistochemistry and light and electron microscopy. All allografted WKA rat hearts transplanted to F344 recipients stopped beating by the 7th day after the transplantation. The population of helper/inducer T cells (Th) and IL2R+ cells was large for the first 3 days, whereas that of cytotoxic/suppressor T cells (Tc-s) and macrophages increased from the 4th day. TheTh/Tc-s ratios were more than 2.0 until the 3rd day, then decreased to less than 1.0. In circulating T lymphocytes; theTh/Tc-s ratios were under 1.0 on the 1st, 6th and 7th days. Electron microscopically IL2R+ cells, Tc-s and macrophages were often seen in close contact with the plasma membrane of the cardiocytes. The majority of IL2R+ cells are NK cells, Tc-s andTh. Of these, the population of Tc-s was small until the 3rd day. Thus, NK cells play a pivotal role in the early stage of the rejection, and Tc-s and macrophages then aggravate cell-mediated cardiocyte injury.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01600243
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  • 5
    Digitale Medien
    Digitale Medien
    Ultrastructure of oesophageal melanocytosis (1991)
    Springer
    Virchows Archiv 418 (1991), S. 515-522 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Oesophagus ; Melanocyte ; Melanoma ; Ultrastructure ; Endoscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Four examples of an endoscopically detected oesophageal melanotic lesion were examined by light microscopy, light microscope histochemistry and transmission electron microscopy, and were compared with 13 control samples of normal oesophageal epithelium. By light microscopy, pigmented melanocytes lacking atypia and mitoses were observed amongst the keratinocytes in the basal layer of the oesophageal mucosa. Junctional activity was absent. The mechanism of pigmentation was studied and found to consist of: an increase in the number of melanocytes in the basal layer of the mucosa, an increase in the quantity of melanin in these melanocytes, transfer of melanin from melanocytes to keratinocytes and to macrophages and fibroblasts in the tunica propria. Since all the lesions demonstrated increased numbers of both melanocytes and melanosomes, the term oesophagealmelanocytosis rather thanmelanosis is suggested, to emphasise the essential character of the lesion as a cellular proliferation. The value of sampling these pigmented lesions during endoscopy is emphasised as a means of obtaining well-preserved material for the evaluation of a lesion which some authorities have viewed as a possible precursor for oesophageal malignant melanoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01606502
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  • 6
    Digitale Medien
    Digitale Medien
    Ultrastructural abnormalities of mitochondria and deficiency of myocardial cytochromec oxidase in a patient with ventricular tachycardia (1991)
    Springer
    Virchows Archiv 419 (1991), S. 63-68 
    Details
    ISSN: 1432-2307
    Schlagwort(e): Mitochondrial cardiomyopathy ; Ultrastructure ; Cytochromec oxidase deficiency ; Ventricular tachycardia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A 30-year-old woman presented with lifethreatening ventricular tachycardia without overt heart disease. Ultrastructural investigation of endomyocardial biopsy disclosed abnormally structured and often enlarged mitochondria. Morphometry revealed the ratio of volume density of mitochondria to myofibrils to be markedly increased to 0.667 as compared with five controls (mean: 0.46; range: 0.445–0.479). Investigation of mitochondrial respiratory chain enzymes revealed a 90% reduction in activity of cytochromec oxidase. Our data suggest that mitochondrial cardiomyopathy may induce malignant ventricular arrhythmias.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01600154
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  • 7
    Digitale Medien
    Digitale Medien
    Varicocele in the rat: a new experimental model (1991)
    Springer
    Urological research 19 (1991), S. 319-322 
    Details
    ISSN: 1434-0879
    Schlagwort(e): Varicocele ; Rat, Histology ; Ultrastructure ; Temperature ; Infertility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary With no consistent animal prototype for the study of varicocele, we set out to create a model in the rat by complete ligation of the main branch of left spermatic vein (MBSV) or by partial ligation of the left renal vein. Three months later, the histology, ultrastructure and temperature of the testis and epididymis were studied. Microscopically, spermatogenic arrest was the most frequent anomaly seen. The most frequently noted ultrastructural change of the testis was distension of smooth endoplasmic reticula in Sertoli cells. The microvilli of columnar epithelia in epididymis were sparse and showed local defects. Lesions and increased temperatures in the testis and epididymis induced by the ligation of the left MBSV were similar to those seen in partial ligation of the left renal veins, with no significant differences between left and right. Significant differences were found, however, on comparison with the controls.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00299069
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  • 8
    Digitale Medien
    Digitale Medien
    Distribution of mouse interferon-β in normal and brain tumour-bearing mice (1991)
    Springer
    Acta neurochirurgica 109 (1991), S. 46-51 
    Details
    ISSN: 0942-0940
    Schlagwort(e): Mouse interferon ; mouse glioma ; pharmacokinetics ; radioassay ; autoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The distribution of125I-labelled recombinant mouse interferon-β (rMuIFN-β) in normal and glioma (203 glioma) bearing mice was studied by radioassay and macro-autoradiography at 15 and 30 min after a single intravenous injection. The level of rMuIFN-β in the spleen was about 20-fold higher than in serum. Concentrations higher than the serum level was detected in the lung, liver and kidney. The concentration of rMuIFN-β in the brain was 8% of the serum level and the concentration in the glioma 30 min after administration was about 10-fold higher than in normal mouse brain. Macro-autoradiographic study demonstrated a wide distribution range and selective uptake in glioma tissue. Furthermore, we found that mouse gliomas were sensitive to mouse IFN-β. Our findings demonstrate that in the mouse glioma model, intravenously administered interferon reaches the tumour.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01405697
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  • 9
    Digitale Medien
    Digitale Medien
    Morphology of the synovium during its differentiation and development in the mouse knee joint (1991)
    Springer
    Anatomy and embryology 183 (1991), S. 537-544 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Synovial membrane ; Development ; Ultrastructure ; Scanning electron microscopy ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The prenatal and postnatal development of the mouse knee joint was investigated by transmission and scanning electron microscopy. In the prenatal stage, following the appearance of a narrow intercellular cleft between two skeletal elements on the 16th fetal day, clefting extended into the lateral synovial mesenchyme. In some regions, the extension of the cleft was very rapid, but in a certain region (future fat pad region), it was somewhat slower. Macrophage-like cells appeared in the synovial mesenchyme on the 16th fetal day, and then increased in number, and were distributed as if they were clustering around the presumptive clefting zone in the future fat pad region on the 17th–18th fetal day. This suggests that macrophage-like cells may participate in joint development, as they phagocytize and remove some kinds of solid extracellular matrix, and facilitate the cleft extension. In the early postnatal stage, scanning electron microscopic observations showed that there were two different types of cell in the synovial lining. One of them exhibited a surface morphology corresponding to that of macrophages: a spherical cell body and numerous pseudopodia. The other type of cell exhibited various cell shapes with many cytoplasmic processes extending along the synovial surface.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00187902
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  • 10
    Digitale Medien
    Digitale Medien
    Endothelial heterogeneity in the chick wing bud: A morphometric study (1991)
    Springer
    Anatomy and embryology 184 (1991), S. 47-53 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Wing bud ; Endothelial cell ; Development ; Ultrastructure ; Morphometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The microvascular endothelium of the chick wing bud at stages 22, 27, and 32 was evaluated by ultrastructural morphometry. The rationale for this study is based on the hypothesis that endothelial cells exhibit variation in structure and function during cytodifferentiation. The microvessels had a luminal diameter range such that they were classified as capillaries. The thin continuous endothelium was devoid of a basal lamina. The endothelium had a very small number of plasmalemmal vesicles; vacuoles were however present for all stages and in some cases were abundant. The temporal findings were that endothelial cell thickness increases, plasmalemmal vesicle densities decrease, and the densities of cytoplasmic vacuoles increase. The spatial results were that endothelial cells in proximal regions of the limb have a greater thickness, contain fewer vesicles and have more vacuoles than those in distal regions. In general, these results indicate that endothelial ultrastructural heterogeneity occurs within a 31/2 day timespan of wing bud development. The discussion considers the results with regard to recent reports on endothelial cell heterogeneity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01744260
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  • 11
    Digitale Medien
    Digitale Medien
    Development of taste organs inRana temporaria (1991)
    Springer
    Anatomy and embryology 184 (1991), S. 363-369 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Taste organs ; Amphibia ; Development ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In tadpoles ofRana temporaria two successive generations of taste organs: taste buds (TBs) and taste disks were studied. The TBs are located in the apices of oral premetamorphic papillae. Each TB consists of vertically elongated receptor cells (probably taste) and supporting cells. No basal (Merkel) cells were observed there. Morphologically, two types of receptor cells have been distinguished in a TB. Complete synaptic structures were observed in the TBs between the 30th and 41st of Gosner's (1960) developmental stages, though synaptic vesicles occur already at stage 26. The taste disks consist of taste cells, supporting cells and basal cells. Dense-core synaptic vesicles occur in the gustatory cells at stage 41, but complete synaptic structures were not observed earlier than at stage 45. Synaptic junctions observed at some of the gustatory cells seem to be reciprocal (bidirectional).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00957898
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  • 12
    Digitale Medien
    Digitale Medien
    The anatomy and fine structure of the echidnaTachyglossus aculeatus snout with respect to its different trigeminal sensory receptors including the electroreceptors (1991)
    Springer
    Anatomy and embryology 184 (1991), S. 371-393 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Tachyglossus aculeatus (echidna) ; Echidna bill ; Sensory receptors ; Electroreceptor ; Mechanoreceptor ; Trigeminal nerve ; Monotreme ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The gross anatomy and nerve supply of the bill of echidna (Tachyglossus aculeatus) is described in relation to its function as an outstanding sensory organ. The sensory innervation of the skin of the echidna snout was investigated by means of frontal serial sections, after decalcification of the specimens. A comprehensive light and electron microscopic description of the location and fine structure of cutaneous sensory receptors of the trigeminal system was made by this means. The encapsulated and non-encapsulated Ruffini receptors, the types of other free receptors in the connective tissue and the Merkel cell receptor do not differ morphologically from those of higher mammals, whereas the pacinian-like corpuscle shows a unique organization of its outer core. This is composed of large perineural cells containing a unique reticulum of parallel-orientated endoplasmic membranes. Lamellated corpuscles, seen in isolation or in association with push rods, are numerous in the snout and in the tip of the tongue of echidna. Push rod receptor organs occur in the hairless skin of the bill with a very dense array at its rostral end and in the pseudopalatal ridges. Gland duct receptors are restricted to the skin adjacent to the nostrils and the mouth opening, including the pseudopalatal plates. Only about one quarter of the total number of 400 seromucous glands receive a sensory innervation of their intraepidermal duct segment. Within each innervated gland two types of receptor terminals are identified. The distributions of the different receptor types are mapped for different regions of the skin, the mucous membrane of the nasal and oral vestibule and the tip of the tongue. The fine structure of nerve terminals is discussed from a comparative anatomical point of view, and some speculations are made about possible transduction processes that underlie the known electrophysiological properties. The sensory organs such as the “push rod” and “gland duct receptor”, and most of their sensory terminals, are less differentiated in echidna snout than in the platypus (Ornithorhynchus anatinus) bill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00957899
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  • 13
    Digitale Medien
    Digitale Medien
    Immunocytochemical and ultrastructural studies of hyaline inclusions in sporadic motor neuron disease (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 295-301 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Hyaline inclusions ; Motor neuron disease ; Amyotrophic lateral sclerosis ; Immunocytochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We investigated hyaline inclusion bodies (HI) immunocytochemically and ultrastructurally in six cases of sporadic motor neuron disease (MND). All HI contained large amounts of ubiquitin and some HI were stained at the core or the center with anti-neurofilament antibody, with the surrounding halo unstained. No HI were stained with antibodies raised against cytoskeletal proteins such as high-molecular weight microtubule-associated proteins and phosphorylated tau. Ultrastructurally, HI were chiefly composed of filaments measuring about 20 nm in diameter thicker than neurofilaments, and contained fine granules and frequently one or more of four characteristic profiles, i.e., small electron-dense materials resembling Bunina bodies, bundles of tubular filaments measuring approximately 20 nm in diameter, large electron-dense cores, and focal accumulations of randomly arranged neurofilaments. Hyaline inclusions can be regarded as one of the characteristic markers for sporadic MND as well as familial amyotrophic lateral sclerosis. Hyaline inclusions have a markedly heterogeneous ultrastructure and, therefore, differences in immunoreactivity with antineurofilament antibodies are not unexpected.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00308815
