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  • 1995-1999
  • 1975-1979  (7,083)
  • 1955-1959
  • 1925-1929
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 25 (1978), S. 145-159 
    ISSN: 1432-0827
    Keywords: Bird egg shell ; Ultrastructure ; Calcification ; Electron diffraction ; Microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The egg-shell of Japanese quail was studied by several techniques. Semithin sections (1μm thick) of non-decalcified shell were observed by normal and polarized light microscopy. Thin sections of non-decalcified shell, examined by transmission electron microscopy, permitted us to observe the forms and dimensions of crystals of calcite within different layers of the shell: mammilary layer, layer of cones, palissade layer and surface crystal layer. There appears to be two distinct zones in the layer of cones as well as in the superficial crystal layer. Electron microdiffraction revealed the orientation of calcite crystals in the columns. Some crystal defects (twins?) were described and the possibility of their artefactual formation during ultramicrotomy is discussed. Localization of Ca, Mg, P and S were made by X-ray microanalysis of semithin sections. This technique shows that shell membranes, and chiefly the true cuticle, are also mineralized but, in these layers, minerals are not crystallized. Otherwise the distribution of Mg is not uniform throughout the shell thickness; it is less concentrated in the external zone of the layer of cones. These results together with observation of developing shells by scanning electron microscopy allowed us to propose a scheme for shell organization of the quail egg. This organization was related with decalcification which occurs during hatching.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 31 (1978), S. 433-443 
    ISSN: 1432-1106
    Keywords: Rat ; Soleus ; Fusimotor innervation ; Skeletofusimotor innervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the small segmental tail muscles of the rat beta fibres provide exclusively the dynamic fusimotor control, while gamma fibres provide exclusively the static fusimor control. The present experiments were made to investigate the fusimotor innervation of spindles in a large muscle of the rat, the soleus, and thus to determine the occurrence and significance of beta innervation in this muscle. Our results have revealed no case of beta innervation in the rat soleus. As a consequence of our experimental method, however, we would not claim that beta innervation does not exist in the soleus, only that it must play an insignificant role relative to that seen in the tail segmental muscles. Investigations of the fusimotor innervation of eight spindles were sufficiently complete to warrant detailed illustration. The number of gamma fibres ranged from two to four. In every case the slowest conducting gamma fibre was dynamic. However, the conduction velocity spectra for the static and dynamic gamma fibres to rat soleus overlap to such an extent that it is impossible to use conduction velocity as the sole guide to functional gamma fibre classification. The pooled results from the eight spindles fully investigated provide a ratio of static to dynamic gamma fibres of approximately 1:1. Other evidence discussed in the paper suggests that in the muscle nerve the ratio is considerably higher. These differences are reconciled if the dynamic gamma fibres branch more profusely and innervate more spindles than do the static gamma fibres.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 31 (1978), S. 573-590 
    ISSN: 1432-1106
    Keywords: Hippocampus ; Place units ; Unit recording ; Sensory cues ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Place units in the dorsal hippocampus of the freely-moving rat signal the animal's position in an environment (place field). In the present experiments, thirty four place units were recorded in two different environments: one, a small platform where the rat had received neither training nor reward; the other, an elevated T-maze inside a set of black curtains where the rat had been trained on a place discrimination. The places within the curtained enclosure were specified by four cues (a light, a card, a fan, and a buzzer) in addition to the food. Other cues were eliminated by rotating the maze and the four controlled cues relative to the external world from trial-to-trial. Some units had place fields in both environments while others only had a place field in one. No relationship could be seen between the place fields of units with fields in both environments. All twelve units tested extensively in the controlled enclosure had place fields related to the controlled cues. Probe experiments in which only some of the controlled cues were available showed that some of these units were being excited by one or two cues while others were influenced in a more complex way. The fields of these latter units were maintained by any two of the 4 cues and were due to inhibitory influences which suppressed the unit firing over the rest of the maze.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 32 (1978), S. 365-375 
    ISSN: 1432-1106
    Keywords: Intraspecific aggression ; Lateral hypothalamus ; Electrical stimulation ; Specificity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of electrical stimulation of the lateral hypothalamus (LH) of rats on intraspecific aggressive behaviour were studied. In order to investigate the specificity of the stimulation effects, each experimental animal was stimulated in a number of different social situations. Stimulation of the LH in the presence of a subordinate male increased the amount of time spent on aggressive behaviour patterns and locomotion. In the presence of a dominant male, however, the stimulated animal never initiated a fight, whereas in the presence of an estrous female attack occurred in some rare occasions and sexual behaviour disappeared almost entirely. Stimulation of some sites also elicited mouse killing behaviour. Many of the electrodes that elicited intraspecific aggressive behaviour also supported intracranial self-stimulation. It is concluded that 1. electrical stimulation of this area of the LH predominantly potentiates intraspecific aggressive behaviour, 2. that this behaviour becomes overt depends on the external situation, including the behaviour of the opponent.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 33 (1978), S. 213-225 
    ISSN: 1432-1106
    Keywords: Rat ; Hypoglossal nucleus ; Axotomy ; ATP-ase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hypoglossal nuclei of adult male albino rats, either normal, or from 1 to 70 days after left hypoglossal nerve transection, were studied cytochemically with a lead method for sodium- and potassium-activated membrane ATP-ase, using light and electron microscopy. Reaction product was measured at the light microscopical level by microdensitometry, and significance determined statistically. Light microscopy revealed a brown reaction product in the neuropil, but none in cell bodies. Blood vessel walls were more strongly coloured. Reaction product was undiminished by ouabain pre-incubation, or by incubation without sodium or potassium, or by incubation with calcium instead of magnesium. Reaction product was diminished by absence of magnesium if calcium was also absent, and abolished if sections were boiled before incubation, or if substrate was absent. Axotomy caused a statistically significant increase in neuropil reaction product in injured nuclei, maximal at 35 days postoperatively, and subsequently decreasing to normal at 70 days. Electron microscopy showed a predominantly surface membrane reaction product, with occasional positive intracellular cisternae. Basal lamina and intra-endothelial vacuoles were also positive. Axotomy resulted in the arrival and disappearance of microglia (2 to 35 days), followed by astrocyte hypertrophy (35 days), and increase in thickness and homogeneity of surface membrane reaction product. The results suggest the presence of one or more calcium- or magnesium-dependent membrane ATP-ases. The peak of the increase after axotomy is probably partly attributable to hypertrophic astrocytes, and partly to the surfaces of neuronal processes. Increase of membrane movements might explain such enzyme activity.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 377 (1978), S. 157-174 
    ISSN: 1432-2307
    Keywords: Pancreatic diabetes ; Endocrine pancreas ; Islet composition ; Immunocytochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The endocrine pancreatic tissue from patients with severe primary chronic pancreatitis (n=6), secondary chronic pancreatitis due to duct obstruction by carcinoma (n=6) and non-diabetic, non-pancreatitic controls (n=4) was studied qualitatively and quantitatively using specific immunocytochemistry and electron microscopy. Grouping of variously sized islets in the sclerotic tissue (sclerosis islets), islet neoformation by ductuloinsular proliferation, and intrainsular fibrosis were the main qualitative findings. Immunocytochemical quantitation of the distribution of insulin (B), glucagon (A), somatostatin (D) and pancreatic polypeptide (PP) producing cells revealed a significant relative increase in the number of A cells and a decrease in the number of B cells of the sclerosis islets in primary chronic pancreatitis (B-44.1±9.3%:A-38.3±2.4%:D-8.6±5.1%:PP-4.6±4.1%) as well as in secondary chronic pancreatitis (B-38.0±14.3%:A-38.4±19.0%:D-9.1±5.8%:PP-14.5±23.4%) compared with controls (B-71.1±8.1%:A-24.3±5.5%:D-8.0±2.8%:PP-0.5±0.4%). The number of PP cells was significantly increased in primary chronic pancreatitis only. It is suggested that scarring of the exocrine pancreas affects islet composition, probably by impairment of the local circulation and of glucose diffusion, thus leading to reduction of the number and glucose sensitivity of B cells. The hyperplasia of A and PP cells appears to be a secondary phenomenon due to the loss of B cells.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2307
    Keywords: Pitutary ; Ultrastructure ; Vasopressin ; Prostaglandin ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ziel dieser Untersuchung war es, quantitative and qualitative Änderungen der ACTH-Zelle in der Rattenhypophyse nach Gabe eines spezifischen und eines unspezifischen Stimulus zu untersuchen. Es wurden ein CRF-Analogon (Lysin-Vasopressin) und ein Prostaglandin (Prostaglandin E1) benutzt. Jeweils 20 Ratten wurden für 4 Wochen Lysin-Vasopressin oder Prostaglandin E1 intraperitoneal injiziert. Die Hypophysen wurden licht- und elektronenoptisch sowie morphometrisch untersucht. Nach Gabe beider Stoffe konnte man eine Aktivierung der ACTH-Zellen beobachten. Die Vergrö\erung des Kerns, des Cytoplasmas und der an der Hormonherstellung beteiligten Zellorganellen lie\ sich morphometrisch nachweisen, wobei die Wirkung von Lysin-Vasopressin ausgeprÄgter war als die des Prostaglandins. Darüber hinaus konnte eine Zunahme der ACTH-Zellzahl gefunden und mit einem statistischen Test als signifikant nachgewiesen werden. Im Gegensatz zu Lysin-Vasopressin erstreckte sich die Wirkung des Prostaglandins auch auf andere Hypophysenzellen.
    Notes: Summary The aim of this study was to investigate the qualitative and quantitative changes of ACTH-cells in the rat after application of a specific and a non-specific stimulus. A CRF-analog (lysin-vasopressin) and a prostaglandin (prostaglandin E1) were used. 40 rats were injected lysin-vasopressin or prostaglandin E1, respectively, for 4 weeks. The pituitary glands were investigated by means of light microscopy, electron microscopy and morphometry. Activation of the ACTH-cells could be observed after use of both substances, the effect of lysin-vasopressin being more intense than that of prostaglandin E1. Enlargement of the nucleus, the cytoplasm and the organelles involved in hormone-production and -transport were found and verified by morphometry. Additionally an increase in number of the cells could be demonstrated. Prostaglandin influenced not only ACTH-cells, but also other cells of the anterior pituitary.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 379 (1978), S. 229-241 
    ISSN: 1432-2307
    Keywords: Placenta ; Ultrastructure ; Rhesus incompatibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electronoptical study has been made of eleven placentae from cases of materno-fetal rhesus incompatibility. The characteristic findings are focal, but sometimes quite extensive, syncytial necrosis, retention of normal pinocytotic and secretory activity in the non-necrotic syncytiotrophoblast, cytotrophoblastic hyperplasia, thickening of the trophoblastic basement membrane, immature-type endothelial cells in the fetal villous vessels and thickening or lamination of the capillary basement membranes. The pathogenesis of many of these changes is not clear but there is no evidence that they are immunologically mediated. It is suggested that the syncytial necrosis may be due to narrowing of the intervillous space as a result of increased villous size, that the cytotrophoblastic hyperplasia is a response to the syncytial damage and is responsible for the changes in the trophoblastic basement membrane and that the fetal capillary changes are indicative of endothelial cell damage due, possibly, to fetal anaemia. Despite the damage suffered by the placenta in materno-fetal rhesus incompatibility there is little evidence of impaired functional efficiency.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 56 (1978), S. 211-215 
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; d-Amphetamine ; Response force ; Punishment ; Stereotyped behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were reinforced with water on a continuous reinforcement schedule and were also punished with electric shock for every fifth response applied to a silent, isometric, force-sensing manipulandum. Oral doses of chlordiazepoxide (3.0, 9.0, 27.0 mg/kg) increased both conventional rate and force of punished responding. In contrast, d-amphetamine (0.8, 1.6, 3.2 mg/kg, by gavage) further decreased conventional rate and force of response, but this latter drug increased the rate of recorded responses that were lower than the 15-g force criterion for response consequences. The results for chlordiazepoxide are viewed in terms of its anxiolytic properties, while the d-amphetamine data appear to support a theory of amphetamine effects based on the concept of stereotyped behaviors.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; Behavioral augmentation ; Physical dependence ; Carry-over ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult male rats were subjected to 1–4 cycles of daily gastric intubation with ethanol (6 g/kg) for 16 days, separated by 17-day alcohol-free periods. Tolerance produced by this treatment (designated ‘physiological tolerance’) was measured by change in effect of a 2.2 g/kg i.p. dose of ethanol on the moving-belt test. It occurred in each cycle, disappeared completely in the drug-free periods, and developed more rapidly in the second and later cycles than in the first. Tolerance produced by the ‘behavioral augmentation’ technique (daily test practice under the influence of ethanol) also developed more rapidly on a second than on a first cycle. The progression from within-session to between-session tolerance was still evident, but accelerated. With 25-day alcohol cycles, separated by a one-month drug-free period, the ‘carry-over’ effect (i.e., more rapid acquisition of tolerance in the second cycle) applied equally, regardless of whether or not tolerance was produced by the same technique in both cycles, or by a crossover in either direction between the two techniques.