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  • 14
    Digitale Medien
    Digitale Medien
    Meningiomas differentiating to arachnoid trabecular cells: a proposal for histological subtype “arachnoid trabecular cell meningioma” (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 327-330 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Meningioma ; Microcystic meningioma ; Vacuolated meningioma ; Arachnoid trabecular cell ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Three cases of meningiomas which had abundant small vacuoles in the tumor tissue are reported. By electron microscopy, the tumor cells exhibited long and thin processes, the tips of which were united by desmosomes. The tumor tissue was revealed to have wide extracellular spaces which corresponded to the vacuoles observed by light microscopy. In previous literature, various terms have been used when referring to this meningioma, such as microcystic meningioma or vacuolated meningioma. Since the ultrastructure of the tumor showed similarity to that of normal arachnoid trabecular cells, we propose to call the tumor “arachnoid trabecular cell meningioma” denoting its morphological nature clearly.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00296542
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  • 15
    Digitale Medien
    Digitale Medien
    Galactosialidosis: neuropathological findings in a case of the late-infantile type (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 331-339 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Galactosialidosis ; Neuronal storage disease ; Neuropathology ; Ultrastructure ; Neuronal loss
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The neuropathological findings in a 13-year-old Japanese male showing decrease of sialidase and β-galactosidase activities are reported. The patient was the product of normal pregnancy to consanguineous parents. He started to sit at 8 months, stand at 20 months and walk at the age of 2; mental retardation, visual disturbance, cerebellar ataxia, myoclonus and epilepsy developed by the age of 10, and he died at 13. Neuropathological investigation revealed neuronal loss and storage. Severe loss of neurons was observed in the thalamus, globus pallidus, lateral geniculate body, gracile nucleus, Purkinje and retinal ganglion cells. Marked ballooning was seen in the Betz cells and neurons in the basal forebrain, the motor neurons in the cranial nerve nuclei and spinal cord, and in the trigeminal and spinal ganglia. The storage material varied in staining from region to region and from neuron to neuron. Electron microscopic investigation revealed a variety of intracytoplasmic and intranuclear inclusions: membranous cytoplasmic bodies, parallel, wavy-lamellar or tortuous tubular structures, lipofuscin-like irregular-shaped pleomorphic bodies, and cytoplasmic vacuoles with fine granules and lamellar materials. The severity of the neuronal loss did not seem to correlate with the amount of the storage materials, but with the presence of tortuous tubular inclusion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00296543
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  • 16
    Digitale Medien
    Digitale Medien
    Intramedullary secretory gangliocytoma (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 402-407 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Gangliocytoma ; Ultrastructure ; Catecholamines ; Hypertension ; Spinal cord
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An 8-year-old boy developed severe systemic hypertension during resection of an intramedullary tumor. The histological, ultrastructural and immunocytochemical characteristics of the tumor are those of a gangliocytoma. Based on the demonstration of tyrosine hydroxylase in neuronal tumor cells, it is postulated that catecholamine secretion was responsible for the systemic hypertension.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00296552
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  • 17
    Digitale Medien
    Digitale Medien
    Immunocytochemical and ultrastructural studies of Werdnig-Hoffmann disease (1991)
    Springer
    Acta neuropathologica 81 (1991), S. 408-417 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Werdnig-Hoffmann disease ; Immunocytochemistry ; Ultrastructure ; Cytoskeleton ; Ubiquitin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Neuronal alterations in two cases of Werdnig-Hoffmann disease (WH) were investigated immunocytochemically and ultrastructurally. Ballooned neurons (BNs) were found in anterior horn, Clarke's column, dorsal root ganglion and thalamus. Anti-phosphorylated neurofilament antibodies preferentially stained the peripheral perikarya and proximal neuronal processes of BNs, whereas anti-ubiquitin antibodies preferentially stained the central perikarya of BNs. Ultrastructurally, BNs showed degenerative changes ranging from a diffuse increase of neurofilaments to a centrally accentuated accumulation of mitochondria and vesicular or membranous profiles. Our studies suggest that ubiquitinated degradation products accumulate in the center of the BN's perikaryon and displace aberrantly phosphorylated neurofilaments to the periphery. BNs in WH probably reflect an intrinsic alteration in the metabolism of neurofilaments that is associated with regressive changes in the neuron and eventually neuronal death.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00293462
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  • 18
    Digitale Medien
    Digitale Medien
    The effect of denervation on the morphology of regenerating rat soleus muscles (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 21-32 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Muscle ; Regeneration ; Denervation ; Ultrastructure ; Snake toxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This study examines the level to which muscle regeneration proceeds in the absence of innervation. Regeneration was monitored in rat soleus muscles following localised injection of a snake toxin, notexin. Muscles which had been concomittantly denervated were compared with those that were normally innervated. Until 3–4 days following toxin administration regeneration is identical in both groups. The muscles contain new myotubes in place of the degenerated “parent” fibres. Thereafter, the non-denervated muscles grow rapidly and by 28 days their myofibres attain the size of those from the contralateral controls. Growth of denervated regenerating muscles, however, is retarded and is superseded by a gradual atrophy. In such muscles we further identify ultrastructural abnormalities from 7 days post-injection. These a re loss of individual myosin filaments and the presence of immature and abnormal configurations of the transverse system and triads. We, thus, conclude that innervation is an obligatory requirement for the restoration of normal myofibrillar and sarcotubular morphology, as well as growth, but is not necessary for the neo-formation of myofibres.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00310919
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  • 19
    Digitale Medien
    Digitale Medien
    Bone marrow transplant in a case of mucopolysaccharidosis I Scheie phenotype: skin ultrastructure before and after transplantation (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 33-38 
    Details
    ISSN: 1432-0533
    Schlagwort(e): MPS I-S ; Skin biopsy ; Ultrastructure ; Bone marrow transplant
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An 11-year-old girl with mucopolysaccharidosis I Scheie phenotype (MPS I-S) received a bone marrow transplant (BMT) from her heterozygous HLA-identical LMC-non-reactive mother. Multidisciplinary studies were carried out and results evaluated 21 months after transplantation. Herein we report the ultrastructural findings pre-and post-BMT in skin. Multidisciplinary studies are commonly used to evaluate the benefits of metabolic correction following BMT in some MPS and other inherited metabolic disorders, and changes in morphology have been described in liver and few other tissues. In this case, we elected skin, since connective tissue is universally involved in MPS and is safely and easily obtainable. Comparison of skin biopsy specimens taken before and after BMT showed a considerable change in dermal fibroblast morphology, with marked reduction in cell size and the number and size of abnormal lysosomes, thus indicating the clearance of storage. Our results demonstrate that dermal cells respond to enzyme replacement therapy in MPS I-S, with the clearance of glycosaminoglycan lysosomal accumulation in connective tissue fibroblasts, which had near-normal morphology 21 months after BMT. Therefore, the practice of skin biopsy after BMT in MPS and other metabolic disorders in which dermal cells are involved should be encouraged.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00310920
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  • 20
    Digitale Medien
    Digitale Medien
    Idiopathic prolactin cell hyperplasia of the pituitary mimicking prolactin cell adenoma: a morphological study including immunocytochemistry, electron microscopy, and in situ hybridization (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 147-151 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Hyperplasia ; Pituitary ; Pathology ; Prolactin ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Prolactin cell adenoma is the most frequently found lesion in surgically removed pituitaries of patients with hyperprolactinemia. However, in several instances, instead of prolactin cell adenoma, other lesions are encountered by morphological investigation. We report here the morphological findings in a patient with hyperprolactinemia who underwent transsphenoidal pituitary surgery for suspected prolactin cell adenoma. A morphological diagnosis of tumor could not be confirmed and massive diffuse prolactin cell hyperplasia was identified. The aim of this publication is to describe the lesion by histology, immunocytochemistry, electron microscopy, and in situ hybridization and to call attention to primary prolactin cell hyperplasia which can mimic prolactin cell adenoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00293958
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  • 21
    Digitale Medien
    Digitale Medien
    Fulminant blastomycosis with blastomycotic infection of a cerebral glioma (1991)
    Springer
    Acta neuropathologica 82 (1991), S. 420-424 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Blastomycosis ; North American Blastomy-cosis ; Brain tumor ; Opportunistic infection ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Except for isolated case reports, blastomycosis has not been identified as a significant problem in immunosuppressed patients. We describe an unusual case with blastomycotic infection of a cerebral glioma in a 56-year-old man who underwent radiotherapy for his tumor and died of fulminant blastomycotic pneumonia. This is believed to be the first reported case of Blastomyces dermatitidis infection of a cerebral glioma. The light microscopic and ultrastructural features of B. dermatitidis, the giant forms of which were encountered in our patient, are described, and the role of immuno-suppression due to steroid therapy in the pathogenesis of this fulminant infection are reviewed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00296555
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  • 22
    Digitale Medien
    Digitale Medien
    Scrapie inoculation of mice: light and electron microscopy of the superior colliculi (1991)
    Springer
    Acta neuropathologica 81 (1991), S. 562-571 
    Details
    ISSN: 1432-0533
    Schlagwort(e): Scrapie ; Ultrastructure ; Vacuolation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Ultrastructural examination of the superior colliculi of mice intraocularly inoculated with the ME7 strain of scrapie showed vacuolation early in the course of infection. Brains were examined between 85–260 days after monocular inoculation with scrapie. The mean incubation period for the development of clinical disease was 302 days. Vacuolation was seen initially in the contralateral superior colliculus and subsequently in the ipsilateral colliculus. In coded trails light microscopical vacuolation was seen from 218 days but ultrastructural examination showed that sparse vacuoles were inconsistently present in either or both of the ipsilateral and contralateral colliculi from 85 days; frequent vacuoles were seen from 190 days. Scrapie-induced vacuoles were differentiated from vacuoles present in control tissue by the presence of loculation or by a limiting double membrane which showed protrusion or proliferation of the innermost lamella. Vacuolation was seen in neuronal perikarya, myelinated fibres, dendrites and axonal presynaptic terminals. Vacuoles of myelinated fibres were observed within myelin and possibly also in the inner tongue of oligodendroglial cytoplasm. Whorled membrane configurations were also seen. Tubulovesicular particles, 40 nm in diameter, were recognised in two scrapie-infected mice. It is suggested that some scrapie vacuoles arise as a result of incorporation of abnormal membrane into organelles, possibly mitochondria, in neuronal perikarya and neurites and probably also within oligodendroglial cytoplasm and myelin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00310139
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  • 23
    Digitale Medien
    Digitale Medien
    Histopathogenesis of inflammatory linear verrucose epidermal naevus: histochemistry, immunohistochemistry and ultrastructure (1991)
    Springer
    Archives of dermatological research 283 (1991), S. 491-499 
    Details
    ISSN: 1432-069X
    Schlagwort(e): Inflammatory linear epidermal naevus ; Keratinization ; DACM ; Involucrin ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00371921
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  • 24
    Digitale Medien
    Digitale Medien
    The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones (1991)
    Springer
    Archives of dermatological research 283 (1991), S. 100-107 
    Details
    ISSN: 1432-069X
    Schlagwort(e): Rhino mouse skin ; All-trans retinoic acid ; CD271 ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The histological and ultrastructural effects following 3 weeks' topical treatment with two agents (all-trans retinoic acid and a new synthetic retinoid-like substance, CD271) were evaluated on the epidermis and the epithelial wall of the pseudocomedones in rhino mouse skin. The comedolytic effects of these drugs were similar, and consisted of a reduction of the utricular diameter, with normalization of follicular units. Morphological examinations revealed a hyperplastic response with an increase in the number of cell layers of both epidermis and follicular epithelium, and modifications in keratinocyte differentiation. Ultrastructural changes in the epidermis and epithelial wall were observed mainly in the granular and horny layers, with increased desquamation, and a decrease in the cohesiveness of corneocytes. During the first week of treatment, some cutaneous toxic effects were noticed, but they normalized within two weeks. On the other hand, a fine granular material persisted in the intercellular spaces. It is confirmed that the skin of the rhino mouse is a good model for the evaluation of the comedolytic effects of drugs. Moreover, it reveals the specific effects of retinoids on epidermal differentiation. We have demonstrated that topically applied CD271 induces modifications similar to those obtained with all-trans retinoic acid. It is thus concluded that CD271 is a potentially effective anti-acne agent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00371617