    Type of Medium: Electronic Resource
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  • 11
    ISSN: 1432-2072
    Keywords: Polyphloretin phosphate ; Prostaglandins ; Behaviour ; Temperature ; Bram biogenic amines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possibility that polyphloretin phosphate (PPP) antagonizes the central effects elicited by prostaglandin (PG) E2 and F2α was investigated. PPP was administered i.c.v. to male Wistar rats (10 or 25 μg) 10 or 30 min before i.c.v. injection of PGE2 or PGF2α (1 or 10 μg). The duration of several components of behavior, the degree of irritability, and the rectal temperature of rats were measured; the levels of noradrenaline, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were measured spectrophotofluorometrically in discrete brain areas. PPP antagonized temperature and behavioral changes induced in rats by PGF2α, but not those induced by PGE2. The magnitude of antagonism depended on the dose of PPP and on the time of the pretreatment before PGF2α administration. Changes in the level of biogenic amines in discrete brain areas evoked by PGs were not affected by PPP. We found that PPP antagonizes the central effects of PGF2α but not those of PGE2, and that changes of biogenic amines in discrete brain areas elicited by PGs are not specific.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 378 (1978), S. 45-53 
    ISSN: 1432-2307
    Keywords: Alcohol ; Myopathy ; Histochemistry ; Electrophysiology ; Human ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscles of the lower legs of rats given 25% ethanol in water ad libitum for up to 9.5 months were studied using histological, histochemical and electrophysiological techniques. Ethyl alcohol was substituted for about 20% of the total calorific input of the animals. The observations were compared with the structure of the gastrocnemius muscle of five alcoholics with clinical neuropathy. Fibrillation potentials and angulated atrophic fibers were observed in the muscles of animals on alcohol for 9.5 months. No fiber type grouping was present. There was also phagocytosis of the muscle fibers and changes in their internal structure, as reflected by the distribution of NADH-diaphorase. The observed muscle changes in the alcoholics and those in the experimental animals on alcohol differed mainly quantitatively, the only exception being the presence of fiber type grouping in the biopsies from the alcoholics.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 378 (1978), S. 161-172 
    ISSN: 1432-2307
    Keywords: Chemodectoma ; Larynx ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present case report is concerned with a clinico-pathological study, including ultrastructural investigation, of a rare and uncommon laryngeal tumour, a chemodectoma, in a 62 year old patient. There have been 23 cases of laryngeal chemodectomas reported in the literature, and only three of them, including our own report, were investigated by electron microscopy. The tumours arise from the superior and inferior laryngeal nonchromaffin paraganglia or possibly from Kultschitzky-cells of the normal bronchial mucosa. Ultrastructurally they have all the characteristics of apudomas whose parent cells (the APUD-cells), usually show endocrine function and probably have their origin in the neural crest. The tumours show an aggressive type of behaviour, despite usually benign histological features when compared to chemodectomas at other sites in the head and neck region. Surgery is thus the therapy of choice.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 378 (1978), S. 287-295 
    ISSN: 1432-2307
    Keywords: Giant cell tumor ; Ultrastructure ; Alkaline phosphatase ; Human bone neoplasias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structural localization of nonspecific alkaline phosphatase was elucidated in two giant cell tumors of bone using lead as capturing ion and Β-glycerophosphate as substrate in the incubation solution. Lead phosphate precipitate — indicating presence of alkaline phosphatase — was demonstrated on the plasma membranes, and the membranes bordering vesicles and vacuoles of presumed endocytotic nature, in giant cells and type 1 stromal cells (fibroblast-like cells). The findings support the view that stromal cells type I and giant cells are histogenetically related.
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  • 15
    ISSN: 1432-2307
    Keywords: Primary hyperparathyroidism ; Bone cells ; Bone matrix ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electron microscope investigation has been carried out on needle biopsies of the iliac crest of 8 patients suffering from primary hyperparathyroidism. A marked increase in bone resorption was the most conspicuous finding. It was due both to increased osteoclastic activity and to periosteocytic osteolysis. The osteoclasts had a more strongly developed brush border and contained more cytoplasmic vacuoles than those in controls. Many osteocytes were found within enlarged, irregular lacunae, and were surrounded by a space containing amorphous, granular and filamentous material. Their mitochondria were sometimes calcified. Osteoblasts were more active than in controls as shown by the developed rough ergastoplasmic cysternae and thick osteoid borders found near some of them. The osteoid tissue, however, was uncalcified; ultrastructurally, lack of the calcification front and incomplete matrix calcification were demonstrable. Mast cells, and osteoclast- and macrophage-like giant cells were often found in the fibrotic marrow spaces. These results confirm that both the resorption and the formation of bone are stimulated in hyperparathyroidism. The calcification process is delayed and often remains incomplete.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 379 (1978), S. 185-201 
    ISSN: 1432-2307
    Keywords: Giant cell tumor ; Ultrastructure ; Acid phosphatase ; Lysosomes ; Bone tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 379 (1978), S. 321-333 
    ISSN: 1432-2307
    Keywords: Pinguecula ; Pterygium ; Histology ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two pingueculae combined with pterygia were studied by light and electron microscopy. Hyaline degeneration of the collagen, dark staining granular, von Kossa negative concretions and elastotic material were observed in both conditions together with marked changes in the fibroblasts, endothelial cells, pericytes and the basement membrane of conjunctival capillaries and small veins. The elastotic material is similar to that observed in solar elastosis, where the collagen fibers are less severely damaged. Chronic sun exposure of the pericorneal conjunctiva may damage endothelial cells primarily and disturb vascular exchanges. This would result in accelerated degeneration and regeneration of endothelial cells, in thickening of the basement membrane and, secondarily, disturbed metabolism of fibroblasts with alterations of the collagen and elastic fibers.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 173 (1978), S. 239-244 
    ISSN: 1433-8580
    Keywords: Experimental chronic uremia ; Rat ; Oxygen consumption ; Body weight ; Experimentelle chronische Urämie ; Ratte ; Sauerstoffverbrauch ; Körpergewicht
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die verminderte Gewichtszunahme bei experimenteller chronischer Urämie führte zu der Bestimmung des Sauerstoffverbrauches chronisch urämischer Ratten und eines normalen Vergleichskollektivs. Die Messung des Sauerstoffverbrauches wird als Hinweis auf den Energiebedarf des Gesamtstoffwechsels gewertet. Drei Gruppen von Versuchstieren wurden untersucht: urämische Ratten (CU) von geringerem Gewicht (403,66 ± 9,9 g) als deren gesunde Vergleichstiere (NA) (498,31 ± 26,13) und jüngere Normaltiere (NJ), welche ein annähernd ähnliches Körpergewicht wie die chronisch Niereninsuffizienten aufwiesen (376,0 ± 8,8). Signifikante Unterschiede des Sauerstoffverbrauches, bezogen auf das Körpergewicht, wurden zwischen den Gruppen NJ (0,927 ± 0,042 ml O2/mn/100 g Ratte) und beiden Gruppen CU und NA (0,788 ± 0,036 und 0,788 ± 0,028 jeweils) gefunden. Eine proportionale Verminderung der energetisch aktiven Körpermasse mag die Ursache der Sauerstoff-Meßergebnisse bei chronischer experimenteller Urämie sein.
    Notes: Summary Impaired weight gain, a common feature in experimental chronic uremia, led to compare oxygen consumption values of chronic uremic rats and their controls. Oxygen consumption measurement may allow an approach to the evaluation of total energy requirement. Three groups of animals were considered: uremic rats (CU) of less weight (402.66 ± 9.9 g) than their control group (NA) (498.31 ± 26.13) and younger normal animals (NJ), showing a similar weight (376.0 ± 8.8) to that of the uremics. Significant differences in oxygen consumption values/body weight were found between group NJ (0.927 ± 0.042 ml O2/mn/100 g rat) and both groups CU and NA (0.788 ± 0.036 and 0.788 ± 0.028 respectively). Proportional decrease of energetically active body mass in chronic uremic animals may be the reason of the findings.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 174 (1978), S. 57-65 
    ISSN: 1433-8580
    Keywords: Complement system ; Sodium taurocholate ; Acute experimental pancreatitis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of the complement system was studied in Na-taurocholate pancreatitis in rats. Complement activity (CH 50) was determined at various times in the course of pancreatitis. Immediately after induction of acute pancreatitis, serum complement activity declined and massive C 3 deposits could be detected in the vicinity of acinar necroses and necrobioses. After a phase of recovery three to six hours postoperatively a second complement consumption occurred. Lethality rate increased as serum complement activity fell below 50% of preoperative values. The degree of C 3 deposition increased up to six hours. Decline of serum complement activity and deposition within the pancreas seemed to be correlated with histologically demonstrable tissue lesion. The first decline of complement activity in serum is thought to be caused by liberation of complement activating substances within the pancreas due to the detergent action of Na-taurocholate itself. The second decline, however, may be due to the liberation of complement activating and/or destroying enzymes into the blood stream.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 172 (1978), S. 247-253 
    ISSN: 1433-8580
    Keywords: Rat ; Parotid saliva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method is described, which is suitable to collect continuously and quantitatively saliva from both parotid glands in rats under in vivo conditions and which allows to investigate salivary electrolyte composition in relation to flow rate during several hours. This might be of expanding scientific interest in disturbances of transepithelial electrolyte transport in various pathophysiological situations (for instance different forms of experimental hypertension, endstage renal failure and so on).
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 154 (1978), S. 27-37 
    ISSN: 1432-0568
    Keywords: Capillarization ; Cortex ; Rat ; 6-Aminonicotinamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During different embryonic and postnatal stages, 6-aminonicotinamide (6-AN) was administered to Wistar albino rats. The capillarization of the occipital cortex has been examined morphometrically. A 6-AN-vulnerable stage of prenatal development was found, which lasted to the 19th prenatal day and which only partly corresponds to the so-called ‘critical stage’ of capillary sprouting (Kapillarsprossung). Capillary sprouting was not impaired by 6-AN during postnatal stages. Impairment of capillarization by 6-AN might be the result of glial lesion. The importance of glia for capillarization is discussed.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 44 (1978), S. 249-250 
    ISSN: 1432-0533
    Keywords: Organelle complex ; Ribosomes ; Meningioma (malignant) ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural study of a malignant meningioma revealed an organelle complex composed of: (1) A band-like densification of the cell cytoplasm adjacent to and in contact with the cell membrane. (2) An arciform filament immediately subjacent to it, with concavity directed away from the cell membrane. (3) A row of regularly spaced ribosomes located in the concavity, but at some distance from the arciform filament. (4) A pericellular condensation of interstitial ground substance. Occasionally, a second, thinner filament was seen “threading” the ribosomes together. Its morphology was consistent with that described for messenger RNA. It is suggested that the ribosomes are engaged in the synthesis of proteins for other portions of the organelle complex and that the ultimate role of the specialized unit would be that of an attachment device.
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  • 23
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    Anatomy and embryology 153 (1978), S. 1-8 
    ISSN: 1432-0568
    Keywords: Ileal epithelial cell ; Suckling period ; Rat ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ileal epithelial cells containing the tubulo-vacuolar systems and supranuclear vacuoles in suckling rats were investigated with scanning electron microscopy, using specimens treated with osmium-thiocarbohydrazide-osmium staining methods, and critical point drying and cracking. The cracked surface of the apical cytoplasm is seen as irregular and small hollows and pores of the anastomosing and branching tubulo-vacuolar system. The cracked surface of the supranuclear vacuoles shows the ellipsoidal structures. Numerous pores of various size and irregular shape are present on the apical inner surface of the supranuclear vacuole. These pores are clearly the openings from the tubulo-vacuolar system to the supranuclear vacuole. Some small pores are visible on the inner lateral surface of the supranuclear vacuole, especially near the nucleus. They are probably the pathways of the absorbed materials from the supranuclear vacuole into the lateral cytoplasm. Usually, the inclusions of the supranuclear vacuole reveal the globes or coarse and sponge-like networks.
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  • 24
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    Anatomy and embryology 154 (1978), S. 1-25 
    ISSN: 1432-0568
    Keywords: Bile canaliculus ; Development ; Glycogenesis ; Hepatocytes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural changes during development and metamorphosis in the liver ofXenopus laevis have been investigated. In this species it was found that developmental processes, which ultimately lead to the formation of bile canaliculi, can be detected in the liver anlage as early as stage 35. While the wall of the primary liver cavity is thrown into folds which form the liver parenchyma, the bile canaliculi are formed (st. 36–38). Secretion into the lumen of the bile canaliculi was not found to occur before stage 47 and IDP-ase activity could not be detected in the bile canaliculi before stage 49. The intra- and extrahepatic portions of the hepatic duct system were found to be formed during the stages 40–41. The formation of the duct system involves cellular degeneration in the lumen of the future ducts. These processes are described in detail. The glycogen content of the developing hepatocytes received particular attention during the course of this study. It was found that after depletion of the embryonal glycogen the hepatocytes are completely free from glycogen during the stages 43–45. At stage 46, after the begin of feeding, beta as well as alpha particles of glycogen appear in the hepatocytes. These first reappearing glycogen particles are formed without the participation of SER membranes, in areas which are loaded with RNA particles. It was found that only after the synthesis of glycogen had been initiated SER membranes started to proliferate in the hepatocytes, where they were mostly found intermingled with glycogen particles. From stage 54 on, where the liver glycogen content was found to be 0.2%, the glycogen content of the liver almost continuously increased until it reached a temporary peak of 10% at the end of metamorphosis. These findings strongly contrast results reported for other amphibia, which at the end of metamorphosis have depleted their glycogen content completely. Details of the ultrastructural changes occuring during development of the hepatocytes, are also reported in this paper.
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  • 25
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    Anatomy and embryology 154 (1978), S. 67-82 
    ISSN: 1432-0568
    Keywords: Urodeles ; Spinal cord ; Ependyma ; Glia ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The structural organization of the ependymal and macroglial components of the central field of the spinal cord of postmetamorphic ribbed newts has been reinvestigated using elaborate fixation procedures for transmission electron microscopy. All along the central canal, the ependymal cells display ultrastructural features that strongly suggest a secretory activity. Infrequent mitotic images, occurring spontaneously among the ependymal cells, were observed. The tightly compacted periependymal stratum contains two types of glial cells: 1. oligodendrocytes, also observed outside this stratum as neuronal satellites, and 2. radial astrocytic cells, whose somata, exclusively located in the periependymal stratum, send their processes to the subpial lamina. The intercellular relationships between ependyma, oligodendrocytes and astrocytic cells are illustrated to show the continuity of the neuroepithelial configuration. Morphologic clues for identifying the cells of the central field of the urodele spinal cord are given. A gradient of differentiation of the oligodendroglial components could be postulated. In normal conditions, the astroglial differentiation is permanently arrested at the stage of radial glia. Some considerations concerning regeneration in the urodele spinal cord are submitted.
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  • 26
    ISSN: 1432-0568
    Keywords: Rat ; Iris ; Cornea ; Catecholamine fluorescence ; Cholinesterase ; Histochemistry ; Ontogenesis ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glyoxylic acid-induced fluorescence technique and a copper thiocholine method were used to investigate the ontogenesis of the catecholamine-containing and cholinesterase-positive nerves of the rat iris and cornea. First fluorescent nerve fibres appeared in the iris on the 18th gestation day and in the cornea on the 19th day. A rapid increase in the density of the adrenergic nerve fibres of the iris continued to the age of three weeks, while the number of such fibres were small in the cornea. Acetylcholinesterase-positive fibres appeared both in the cornea and in the iris on the 19th gestation day. Their density increased more rapidly in the iris, especially in the sphincter muscle, than in the cornea. Non-specific cholinesterase activity was localized in the Schwann cells and the reaction was more intense during development than in the nerves of the cornea of adult rats.
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  • 27
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    Anatomy and embryology 154 (1978), S. 185-211 
    ISSN: 1432-0568
    Keywords: Adenohypophysis ; Cellular types ; Ultrastructure ; Birds ; Excalfactoria chinensis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural analysis of the adenohypophysis in the male Chinese quail reveals seven different types of granular cells, and agranular folliculo-stellate cells. The cell types are assumed to be endocrine cells and are classified as: Type I cells (presumptive LH-gonadotrophs), with dilated endoplasmic reticulum, perinuclear spaces, and granules of 150–260 nm; Type II cells (presumptive FSH-gonadotrophs), with regularly-shaped cytoplasmic cisterns and small granules (80–150 nm); Type III cells (presumptive thyrotrophs), very close in appearance to the type II cells of normal birds; Type IV cells (presumptive prolactin cells), with very large secretory granules (up to 400 nm), Type V cells (presumptive corticotrophs), with abundant and electrondense granules (160–300 nm); Type VI cells, with irregularly-shaped granules; Type VII cells (presumptive somatotrophs), with abundant granules (130–220 nm) and less cytoplasmic structures. Cytological characteristics of the nucleus, and more particularly the presence of a Feulgen-positive nucleolus with a very particular ultrastructure are here reported. It is proposed that heterospecific associations of Chinese quail cells with chick cells can be used in embryological work for the study of cellular interactions.
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  • 28
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    Anatomy and embryology 154 (1978), S. 241-251 
    ISSN: 1432-0568
    Keywords: Nervous system ; Serotonin ; Raphe nuclei ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pre- and early postnatal development of serotonin neurons in the rat brainstem was studied using the fluorescence histochemical method. The technique utilized does not require drug pretreatment to visualize an intense serotonin fluorophore localized in neuronal perikarya, dendrites, and axons. All the serotonin neuron groups develop as bilateral nuclei which extend from the midbrain through the medulla. Six of the nine groups undergo a midline fusion from embryonic day 18 (E 18) through postnatal day 6 (P 6) in a rostrocaudal gradient. Cells of the nucleus raphe dorsalis fuse first (by P1), whereas the serotonin neurons located in nucleus raphe pallidus do not fuse until P 6. This gradient is comparable to the one described for the first observable fluorescence in the serotonin neurons groups. After final cell division, the serotonin neurons undergo a primary migration from the ventricular zone along the midline, where they are situated during embryogenesis, and a secondary migration extending into postnatal life which concludes with fusion in the midline. The bilateral origins of the serotonin cell groups are maintained in the adult. This is expressed by the apparent ipsilateral projections of some of the raphe neurons determined recently in our laboratory utilizing autoradiographic and horseradish peroxidase techniques.
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  • 29
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    Archives of dermatological research 263 (1978), S. 207-214 
    ISSN: 1432-069X
    Keywords: Wound healing ; Collagen metabolism ; Collagen degradation ; Fibroblasts ; Ultrastructure ; Wundheilung ; Kollagenstoffwechsel ; Kollagenabbau ; Fibroblasten ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Kollagenstoffwechsel in granulierenden Hautwunden der Ratte wurde mittels biochemischer, tracerkinetischer und elektronenmikroskopischer Methoden untersucht. Die Ablagerung von Kollagen in Hautwunden der Ratte war nicht nur das Ergebnis eines Anstiegs der Kollagensynthese, sondern wurde ebenso durch eine Abnahme des Kollagenabbaus bedingt. Unsere Ergebnisse zeigten signifikante Unterschiede im Kollagenumsatz zu verschiedenen Zeiten der Wundheilung. Der herabgesetzte Kollagenkatabolismus in den frühen Stadien der Wundheilung steuerte in entscheidender Weise zur Kollagenakkumulation im Wundgebiet bei. Während späterer Stadien, zum Zeitpunkt der Wundkontraktion und der Remodellierung der Narbe, stieg die Umsatzrate des Kollagens an. Die dargestellten Ergebnisse werden im Zusammenhang mit den allgemeinen Kriterien der Narbenbildung diskutiert.
    Notes: Summary Collagen metabolism in granulating wounds of rat skin was studied with biochemical, isotopic and electron microscopical methods. Deposition of collagen in rat skin wounds was not only the result of an increase in collagen synthesis but it was also caused by a decrease in collagen degradation. Our investigations showed significant differences in the collagen turnover at different times of wound healing. Decreased collagen catabolism at the early stages of wound healing contributed decisively to collagen accumulation in the wound area. At later stages, during wound contraction and remodelling of the scar, the rate of collagen degradation rose. The above-mentioned results are discussed in the context of general criteria of scar formation.
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  • 30
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    Annals of hematology 37 (1978), S. 295-306 
    ISSN: 1432-0584
    Keywords: Β-adrenerge Rezeptoren ; (3H) (−) Dihydroalprenolol ; Erythrozyten ; Ratte ; Β-Adrenoceptors ; (3H) (−) Dihydroalprenolol ; Erythrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary By means of the radioactive antagonist ligand (3H) (−) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized asΒ-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temparature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited byΒ-adrenergic antagonists (pindolol 〉 alprenolol ≧ propranolol 〉 practolol) and agonists (isoprenaline 〉 adrenaline). The (−) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80 % treatment of the animals with increasing doses of acetyl phenylhydrazine.
    Notes: Zusammenfassung Mittels des radioaktiv markierten Antagonist-Liganden (3H) (−) Dihydroalprenolol (DHAP) wurden spezifische Bindungsstellen in Membran-PrÄparationen von Erythrozyten der Ratte identifiziert, die aus folgenden Gründen alsΒ-adrenerge Rezeptoren angesprochen werden können: Im Gegensatz zur unspezifischen Bindung von DHAP war die spezifische Bindung abhÄngig von der Inkubationszeit und der Temperatur. Sie folgte einer SÄttigungskinetik, war — in AbhÄngigkeit von der Temperatur — reversibel und wies eine hohe AffinitÄt auf (KD für DHAP = 6,51 nM). Die rezeptorspezifische Bindung von DHAP wurde durchΒ-Rezeptorenblocker (Pindolol 〉 Alprenolol ≧ Propranolol 〉 Practolol) oderΒ-Sympathomimetika (Isoprenalin 〉 Adrenalin) kompetitiv gehemmt. Die (−) Enantiomeren von Pindolol und Isoprenalin hatten eine wesentlich höhere AffinitÄt als die antsprechenden (+) Enantiomeren. Die Dichte Β-adrenerger Rezeptoren (pmole/mg Eiwei\) nahm mit steigendem Retikulozytosegrad zu: Sie stieg auf das 4-bis 5fache an, wenn die Retikulozytenwerte durch Vorbehandlung der Tiere mit Azetylphenylhydrazin von 3 auf 80 % gesteigert wurden.
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  • 31
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    Archives of dermatological research 263 (1978), S. 159-169 
    ISSN: 1432-069X
    Keywords: Leiomyosarcoma of the skin ; Ultrastructure ; Cellular differentiation ; Accumulation of centrioles ; Cutanes Leiomyosarkom ; Ultrastruktur ; celluläre Differenzierung ; multiple Centriolen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine 61jährige Patientin hatte sich vor 15 Jahren einen Tumor vom linken Unterschenkel entfernen lassen. Im Bereich der Narbe kam es zu erneuter Tumorbildung. Die histologische Untersuchung zeigte einen aus meist spindeligen Zellen zusammengesetzten Tumor mit vielen Mitosen und Kernpolymorphie. Die Diagnose eines cutanen Leiomyosarkoms wurde durch den elektronenmikroskopischen Nachweis der für glatte Muskelzellen charakteristischen Zellelemente gesichert. Der Differenzierungsgrad der Tumorzellen variierte zwischen relativ differenzierten, filamentreichen Zellen, die noch an normale glatte Muskelzellen erinnerten, und ödematösen, filamentarmen, aber organellenreichen entdifferenzierten Zellen. Eine auffallende morphologische Besonderheit war der wiederholte Nachweis von zahlreichen akkumulierten Centriolen.
    Notes: Summary A 61-year old woman developed a tumourous nodule in her left leg. Fifteen years ago a similar tumour had been removed in the same localization. Histological examination performed on biopsy material showed bundles of predominantly fusiform tumour cells with nuclear pleomorphism and many mitotic figures. Electron microscopic examination confirmed the diagnosis of leiomyosarcoma by demonstration of the ultrastructural characteristics of smooth muscle cells. Cellular differentiation showed various degree ranging from smooth muscle cell type to dedifferentiated edematous tumour cells with scanty myofilaments. An important finding was the demonstration of multiple accumulated centrioles.
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  • 32
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    Archives of dermatological research 261 (1978), S. 231-244 
    ISSN: 1432-069X
    Keywords: Colloid Milium ; Different types ; Histopathology ; Ultrastructure ; Colloid Milium ; Verschiedene Typen ; Histopathologie ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Unterschiede im Verlauf und Erbmuster des Colloid Milium deuten an, daß zwischen dem juvenilen und adulten Typ dieser Dermatose wesentliche Unterschiede bestehen. Ziel der vorliegenden Untersuchungen war, mit Hilfe von Licht-, Immunfluorescenz- und elektronenoptischen Methoden nach Unterschieden im mikroskopischen Bereich anhand je eines Falles zu suchen. Folgende Befunde wurden erhoben: Beim juvenilen Colloid Milium sind die Kolloidmassen nicht nur direkt unter dem Epithel abgelagert, sondern auch innerhalb der Epidermis häufig zu finden. Sie zeigen nach Kongorotfärbung einen Dichroismus und können Immunglobuline, Komplement und Fibrin enthalten. Elektronenmikroskopisch zeigt sich, daß sie aus dicht gepackten wellig verlaufenden Fibrillen bestehen, deren individueller Durchmesser etwa 80 Å beträgt. Innerhalb dieser fibrillären Massen sind häufig Melanosomen, Reste von Kernen und anderen Zellorganellen sowie Desmosomen nachweisbar. Beim adulten Colloid Milium sind die Kolloidmassen meist von der Epidermis durch einen Elastika-positiven Bindegewebsstreifen getrennt. Mit Kongorot sind sie nur schwach darstellbar und zeigen keinen Dichroismus. Fluorescenzoptisch zeigen sie eine bläuliche Autofluorescenz, aber keine spezifischen Ablagerungen. Elektronenmikroskopisch kann das adulte Kolloid als feingranuläres Material mit wenigen feinsten Mikrofibrillen charakterisiert werden, das in enger Nachbarschaft von Gefäßen mit verdichteter Basalmembran und von aktiven Fibroblasten gelegen ist. Auf Grund dieser Unterschiede können der juvenile und adulte Typ des Colloid Miliums klar auch mikroskopisch voneinander differenziert werden. Die Ergebnisse deuten darauf hin, daß beim juvenilen Typ vorwiegend epidermale Läsionen, beim adulten jedoch dermale Störungen eine wesentliche Rolle in der Pathogenese spielen.
    Notes: Summary Two different types of colloid milium are characterized on the basis of clinical and genetical parameters. In order to establish morphological criteria allowing a differentiation also at microscopic levels comparative histopathological, histo- and immunochemical as well as ultrastructural investigations were performed in a case of juvenile and a case of adult colloid milium. The following results were obtained: In juvenile colloid milium the colloid material is deposed in direct apposition to the basal epidermal layers and can be found also in suprabasal position within the epidermis. No actinic elastosis is present in the periphery of the deposits but they exhibit a green birefringency by investigation of Congo-red stained frozen sections in polarized light. Immunoglobulins, complement and fibrin can be demonstrated within the deposits by direct immunofluorescence. Electron microscopy reveales a fibrillar ultrastructure of the colloid masses, which contain numerous melanin granules and desmosomes. Therefore the colloid material in the juvenile type is most likely of epidermal origin. In adult colloid milium the colloid is usually separated from the epidermis by a band of connective tissue elements containing a considerable amount of elastin. The surrounding superficial dermis frequently exhibits elastotic changes. Congo-red reaction is only weakly positive and no dichroisms can be found. Direct immunofluorescence reveals no specific staining, but a blue autofluorescence of the material. Ultrastructurally, the adult colloid represents mainly finely granular material, with only few microfilaments. The masses are situated in the dermis, often near duplicated vascular basement membranes and in close apposition to active fibroblasts. Thus, the colloid material seems to be of dermal origin. The microscopic findings strongly indicate, that the two different types of colloid milium indeed represent different entities, discernable not only by clinical or genetic but also by histomorphologic parameters.