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  • 25
    Digitale Medien
    Digitale Medien
    Ultrastructural study of the skin in Sjögren — Larsson syndrome (1991)
    Springer
    Archives of dermatological research 283 (1991), S. 141-148 
    Details
    ISSN: 1432-069X
    Schlagwort(e): Sjögren ; Larsson syndrome ; Ichthyosis ; Ultrastructure ; Lamellar body ; Keratinization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The ichthyosiform skin and the uninvolved skin of a 5-year-old Japanese female with Sjögren — Larsson syndrome were examined by light and electron microscopy to elucidate the keratinization disorder. Light microscopically, the epidermis of the ichthyosiform skin showed acanthosis, papillomatosis and hyperkeratosis. The horny cells had a basket-weave appearance. The granular cell layer was slightly thickened. Slight round cell infiltration and vascular dilatation were seen in the upper dermis. The uninvolved skin was histologically normal. Electron microscopically, in both ichthyosiform and uninolved skin, abnormal lamellar or membranous inclusions were present in the cytoplasm of horny cells of the epidermis. These inclusions appeared to be derived from some of the lamellar bodies and/or abnormal membranous structures found in the cytoplasm of spinous and granular cells. Mitochondria in the epidermal basal cells were more numerous in the ichthyosiform skin than in the uninvolved skin. These findings indicate that, whether the skin is involved or not, the epidermis of the patient with this disorder may always have a structural abnormality, which may be genetically determined. Local environmental factors may play a role in inducing the acanthosis and papillomatosis of the epidermis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00372053
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  • 26
    Digitale Medien
    Digitale Medien
    Are accessory nuclei involved in the establishment of developmental gradients in hymenopteran oocytes? (1991)
    Springer
    Development genes and evolution 199 (1991), S. 423-426 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Oogenesis ; Accessory nuclei ; Developmental gradients ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary In the oocytes ofTenthredo olivacea, accessory nuclei (AN) are formed by budding from the nuclear envelope of the oocyte nucleus. Newly formed AN contain electron-dense material of nuclear origin and are surrounded by a double envelope devoid of pores. Such structures are subsequently transported to the peripheral ooplasm (periplasm), where they grow to reach a final diameter of 5 µm. In the envelopes of advanced AN nuclear pores arise. Through these pores “nuage” material is extruded into the surrounding periplasm. These findings are discussed with respect to a possible involvement of AN in the establishment of developmental gradients in hymenopteran oocytes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01705853
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  • 27
    Digitale Medien
    Digitale Medien
    The origin of the nascent blastocoele in preimplantation mouse embryos ultrastructural cytochemistry and effect of chloroquine (1991)
    Springer
    Development genes and evolution 200 (1991), S. 77-85 
    Details
    ISSN: 1432-041X
    Schlagwort(e): Lysosomes ; Ultrastructure ; Chloroquine ; Blastocyst ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Mouse morulae are known to undergo cavitation as soon as some external cells have entered the sixth cell cycle (Garbutt et al. 1987). Since the early cytological features of cavitation are still unclear, we undertook a careful ultrastructural analysis of late morulae-nascent blastocysts. In addition, since maturation of lysosomes might be involved in the first step of cavity formation, we focused our attention on these organelles by means of the cytochemical localization of trimetaphosphatase activity and by the study of the effects of chloroquine on precavitation embryos. Our results suggest that cavitation starts in a few external cells (presumably competent cells entering the sixth cell cycle), by the chloroquine-sensitive formation of degradative autophagic vacuoles engulfing lipid droplets and vacuoles containing osmiophilic material. These complex structures enlarge (as a result of lipid metabolism?) and so transform into intrablastomeric cavities which, by means of a membrane fusion process, very rapidly become extracellular cavities that coalesce. The abembryonic pole of the blastocyst is determined in this way. Moreover, we suggest that the juxtacoelic cytoplasmic processes covering the inner cell mass (ICM) cells, which are known to restrict the expression of their totipotency during early cavitation (Fleming et al. 1984), are the latest remnants of the walls of the growing intrablastomeric cavities.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637187
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  • 28
    Digitale Medien
    Digitale Medien
    Contributions of sodium and chloride to ultrastructural damage after dendrotomy (1991)
    Springer
    Experimental brain research 86 (1991), S. 60-72 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Trauma ; Neuron ; Sodium ; Chloride ; Ultrastructure ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To determine the contributions of sodium and chloride to ultrastructural changes after mechanical injury, we amputated primary dendrites of cultured mouse spinal neurons in low calcium medium in which sodium chloride had been replaced with either choline chloride or sodium isethionate or sodium propionate. Uninjured cultured neurons were also exposed to the sodium ionophore, monensin. A third set of neurons was injured in medium in which all sodium and calcium chloride had been replaced with sucrose. Neurons injured in low-calcium, low-sodium medium exhibited few ultrastructural changes, except very near the lesion, where there was some dilation of mitochondria and cisternae of the smooth endoplasmic reticulum (SER). Mitochondria in other regions of the neurons developed an electron opaque matrix, and those nearer to the lesion converted to the condensed configuration, characterized by expanded intracristal spaces as well as a dense matrix. If sodium but not chloride was present in the medium, there was some dilation of the Golgi cisternae after injury, as well as some increased electron opacity of the mitochondria. Monensin treated neurons also exhibited dilation of the Golgi cisternae. Neurons injured in sucrose-substituted medium showed none of the changes associated with injury in normal culture medium. These results indicate that sodium influx through the lesion is involved in the dilation of the SER, which is seen even in low-calcium medium, and that a permeant anion, such as chloride, is also involved. This dilation of the SER may result from uptake of calcium released from mitochondria in response to elevated cytosolic sodium. Dilation of the Golgi cisternae appears to be a response only to elevated intracellular sodium. Condensation of the mitochondria after injury is thought to be due to increased demands for ATP synthesis and may involve a “futile cycling” of calcium across the mitochondrial membrane, involving sodium-mediated calcium release in response to elevated intracellular calcium.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00231040
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  • 29
    Digitale Medien
    Digitale Medien
    Secretory tapetum of Brassica oleracea L.: polarity and ultrastructural features (1991)
    Springer
    Sexual plant reproduction 4 (1991), S. 28-35 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Tapetal cells ; Brassica oleracea L ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The ultrastructure of the secretory, binucleate tapetum of Brassica oleracea in the micro spore mother cell (MMC) stage through to the mature pollen stage is reported. The tapetal cells differentiate as highly specialized cells whose development is involved in lipid accumulation in their final stage. They start breaking down just before anther dehiscence. Nuclei with dispersed chromatin, large nucleoli and many ribosomes in the cytoplasm characterize the tapetal cells. The wall-bearing tapetum phase ends at the tetrade stage. The dissolution of tapetal walls begins from the inner tangential wall oriented towards the loculus and proceeds gradually along the radial walls to the outer tangential one. The plasmodesmata transversing the radial walls between tapetal cells persist until the mature microspore, long after loss of the inner tangential wall. After wall dissolution, the tapetal protoplasts retain their integrity and position within the anther locule. The tapetal cell membrane is in direct contact with the exine of the microspores/pollen grains and forms tubular evaginations that increase its surface area and appear to be involved in the translocation of solutes from the tapetal cells to the microspores/ pollen grains. The tapetal cells exhibit a polarity expressed by spatial differentiation in the radial direction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194568
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  • 30
    Digitale Medien
    Digitale Medien
    Brassica napus pollen development during generative cell and sperm cell formation (1991)
    Springer
    Sexual plant reproduction 4 (1991), S. 176-181 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Pollen ; Brassica napus ; Mitoses ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Brassica napus pollen development during the formation of the generative cell and sperm cells is analysed with light and electron microscopy. The generative cell is formed as a small lenticular cell attached to the intine, as a result of the unequal first mitosis. After detaching itself from the intine, the generative cell becomes spherical, and its wall morphology changes. Simultaneously, the vegetative nucleus enlarges, becomes euchromatic and forms a large nucleolus. In addition, the cytoplasm of the vegetative cell develops a complex ultrastructure that is characterized by an extensive RER organized in stacks, numerous dictyosomes and Golgi vesicles and a large quantity of lipid bodies. Microbodies, which are present at the mature stage, are not yet formed. The generative cell undergoes an equal division which results in two spindle-shaped sperm cells. This cell division occurs through the concerted action of cell constriction and cell plate formation. The two sperm cells remain enveloped within one continuous vegetative plasma membrane. One sperm cell becomes anchored onto the vegetative nucleus by a long extension enclosed within a deep invagination of the vegetative nucleus. Plastid inheritance appears to be strictly maternal since the sperm cells do not contain plastids; plastids are excluded from the generative cell even in the first mitosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00190001
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  • 31
    Digitale Medien
    Digitale Medien
    Ultrastructure of the micropyle and its relationship to pollen tube growth and synergid degeneration in sunflower (1991)
    Springer
    Sexual plant reproduction 4 (1991), S. 166-175 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Helianthus annuus ; Ultrastructure ; Micropyle ; Pollen tube ; Synergid degeneration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Ultrastructural studies made on the micropyle of sunflower before and after pollination resulted in the following observations. (1) The micropyle is closed instead of a hole or canal. The inner epidermis of the integument on both sides of the micropyle is in close contact at the apex of the ovule. The boundary between the two sides consists of two layers of epidermal cuticle. (2) The micropyle contains a transmitting tissue. The micropyle is composed of an intercellular matrix produced by the epidermal cells of the integument. (3) The micropyle is asymmetrical, and is much wider on the side proximal to the funicle. On the funicle side the cells adjacent to the micropyle are similar to those of the transmitting tissue: they have large amounts of intercellular matrix and contain abundant dictyosomes, rough ER, and starch grains, and provide an appropriate environment for growth of the pollen tubes. The cells distal to the funicle are rich in rough ER and lipid bodies; they lack large intercellular spaces. (4) The micropyle is variable in the axial direction, i.e., it is much larger and more asymmetric at the level distal to the embryo sac than at a level close to the embryo sac. After pollination, one to four pollen tubes are seen in a micropyle. During their passage through the micropyle, most pollen tubes are restricted to the side proximal to the funicle. There is a greater tendency (81%) for the degenerate synergid to be located toward the funicle, i.e., at the same side as the pollen tube pathway. The data indicate a close relationship between micropyle organization, orientation of pollen tube growth, and synergid degeneration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00190000
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  • 32
    Digitale Medien
    Digitale Medien
    Sperm cells of the pollen tubes of Brassica: Ultrastructure and isolation (1991)
    Springer
    Sexual plant reproduction 4 (1991), S. 226-234 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Male germ unit ; Sperm cells ; Isolation ; Pollen tubes ; Brassica napus ; Pollen-tube inner plasma membrane ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Sperm cells of pollen tubes grown both in vivo and in vitro form a male germ unit. Extensions from both sperm cells of each pollen tube are closely associated with the tube nucleus. A high yield (2.7 × 104. 20 mg−1 pollen grains germinated) of intact sperm cells was obtained following release by osmotic shock from pollen tubes grown in vitro. Structural integrity of isolated sperm was maintained by isolation at low temperature in an osmotically balanced medium. At 4° C many isolated sperm pairs were still enclosed within the pollentube inner plasma membrane. Sperm cells not enclosed within this membrane no longer remained connected as a pair. During isolation vesicles formed on the sperm cell surface from disruption of the fibrillar components bridging the periplasmic space. Both in the pollen tube and after isolation the sperm nucleus is in close association with at least one region of the sperm plasma membrane. Sperm isolated at room temperature showed the presence of nucleopores, and nuclei were euchromatic, instead of heterochromatic as in intact sperm in the pollen tube.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00190009
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  • 33
    Digitale Medien
    Digitale Medien
    Microsporogenesis and tapetal development in fertile and cytoplasmic male-sterile sugar beet (Beta vulgaris L.) (1991)
    Springer
    Sexual plant reproduction 4 (1991), S. 215-225 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Cytoplasmic male sterility ; Beta vulgaris ; Microsporogenesis ; Tapetum ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The development of sporogenous and tapetal cells in the anthers of male-fertile and cytoplasmic male-sterile sugar beet (Beta vulgaris L.) plants was studied using light and transmission electron microscopy. In general, male-sterile anthers showed a much greater variability in developmental pattern than male-fertile anthers. The earliest deviation from normal anther development was observed to occur in sterile anthers at meiotic early prophase: there was a degeneration or irregular proliferation of the tapetal cells. Other early aberrant events were the occurrence of numerous small vesicles in the microspore mother cells (MMC) and a disorganized chromatin condensation. Deviations that occurred in sterile anthers at later developmental stages included: (1) less distinct inner structures in the mitochondria of both MMC and tapetal cells from middle prophase onwards. (2) dilated ER and nuclear membranes at MMC prophase, in some cases associated with the formation of protein bodies. (3) breakdown of cell walls in MMCs and tapetal cells at late meiotic prophase. (4) no massive increase in tapetal ER at the tetrad stage. (5) a general dissolution of membranes, first in the MMC, then in the tapetum. (6) abortion of microspores and the occurrence of a plasmodial tapetum in anthers reaching the microspore stage. (7) no distinct degeneration of tapetal cells after microspore formation. Thus, it seems that the factors that lead to abortive microsporogenesis are structurally expressed at widely different times during anther development. Aberrant patterns are not restricted to the tetrad stage but occur at early prophase.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00190008
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  • 34
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics and tolerability of alpidem in healthy subjects given increasing single doses (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 369-374 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314970
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  • 35
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 449-452 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626367
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  • 36
    Digitale Medien
    Digitale Medien
    Dopamine pharmacokinetics in critically ill newborn infants (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 593-597 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279976
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  • 37
    Digitale Medien
    Digitale Medien
    The concentration-dependent disposition and kinetics of inulin (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 619-624 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279982
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  • 38
    Digitale Medien
    Digitale Medien
    Effect of ampicillin on mefloquine pharmacokinetics in thai males (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 631-633 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279985
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  • 39
    Digitale Medien
    Digitale Medien
    Lack of effect of multiple dose sucralfate on the pharmacokinetics of roxatidine acetate (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 637-638 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Roxatidine acetate ; sucraflate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279987
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  • 40
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of halofantrine and n-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 161-164 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Halofantrine ; Malaria falciparum ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax)=896 and 491 ng·ml−1; time to reach the Cmax (tmax)=15 and 56 h; elimination half-life (t1/2)=91 and 79 h and the mean residence time (MRT)=71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265910
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  • 41
    Digitale Medien
    Digitale Medien
    Fosinopril pharmacokinetics and pharmacodynamics in chronic ambulatory peritoneal dialysis patients (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 165-169 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Fosinopril ; fosinoprilat ; CAPD ; ACE-inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng·ml−1, 4.8 h, and 3.19 μg·h·ml−1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng·ml−1, tmax of 9 h, and AUC of 18.1 μg·h·ml−1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml·min−1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265911
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  • 42
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous bisoprolol in obese and non-obese volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 171-174 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bisoprolol ; pharmacokinetics ; obesity ; blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single i. v. dose of dlbisoprolol 0.16 mg·kg−1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 135 1) and a decrease in Vz per kg body weight (2 vs 2.7 l·kg−1). There was a negative correlation between Vz l·kg−1 and the percentage of ideal body weight (r=−0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265912
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  • 43
    Digitale Medien
    Digitale Medien
    Steady state pharmacokinetics of hydrolysed bopindolol in young and elderly men (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 175-178 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bopindolol ; pharmacokinetics ; beta-adrenoceptor blocker ; age ; hydrolysed bopindolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Steady-state pharmacokinetic parameters of the new, long-acting beta-adrenoceptor blocker bopindolol have been measured in 17 young and 20 elderly healthy men. The t1/2β and the AUC(0→24 h) of hydrolysed bopindolol (the active metabolite) were both increased (40% and 26%, respectively) in the elderly subjects but tmax, Cmax and CL/f were not altered. However, after adjusting the parameters to allow for the different average body weights of the two groups, Cmax and CL/f became significantly different (+29% and −30%, respectively). AUC(0→24 h) was increased by 41%. The changes of up to 41% in pharmacokinetic parameters were smaller than the alterations of 50–100% usually seen when titrating doses of antihypertensive drugs. The clinical relevance of the effects was not examined, but similar changes have been reported for other beta-blockers which did not appear to be clinically relevant and did not affect the dosage required to treat hypertension.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265913
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  • 44
    Digitale Medien
    Digitale Medien
    Dose-dependent absorption and elimination of cefadroxil in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 179-183 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cefadroxil ; saturable absorption ; saturable renal tubular reabsorption ; cephalexin ; competitive inhibition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg · kg−1. As the dose of cefadroxil increased from 5 to 15 and 30 mg · kg−1, the peak plasma concentrations, normalized to 5 mg · kg−1, decreased significantly from 15.1 to 10.7 and 7.6 mg·l−1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min·mg·l−1. When the same subjects were given 5 mg·kg−1 of cefadroxil together with 45 mg·kg−1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose of cefadroxil. Although the absorption rate decreased as the dose increased, the systemic availability of cefadroxil was essentially complete at all doses, as judged by the 24 h urinary recoveries of the antibiotic. Kinetic analysis of the plasma concentration-time curves gave the best fit with a zero-order followed by a first-order absorption process, consistent with saturable intestinal absorption of cefadroxil. The elimination rate of cefadroxil was directly related to dose and plasma concentrations, and the clearance at the dose of 5 mg·kg−1 was significantly increased by the simultaneous administration of high-dose cephalexin. The renal clearance of cefadroxil ranged from 98 ml·min·l−1 at total plasma cephalosporin (cefadroxil + cephalexin) concentrations less than 2.5 mg·l−1 to 156 mg·l−1 at concentrations greater than 40 mg·l−1. These findings are consistent with saturable active gastrointestinal absorption and renal tubular reabsorption of cefadroxil, with competitive inhibition of both processes by cephalexin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265914
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  • 45
    Digitale Medien
    Digitale Medien
    Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 245-250 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Org 10172 ; Digoxin ; heparinoid ; pharmacokinetics ; pharmacodynamics ; drug interactions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml·min−1, while plasma anti-thrombin and thrombin generation inhibiting (TGI) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng·ml−1·h, and a significant reduction in the average serum digoxin conentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315437
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  • 46
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tiaprofenic acid in children after a single oral dose (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 251-253 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tiaprofenic acid ; children ; pharmacokinetics ; NSAID
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary. Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg · kg−1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age; tmax=2.12h, Cmax=8.78mg · l−1, AUC(0→8 h) 33.9mg · h · l−1, AUC=39.3 mg · h · l−1, t1/2=2.35 h, Vz=0.319 l · kg−1, CL=0.094 l · h−1 · kg−1. Renal clearance was 14 ml · h−1. kg−1. 33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg · kg−1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3–11 year-old children from that in adults.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315438
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  • 47
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 355-357 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Midazolam ; pharmacokinetics ; intranasal ; intravenous ; children ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twelve children 1–5 y old were randomly assigned to receive midazolam 0.2 mg·kg−1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314967
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  • 48
    Digitale Medien
    Digitale Medien
    Antipyrine kinetics in undernourished diabetics (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 359-361 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes ; Antipyrine ; undernutrition ; drug metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits. The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314968
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  • 49
    Digitale Medien
    Digitale Medien
    Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 379-382 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314972
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  • 50
    Digitale Medien
    Digitale Medien
    Relationship between renal function and disposition of oral cefixime (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 579-583 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cefixime ; renal failure ; pharmacokinetics ; volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulte in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 μg·ml−1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL·f−1) was 154 ml·min−1, the mean renal clearance (CLR) was 39.1 ml·min−1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12–14 h in patients with an endogenous creatinine clearance below 20 ml·min−1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314988
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  • 51
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of chlormezanone in elderly patients (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 603-607 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlormezanone ; pharmacokinetics ; elderly
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of Chlormezanone (CM) has been determined after a single oral dose of 400 mg CM in 5 young volunteers (28 y) and in 8 elderly patients (79 y). In the young subjects, CM was rapidly absorbed and distributed, and was slowly eliminated with a half-life of 38 h major metabolites were not detected in plasma or urine. Only 3% of CM was excreted unchanged in urine. In elderly patients absorption was delayed but not reduced; the Cmax and AUC did not differ from those in younger subjects, the elimination rate was reduced compared to the younger subjects (mean 54 h). The increase was in part related to the reduction in renal function and metabolism observed in aging. However, the change in pharmacokinetics was moderate and no adjustment in dosage seems necessary for treatments of limited duration in elderly patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314993
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  • 52
    Digitale Medien
    Digitale Medien
    Clinical chronopharmacology of oral sustained-release isosorbide-5-mononitrate in healthy subjects (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 71-75 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Isosorbide-5-mononitrate ; sustained-release formulation ; pharmacokinetics ; cardiovascular effects ; chronopharmacology ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in relation to the individual circadian control values. The pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) did not differ after morning and after evening dosing, tmax being 5.2 h and 4.9 h, respectively. In contrast, the cardiovascular effects of IS-5-MN were clearly circadian phase-dependent. The maximum decrease in blood pressure decrease and increase in heart rate occurred significantly earlier after the evening (BPsys 2.8 h; BPdia 2.9 h; HR 3.8 h) than after the morning dose (BPsys 5.0 h; BPdia 6.0 h; HR 5.2 h). Thus, the peak haemodynamic effects coincided with the peak drug concentration after the morning dose, whereas the peak effect was in advance of the peak drug concentration after the evening dose of IS-5-MN. The data provide evidence of circadian phase-dependency in the dose-response relationship of oral IS-5-MN.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315142
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  • 53
    Digitale Medien
    Digitale Medien
    Pitfalls of pharmacokinetic dosage guidelines in renal insufficiency (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 87-93 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Pharmacotherapy ; renal insufficiency ; pharmacokinetics ; renal drug elimination ; drug monitoring ; dosage guidelines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary As the renal elimination of most drugs is closely correlated with the endogenous creatinine clearance, it is possible to use this parameter of kidney function to adjust drug dosage in renal failure. However, this simple procedure neglects possible changes in the volume of distribution, plasma protein binding, drug metabolism, intestinal absorption, and pharmacodynamics in renal insufficiency, as well as the occurrence of biologically active drug metabolities. Because of these uncertainties in critical cases the validity of the dosage calculated using the creatinine clearance should be checked by clinical surveillance and measurements of drug blood concentrations. Further, pharmacokinetic dosage guidelines based on the individual creatinine clearance may not be applicable to diuretics and drugs which have markedly differing kinetics of pharmacodynamic effects and blood levels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315145