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  • 33
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    Archives of dermatological research 262 (1978), S. 219-227 
    ISSN: 1432-069X
    Keywords: Nude mice ; Skin pigmentation ; Ultrastructure ; Tyrosinase activity ; Hair cycle ; Nackte Mäuse ; Hautpigmentierung ; Ultrastruktur ; Tyrosinaseaktivität ; Haarcyclus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Autoren untersuchten die Pigmentveränderungen an Haut und Haar an pigmentierten nackten Mäusen. Histologische und elektronenmikroskopische Untersuchungen und die Polyacrylamid-Elektrophorese der Tyrosinaseaktivitäten zeigten vom morphologischen und biochemischen, daß die Veränderungen der Programmierung solcher “nude” Mäuse auf den Haarcyclus und auf das Haarwachstum bezogen werden kann. In der Tat entwickeln sich die Haarfollikel cyclisch wie die der Mäuse mit normaler Haut. In depigmentierter Haut waren die Haare in der Ruhepause und es konnte keine lösliche Tyrosinase aufgefunden werden.
    Notes: Summary The authors have studied pigmentary changes of skin and hair due to the presence of the “nude” gene in pigmented species (C 57 Bl. 6J, C 3H). Morphological (histology, electron microscopy) and biochemical (polyacrylamide gel electrophoresis of tyrosinase activities) studies showed that the pigmentary alterations of the “nude” mice were related to the hair cycle and hair growth wave pattern. In fact, in the “nude” mice the hair follicles evolves cyclically similarly to mice of normal coat. In depigmented skin, the hair follicles were in the resting phase and no soluble tyrosinase could be demonstrated.
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  • 34
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    Archives of dermatological research 262 (1978), S. 135-141 
    ISSN: 1432-069X
    Keywords: Pseudolymphoma ; Oriental hornet venom ; Ultrastructure ; Pseudolymphoma ; Orientalische Wespe ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine einmalige sucutane Injektion des Giftes der orientalischen Wespe führt bei schwarzen Mäusen zu der Entwicklung eines subcutanen Knötchens, welches sich über 1 Jahr hält. Ultrastrukturell zeigt sich eine Anreicherung von Lymphocyten und Lymphoblasten und einige Plasmazellen mit Russelkörperchen. Zusätzlich werden einige Melanin enthaltende Makrophagen und auch solche mit aufgenommenen cellulären Abbauprodukten beobachtet. Die gesamte Reaktion wird mit anderen pseudolymphomatösen Reaktionen in der Haut in Beziehung gesetzt.
    Notes: Summary A single subcutaneous injection of Oriental hornet venom into black mice led to the development of a subcutaneous nodule which showed no change during the period of 1 year. Study of the ultrastructure revealed an accumulation of lymphocytes and lymphoblasts and a few plasma cells with formation of Russel bodies. In addition, a few melanin-containing macrophages and macrophages filled with cellular debris were found. This reaction is compared to other pseudolymphomatous reactions in the dermis.
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  • 35
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    Archives of dermatological research 262 (1978), S. 167-172 
    ISSN: 1432-069X
    Keywords: Rat ; Oxygen uptake ; Induced skincycle ; Spontaneous skincycle ; Diurnal rhythm ; Ratte ; Sauerstoffverbrauch ; Induzierter Hautcyclus ; Spontaner Hautcyclus ; Tagesschwankung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vom Panniculus carnosus gereinigten “glatten” Rattenhaut wurde der Sauerstoffverbrauch des spontanen und induzierten Hautcyclus zu verschiedenen Tageszeiten ermittelt. Das Niveau des Sauerstoffverbrauches korrelierte mit den Tag-Nacht-Zeiten. Der Sauerstoffverbrauch zeigte während des Hautcyclus Schwankungen. Ferner fanden sich Anhaltspunkte, daß der frühanagene Wert des Sauerstoffverbrauches von der Cyclusphase mit beeinflußt wird, während welcher der neue Cyclus künstlich induziert wird. Weiter wurde festgestellt, daß eine gewisse Abnahme des Sauerstoffverbrauches die ruhenden Haarfollikel zur spontanen Proliferation anregt. Während des Katagen schien der Maximalwert des Sauerstoffverbrauches mit speziellen morphofunktionellen perifollikulären Veränderungen in Beziehung zu stehen. Die Übertragung dieser Befunde auf die Pathophysiologie menschlicher Haarwachstumsstörungen wird erwogen.
    Notes: Summary In the “clean” rat skin purified from the panniculus carnosus the oxygen consumption of the spontaneous and artificially induced skincycle was measured at different times of day. The level of oxygen consumption correlated to diurnal and nocturnal periods. During the skincycle the oxygen consumption showed fluctuations. There were indications that the value of oxygen consumption of the early anagen is influenced by that phase of the cycle at which the new cycle is artificially induced. Furthermore, it was found that a certain decrease of oxygen consumption stimulates the quiescent hair follicles to spontaneous proliferation. During the katagen the peak value of the oxygen consumption seemed to be correlated with specially morphofunctional perifollicular changes. The application of these findings to the pathophysiology of human hair growth disturbances is discussed.
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  • 36
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    Archives of dermatological research 262 (1978), S. 205-217 
    ISSN: 1432-069X
    Keywords: Mycobacterium marinum ; Ultrastructure ; High-turnover granuloma ; Immunogenic orgin ; Intracellular collagen precursor ; Mycobaterium marinum ; Ultrastruktur ; High-turnover Granulom ; Immunogenes Granulom ; Intracelluläre Kollagenpräcursoren
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Drei Knoten (klinisches Alter 3–5 Wochen) von 2 Patienten mit sogenannten Swimmingpool- oder Aquariumgranulomen wurden elektronenoptisch untersucht. Das cytohistologische Spektrum umfaßt sowohl akute exsudative, als auch chronische proliferative Entzündungszeichen. Bereits im 3 Wochen alten Granulom sind Epitheloidzellen und Kollagen produzierende Fibroblasten nachweisbar. Das Mycobacterium marinum-Granulom stellt gemäß dem cytologischen Aufbau ein sog. High-turnover Granulom mit allergischer Genese dar. Es entspricht damit mycobacteriellen Dermatosen bei bestehender guter Abwehrlage (Lupus vulgaris, tuberkuloide Lepra). In Abbau befindliche Mycobacterien konnten in wenigen Phagocyten entdeckt werden. Die Ultrastruktur des lebenden Erregers wird vergleichsweise von tierexperimentellem Material präsentiert. Geschwungene und ringförmige parallele Membranen (“Worm-like structures”) wurden im Cytoplasma von transformierten Makrophagen und in Fibroblasten beobachtet. Fadenförmige quergebänderte Strukturen (Periodizität 170–180 Å) im Lumen des rauhen endoplasmatischen Reticulums von einigen Fibroblasten werden als intracellulär aggregierte Kollagenpräcursoren interpretiert.
    Notes: Summary 3 biopsies of 3–5 week-old nodular lesions in 2 patients with socalled swimming-pool (aquarium-) granuloma have been examined by electron microscopy. The cytohistological spectrum simultaneously comprises acute exudative as well as chronic proliferative phenomena. Epithelioid cells and collagen producing fibroblasts already conspicious in 3 week-old granuloma. According to the cytological composition the Mycobacterium marinum granuloma represents a high-turnover granuloma with immunogenic origin. It is comparable to mycobacterial diseases in the presence of well developed cell mediated immunity (Lupus vulgaris, tuberculoid leprosy). Degrading mycobacteria have been rarely detected in phagocytes and are compared with viable bacilli in macrophages of experimentally infected mice. Curved and annular parallel membranes (“worm-like structures”) in the cytoplasm of transformed macrophages and in fibroblasts presumably originate from the membranes of endoplasmic reticulum. Cord-like structures with transverse bands (periodicity 170–180 Å) in the lumen of RER of some fibroblasts are interpreted as intracellularly aggregated collagen precursors.
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  • 37
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    Archives of dermatological research 263 (1978), S. 153-157 
    ISSN: 1432-069X
    Keywords: Chancroids ; Biopsies ; Haemophilus ducreyi ; Ultrastructure ; Ulcera mollia ; Biopsien ; Haemophilus ducreyi ; Ultrastruktur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Anläßlich einer lokalen Häufung von insgesamt 26 Ulcus molle-Fällen in Berlin (West) wurden in Biopsien coccoide Stäbchen durch ultrastrukturelle Untersuchung entdeckt. Ihre Zellwand ist ca. 120 Å dick und trilaminar entsprechend Gram-negativen Bakterien. Die Bakterien sind hinsichtlich der Zellwandstruktur sowie der Cytoplasmazusammensetzung identisch mit Haemophilus ducreyi, die kulturell von typischen Ulcera mollia gezüchtet, intermittierend mikroskopisch auf Reinheit geprüft, in tierisches Material geimpft und anschließend ultrastrukturell untersucht wurden. In menschlichem ulcerösen Gewebe finden sich die Bakterien überwiegend im Extracellulärraum und in Gruppen gelagert.
    Notes: Summary During an endemic appearance of chancroids (26 cases) in Berlin (West) coccobacilli were disclosed in biopsies by electron microscopy. The bacteria were aggregated predominantly in groups in the extracellular space. Their cell wall is approximately 120 Å thick and trilaminar as in Gram-negative bacteria. Concerning the cell wall structure and the cytoplasmic composition, the detected coccobacilli are identical to culturally grown Haemophilus ducreyi obtained from chancroids.
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  • 38
    ISSN: 1432-041X
    Keywords: Ultrastructure ; Scanning cytophotometry ; Chromatin ; Chondrocytes ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les cellules cartilagineuses des membres postérieurs deTriturus cristatus en régénération après amputation, ont été étudiées en microscopie électronique et par cytophotométrie à balayage. Nous nous sommes intéressés à la structure et à la distribution de la chromatine mais aussi à différents organites cytoplasmiques. Dans l'étude de cytophotométrie à balayage, la chromatine a été considérée à travers son constituant majeur, l'ADN, coloré par la réaction de Feulgen. Au cours de la régénération du membre, l'hétérochromatine initialement condensée, essentiellement accolée à la membrane nucléaire se décondense. Les vacuoles du cytoplasme, caractéristiques des animaux âgés par rapport aux animaux jeunes, disparaissent, les mitochondries et le reticulum endoplasmique rugueux deviennent plus abondants. Les caractéristiques nucléaires de l'activation cellulaire apparaissent précocement, précédent les modifications cytoplasmiques et conduisent à des cellules en tous points identiques aux cellules d'animaux jeunes en dehors de tout processus régénératif. Cette phase d'euchromatisation et de restructuration cytoplasmique est peut-être nécessaire à l'accroissement d'activité métabolique et à la division cellulaire qui suivent. Son déroulement peut expliquer tout au moins le ralentissement de la régénération observé chez les animaux âgés par rapport aux animaux jeunes.
    Notes: Summary Cartilaginous cells of aged newts (Triturus cristatus) were studied during hind limb regeneration. The electron microscope was used to study the structure and distribution of chromatin in the cell nuclei, while the DNA content of the chromatin was measured by means of a scanning cytophotometer. Changes in the ultrastructure of the cytoplasm during regeneration were also studied. It was observed that the structure and distribution of chromatin in the activated cell is greatly modified. In the non-activated cell of the aged newt, the chromatin is found highly condensed and distributed peripherally close to the nuclear membrane. In contrast, in the activated cells, the chromatin is much less condensed and is distributed throughout the nucleus. Moreover, cytoplasmic vacuoles, found only in the non-activated aged cells, disappear and an increase in the mitochondria and rough endoplasmic reticulum is also observed. Changes in the nuclear structure are observed prior to the cytoplasmic modifications. It is interesting to note that the process of activation induces structural changes in the aged cells which make these cells appear to be structurally identical to the young cells. This process of rejuvenation takes 3–5 days in the newt. We suggest that these structural changes of the chromatin and cytoplasm in the aged cells are necessary to increase the metabolic activity which precedes cell division. It may also explain why regeneration takes a longer time in the aged animals than in the young ones.
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  • 39
    ISSN: 1432-0533
    Keywords: Nemaline myopathy ; Neuromuscular junction ; Myotendinous junction-like structure ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histological, histochemical and ultrastructural studies were performed on muscle biopsies from three siblings with congenital nemaline myopathy. Histological studies revealed type I fibre atrophy and type II fibre paucity. Ultrastructural studies of intramuscular nerves showed that the axonal diameters were very narrow compared with the width of myelin lamellae. Granular or membranous osmiophilic material occurred in the adaxonal Schwann cell cytoplasm and had a periodicity of 33–38Å. The neuromuscular junctions showed degenerative features such as glycogen granules or myelin figures in 27.1% of total terminal axons. The secondary synaptic clefts were markedly decreased in number and short in length. Myotendinous junction-like structures were found in 5.5% of the muscle fibres near the neuromuscular junctions, and often near sites of fibre-splitting. Rods in nemaline myopathy might be caused as a result of longitudinal splitting and disruption of fibres due to deficient regeneration of the muscle fibres associated with neurotrophic abnormalities.
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  • 40
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    Acta neuropathologica 42 (1978), S. 159-164 
    ISSN: 1432-0533
    Keywords: Perhexiline maleate ; Pexid ; Abnormal inclusion ; Rat ; CNS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The basic cellular lesion in CNS of suckling rats treated with Pexid was studied by light and electron microscopy. The most pronounced abnormality, the formation of various intracytoplasmic inclusions, was found in neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells and fibroblasts. These abnormal inclusions were generally membrane-bound, although clearly non-membrane-bound inclusions were occasionally found. The several internal patterns of the inclusions were (1) lamellar, both concentric and parallel, (2) reticular and (3) crystalloid. These alterations were completely resersed following withdrawal of the drug. The structural characteristics of the abnormal inclusions in Pexid-treated animals were similar to those found with certain hypocholesterolemic, neuroleptic, anorectic, and antimalarial drugs. This suggests that the inclusions occurring within the cells of animals treated with any of these drugs may develop in a similar manner, and that the formation of such inclusions is likely to be a form of cellular reaction common to certain metabolic disturbances.
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  • 41
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    Acta neuropathologica 44 (1978), S. 53-56 
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Air embolism ; Horseradish peroxidase ; Cerebral cortex ; Electron microscopy ; Carotid artery ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male albino rats were anaesthetized with diazepam, injected with horseradish peroxidase and Evans blue-labeled albumin and given an embolus of 0.01 ml air in the right common carotid artery after ligation of the external carotid branch. The pial arteries of the right cerebral hemisphere were stained blue, particularly the middle cerebral artery and its main arterial branchlets. Ultrastructurally, some endothelial cells in the right middle cerebral artery, small arteries and arterioles showed a diffuse distribution of horseradish peroxidase in their cytoplasm, although these vessels only occasionally showed peroxidase in their basement membranes. Other endothelial cells in these arterial branchlets showed few if any signs of a diffuse distribution of peroxidase but displayed several pinocytotic vesicles and occasionally trans-endothelial channels filled with peroxidase, sometimes with a slight leakage of peroxidase into adjacent basement membranes and neuropil. Scattered pinocytotic vesicles were observed in capillaries and venules, but there was usually no extravasation of peroxidase around these vessels.
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  • 42
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    Acta neuropathologica 44 (1978), S. 147-149 
    ISSN: 1432-0533
    Keywords: Cadmium ; Endothelial cell ; Capillary ; Fetal brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pregnant rats received a single administration of 0.5, 1.0, or 2.0 mg/kg of cadmium on day 18 or 20 or gestation Maternal animals were killed on day 21 and samples of the caudate nucleus from fetal brains were examined using the transmission electron microscope. A 2.0 mg/kg dose of cadmium administered to maternal rats on day 20 of gestation caused the formation of vacuoles in the endothelial cells of capilaries in the fetal brain. Significant endothelial cell vacuolization was not observed in the brain of fetuses from other treatment groups. The vacuoles occurred singly, were spherical in shape, were located adjacent to the intercellular junctions and caused focal distortion of the endothelial cell. Vacuoles were the only ultrastructural alteration observed in the caudate nucleus of fetal brains.
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  • 43
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    Acta neuropathologica 44 (1978), S. 235-239 
    ISSN: 1432-0533
    Keywords: Choroid plexus papilloma ; Ultrastructure ; Cytoplasmic ; Inclusions ; Silver bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three cases of choroid plexus papilloma were studied by light and electron microscopy. All had the typical papillary pattern, and, in addition, two exhibited solid areas of tumor growth which predominated in one case. PAS positive (diastase resistant) and argyrophilic cytoplasmic inclusions were present in all three tumors but were particularly abundant in the predominantly solid one. Ultrastructurally, the inclusions appeared as irregularly shaped structures containing lipid droplets, filamentous material and microtubules, and resembled the “silver bodies” of Biondi found in normal choroid plexus. Along with other ultrastructural features of normal choroid plexus, these cytoplasmic inclusions may be helpful in the differential diagnosis of papillary tumors involving the ventricular system.
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  • 44
    ISSN: 1432-0533
    Keywords: Protein-calorie malnutrition ; Rat ; Spinal root ; Sciatic nerve ; Internodal length
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The current investigation comprised normal young rats as well as rats submitted to a 50% food reduction or severe protein restriction. Isolated nerve fibres from lumbar spinal roots and sciatic nerves were investigated with reference to the relation between length and diameter of internodes as well as variation of internodal length along single nerve fibres. The present results do not support the view that protein-calorie malnutrition should cause neuropathy. Internodal segments were, on an average, shorter in relation to their thickness in young rats submitted to severe protein restriction or a 50% food reduction. The deviation was most marked in low-protein animals and particularly among coarser internodal segments. An inhibition of longitudinal growth was considered to be the main factor behind the difference between malnourished and normal rats.
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  • 45
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    Acta neuropathologica 41 (1978), S. 169-171 
    ISSN: 1432-0533
    Keywords: Pituitary gland ; Oncocytic adenoma ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two cases of oncocytic adenoma occurring in the pituitary are reported. Both were men aged 40 and 50 years respectively and there was no evidence of endocrine abnormality. In both the tumours many cells showed abundant acidophilic finely granular cytoplasm which had not stained positively with PAS-orange G stain. Electron microscopically the cells contained numerous mitochondria associated with marked reduction of other cytoplasmic organelles including the secretory granules.
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  • 46
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    Acta neuropathologica 43 (1978), S. 153-159 
    ISSN: 1432-0533
    Keywords: Myelin ; Oligodendroglia ; Human pathology ; Ultrastructure ; Carbon monoxyde ; Anoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 24-year-old woman was found comatose after 2 days of cephalalgia and vomiting. An immediate diagnosis of carbon monoxyde poisoning was disclaimed when blood carbon monoxyde was found to be 1.75 ml/100. A diagnosis of acute intracranial hypertension led to trephination with ventricular punction and brain biopsy on the third day. The patient died on the eleventh day. Ultrastructural study of biopsy tissue showed nearly normal cortex, and injured white matter, with disrupted or destroyed myelin and pycnotic oligodendroglia in contrast with nearly normal axons, astrocytes, and capillaries. Autopsy showed a typical semioval center myelinopathy. After discussion of the histotoxic, vascular, and edema theories for myelinopathy pathogenesis, primary oligodendrogial lesion is considered, and correlated with the diphasic evolution often observed in the course of carbon monoxyde myelinopathy.
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  • 47
    ISSN: 1432-0533
    Keywords: Cultured ; Craniopharyngioma ; Typical ; Atypical ; Ultrastructure ; Electron microscopy ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Craniopharyngiomas are tumors of the suprasellar area, which are often cystic, encapsulated and slow-growing. Certain of these tumors can behave in an aggressive manner and either invade surrounding structures or recur. In order to determine characteristics which may aid in distinguishing typical from atypical lesions, a study of biopsy and tissue culture specimens from 25 human craniopharyngiomas was undertaken. Tissue culture observations reveal two distinct cell populations. Typical lesions grew in culture in an orderly epithelial pattern and had desmosome-tonofibril aggregates and smooth surface topography demonstrable by electron microscopy. In the atypical tumors the cell growth was irregular, with mitotic activity, cholesterol crystals and features characteristic of neoplastic transformation, such as surface microvilli, an increase of cytoplasmic basophilia, size and number of nucleoli and retraction of cytoplasm. Correlation with the clinical status of the patients suggests that tumors of the four patients which exhibited atypical features in culture behaved more aggressively.
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  • 48
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    Acta neuropathologica 41 (1978), S. 119-124 
    ISSN: 1432-0533
    Keywords: Neuroblastoma ; Small-cell neoplasm ; Cerebral ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A small-cell neoplasm in the left temporal lobe of a 10 and a half year old boy was studied by light and electron microscopy. Routine sections of the mass showed a differentiating neuroblastoma with Homer Wright rosettes, several foci of immature neoplastic neurons (ganglion cells), many mitoses, arcas of necrosis and tumor vessels showing endothelial proliferation. Ultrastructurally, most cells resembled early fetal neuroblasts and also were similar to those in murine and peripheral human neuroblastomas.
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  • 49
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    Acta neuropathologica 42 (1978), S. 1-5 
    ISSN: 1432-0533
    Keywords: Dysplastic gangliocytoma ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of dysplastic gangliocytoma of the cerebellum, a rare disorder with unknown etiology and pathogenesis, was studied ultrastructurally. The intranuclear inclusions identified were not seen to be of viral origin. The ultrastructural characteristics of the abnormal cells support the prevailing theory that these cells represent hypertrophied granular neurons.
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  • 50
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    Acta neuropathologica 42 (1978), S. 223-229 
    ISSN: 1432-0533
    Keywords: Irradiation edema ; Gravimetry ; Ultrastructure ; Vesicular transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area could be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min following irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weight of the tissue. After 4 h an edema front can be observed spreading from the perinecrotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48 h post irradiation with normalisation of the tissue water content after 96 h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25 mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.
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  • 51
    ISSN: 1432-0533
    Keywords: Experimental brain gliomas ; Chemically induced ; Rat ; Cell cultures ; Humoral antibodies ; Immunofluorescence staining ; Microcytotoxicity assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain tumors were induced in Sprague-Dawley and Long-Evans rats by administration of N-methyl-N-nitrosourea in the drinking water. Of these tumors, a grade 2 mixed glioma, a grade 2 to 3 astrocytoma and a grade 1 to 2 oligodendroglioma were established in vitro, maintained in culture and designated 75SD-G-376, 75SD-G-420 and 77LE-G-180, respectively. Of these mass cultures, two were successfully cloned and are currently available as 75SD-G-376C and 75SD-420C cell lines. Clonal lines produce S-100 protein and grow as tumors when isografted in young rats. Using the cultured cells as target cells, specific antibodies were searched for in the sera of the rats with the primary tumors by means of an indirect fluorescent antibody staining method and a complement-dependent antibody-mediated microcytotoxicity assay. Fluorescent and cytotoxic antibodies were demonstrated in the sera of the mixed glioma- and astrocytoma-bearing animals. However, a variable proportion of cells of the 75SD-G-376 and 75SD-G-420 lines showed no reaction with the corresponding sera. Furthermore, cytotoxic anfibodies had a lytic effect on the autologous glioma cells only in the presence of rabbit complement.
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  • 52
    ISSN: 1432-0533
    Keywords: Tissue cultures ; Cytochalasin B and colchicine ; Cell motility ; Ultrastructure ; Glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary tissue cultures of human gliomas were treated with cytochalasin B (0.5–60 μg/ml for 90 min). Cell motility was inhibited irreversibly in glial tumour cells, but the effect was reversible on the mesenchymal cells growing in culture in the lower dose range. Cell adhesion was considerably reduced as the dose was increased, as was the capacity for cells to spread on a surface from suspension. Low concentrations of cytochalasin B caused negligible cell death and little disruption of cell ultrastructure. However, increases in dose were accompanied by a greater predominance of rough endoplasmic reticulum and inclusions and aggregation of microfilament bundles. As seen by scanning electron microscopy, cytochalasin B caused the withdrawal of peripheral cell borders, disappearance of ruffles and the breakdown of cytoplasmic lamellae. Charateristic surface blebs and folds appeared in their place. By comparison, colchicine (1–10 μg/ml) caused a less marked and non-specific reversible reduction in cell motility on both glial and mesenchymal cells. No significant change in cell adhesion or spreading took place even at high doses, although at all concentrations gross disruption of the cell surface took place with changes in ultrastructure characterised by loss of cytoplasmic microtubules and aggregation of 10 nm filaments.
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  • 53
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    Acta neuropathologica 44 (1978), S. 245-247 
    ISSN: 1432-0533
    Keywords: Schwann cells ; PNS myelin ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Within the retinal nerve fiber layer of a 6-week-old Sprague-Dawley rat, scattered aggregates of PNS myelinated axons have been found and described. We believe this is likely to represent a normal but rare phenomenon in the rat.
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  • 54
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    Development genes and evolution 185 (1978), S. 235-248 
    ISSN: 1432-041X
    Keywords: Liver ; Primary culture ; Ultrastructure ; Albumin synthesis ; Xenopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Electron microscopic analysis of primary cultures derived from larvalXenopus liver has shown that these cells, although they form only two-dimensional aggregates, retain and presumably also develop structural characteristics typical of liver parenchyma cells, such as bile canaliculi with microvilli and epithelial junctional complexes. As judged from structural criteria, primary cultures contain 80–90% hepatocytes. In contrast to the intact tissue, primary cultures showed excessive development of microfilaments, however. Incorporation of labeled amino acids has revealed further that the capacity for protein synthesis is maintained in culture and that synthesis of liverspecific protein albumin is maintained in vitro, even in liver cultures derived from thyrostatic tadpoles. This latter result suggests that initiation of albumin synthesis in the larval liver is probably not dependent upon thyroid hormones but rather reflects the protodifferentiated state of this tissue.
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  • 55
    ISSN: 1432-0827
    Keywords: Shell formation ; Free nerve endings ; Ultrastructure ; Lymnaea stagnalis ; Biomphalaria pfeifferi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The mantle edge of the freshwater pulmonate snailsLymnaea stagnalis andBiomphalaria pfeifferi was investigated with histochemical and ultrastructural methods. The mantle edge gland, which is involved in shell formation, consists of the periostracal groove and the belt. This belt appears to be composed of various regions. In the area of the periostracal groove a number of subepithelial gland cell types occur; these release their products into the groove. Between the groove cells ciliated free nerve endings terminate; the corresponding perikarya occur in the subepidermal connective tissue. Also in the posterior belt region free nerve endings were observed between the epithelial cells; in addition, a particular type of subepithelial gland cell was found in this area. The epithelial cells of this part of the belt have the ultrastructural characteristics of ion and water transporting cells; they are probably involved in calcium deposition and resorption. The possible role of the free nerve endings and of the subepithelial gland cells is discussed.
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  • 56
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    Calcified tissue international 25 (1978), S. 75-83 
    ISSN: 1432-0827
    Keywords: Rat ; Fluorosis ; Enamel ; Scanning electron microscopy ; Low temperature incineration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Sixteen 58-day-old male rats of Wistar strain, with a mean body weight of 179 g, were divided into two equal groups. Each group of eight animals was maintained for 70 days on drinking water, ad lib., containing no fluorine (control group) and 100 ppm of fluorine (experimental group). All specimens examined were obtained from the incisal portions of the incisors. The following types of enamel specimens were prepared for scanning electron microscopy: (1) acid-etched specimens; (2) acid-etched specimens followed by low temperature microincineration; and (3) fractured specimens. The enamel formed during high fluoride exposure showed marked hypocalcification, that is, the crystallite density in the prism core and interprismatic region was lower than that of control animals. The organic substances appeared to increase in these regions. These changes were prominent in the outer and middle enamel layers. Such changes following fluoride administration appear to indicate an inhibition of enamel maturation, that is, an inhibition of the mineral deposition and/or an inhibition of organic matrix withdrawal.