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  • 54
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 101-106 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Ximoprofen ; pharmacokinetics ; normal subjects ; hepatic disease ; renal disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of ximoprofen, a potent new non-steroidal anti-inflammatory agent, has been investigated in normal healthy subjects and in patients with hepatic or renal disease. After intravenous infusion of 22.8 mg to healthy subjects, plasma ximoprofen concentrations declined in a polyexponential manner with a terminal phase half-life of 1.9 h. The systemic clearance of ximoprofen was 115 ml·min−1 and the volumes of distribution were 18.0 l Vz and 13.8 l Vss. Ximoprofen was 80–90% bound to plasma proteins. The systemic availabilities (f) of orally and rectally administered doses of 30 mg of ximoprofen were 98% and 56% respectively and, in the case of the rectal dose, absorption appeared to be prolonged leading to “flip-flop” kinetics. After single oral doses of 30 mg of ximoprofen to patients with hepatic disease, half-life (2.2 h), peak plasma concentrations (1.55 μg·ml−1 cf 1.04 μg·ml−1 in healthy subjects) and areas under the curve (6.12 μg·h·ml−1 cf 3.54 μg·h·ml−1 in healthy subjects) were significantly different from those in healthy subjects. After single oral doses of 30 mg of ximoprofen to patients with renal disease, pharmacokinetic parameters of half-life (4.0 h), mean residence time (6.0 h) and area under the curve (9.2 μg·h·ml−1) were significantly different from those in healthy subjects. There were no significant differences in pharmacokinetic parameters between patients having differing degrees of renal disease. These data nevertheless suggest that accumulation of ximoprofen in hepatic or renal disease would be of slight or negligible clinical relevance and that no alteration of the dose regimen (up to 15 mg twice daily) may be required when ximoprofen is administered in these disease states.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315147
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  • 55
    Digitale Medien
    Digitale Medien
    CSF Baclofen levels after intrathecal administration in severe spasticity (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 363-365 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Baclofen ; severe spasticity ; pharmacokinetics ; CSF ; intrathecal injection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters in the CSF of baclofen given to 4 patients as an intrathecal bolus are reported. Considerable inter-individual variability in the parameters was observed. The elimination half-life ranged from 0.9 to 5 h and the clearance from 0.013 to 0.08 l·h−1. In order to optimize treatment, it is suggested that CSF baclofen levels be matched to changes in Hoffman's monosynaptic reflex (H reflex).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265844
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  • 56
    Digitale Medien
    Digitale Medien
    Evaluation of proposed sulphoxidation pathways of carbocysteine in man by HPLC quantification (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 387-392 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Carbocysteine ; pharmacogenetics ; drug metabolism ; sulphoxidation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A quantitative study has been made of the metabolism of S-carboxymethyl-L-cysteine (CMC) and its sulphoxides in volunteers by HPLC. Precolumn derivatization was applied prior to gradient reversed phase HPLC separation and fluorescence detection. For CMC and its metabolites containing a primary amino group the reagent 9-fluorenylmethylchloroformate was used. The other metabolites of CMC were derivatized at their carboxylic group with 1-pyrenyldiazomethane to give stable fluorescent products. Urine samples were collected for 8 h after oral administration of 1.125 g CMC to 33 healthy volunteers. Elimination of CMC in urine as sulphoxides did not account for more than 1% of the dose in any of the volunteers. Thus, CMC-sulphoxide metabolites are not quantitatively important. Recovery of the original substance in 8-hour urines ranged from 10 to 30% and a further 2 to 20% was recovered as the metabolite thiodiglycolic acid. Oral doses of 0.19, 1.125, and 2.25 g CMC in a second group of 12 healthy volunteers did not reveal dose dependence of the urinary excretion of the sulphoxides or of thiodiglycolic acid. Serum concentration-time-curves of CMC, (S)- and (R)-CMC sulphoxide were measured in a group of 9 healthy volunteers. The CMC sulphoxides in serum reached 1.5% of the parent substance after 4 hours. The ratio of CMC to its sulphoxide metabolites was similar in serum and urine. Pharmacogenetic polymorphism of sulphoxidation was not confirmed by the specific HPLC methods used.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265849
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  • 57
    Digitale Medien
    Digitale Medien
    Interaction of metoprolol with lorazepam and bromazepam (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 405-409 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Metoprolol ; lorazepam ; bromazepam ; interaction ; psychomotor tests ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The interaction between metoprolol and bromazepam and lorazepam was studied in 12 healthy male volunteers aged 21–37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, bromazepam AUC was 35% higher in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but not on diastolic blood pressure or pulse rate. Lorazepam had no effect on either blood pressure or pulse. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol caused a small increase in critical flicker fusion threshold with lorazepam but had no effect on the other tests. Lorazepam (2 mg) was more potent than bromazepam (6 mg) in the doses used in this study. The interaction of metoprolol with bromazepam and lorazepam is unlikely to be of clinical significance. No change in dose is necessary when using these drugs together.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265852
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  • 58
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of ibuprofen in febrile children (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 427-428 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Ibuprofen ; children ; fever ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients. We studied 17 patients (age 3–10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media. Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients). Multiple blood samples were collected over 8 hours and analyzed by HPLC. The maximum observed serum concentrations of ibuprofen ranged from 17–42 μm·ml−1 at 5 mg·kg−1 and 25–53 μm·ml−1 at 10 mg·kg−1 doses. Pharmacokinetics did not appear to be affected by ibuprofen dose. Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml·min−1·kg−1, and 1.6 h, respectively in patients at 5 mg·kg−1 doses; the corresponding values were 1.2 h, 1.4 ml·min−1·kg−1, and 1.6 h in those receiving 10 mg·kg−1 doses. There was no relationship between age and ibuprofen kinetics. No adverse effects occurred in any patients. These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265858
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  • 59
    Digitale Medien
    Digitale Medien
    Disposition of epirubicin and metabolites with repeated courses to cancer patients (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 481-487 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Epirubicin ; pharmacokinetics ; plasma concentrations ; cancer patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Thirteen cancer patients were studied following a total of 41 courses of epirubicin (EPI) (38–50 mg·m−2, mean 49.2 mg·m−2, administered by a 60 min infusion), together with other cancer chemotherapeutic agents. The aim was to consider the disposition of EPI and metabolites following subsequent courses as it has been reported that doxorubicin (the 4′-epimer parent of EPI) clearance is increased following the first administration. We have observed that EPI-glucuronide accounted for a mean 78.0%, epirubicinol 0.2% and epirubicinol-glucuronide 19.3% and that parent EPI accounted for only 2.4% of the EPI-compounds measured (mean of all patients and courses) for the 3 h period immediately following the infusion. These data confirm the rapid metabolism of EPI and the dominance of the glucuronidation metabolite pathway (which is not available to doxorubicin) and are compared with the metabolite profile observed in other reports. Large inter- and intra-individual variability in area under the plasma concentration/time curve were observed with no clear evidence of any consistent directional trend for such fluctuations, suggesting that factors contributing to EPI disposition are multivariate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315227
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  • 60
    Digitale Medien
    Digitale Medien
    Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 155-162 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; sparteine/debrisoquine polymorphism ; metabolism ; enantiomers ; pharmacokinetics ; stereoselectivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of R- and S-flecainide have been determined in five poor (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under conditions of uncontrolled urine flow and pH. The half-lives of R- and S-flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide were lower in PMs (R 313 ml·min−1; S 379 ml·min−1) than in EMs (R 783 ml·min−1; S 828 ml·min−1). The renal clearance, however, was comparable for both enantiomers in both EMs and PMs, and therefore the phenotypic differences in flecainide disposition observed must be due to differences in metabolic clearance. The nonrenal clearance of both enantiomers was significantly lower in poor (R 123 ml·min−1; S 201 ml·min−1) relative to extensive metabolisers (R 533 ml·min−1; S 586 ml·min−1). The partial clearance to the two major metabolites meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) was significantly lower in poor (62 ml·min−1) than extensive (267 ml·min−1) metabolisers. The impairment in flecainide metabolism in poor metabolisers of sparteine/debrisoquine has therefore been confirmed. Under conditions reflecting the clinical situation the difference in disposition between EMs and PMs would be considerable. However, it may be predicted that at standard doses concentrations greater than 1000 ng·ml−1 would not be attained in the PMs studied. The serum protein binding of R- and S-flecainide was studied in each subject and no differences between the enantiomers or the phenotypes were observed (Free fraction EM: R 0.43; S 0.42; PM R: 0.46; S: 0.46). Enantioselective disposition was noted in all PMs studied, due to a significantly lower nonrenal clearance of the R-enantiomer. In extensive metaboliser subjects, considerable interindividual variation in the enantioselective disposition of flecainide was noted, ranging from metabolism favouring either enantiomer to the absence of any selectivity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280070
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  • 61
    Digitale Medien
    Digitale Medien
    The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 163-168 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tolbutamide ; diabetes mellitus ; non-insulin dependent ; pharmacokinetics ; pharmacodynamics ; glucose ; insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The interrelationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol·l−1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280071
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  • 62
    Digitale Medien
    Digitale Medien
    The origin and abundances of the chemical elements revisited (1991)
    Springer
    The astronomy and astrophysics review 3 (1991), S. 1-46 
    Details
    ISSN: 1432-0754
    Schlagwort(e): Nucleosynthesis ; Nuclear reactions ; Stars: abundances ; Interstellar Medium: abundances ; Cosmology ; Galaxies: evolution of
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Physik
    Notizen: Summary The basic scheme of nucleosynthesis (building of heavy elements from light ones) has held up very well since it was first proposed more than 30 years ago by E.M. Burbidge, G.R. Burbidge, A.G.W. Cameron, W.A. Fowler, and F. Hoyle. Significant advances in the intervening years include (a) observations of elemental and a few isotopic ratios in many more extrasolar-system sites, including metal-poor dwarf irregular galaxies, where very little has happened, and supernovae and their remnants, where a great deal has happened, (b) recognition of the early universe as good for making all the elements up to helium, (c) resolution of heavy element burning in stars into separate carbon, neon, oxygen, and silicon burning, with fine tuning of the resulting abundances by explosive nucleosynthesis in outgoing supernova shock waves, (d) clarification of the role of Type I supernovae, (e) concordance between elements produced in short-lived and long-lived stars with those that increased quickly and slowly over the history of the galaxy, and (f) calibration of calculations of the evolution and explosion of massive stars against the detailed observations of SN 1987A. The discussion presupposes a reader (a) with some prior knowledge of astronomy at the level of recognizing what is meant by an A star and an AGB star and (b) with at least a mild interest in how we got to where we currently are.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00873456
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  • 63
    Digitale Medien
    Digitale Medien
    Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 459-462 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Levodopa/decarboxylase inhibitor ; Parkinson's Disease ; pharmacokinetics ; duration of therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We address, from a pharmacokinetic viewpoint, the important question of why some patients with clinical idiopathic Parkinson's disease experience a fall off in benefit from levodopa maintenance therapy. Thirteen such patients, of mean age 78 y, without overt fluctuations in motor control in temporal relation to dosing with a levodopa/decarboxylase inhibitor combination, were studied. Levodopa (currently 400 to 800 mg daily) had been started at between 61 and 81 y of age, the mean duration of therapy being 54 months. Plasma concentrations of levodopa and its peripheral metabolite, 3-0-methyldopa, were measured before a morning dose of levodopa (100 mg)/carbidopa (25 mg) and at hourly intervals for 6 h after. There was a significant negative regression between duration of levodopa therapy (but not age or severity of disease) and the area under the plasma concentration/time curve (AUC) for levodopa attributed to the test dose. A significant negative regression was also seen of duration of therapy on the dose absorbed per unit distribution volume, but not on the elimination rate constant, indicating a decrease in bioavailability and/or an increase in distribution volume with duration. There was a tendency for the plasma 3-0-methyldopa concentration, standardised for daily dose, [30MD], to increase with duration of therapy. Although, the regression of duration on [30MD] did not reach statistical significance, that on the ratio, [30MD]/AUC, did so at the 0.01 level. The amount by, and time for which, the plasma levodopa concentration exceeds any critical threshold for the competitive active uptake process into the brain may thus decrease with duration of therapy. This may explain in part the limited reversal of the neurological deficit, which is more typical of later onset Parkinsonism, and, possibly, the decrement in biological half time with duration of therapy, typical of early onset disease. 3-0-Methyldopa is known to compete for active uptake with levodopa; the ratio, [30MD]/AUC, may be a measure of this competition. Intrinsic activity of neuronal uptake mechanisms, capacity of the basal ganglia for storage of dopamine, and post synaptic neuronal activity may, of course, also be determinants of clinical outcome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626369