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  • 57
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    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 165-170 
    ISSN: 1432-1912
    Keywords: Striatum ; Evoked potentials ; Neuroleptics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The interaction of cortico- and nigrofugal inputs to the striatum of the rat was investigated using the technique of evoked potentials. Repetitive, unilateral stimulation of the substantia nigra inhibited potentials which were evoked from the ipsilateral rostral cortex and recorded from the ipsilateral striatum. The inhibition was antagonized by low doses of various intraperitoneally administered neuroleptics such as: pimozide (0.1–0.2 mg/kg), haloperidol (0.1–0.5 mg/kg), chlorpromazine (0.5–2.0 mg/kg) and thioridazine azine (0.5–4.0 mg/kg). These findings are discussed in view of the existing controversy regarding the mode of action of dopamine in the striatum.
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  • 58
    ISSN: 1432-2013
    Keywords: Oxygen dissociation curve ; Oxygen transport ; Cardiac output ; Coronary blood flow ; Blood flow to organs ; Hypoxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A major displacement of the blood O2 dissociation curve (ODC) was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals with a normal position of the ODC received NaCl instead. Arterial and mixed-venous O2 content ( $${\text{C}}_{{\text{O}}_{\text{2}} }$$ ) and O2 consumption were measured during breathing room air, 14.9, 8.0, or 5.6% O2 in N2. Cardiac output was obtained by the Fick principle.86RbCl was administered i.v., the rats were killed and the activity of86Rb in heart, spleen, stomach and intestines, liver, kidney, skeletal muscle, and skin was measured. According to Sapirstein (1956, 1958) the fractional uptake of86Rb in these organs corresponds to the fractions of cardiac output supplying these organs, and from the fractional uptake and cardiac output the nutritional blood flow may be calculated. Arterial and mixed-venous $${\text{C}}_{{\text{O}}_{\text{2}} }$$ was larger in the NaOCN than in the NaCl rats at all levels of oxygenation. At normoxia and 14.9% O2 the venous $${\text{C}}_{{\text{O}}_{\text{2}} }$$ was enlarged more than the arterial one, and so the arterio-venous O2 difference [ $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ ] as an index of the O2 extraction in the body was smaller in the rats with a left-shifted ODC. However, at more severe hypoxia (8.0 and 5.6% O2) the arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ in the NaOCN rats was enlarged more than the mixed-venous one, resulting in a larger $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ (and therefore O2 extraction) when compared with the NaCl animals. Cardiac output was larger in the NaOCN than in the NaCl rats at 14.9 and 5.6% O2, when expressed per kg body weight. At 14.9% O2 the augmented cardiac output compensated for the lower O2 extraction when compared with the NaCl animals. At 5.6% O2 the NaOCN rats had both a larger ( $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ ) and cardiac output than the NaCl animals. In the NaCl rats the decreased O2 extraction was not compensated for by an augmented cardiac output and therefore their O2 consumption was not only lower than that of the NaOCN rats but decreased even below the normoxic value of the NaCl rats. Coronary blood flow was increased in both NaOCN and NaCl animals at deep hypoxia to about the same extent, but due to a much lower arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ of the NaCl animals, their O2 supply to the heart was lower than that of the NaOCN rats. The nutritional blood flow to spleen, kidney, liver, stomach and intestines, and skin in ml/min · g was lower in the rats with a normal position of the ODC than in those with a left-shifted ODC. This, together with the low arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ of the NaCl rats, suggests a serious compromising of the O2 supply to these organs. Results of this study support the conclusion of our theoretical studies (Turek et al., 1973; Turek and Kreuzer, 1976) that a shift of the ODC to the left might be disadvantageous for the O2 transport to tissues at mild hypoxia, but advantageous at severe hypoxia.
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  • 59
    ISSN: 1432-2013
    Keywords: Blood gases ; Cardiac hypertrophy ; Intercapillary distance ; Myocardial infarction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats with a myocardial infarction due to ligation of the left coronary artery a marked right ventricular hypertrophy developed after 41/2 weeks. At this time no difference against control animals was observed in arterial $$P_{{\text{O}}_2 }$$ , $$P_{{\text{CO}}_2 }$$ , pH, ideal alveolar $$P_{{\text{O}}_2 }$$ , and alveolar-arterial O2 pressure difference, as measured in unanesthetized animals at normoxia. In histological sections of the heart stained by PAS reaction capillaries and muscle fibers were counted, and the mean intercapillary distance and muscle fiber diameter were estimated. In the right ventricle of the rats with myocardial infarction both increased when compared with control animals or with sham-operated rats. Fibercapillary ratio was the same in all three groups. Similar results were obtained in the remaining undamaged tissue of the left ventricle of rats with a myocardial infarction when compared with the left ventricle of control or sham-operated rats. Findings concerning intercapillary distance suggest that also in the myocardium which remains intact during the development of the infarction and later hypertrophies, tissue oxygen transport might be impaired, particularly during a stress situation. Results in the right ventricle of rats with myocardial infarction show an opposite trend against rats exposed chronically to simulated high altitude, where in the hypertrophied right ventricle a shorter intercapillary distance occurs and therefore an improvement of tissue oxygen transport might be expected.
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  • 60
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    Pflügers Archiv 376 (1978), S. 245-249 
    ISSN: 1432-2013
    Keywords: Colon ; Amino acid uptake ; Basolateral membrane ; Active transport ; Sheep ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Uptake of the nonmetabolizable model amino acid 2-aminoisobutyric acid (=AIB) through the basolateral membrane into epithelial cells was studied in sheep colon stripped of serosa and muscle layers. Only the antiluminal surface of the mucosa was exposed to the incubation medium. Thus AIB entry into epithelial cells could only occur through the basolateral membrane. AIB was taken up by a saturable process against a high concentration gradient. AIB uptake was inhibited by other neutral amino acids but not by sugars. In a low Na+ medium AIB uptake was impaired, indicating that active transport of amino acids through the basolateral membrane of colon epithelial cells is Na+-dependent. In the rat a saturable concentrative uptake of AIB through the basolateral membrane of colon epithelial cells has also been demonstrated. Concentrative uptake of amino acids through the basolateral membranes is probably important for the supply of colon epithelium with amino acids.
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  • 61
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    Pflügers Archiv 373 (1978), S. 133-138 
    ISSN: 1432-2013
    Keywords: Deoxycholate ; Intestinal perfusion ; Rat ; Enzymatic release ; Localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The release of proteins, sucrase (SA), maltase (MA), leucine aminopeptidase (LA) and alkaline phosphatase (AP) activity from rat jejunum by sodium deoxycholate (DOC) was studied by an in vivo perfusion technique. In our experimental conditions, a 2 mmol/l DOC perfusion for 30 min induced a marked and reversible release of proteins and hydrolases. When specific activities were considered, each enzyme showed a distinct release pattern. Significantly, the SA release was largely increased, the AP release was decreased and there was no correlation between the releases of SA and AP. Furthermore, the various enzymes recovered into the lumen were solubilized at different extents. SA was chiefly present in a soluble and AP in a particular form. The microscopical appearances showed a slight exfoliation of the epithelial cells from the villous tips but no specific changes when compared to the control group. The results are discussed in terms of enzymic localization in the brush border membrane; SA would be located very superficially in the surface membrane and AP buried in the membrane and less accessible than the other enzymes.
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  • 62
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    Pflügers Archiv 374 (1978), S. 229-234 
    ISSN: 1432-2013
    Keywords: Cyclic AMP ; ADH ; Vasopressin ; Isoproterenol ; 3-isobutyl-1-methylxanthin ; Rat ; Water diuresis ; Antidiuresis ; Dehydration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo experiments were performed in male Wistar rats to elucidate the probable relation between renal concentrating ability and medullary cyclic AMP content as influenced by changes of hydration and by administration of antidiuretic hormone (ADH). Cyclic AMP levels were 37% lower in water diuretic than in control animals (P〈0.01), but were not significantly changed during prolonged antidiuresis induced by dehydration or ADH administration. Nor could any change of cyclic AMP levels be demonstrated between 2 and 20 min after ADH injection. Significant increases of medullary cyclic AMP content occurred following stress, anesthesia, and administration of isoproterenol and 3-isobutyl-1-methylxanthin. The results suggest that the level of cyclic AMP in the renal medulla may not be an important determinant of the antidiuretic response produced by ADH in rats.
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  • 63
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    Pflügers Archiv 374 (1978), S. 285-288 
    ISSN: 1432-2013
    Keywords: High altitude ; Blood volume ; Red cell volume ; Plasma volume ; Body haematocrit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Circulating blood volume (BV) as the sum of circulating red cell volume (RCV) and plasma volume (PV) was estimated in rats native to a simulated altitude of 3500 m (“natives”), in rats born at sea level and later in life transferred to the simulated high altitude (“newcomers”), and in control sea-level rats. RCV per kg body weight (b.w.) was significantly larger in both “newcomers” and “natives” than in controls. PV per kg b.w. was in the “newcomers” insignificantly and in the “natives” significantly smaller than in the controls. BV per kg b.w. in both high altitude groups tended to be larger than in controls but the difference was not significant. Arterial haematocrit (Ahct) in the “newcomers” was significantly higher than in the controls, and in the “natives” significantly higher than in both other groups. Body haematocrit (the ratio of RCV and BV in per cent) was smaller than Ahct in all groups; this was more pronounced in the “newcomers” than in the controls and even more so in the “natives”. Apparently the haematocrit in the minute vessels of the organs of animals exposed to chronic hypoxic hypoxia increases much less than might be expected from changes of the Ahct. An attempt was made to evaluate the possible error of the more commonly used method of estimating BV, when only RCV, or only PV, is measured, and BV and its complementary fraction are calculated from arterial or venous haematocrit. When, in our results, BV was calculated from RCV and Ahct, the absolute values and also the differences between groups were somewhat underestimated. When BV was calculated from PV and Ahct, the BV itself, and particularly the differences between groups, were overestimated quite considerably. It is suggested that the only safe way to estimate BV is to measure RCV and PV separately.
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  • 64
    ISSN: 1432-2013
    Keywords: PAH clearance ; PAH extraction ; Glomerular filtration rate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PAH secretion (TPAH) was studied in rats at spontaneously occurring glomerular filtration rate (GFR). At saturated transport, TPAH was found to be correlated to GFR. This relationship was also observed at unsaturated transport where TPAH depends upon the PAH concentration in arterial plasma. However, no significant correlation between TPAH and renal PAH load or renal plasma flow rate was found when the effects of GFR were removed by partial correlation analysis. A dependency of TPAH on GFR explains the correlations found between filtration fraction (FF) and renal PAH extraction (EPAH) or renal tubular PAH extraction fraction (EPAH-FFPAH). Thus, even at low PAH concentration in a. plasma, renal PAH extraction may only be assumed to be constant if the filtration fraction is constant.
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  • 65
    ISSN: 1432-2013
    Keywords: Oxygen dissociation curve ; Oxygen transport ; Blood gases ; Hypoxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Theoretical deductions have shown that a shift of the blood O2 dissociation curve (ODC) to the right might improve O2 transport to tissues at normoxia and at mild hypoxia whereas at severe hypoxia the organism should be better off with an ODC shifted to the left (Turek et al., 1973b; Turek and Kreuzer, 1976). The present study was performed in order to ascertain this ambiguous effect of an ODC shift depending on the degree of hypoxia in intact animals. A major displacement of the ODC to the left was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals received sodium chloride (NaCl) instead. Arterial and mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ , $$P_{{\text{CO}}_{\text{2}} }$$ , and pH were measured at normoxia and during breathing 14.9, 8.0, or 5.6% O2 in N2 in both groups. From $$P_{{\text{O}}_{\text{2}} }$$ , pH, ODC and arterial hematocrit, arterial and mixed-venous O2 contents were estimated and $$({\text{a}} - {\text{v)}}_{{\text{O}}_{\text{2}} }$$ as an index of blood O2 extraction was obtained. At normoxia and during breathing 14.9% O2 the NaOCN rats had a lower mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ than the NaCl rats without any difference in pH. Arterio-venous O2 difference did not differ at normoxia but was lower in NaOCN rats at 14.9% O2. However, at 8.0 and 5.6% O2 the NaOCN rats had a higher mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ , an increased $$({\text{a}} - {\text{v)}}_{{\text{O}}_{\text{2}} }$$ , and a higher pH (arterial and mixed-venous). At 5.6% O2 the NaCl rats developed a severe acidosis concomitant with pronounced hypocapnia. These findings confirm that rats with a left-shifted ODC have an impaired O2 transport to tissues at normoxia and mild hypoxia but a more efficient O2 transport at severe hypoxia as compared with rats with an unshifted ODC, in agreement with our previous theoretical studies.