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  • 64
    Digitale Medien
    Digitale Medien
    Elimination of flecainide as a function of urinary flow rate and pH (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 61-63 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; dose adjustment ; urinary pH ; urinary flow rate ; renal elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In order to evaluate the influence of urinary flow rate at different pH values on the pharmacokinetics of the basic antiarrhythmic drug flecainide 7 healthy men received 50 mg flecainide under 4 different conditions: 1. acidic urine (pH 5) and a high fluid load (125 ml · h−1) 2. acidic urine (pH 5) and a low fluid load (25 ml · h−1) 3. alkaline urine (pH 8) and a high fluid load (125 ml · h−1) 4. alkaline urine (pH 8) and a low fluid load (25 ml · h−1) At acidic pH the half-life, the amount of unchanged drug in the urine (Ae), renal clearance (CLR) and area under the curve (AUC) were independent of the fluid load. At alkaline pH Ae (5.8 vs 2.6 mg) and CLR (73 vs 33 ml · min−1) were significantly affected by fluid load (high vs low), whereas half-life and AUC were not different (15.7 vs 16.0 h, 1480 vs 1540 ng · ml−1 · h). When comparing acidic and alkaline urinary pH conditions, half-life, Ae, CLR, and AUC were different. For a high fluid load the values at acidic vs alkaline pH were half-life 10.0 vs 15.7 h; Ae 15.9 vs 5.8 mg; CLR 288 vs 73 ml · min−1; AUC 976 vs 1480 ng · ml−1 · h. For a low fluid load the corresponding values at acidic vs alkaline pH were half-life 10.1 vs 16.0 h; Ae 15.9 vs 2.6 mg; CLR 267 vs 33 ml · min−1; AUC 1045 vs 1540 ng · ml−1 · h. It is concluded that urinary pH affects flecainide pharmacokinetics independently of urinary flow rate, and that a high flow enhances the elimination of flecainide only with an alkaline urine. This effect of flow rate does not appear to be of clinical relevance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280108
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  • 65
    Digitale Medien
    Digitale Medien
    Kinetics of cholinesterase inhibition by eptastigmine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 83-84 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Eptastigmine ; cholinesterase inhibitor ; Alzheimer's disease ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280116
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  • 66
    Digitale Medien
    Digitale Medien
    Pharmacokinetic investigation of oral and IV dihydroergotamine in healthy subjects (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 597-602 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dihydroergotamine mesilate ; pharmacokinetics ; urinary excretion ; prolonged half-life ; deep compartment ; RIA ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A new radioimmunoassay (RIA) for the specific measurement of dihydroergotamine (DHE), sufficiently sensitive for the determination of low plasma concentrations, has been used to investigate the pharmacokinetics of unchanged DHE. In a randomized crossover trial, eight healthy male volunteers received single doses of DHE 5 mg, 10 mg and 20 mg orally and 0.1 mg and 0.5 mg intravenously. It was possible to determine plasma concentrations and urinary excretion of DHE over the following 48 h. A long terminal plasma elimination phase of unchanged DHE (half-life 15 h) was found. A similar terminal elimination half-life was also calculated from urine data. The multi-exponential decline in plasma DHE with a long terminal half-life suggests that distribution into a deep compartment contributes to the long-lasting effect of the drug. Plasma protein binding was 93%. Despite extensive tissue distribution (Vz=33 l/kg) and a high plasma clearance (CLP=2l/min), dose-independent linear pharmacokinetics was observed. The present assay was at least 20-times more specific than the polyvalent RIA used previously and appears suitable to explore the pharmacokinetics of unchanged DHE in patients on low-dose therapy. The long terminal elimination half-life of DHE only reported previously in studies using 3H-labelled drug, and considered to be due to metabolites, was also true for the parent compound. This, in addition to the sustained pharmacological activity of the 8′-hydroxy metabolite already shown, provides a further explanation for the long duration of action of DHE in animals and man.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314992
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  • 67
    Digitale Medien
    Digitale Medien
    Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 615-617 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Piperine ; Propranolol ; Theophylline ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of piperine on the bioavailability and pharmacokinetics of propranolol and theophylline has been examined in a crossover study. Six subjects in each group received a single oral dose of propranolol 40 mg or theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7 days. An earlier tmax and a higher Cmax and AUC were observed in the subjects who received piperine and propranolol. It produced a higher Cmax, longer elimination half-life and a higher AUC with theophylline. In clinical practice, the enhanced systemic availability of oral propranolol and theophylline could be exploited to achieve better therapeutic control and improved patient compliance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314996
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  • 68
    Digitale Medien
    Digitale Medien
    Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 141-145 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Platelet activating ; Factor RP 48740 ; platelet aggregation ; PAF-antagonist ; dose-response relationship ; adverse effects ; pharmacokinetics ; dose-response relationship
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and exvivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg·l−1. There were no clinical or biological adverse reactions to RP 48740 during the study.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265907
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  • 69
    Digitale Medien
    Digitale Medien
    Enantioselective steady-state kinetics of unbound disopyramide and its dealkylated metabolite in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 481-484 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Disopyramide ; pharmacokinetics ; protein binding ; enantiomers ; metabolism ; metabolite kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Disopyramide is provided as a racemic mixture of R and S enantiomers, which have different pharmacodynamic and pharmacokinetic characteristics. Five volunteers were given racemic disopyramide 100 mg and 200 mg t.d.s. in a cross-over design. Plasma and urine concentrations of disopyramide and its active metabolite monodesisopropyl-disopyramide (MND) were determined at steady state by an enantioselective HPLC method. Unbound drug in plasma was measured after ultrafiltration. There was enantioselective clearance of unbound disopyramide (0.39 l.h−1.kg−1 for R-disopyramide and 0.58 l.h−1.kg−1 for S-disopyramide after 100 mg t.d.s.). The enantioselectivity was due to differences in the metabolism of disopyramide to MND and in further non-renal clearance, and the renal clearance of disopyramide was not enantioselective. The in vivo protein binding of disopyramide, which was saturable for both enantiomers, was also enantioselective. The difference in binding of the two enantiomers was explained by a difference in apparent binding capacity rather than in apparent binding affinity. The renal clearance of S-MND was significantly higher than R-MND (0.29 and 0.19 l.h−1.kg−1, respectively, after 100 mg t.d.s.). The renal clearance of MND also showed a tendency to saturation at higher concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626374
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  • 70
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of oral salbutamol controlled-release in Asian patients with asthma (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 495-496 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Asthma ; Salbutamol ; Asians ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a double blind, double dummy crossover design, single dose and steady state pharmacokinetics of oral controlled release (SCR) salbutamol 4 mg and 8 mg tablets b. d. has been studied in 8 Asian patients. Plasma salbutamol was measured over 12 h. In 8 patients the single dose mean Cmax was 4.2 ng·ml−1 and 7.7 ng·ml−1 after 4 and 8 mg, respectively. In 5 patients the steady state mean Cmax, Cmin and tmax were 8.1 ng·ml−1 and 4.7 ng·ml−1 and 6 h for the 4 mg tablets and 14.1 ng·ml−1 and 7.1 ng·ml−1 and 4 h for the 8 mg tablets. It is concluded that both doses of SCR show features of controlled release and that they produced a relatively constant plasma level of salbutamol in Asian patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626378
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  • 71
    Digitale Medien
    Digitale Medien
    Relation between plasma concentration and clinical efficacy after sublingual single dose apomorphine in Parkinson's disease (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 493-494 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Parkinson's disease ; Apomorphine ; pharmacokinetics ; adverse effect ; on-off effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five patients with Parkinson's disease were given a single sublingual dose of apomorphine in 3 mg tablets (2 patients received 18 mg and 3 patients took 39 mg). The therapeutic effect appeared within 33.0 min and lasted 137 min. There was a significant correlation between peak concentration, area under the curve, dose (mg/kg) and the duration of the therapeutic effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626377
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  • 72
    Digitale Medien
    Digitale Medien
    Therapeutic monitoring of cyclosporin — an update (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 273-283 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporin A ; therapeutic monitoring ; assay techniques ; pharmacokinetics ; dose-response relationships
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The success of organ transplantation is closely related to clinical use of the immunosuppressive drug cyclosporin (CsA). The dosage of CsA is complicated by the large intra- and interindividual variability in its pharmacokinetics, as well as by the narrow concentration range between insufficient immunosuppression and toxicity. Potential sources of error in the sampling procedure and the advantages and disadvantages of the available analytical methods are discussed. Traditionally, 12 or 24 hour trough concentrations of CsA are monitored. Recently, peak concentrations or estimation of AUCs by a limited sampling strategy have been tried to improve the relatively weak concentration-effect and concentration-toxicity relationships found with trough CsA concentration monitoring. Studies of the CsA concentration-effect relationships for various treatment indications are reviewed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314952
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  • 73
    Digitale Medien
    Digitale Medien
    Verapamil in the prophylaxis of bronchial asthma (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 317-319 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Asthma ; Verapamil ; histamine-induced bronchoconstriction ; calcium antagonists ; plasma levels ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced bronchoconstriction in 8 out of 16 asthmatic subjects (maximum increase in PD20FEVHi 416%). There was still significant protection (Δ PD20FEV1Hi〉100%) in the responders 5 h after the oral dose. The relationship of the bronchoprotective effect to the plasma level of verapamil was also examined. Responders and non-responders did not differ significantly in the peak plasma level or the time course of the plasma verapamil concentration. The protective effect was not correlated with the peak plasma level of verapamil or with the baseline bronchial hyperreactivity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314959
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  • 74
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of paroxetine in patients with cirrhosis (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 351-354 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Paroxetine ; Cirrhosis ; pharmacokinetics ; multiple-dose study ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20–30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg. Dose-corrected, trough drug concentration at steady state (CSS min) and dose-corrected AUC24h were significantly higher in the patients with liver diseases than in the control subjects [3.4 vs 1.5 ng · ml−1 per mg paroxetine and 89 vs 43 h (ng) · ml−1 per mg paroxetine]. The elimination t1/2 was prolonged [83 vs 36 h], but the difference was not statistically significant, and the cirrhotic patients were still able to clear almost all the paroxetine by metabolism. All but two patients with cirrhosis experienced nausea during the first two or three days after the first dose, while none of the controls had this symptom. The study showed slower elimination of paroxetine and consequently higher plasma levels in patients with cirrhosis, suggesting that in the latter the dose of paroxetine should be in the lower end of the therapeutic range.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314966
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  • 75
    Digitale Medien
    Digitale Medien
    Dose-dependent pharmacokinetics of benzoic acid following oral administration of sodium benzoate to humans (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 363-368 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Benzoic acid ; hippuric acid ; pharmacokinetics ; hyperammonaemia ; ureagenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentration-time data for benzoic and hippuric acids and urinary excretion-time data for hippuric acid were analyzed simultaneously after oral doses of 40, 80 or 160 mg/kg sodium benzoate administered at least one week apart to 6 healthy subjects. The mean AUCs of benzoic acid after the doses of 80 and 160 mg/kg of sodium benzoate were 3.7- and 12.0-times greater, respectively, than after 40 mg/kg. However, the mean AUC of hippuric acid was roughly proportional to the benzoate doses. The observed data were explained by a one-compartment model with first-order rate absorption and Michaelis-Menten elimination of benzoic acid, together with a one-compartment model with first-order elimination for hippuric acid. Although the maximum rate of biotransformation of benzoic acid to hippuric acid varied between 17.2 and 28.8 mg·kg−1·h−1 among the six individuals, the mean value (23.0 mg·kg−1·h−1) was fairly close to that provided by daily maximum dose (0.5 g·kg−1·day−1) recommended in the treatment of hyperammonaemia in patients with inborn errors of ureagenesis. The individual maximum rate of metabolism can be estimated from the urinary excretion rate of hippuric acid 1.5 to 3 h after the single oral dose of 80 to 160 mg·kg−1 sodium benzoate. The justification of this concept requires further studies in patients with inborn errors of urea synthesis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314969
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  • 76
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intramuscular nicomorphine and its metabolites in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 375-378 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nicomorphine ; 6-nicotinoylmorphine ; morphine ; intramuscular administration ; metabolism ; absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary After i.m. injection nicomorphine is relatively slowly absorbed from the muscular depot and is found in the serum for approximately 1 h. The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound. The relative AUCs were nicomorphine 18%, 6-nicotinoylmorphine 17%, and morphine 65%. Nicomorphine and 6-nicotinoylmorphine have significantly higher AUCs after i.m. injection than after i.v. injection, while the AUC of morphine and the total AUC show no difference between the two modes of administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314971
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  • 77
    Digitale Medien
    Digitale Medien
    Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 305-308 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Zidovudine ; acquired immunodeficiency syndrome (AIDS) ; pharmacokinetics ; bioavailability ; food intake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations 〉1 μmol · l−1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315215
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  • 78
    Digitale Medien
    Digitale Medien
    Absorption of theophylline from a new theophylline controlled-release capsule (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 319-320 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Theophylline ; controlled-release formulation ; absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315219
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  • 79
    Digitale Medien
    Digitale Medien
    Diuretic effect and disposition of furosemide in cystic fibrosis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 333-341 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; cystic fibrosis ; pharmacokinetics ; diuretic effect ; baseline urine flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner. The sweat test was significantly perturbed in those subjects, although the concentration of chloride in sweat did not fall below 60 mEq/l in any of the sweat samples tested.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265840
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  • 80
    Digitale Medien
    Digitale Medien
    The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous, intramuscular, and subcutaneous injection (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 399-403 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Lisuride ; pharmacokinetics ; prolactin concentrations ; healthy volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 μg lisuride hydrogen maleate as an aqueous solution. After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml·min−1·kg−1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration. The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265851
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  • 81
    Digitale Medien
    Digitale Medien
    Disposition of oral quinine in acute falciparum malaria (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 49-52 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Quinine ; pharmacokinetics ; falciparum malaria
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma quinine concentrations following oral quinine sulphate 10 mg salt/kg have been measured by HPLC in 15 adult Thai patients with uncomplicated falciparum malaria. In 10 of the same patients the study was repeated in convalescence. In acute malaria plasma concentrations were approximately 50% higher than in convalescence; the mean acute peak plasma quinine concentration was 8.4 mg·l−1 compared to 5.7 mg·l−1 in convalescence. There was considerable variation in the rate of drug absorption, particularly in acute malaria. The mean time to peak plasma concentration was 5.9 h in acute malaria and 3.2 h in convalescence. The apparent clearance of oral quinine (CL/f) during the illness was 1.51 ml·kg−1·min−1, which was significantly lower than in convalescence — 2.67 ml·kg−·min−1. Estimated free quinine clearance was also lower in the acute phase: 30.6 compared to 49.0 ml·kg−1·min−1 in convalescence. Mean (SD) plasma protein binding of quinine was 94.7% in acute malaria and 92.8% in convalescence. Binding was significantly correlated with the plasma concentration of α1 acid glycoprotein (r=0.5), which was significantly higher in the acute phase; 1.48 g·l−1 compared to 1.05 g·l−1 during convalescence. Oral quinine sulphate was well absorbed in uncomplicated falciparum malaria. High blood concentrations following the administration of oral quinine in acute malaria are probably related to increased plasma protein binding, lower apparent volume of distribution, and a reduction in its systemic clearance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315138
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  • 82
    Digitale Medien
    Digitale Medien
    Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 61-65 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Omeprazole ; substituted benzimidazole ; metoprolol ; interaction ; cytochrome P450 ; debrisoquine hydroxylase ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o. d. as a controlled release formulation, and omeprazole 40 mg o. d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism. As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315140
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  • 83
    Digitale Medien
    Digitale Medien
    Is there a need for more precise definitions of bioavailability? (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 123-126 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bioavailability definition ; health authorities ; pharmacokinetics ; drug registration Participants: L. P. Balant (Geneva, Switzerland), L. Z. Benet (San Francisco, USA), H. Blume (Eschborn, FRG), G. Bozler (Biberach, FRG), D. D. Breimer (Leiden, The Netherlands), M. Eichelbaum (Stuttgart, FRG), U. Gundert-Remy (Berlin, FRG), J. L. Hirtz (Paris, France), E. Mutschler (Frankfurt, FRG), K. K. Midha (Saskatoon, Canada), A. G. Rauws (Bilthoven, The Netherlands), W. A. Ritschel (Cincinnati, USA), L. N. Sansom (Adelaide, Australia), J. P. Skelly (Rockville, USA), and K.-O. Vollmer (Freiburg, FRG)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary After evaluation of the present definitions in a set of particular cases, it was agreed that there was no need for “more precise” definitions and that the current ones were adequate in the majority of cases. However, it was felt that the present definitions might be improved, in particular in view of the existence of non-systemically acting drugs and future “targeted drugs”. Thus, the FDA definition might be modified as follows: “Bioavailability means the rate and extent to which the active drug ingredient or therapeutic moiety from a drug product becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action”.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280064
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  • 84
    Digitale Medien
    Digitale Medien
    Changes in gentamicin pharmacokinetic profiles induced by mechanical ventilation (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 297-302 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Gentamicin ; pharmacokinetics ; mechanical ventilation ; therapeutic dose range
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of controlled mechanical ventilation (CMV) on the pharmacokinetic profile of gentamicin has been examined in 23 patients after elective open heart surgery. A parallel design was adopted in two groups of patients: 13 patients requiring CMV for at least 32 h after surgery, all of whom were able to breath spontaneously (SB) after 72 h (study group), and 10 patients who required CMV for only a brief period and who showed SB at 32 h postsurgery. Haemodynamic parameters remained stable throughout the study. Apparent volume of distribution (Vz), half-life (t1/2), total clearance (CL), peak (C max ss ) and trough (C min ss ) plasma levels at steady-state for target levels (6–8 μg/ml), were measured. In the study group significant differences between CMV and SB conditions were found in Vz (mean 0.36 and 0.25 l/kg), t1/2 (mean 3.63 and 2.90 h) and C max ss (mean 4.30 and 5.53 μg/ml) while C min ss (mean 1.06 μg·ml−1 and 0.92 μg·ml−1) did not change significantly. In contrast, the pharmacokinetics in the control group showed no differences. It appears that CMV leads to an increase in gentamicin Vz, which accounts for the fall in C max ss below the therapeutic dose range (〈5 μg/ml) recommended for gentamicin. It seems advisable to use a larger dose of gentamicin in patients receiving CMV, even before the level is assessed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315213
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  • 85
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 65-68 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlordesmethyldiazepam ; pharmacokinetics ; i.v./p.o. administration ; renal failure ; protein binding ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The kinetics was also examined after a single 2 mg oral dose in 6 of the 11 renal failure patients. After intravenous administration the kinetics of total chlordesmethyldiazepam in renal patients and controls were the same. The unbound fraction of the drug in renal patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed a reduced apparent volume of distribution (47 vs. 140 l · kg−1) and a reduced clearance (5.0 vs. 10.5 ml · min−1 · kg−1) in the patients. The systemic availability of oral chlordesmethyldiazepam was good (82%) despite a relatively slow absorption rate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280109
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  • 86
    Digitale Medien
    Digitale Medien
    Response to furosemide during dehydration with and without naproxen pretreatment of kidney donors and renal transplant recipients (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 209-214 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; renal transplant recipients ; kidney donors ; naproxen ; dehydration ; pharmacokinetics ; salt-regulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The response to 40 mg furosemide p.o. in 6 healthy kidney donors and 6 renal transplant recipients with and without naproxen pretreatment has been studied. No volume replacement was given in order to study the development of tolerance. The subjects showed an average dehydration of 1.5 kg · 6 h−1. While mean creatinine clearance was equal in patients and donors (76 vs 80 ml/min), renal furosemide clearance was significantly lower in the patients (47 vs 81 ml/min; P〈0.05). The patients also excreted a smaller fraction of the dose in the urine (5.7 vs 7.8 mg/6 h; P〈0.05). As the overall renal sensitivity was similar in the two groups, the natriuretic response was correspondingly smaller in transplant recipients as compared to donors. Within the observation period of 6 h after dosing, acute tolerance developed in the donors and in 4 of the 6 patients, as shown by clockwise hysteresis in the dose (urine furosemide excretion rate)-response (natriuresis) curves. Pretreatment with naproxen reduced renal sensitivity to furosemide (right shift of the dose response curve) in all the donors but in only 2 of the patients. In both groups acute tolerance was less pronounced after naproxen, which may indicate involvement of the prostaglandin system in the development of acute tolerance. The results may also indicate regeneration of sympathetic nerves with functional capacity in at least some renal transplants, or that other mechanisms of salt regulation compensate for loss of sympathetic nerve activity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315197
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  • 87
    Digitale Medien
    Digitale Medien
    Monitoring of the free concentration of cyclosporine in plasma in man (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 571-575 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporine ; free drug in plasma ; therapeutic drug monitoring ; renal transplantation ; plasma binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The free fraction of cyclosporine A (CsA) and its total plasma concentration as determined by HPLC(CsAT) were prospectively monitored in 66 recipients of renal transplants. The free CsA levels (CsAu) were calculated. The variability in free CsA levels was no less than for total CsAT levels. The correlation between CsAu and CsAT was high (r=0.90). Both CsAT and CsAu covaried with serum triglycerides and apolipoprotein A1. Fourty-four of the 66 patients suffered acute rejection episodes on 69 occasions. CsAT and CSAu both decreased and to a similar extent at the occurrence of acute rejection (42% and 59% decrease, respectively; significant vs baseline. Notsignificant difference in decrease in CsATvsCsAu). Acute nephrotoxicity occurred on 11 occasions in 10 patients. Both CsAT and CSAu were approximately twice as high at the time of acute nephrotoxicity as compared to one week previously. Both CsAT and CsAu were higher during the first month after transplantation in patients with than in patients without systemic infection. Thus, plasma CsAu gave no additional clinical information or guidance compared to CsAT in renal transplant recipients. Due to the complexity of its assay, which requires two consecutive analyses, there does not appear to be any need for routine monitoring of CsAu in renal transplant recipients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279972
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  • 88
    Digitale Medien
    Digitale Medien
    Flecainide: evidence of non-linear kinetics (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; pharmacokinetics ; ventricular arrhythmias
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of flecainide has been studied in 12 patients with ventricular arrhythmias, both after single administration and during chronic treatment. Both the half-life and the AUC were significantly increased during chronic treatment. This suggests that the kinetics of flecainide might be non-linear also in patients with normal kidney and liver function. The increase in plasma flecainide levels during chronic treatment could not be predicted, so close monitoring of its plasma levels is advisable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280107
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  • 89
    Digitale Medien
    Digitale Medien