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  • 66
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    European journal of clinical pharmacology 13 (1978), S. 275-284 
    ISSN: 1432-1041
    Keywords: Diazepam ; pharmacokinetics ; pregnant women ; plasma clearance ; blood/plasma concentration ratio ; placental transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of diazepam has been studied in pregnant women at parturition. The plasma concentration of diazepam was monitored for at least 3 days in 18 women who received a single intravenous injection of 10 mg during the 10 h-period prior to delivery. Fourteen mothers had uneventful puerperia (Group I) and in 13 of these cases there was a pronounced postnatal increase in the plasma concentration of diazepam. The terminal phase half-life (t1/2) was significantly greater for Group I (mean = 65 h; range = 24–114 h) than for age-matched non-pregnant patients (mean = 29 h; range = 18–44 h from literature). The prolonged t1/2 appeared to be related to changes in the distribution of diazepam and not to a reduction in hepatic elimination since the total plasma clearance (Cltp) in these 14 pregnant patients (mean = 28 ml/min; range = 18–43 ml/min) was not reduced compared to that reported for non-pregnant controls (mean = 30 ml/min; range = 22–45 ml/min). Four mothers underwent postnatal surgery for tubal ligation (Group II) and the plasma concentration-time profiles for this group did not show the same postnatal phenomenon as did the profiles obtained for Group I. The t1/2 for Group II was shorter (mean = 31 h; range = 24–37 h) than for Group I and similar to that for the non-pregnant controls. The Cltp for Group II was greater (mean = 56 ml/min; range = 48–63 ml/min) than for both Group I and non-pregnant controls. These results suggest that delivery alters the disposition of diazepam and is generally associated with a postnatal re-distribution of diazepam into the systemic circulation. The blood/plasma concentration ratio was determined in 9 patients (mean = 0.62; range = 0.54–0.77). There was no difference in the total blood clearance between the pregnant patients of Group I and the non-pregnant controls. In most cases the umbilical venous plasma concentration (Cpuv) of diazepam was greater than the peripheral maternal venous plasma concentration (Cpmv) at delivery. The foetus appears to constitute a slowly equilibrating tissue-group in which diazepam does not reach equilibrium with the maternal systemic circulation for at least 5–10 h at which time the diazepam concentration in maternal and foetal plasma is similar.
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  • 67
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
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  • 68
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    European journal of clinical pharmacology 13 (1978), S. 69-72 
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; hydrocortisone ; elimination rate ; distribution volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a high plasma concentration of hydrocortisone on the metabolism of phenazone in humans has been studied. Two series of experiments were carried out, Group A to demonstrate any enzyme-inducing effect of hydrocortisone, and Group B to study the immediate effect of hydrocortisone on the metabolism of phenazone. 9 subjects (Group A) received a total 250–400 mg hydrocortisone i.m. twice daily for three days and the 24-hour elimination of phenazone was studied before and afterwards. In a further 5 subjects (Group B) the elimination of phenazone was examined during administration of hydrocortisone or placebo. The elimination rate and the apparent volume of distribution of phenazone remained unchanged under both experimental conditions.
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  • 69
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    European journal of clinical pharmacology 13 (1978), S. 97-101 
    ISSN: 1432-1041
    Keywords: Clonidine ; plasma level ; pharmacokinetics ; steady state ; urinary excretion ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single oral dose of clonidine 300 µg was administered to 8 healthy, normotensive subjects and the time course of its plasma concentrations was followed for 24 h. The plasma concentration of clonidine rose to a peak of 1.17±0.12 ng/ml at about 2 h: the absorption half-life was 0.6±0.2 h. Elimination followed first order kinetics with a half-life of 7.7±2.0 h. The correlation between the two most common side-effects of clonidine, sedation and dryness of the mouth, with the time course of its plasma concentrations was highly significant, p〈0.01. All the subjects complained of severe sedation. During continuous administration of clonidine (75 µg t.i.d.) for one week a steady state serum level of 0.30–0.35 ng/ml was achieved. One 75 µg tablet of clonidine raised the serum level to about 0.69±0.13 ng/ml in two hours. After cessation of dosing, the serum level declined with a half-life of 7.5±1.5 h. The urinary excretion of unchanged clonidine was found to be about onethird of the administered dose in 24 h during continuous administration and in the first 24 h after the single oral dose.
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  • 70
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    European journal of clinical pharmacology 14 (1978), S. 203-212 
    ISSN: 1432-1041
    Keywords: Mepivacaine ; pharmacokinetics ; neonates ; healthy adults ; metabolism ; renal excretion ; lignocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of mepivacaine has been studied in premature neonates dosed subcutaneously and in healthy adults dosed intravenously. The pharmacokinetics of mepivacaine in four neonates (N) was compared with that in six adults (A). Newborns had a significantly longer terminal phase half-life than adults (N mean 8.69 h; A mean 3.17 h). Total plasma clearance normalized on body weight was significantly smaller in neonates (mean 2.34 ml/min/kg) than in adults (mean 5.47 ml/min/kg), as was the hepatic blood clearance (N mean 1.37 ml/min/kg; A mean 5.10 ml/min/kg). The renal plasma clearance, however, was significantly greater in neonates (mean 0.76 ml/min/kg) than adults (mean 0.20 ml/min/kg). There was an average six-fold increase in the fraction of the dose excreted unchanged in newborns (mean 43.3%) compared to adults (mean 7.1%) with acidified urine (pH 5.5–6.0). There was significantly more of the mono-N-demethylated metabolite of mepivacaine excreted by newborns (mean 11.4%) than by adults (mean 2.2%), but their capacity to carry out aromatic hydroxylation of mepivacaine was negligible. These results for mepivacaine were compared with those previously reported for lignocaine in premature infants. The immaturity of hepatic function appears to have diminished more profoundly the ability of premature infants to metabolize mepivacaine than lignocaine. These findings are discussed in terms of perfusion theory of hepatic drug elimination.
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  • 71
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    European journal of clinical pharmacology 14 (1978), S. 143-147 
    ISSN: 1432-1041
    Keywords: Children ; leukemia ; high-dose methotrexate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous high-dose methotrexate were studied in two groups of children being treated for malignant diseases, mostly acute lymphatic leukemia. The peak serum level of methotrexate of 2.32·10−5 mol/l was found in children given 500 mg methotrexate/m2 by a 24 h infusion, and another group given 2790 mg/m2 during a 6 h infusion had serum levels as high as 2.16·10−4 mol/l. The decay of serum concentration of methotrexate after completion of the infusion followed a diphasic curve, with an initial serum half-life of 4.8 h, followed by a second half-life of 34.4 h at distribution equilibrium. The apparent volume of distribution was 56.8 litres/m2. Significant levels of methotrexate were found in cerebrospinal fluid, but penetration into cerebrospinal fluid was slow. Urinary excretion of methotrexate was considerable. Four to five days after commencement of the infusion, urinary concentrations of methotrexate still exceeded the serum levels.
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  • 72
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    European journal of clinical pharmacology 14 (1978), S. 335-340 
    ISSN: 1432-1041
    Keywords: Drug binding to muscle ; interindividual differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Binding of 22 drugs to human muscle tissue has been determined by ultrafiltration. All drugs tested were bound, the bound fraction ranging from 13% (aminophenazone) to 〉98% (desipramine). Both linear and nonlinear binding was observed. For chemically related substances, binding to muscle tissue correlated with plasma binding and lipid solubility. There were significant differences in binding to muscle from different individuals. With respect to pharmacokinetics of drugs, it is suggested that binding to muscle tissue may be at least as important as plasma binding.
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  • 73
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    European journal of clinical pharmacology 13 (1978), S. 41-48 
    ISSN: 1432-1041
    Keywords: Furosemide ; pharmacokinetics ; anephric patients ; metabolism ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min · kg and 2.96 ml/min · kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDss. In the patients, but not in the normal subjects, there was a significant positive correlation between $$V_{D_{ss} } $$ and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoylanthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.
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  • 74
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    European journal of clinical pharmacology 13 (1978), S. 29-33 
    ISSN: 1432-1041
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
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    European journal of clinical pharmacology 13 (1978), S. 365-371 
    ISSN: 1432-1041
    Keywords: Etidocaine ; pharmacokinetics ; metabolism ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary elimination of etidocaine and several of its metabolites was investigated in neonates whose mothers had received one or more doses of etidocaine during labour. The urine collection period ranged among the neonates from 21.4 to 47.0 h post-partum. The total amounts of etidocaine and its metabolites recovered in neonatal urine represented a mean of 0.12 per cent of the maternal dose. Some differences in the pattern of urinary metabolites were observed between neonates and adults. Mean half-life of elimination of etidocaine calculated from sigma-minus plots of the neonatal urinary data was 6.42 h. This is greater than that previously reported following intravenous administration of etidocaine to adults (2.6 h). The slower rate of elimination in neonates is probably due to an increased neonatal volume of distribution since there is evidence to show that etidocaine is extensively metabolised by the neonate.
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  • 76
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    European journal of clinical pharmacology 13 (1978), S. 379-383 
    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; phenzone ; posture ; immobilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of phenazone was studied in six subjects while ambulant and during bed rest for 3 days. Elimination of the drug was followed for 12 h after oral and intravenous administration. The elimination rate constant and total body clearance were significantly increased during bed rest as compared to the ambulant period, but the differences were small. The apparent volume of distribution decreased significantly. No consistent change due to bed rest was found in the rate of absorption or bioavailability of the oral dose.
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  • 77
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    European journal of clinical pharmacology 13 (1978), S. 209-212 
    ISSN: 1432-1041
    Keywords: Paracetamol ; acetaminophen ; Gilbert's syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of paracetamol after intravenous and oral administration has been studied in 6 patients with Gilbert's syndrome, and 6 healthy controls. Paracetamol clearance was significantly less in the patients (255 ml/min SE±23 ml/min) than in the normal subjects (352 ml/min SE±40 ml/min). Moreover, whilst paracetamol concentrations declined monoexponentially in the patients, the decline was biexponential in the controls. No difference in the bioavailability of 500 mg paracetamol given orally was observed between the two groups. The results suggest that not only is paracetamol elimination impaired in Gilbert's syndrome, but that its distribution kinetics are also abnormal. Both these findings could be attributed to a decrease in hepatic glucuronyl transferase activity.
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  • 78
    ISSN: 1432-1041
    Keywords: Aminopyrine ; pharmacokinetics ; 14CO2 breath test ; hepatic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of aminopyrine in plasma and of14CO2 in breath was determined for 6 hours after oral administration of (14C-methyl) aminopyrine to healthy controls and to patients with hepatitis and hepatic fibrosis, cirrhosis and hepatic bilharziasis.14CO2 in breath declined about 1.8 times more slowly than aminopyrine plasma levels, which suggests the occurrence of metabolite demethylation. This was confirmed by the slow elimination of14C from plasma, the formation of14CO2 after aminopyrine had disappeared and the presence of a considerable amount of monomethyl-aminopyrine in plasma. The mean14CO2 concentration in breath was correlated with but was not proportional to aminopyrine clearance, which was attributed to individual differences in aminopyrine half-life. Both a correlation and proportionality were found when14CO2 extrapolated to zero time was used as a parameter of14CO2 production. Hepatic disease affected aminopyrine clearance to a variable extent. In the hepatitis and fibrosis group, aminopyrine clearance was affected in 2 out of five subjects. In all except one cirrhotic subject aminopyrine clearance was markedly decreased. Moreover, in three out of seven cases aminopyrine absorption was impaired, presumably due to decreased gastrointestinal blood-flow. This may produce an erroneously low14CO2 concentration in breath during the first two hours after aminopyrine administration. Hepatic bilharziasis was accompanied by very low aminopyrine clearance in all four cases. In two patients high apparent Vd values were observed, probably due to “first-pass” metabolism. Patients with ascites had Vd values within normal limits.
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  • 79
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    European journal of clinical pharmacology 14 (1978), S. 57-67 
    ISSN: 1432-1041
    Keywords: Chemotherapy ; sulfadiazine ; trimethoprim ; pharmacokinetics ; acetylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual “peak” concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 µg/ml for SDZ and 0.3 to 1.1 µg/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h) – 145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 µg/ml for SDZ and from 13.8 to 93.4 µg/ml for TMP. The fraction acetylated SDZ/acetylated SDZ + SDZ was 21% during the 0–8 h period, 33% during the 8–15 h period and 41% during the 15–24 period. The average values for the notional volume of distribution, Vd, were 0.36±0.13 1/kg for SDZ and 1.39±0.25 1/kg for TMP. The average “t1/2” was 15.2±7.4 h for SDZ and 7.4±1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p〈0.01) and also between the renal clearance of the two drugs (p〈0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ Vd was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for “acetylated SDZ”. The renal clearance of “acetylated SDZ” averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.
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    European journal of clinical pharmacology 14 (1978), S. 237-244 
    ISSN: 1432-1041
    Keywords: Furosemide ; arterial hypertension ; protein binding ; sodium excretion ; renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was injected intravenously in 7 patients with severe hypertension and vascular complications. A two compartment, open model was used to describe the disappearance of the drug from serum. The mean serum clearance (Cls=1.83 ml/min · kg) was significantly reduced compared to the mean Cls-value of a group of normals (2.96 ml/min · kg). A significant correlation was found between Cls and mean blood pressure, as well as between Cls and renal clearance (mean Clr=0.83 ml/min · kg); extrapolation of the regression line yielded a Cls-value of 50 ml/min for Clr=0. The Clr was also significantly negatively correlated with mean blood pressure. Protein binding of furosemide was normal, except in one patient, who had considerable impairment of renal function. Apparently more than 90% of unchanged furosemide passed in urine was excreted by tubular transport. A highly significant negative correlation was found between Cls and the fraction of furosemide excreted as a glucuronide. During the first two hours, significantly less sodium was excreted by the patients than by a comparable group of normal subjects. The correlation between serum concentration of furosemide and the amount excreted of sodium was not significant, but highly significant correlations were found between the amounts of furosemide and sodium excreted by the kidney in 0–30 and 0–60 min. In all the individual patients an approximately linear relationship with wide variation in the slope was found between the cumulative excretion of furosemide and sodium from 0–30 min to 0–60 and to 0–120 min. After 120 min deviations were observed in the curves from 4 of the patients, which indicated that smaller and smaller additional amounts of sodium were excreted with constant additional amounts of furosemide.