    Pharmacokinetic profile and tolerability of pimobendan in patients with terminal renal insufficiency (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 107-111 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Pimobendan ; pharmacokinetics ; tolerability ; renal impairment ; adverse effects ; haemodynamic actions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of an i.v. bolus of pimobendan (P) 2.5 mg and 5.0 mg, its tolerability and the effect on heart rate and blood pressure have been studied in 12 subjects (42–70 y) suffering from severe terminal renal impairment. Plasma level data were compared with those obtained in a previous investigation in healthy volunteers. Pharmacokinetics were dose linear and were comparable to those in healthy subjects. No adjustment of the dose of P is necessary in patients with severe renal impairment. Tolerability of P, observed by means of blood pressure monitoring, clinical chemistry tests, electrocardiography and subjective judgement resulted in 4 complaints out of 12 patients: three suffered from orthostatic problems and vomiting, and one patient had nausea. Mean heart rate was elevated by 19% (2.5 mg) and 16% (5.0 mg). Blood pressure was significantly reduced after 2.5 mg P (23% systolic and 26% diastolic pressure), and after 5.0 mg P by 25% systolic and 23% diastolic pressure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315148
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  • 90
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of 3-day continuous infusion cisplatin and daily bolus 5-Fluorouracil (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 115-117 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cisplatin ; 5-Fluorouracil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315150
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  • 91
    Digitale Medien
    Digitale Medien
    Continuous infusion of high-dose metoclopramide: comparison of pharmacokinetically adjusted and standard doses for the control of cisplatin-induced acute emesis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 283-286 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Metoclopramide cancer chemotherapy ; emesis ; continuous infusion ; pharmacokinetics ; cisplatin ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Metoclopramide was administered by continuous infusion to two groups each of 14 patients on chemotherapy, randomized to receive either doses adjusted to individual pharmacokinetic parameters or doses adjusted as usual to body weight. The mean plasma concentration at the end of the infusion in the adjusted group was 1.01 mg · 1−1, close to that aimed for (1.20 mg · 1−1). It was significantly different from that in the other group, v0.54 mg · 1−1. Antiemetic efficacy, defined as ⩽2 emetic events in the 24 h following cisplatin, was similar in both groups (being found in 12/14 (86%) and 10/14 patients (71%), respectively). Analysis of the cumulative percentage of responders according to plasma concentration showed a clear plasma concentration-effect relationship. Routine MCP pharmacokinetic dosage adjustment is not indicated, but this therapeutic approach can be used to optimize antiemetic therapy in poor responder patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315210
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  • 92
    Digitale Medien
    Digitale Medien
    Cyclosporine pharmacokinetics in liver transplant recipients: evaluation of results using both polyclonal radioimmunoassay and liquid chromatographic analysis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 513-519 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporine ; liver transplant recipients ; radioimmunoassay ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic variables were derived from cyclosporine measurements using liquid chromatography (HPLC) and radioimmunoassay with a non-selective polyclonal antibody (PARIA) in 11 orthotopic liver transplant recipients studied in paired oral and intravenous studies both before and after permanent clamping of the biliary T-tube. After oral drug administration, mean areas under blood cyclosporine concentration versus time curves before clamping were around 5.2-fold greater by PARIA than HPLC but 2.9-fold greater after clamping and closer to comparable values after intravenous cyclosporine (2.5 and 2.3-fold, respectively). Cyclosporine clearance was smaller by PARIA than HPLC (mean 7.3 versus 3.3 ml · min−1 · kg−1, respectively, before clamping). Both values decreased by 25% after clamping (to 5.5 and 2.4 ml · min−1 · kg−1, respectively), although there was no significant change in distribution or elimination half-lives (around 0.5 and 8 h, respectively). The mean bioavailability of oral cyclosporine increased significantly after clamping in 9 patients (from 10.6% to 28.1% by HPLC and from 14.8 to 35.1% by PARIA) but in two patients who developed the vanishing bile duct syndrome values fell to 〈 10% and the proportional overestimation of cyclosporine concentrations by PARIA increased. Clamping had no significant effect on the mean apparent volumes of distribution but values of Vz were approximately twice those of Vss (around 2.6 and 1.3 l · kg−1 by PARIA and HPLC respectively). Mean half lives after clamping were shorter following oral than intravenous cyclosporine (t1/2λ2 around 15 h enterally versus 8 h parenterally). These data suggest delays in cyclosporine absorption and significant first pass metabolism which may contribute to higher PARIA:HPLC ratios after oral dosing and to reduced bioavailability before clamping.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315232
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  • 93
    Digitale Medien
    Digitale Medien
    Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients — a comparison of two oral formulations (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 585-591 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Morphine ; metabolites ; clinical trial ; pharmacokinetics ; controlled release formulation ; cancer patients ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC. There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The tmax was 3.3 h for the tablets compared to 1.1 h for the solution. After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively. Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer tmax and greater fluctuation in morphine concentrations after the controlled-release tablets.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279975
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  • 94
    Digitale Medien
    Digitale Medien
    Sublingual captopril — a pharmacokinetic and pharmacodynamic evaluation (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 393-398 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265850
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  • 95
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 411-414 
    Details
    ISSN: 1432-1041
    Schlagwort(e): SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265853
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  • 96
    Digitale Medien
    Digitale Medien
    Fluoride effects on leaf cell ultrastructure of olive trees growing in the vicinity of the Aluminium Factory of Greece (1991)
    Springer
    Trees 5 (1991), S. 83-89 
    Details
    ISSN: 1432-2285
    Schlagwort(e): Air pollutants ; Chloroplasts ; Fluoride ; Olive tree leaves ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Summary Leaves of olive trees growing in the vicinity of the Aluminium Factory of Greece were ultrastructurally investigated in order to determine any malformations caused by environmental air pollutants, especially hydrogen fluoride, in comparison with control samples and normal seasonal senescence. Estimation of some elements accumulated by these leaves showed that they contained high amounts of F and Al attributable to the operation of the nearby factory. The most seriously effected cell components were found to be the mesophyll chloroplasts that show a dilation of the intrathylakoid space, increase of the number of plastoglobuli, discoloration of plastoglobuli, accumulation of large starch grains and an overall disorganized appearance of the organelle. The nuclear crystalloid inclusions have unusual shapes, while the vacuoles contain a fibrillar/granular material that increases their electron density. It is concluded that the ultrastructural malformations are caused by a combination of environmental stresses and air pollutants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227489
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  • 97
    Digitale Medien
    Digitale Medien
    Different epithelia in the distal human male urethra (1991)
    Springer
    Cell & tissue research 264 (1991), S. 23-32 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Male urethra ; Urethral epithelium ; Immunocytochemistry ; Ultrastructure ; Man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distal segment of the human male urethra, in particular the fossa navicularis, was studied with light- and electron microscopy as well as by means of histochemical and immunocytochemical methods. The fossa navicularis of the urethra contains a circumscribed zone of extremely thick, non-keratinized stratified squamous epithelium composed of cells containing a large amount of glycogen. These cells lack acid phosphatase activity and lysozyme-like immunoreactivity, both of which can be demonstrated to varying extents in the other zones of the distal male urethra. These glycogen-rich cells are considered to be the substrate for an endogenous flora of lactobacteria, whereas the acid-phosphatase activity and the lysozyme-like immunoreactivity indicate the presence of macrophages and the secretion of bactericidal agents at the epithelial surface. These observations suggest that the different zones with heterogeneous properties in the distal male urethra probably represent a defense system against the invasion of pathogenic microorganisms. Moreover, the glycogen-rich zone, which resembles the glycogen-rich epithelium of the vagina, is estrogen-dependent. This is demonstrated in cases of sex reversal in which after long-lasting estrogen treatment the glycogen-rich zone becomes extremely extended by displacement of the neighbouring epithelium.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00305719
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  • 98
    Digitale Medien
    Digitale Medien
    Ultrastructure of melatonin-responsive cells in the ovine pars tuberalis (1991)
    Springer
    Cell & tissue research 263 (1991), S. 529-534 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Melatonin ; Pituitary gland, pars tuberalis ; Secretory cells ; Cyclic AMP ; Ultrastructure ; Cell culture ; Sheep
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Functional receptors for melatonin have been localized and characterized on the pars tuberalis (PT) of a number of mammalian species, but the cell-type responsive to melatonin is unknown. The ultrastructure of the ovine pars tuberalis has been examined and these findings correlated with the functional response of the gland to melatonin. This study revealed that two secretory cell types predominate in the ovine PT, which differ in the abundance of dense-core granules. The most abundant of the cells are either agranular or very sparsely granulated and represent 90% of the total population, with the remaining 10% being composed of cells with abundant dense-core vesicles. Few follicular cells were observed. This ratio of secretory cell-types persisted in primary culture, with the two types non-separable by Percoll gradient centrifugation. Using forskolin, as a non-specific stimulant of adenylate cyclase, melatonin was shown to inhibit the formation of cyclic AMP by 80–90% in cells both before and after Percoll centrifugation. The results demonstrate that the agranular secretory cells of the ovine pars tuberalis are the melatonin responsive cell-type of this gland.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00327285
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  • 99
    Digitale Medien
    Digitale Medien
    Ultrastructure and distribution of somatostatin-like immunoreactive neurons and nerve fibres in the coeliac ganglion of cats (1991)
    Springer
    Cell & tissue research 263 (1991), S. 567-572 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Somatostatin ; Coeliac ganglion ; Autonomic innervation ; Ultrastructure ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Somatostatin-like immunoreactivity was localized in nerve cell bodies and nerve terminals in the cat coeliac ganglion. Two types of somatostatin-immunoreactive cell bodies were revealed, the first being large (diameter 35 μm), numerous and weakly labelled, where—as the second was considerably smaller (diameter 10.4 μm), sparsely distributed and heavily stained. The immunoreactive nerve terminals were in synaptic contact with many immunonegative large neurons and dendrites. However, in a few cases, somatostatin-immunoreactive nerve terminals could also be observed on the surface of lightly stained neurons. Transection of vagal or mesenteric nerve failed to affect the distribution or density of somatostatin-like immunoreactive nerve terminals. These results demonstrate the existence of a synaptic input to the principal neurons of the coeliac ganglion of the cat by somatostatin-containing nerve terminals and suggest that this peptide may act as a neuromodulator or neurotransmitter. It is proposed that somatostatin-positive neurons provide intrinsic projections to other somatostatin-positive and to somatostatin-negative neurons throughout the coeliac ganglion, thereby creating a complex interneuronal system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00327290
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  • 100
    Digitale Medien
    Digitale Medien
    Islets of preadipocytes highly committed to differentiation in cultures of adherent rat adipocytes (1991)
    Springer
    Cell & tissue research 264 (1991), S. 243-251 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Preadipocytes ; Adipocyte precursor cells ; Adipose tissue ; Differentiation-cell cultures ; Ultrastructure ; Rat (Fischer 344)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Cultures of adherent mature adipocytes, obtained from collagenase-digests of adipose tissue of the rat, invaribly contain rapidly proliferating, fibroblastlike cells despite the washing and centrifugation procedures empolyed during isolation of the fat cells. Such spindle-like cells originate from low-density structures, which we term “islets”, that are present, together with the mature adipocytes, in the floating layer of the digest of adipose tissue. Islets are found in preparations from adult (3–4 months old) as well as aging (17–24 months old) rats. By light-and electron microscopy, the islets appear as clusters of closely associated cells containing a variable amount of lipid-like material. Cells of endothelial or pericytic origin are also present in the islets. Within a few hours of culture, the islets give rise to those spindle-like cells that have been seen to proliferate in the cultures. By 36–48 hours, such cells begin to accumulate lipid droplets and, by 150 hours, assume the morphology of small mature adipocytes (diameter 20–35 μm) with a large central lipid droplet. The pattern of differentiation of these cells recalls that of preadipocytes derived from the stromal-vascular fraction of adipose tissue digests. Nonetheless, the extent and rapidity of their adipose conversion, as well as the culture conditions necessary for differentiation, are different and suggest that these cells are a substantially uniform subpopulation of adipocyte-precursor cells highly committed to differentiation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00313961
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