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  • 81
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    European journal of clinical pharmacology 14 (1978), S. 267-271 
    ISSN: 1432-1041
    Keywords: Lithium ; sustained-release ; pharmacokinetics ; manic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An ordinary and a sustained-release lithium carbonate preparation were administered acutely at equivalent dosage (1.80 g=24.3 mmol) in a crossover fashion to manic patients. Serum lithium levels were determined by atomic absorption spectroscopy and pharmacokinetic parameters were calculated. Maximum mean serum levels of 1.13 mmol/l and 0.78 mmol/l were achieved at 6 h and 12 h respectively with the ordinary and sustained-release forms. The mean half-lives of absorption, redistribution and elimination were 0.78 h±0.05 (SE), 5.06 h±0.23, 26.8 h±4.5 and 3.73 h±0.37 (SE), 4.42 h±0.28 and 25.6 h±5.5 for the ordinary and sustained-release forms respectively. In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects. Lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.
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  • 82
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    European journal of clinical pharmacology 14 (1978), S. 277-280 
    ISSN: 1432-1041
    Keywords: Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.
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  • 83
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    European journal of clinical pharmacology 14 (1978), S. 69-73 
    ISSN: 1432-1041
    Keywords: Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.
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  • 84
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    European journal of clinical pharmacology 14 (1978), S. 431-434 
    ISSN: 1432-1041
    Keywords: Timolol ; pharmacokinetics ; oral and intravenous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volume of distribution was 3.5 l/k. It is suggested that timolol is little affected by the ‘first pass effect’, even though there is marked interindividual variation in availability and peak plasma level.
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  • 85
    ISSN: 1432-0738
    Keywords: Cadmium ; Drug Metabolism ; Metallothionein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (〉 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbital hypnosis and inhibition of hepatic microsomal metabolism of hexobarbital and aniline. Administration of cadmium in the drinking water at levels of 100 or 200 ppm Cd for periods of 2–12 weeks or at levels of 5 or 20 ppm Cd for 50 weeks did not produce alterations in either drug response or hepatic drug metabolism. Significant levels of metallothionein, a cadmium binding protein, found in the liver of the rats receiving cadmium chronically may offer an explanation for the observed differences in drug metabolism between the acute and chronic administration of cadmium. In additional studies, pretreatment of the rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) intraperitoneally produced a tolerance to the alterations in drug metabolism induced by the previous cadmium dose (0.84 mg Cd/kg, i.p.). However, chronic cadmium treatment (5 or 20 ppm Cd for 50 weeks) did not impart any such tolerance to subsequently administered Cd (0.84 mg/kg) by the intraperitoneal route. The hepatic levels of metallothionein induced by the chronic cadmium treatment were only 30–60% of those induced by the subthreshold cadmium and thus may not have bound enough of the large challenge cadmium dose to produce the tolerance phenomenon.
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  • 86
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    Archives of toxicology 39 (1978), S. 267-287 
    ISSN: 1432-0738
    Keywords: Rat ; Plasma ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report describes the application of a test system which applies different substrates, inhibitors and acrylamide electrophoresis to the study of the alkaline phosphatase activity of rats. The system, which was specifically devised to characterise the alkaline phosphatase activity of small quantities of plasma from rats in toxicological studies, was also used to examine the plasma from rats under several physiological conditions, e.g. time of day, age, diet, etc. These physiological factors can influence the measurement of plasma alkaline phosphatase activity and should be taken into account when designing toxicological studies. Different experimental regimes were used to produce increases in liver, bone and intestinal alkaline phosphatase isoenzymes in the plasma of rats and these were reflected in the characterisations by the system. Although much remains unknown, a few concepts of rat plasma alkaline phosphatase activity emerged under our conditions. There is a ‘tidal’ intestinal component which arises from feeding and is approximately 60% of the total activity of the fed rat. In the fasted rat this ‘tidal’ component has largely disappeared and the ‘core’ activity which remains is composed of approximately equal proportions of bone isoenzyme and another as yet ill-defined component. The liver isoenzyme which appears in the plasma of the cholestatic rat appears to be either a very minor component or absent from the plasma of our normal CFE derived rat.
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  • 87
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    Archives of toxicology 40 (1978), S. 7-16 
    ISSN: 1432-0738
    Keywords: Thallium ; Furosemide ; Acetazolamide ; Renal elimination ; Oral absorption ; 204Tl ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen einer Untersuchung über das Schicksal von Thallium im Organismus und über den Einfluß von Diuretika auf die Eliminationsgeschwindigkeit dieses Giftes wurde Tl2SO4 (48.9 μmol = 10 mg/kg) an wachen Ratten oral verabreicht. Die Blutspiegel von Tl+ wurden anschließend als Funktion der Zeit ermittelt, sie konnten mit einer klassischen Bateman-Funktion nicht richtig beschrieben werden. Etwa l Std nach oraler Verabreichung war die Blutkonzentration maximal. Die Behandlung mit Furosemid (30 mg/kg) beschleunigte die Entfernung von Thallium aus dem Organismus auf signifikante Weise. Etwa 35% der zugeführten Menge Thallium wurde während einer Woche nach der Injektion dieses Diuretikums mit dem Urin ausgeschieden. Auch die Ausscheidung von Natriumionen und Wasser war signifikant erhöht, die von Kaliumionen blieb jedoch fast unverändert. Thallium selbst verursachte eine schwache diuretische Wirkung. Nach fortgesetzter Behandlung mit Furosemid (bis 2 Wochen) blieb die Eliminationsgeschwindigkeit von Thallium, Wasser und Natrium beschleunigt, während die Ausscheidung von Kaliumionen im Vergleich zu Kontrolltieren etwas herabgesetzt war. Ethacrynsäure verursachte nach wiederholter Gabe in diuretisch wirksamen Dosen eine retroperitoneale Fibrose. Dieses wirksame Diuretikum konnte daher nicht in die Untersuchung einbezogen werden. Acetazolamid (30 mg/kg) erhöhte ebenfalls die Ausscheidung von Thallium, vor allem innerhalb der anfänglichen 24 Std. Die Wirkung war weniger intensiv als die von Furosemid, sie war außerdem bald erschöpft. Die Ergebnisse legen den Schluß nahe, Furosemid in hohen Dosen sei eine wirksame Maßnahme zur Beschleunigung der Thalliumentfernung aus dem Organismus, zumindest im vorliegenden Tiermodell. Acetazolamid ist zu diesem Zwecke wahrscheinlich nicht geeignet.
    Notes: Abstract In connection with a programme of investigations concerning the disposition of thallium in the rat and the influence of diuretic agents on the rate of elimination of thallium from the body, Tl2SO4 (48.9 μmol = 10 mg/kg) was given by mouth to conscious rats. Blood levels were studied as a function of time. They could not be described adequately by means of a classical Bateman function. The maximum blood level was achieved approximately 1 h following oral ingestion. Treatment with furosemide for 11 days (30 mg/kg twice daily) significantly accelerated the removal of thallium from the body with the urine. Approximately 35% of the administered thallium was excreted within one week following the injection of this diuretic agent. The excretion of sodium and water was also considerably enhanced, that of potassium hardly changed. Thallium itself displayed weak diuretic activity. Upon prolonged treatment (1–2 weeks) with furosemide the elimination of thallium, water and Na+ was still accelerated, although that of potassium proved diminished with respect to controls. Ethacrynic acid when administered repeatedly in appropriate doses caused retroperitoneal fibrosis. Therefore, this potent diuretic agent was not included in the investigations. Acetazolamide (30 mg/kg) also enhanced the excretion of thallium, especially within the initial 24 h of treatment. The effect was less pronounced than that of furosemide and rapidly exhausted. The results suggest that furosemide in a high dose is effective in accelerating thallium elimination from the body in the present animal model. Acetazolamide is probably not suitable for this purpose.
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  • 88
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    Archives of toxicology 41 (1978), S. 99-105 
    ISSN: 1432-0738
    Keywords: Rat ; Method ; Gastric ulceration ; Distention of stomach ; Stress ; Anti-inflammatory drugs ; Ulcerogenic side effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das sog. „distention“-Ulkus wurde an Albinoratten untersucht und als neue Möglichkeit für die Feststellung ulzerogener Nebenwirkungen von Substanzen beschrieben. Die Dehnung des Magens in sich war nicht ausreichend um ulzerogene Läsionen auszulösen, denn die Dehnung des Magens mit physiologischer Kochsalzlösung führte nicht zur Ulzeration. Die Säure ist ein entscheidender Faktor in der Bildung des „distention“-Ulkus. Große Volumina von 0,1 N Salzsäure riefen innerhalb von 1 Std massive Ulzeration hervor. Kleine Mengen von dieser Säurelösung verursachten keine Ulzeration im Magen. Entzündungshemmer, die in noch von ulzerogenen Nebenwirkungen freien therapeutischen Dosen verabreicht wurden, erhöhten die Empfindlichkeit der gastralen Mukosa dem aggressiven Faktor, der Säure, gegenüber. Bei den mit bekanntlich ulzerogen wirkenden Dosen von Entzündungshemmern vorbehandelten Ratten wurde eine schnellere Bildung von Ulzera durch die Dehnung des Magens mit Säure beobachtet. Auch die Stressvorbehandlung beschleunigte und verstärkte die Bildung der durch Dehnung hervorgerufenen ulzerogenen Veränderungen im Magen.
    Notes: Abstract A modification of the distention ulcer was studied in albino rats and a new possibility of testing ulcerogenic side effects of drugs was described. The distention alone was not sufficient to produce lesions. The severity of ulcer lesions was highly dependent on the volume of the acid solution. Large volumes of 0.1 N HCl evoked severe ulcers within 1 h. Small amounts of weak acid solution did not cause any ulceration. Anti-inflammatory drugs administered in therapeutic doses, which did not yet produce any ulcers in animals, increased the sensitivity of the gastric mucosa against the aggresive factor, the acid. In animals pretreated by anti-inflammatory drugs in toxic doses an earlier development of ulceration was observed by distention with acid. Stress also accelerated and aggravated the formation of distention ulcers.
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  • 89
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    Archives of toxicology 39 (1978), S. 249-266 
    ISSN: 1432-0738
    Keywords: Rat ; Alkaline phosphatase ; Plasma ; Organs ; Toxicity testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A manual system of various estimations of rat plasma alkaline phosphatase activity has been devised for small volumes of plasma which uses different inhibitors, compares the utilisation of two substrates and includes acrylamide gel electrophoresis. The different inhibitors etc. allow a degree of discrimination between alkaline phosphatase extracts of rat organs. The properties of isoenzymes, e.g. intestinal alkaline phosphatase, differ depending upon the environment in which they are studied. In conjunction, if necessary, with the methods described for the estimation of liver and intestinal alkaline phosphatase activity, it is hoped to use the system to discriminate between the isoenzymes present in the plasma alkaline phosphatase of rats in toxicological studies.
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  • 90
    ISSN: 1432-0738
    Keywords: Mercury ; Selenium ; Retention ; Liver ; Kidney ; Ultrastructure ; Interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Distribution and retention of mercury and selenium was studied in rats exposed repeatedly to HgCl2 injections (0.5 mg Hg/kg to the tail vein every other day) and intragastrically to Na2SeO3 (0.5 mg Se/kg every day), applying combined and separate administration of these metals for 2 weeks. Whole-body retention of mercury in the presence of selenium was augmented by 20% and that of selenium in the presence of mercury by 4% with respect to the administered dose. Combined administration of mercuric chloride and sodium selenite brought about damage to the epithelial cells of renal proximal convolutions and formation of protein casts in their lumen. These changes had the same pattern as those induced by administration of mercuric chloride alone, but the intensity was lower. Submicroscopic studies revealed that repeated combined administration of sodium selenite and mercuric chloride did not completely abolish the mercury-induced mitochondrial swelling and contributed to chromatin destruction in the hepatocyte nuclei.
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  • 91
    ISSN: 1432-1041
    Keywords: Lignocaine ; pharmacokinetics ; neonates ; metabolism ; renal excretion ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of lignocaine in premature neonates was studied after subcutaneous administration. The collection of serial urine together with a limited number of blood samples from neonates enabled simultaneous computer fitting of data to a pharmacokinetic model. The disposition kinetics of lignocaine in four neonates were compared with similar data reported for adults. Neonates had prolonged t1/2 (neonate mean: 3.16 h; adult mean: 1.80 h), and an increased total volume of distribution (neonate mean: 2.75 l/kg; adult mean: 1.11 l/kg) compared with adults. Total plasma clearance (Cltp) normalised on body weight showed no significant difference between neonates (mean: 0.610 l/h/kg) and adults (mean: 0.550 l/h/kg). The urinary excretion of lignocaine and several of its metabolites was studied in 8 neonates and 11 adults. Neonates were shown to excrete much more unchanged lignocaine (mean: 19.67%) compared with adults (mean: 4.27%) and the proportion of the dose excreted as 4-hydroxyxylidine is considerably reduced in neonates (neonate mean: 8.89%; adult mean: 63.78%). The use of the two pharmacokinetic parameters, t1/2 and Cltp, as indices of drug elimination ability are discussed.
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  • 92
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    European journal of clinical pharmacology 13 (1978), S. 219-222 
    ISSN: 1432-1041
    Keywords: Glaziovine ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; enteral absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of Glaziovine, a pro-aporphine alkaloid with neuropharmacological properties, were investigated in healthy human volunteers. Glaziovine-14C 20 mg was administered in capsules (oral route) and in vials (i.v. route). Total radioactivity was measured in plasma, urine and faeces. When administered orally, peak plasma levels were encountered at 2 h. The cumulative urinary excretion of total radioactivity over a 24 h period was 38% after oral and 50% after i.v. administration. Investigation of metabolites in urine revealed Glaziovine glucuronide as the sole metabolite of the drug. By comparing the percentage of urinary excretion or the area under the plasma level-time curve (AUC) obtained in the first 24 hours after i.v. and oral administration, enteral absorption was found to range from 78 to 84%. Thus, glaziovine appears to show very high enteral absorption.
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  • 93
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    European journal of clinical pharmacology 13 (1978), S. 55-60 
    ISSN: 1432-1041
    Keywords: Valproic acid ; pharmacokinetics ; liver disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of valproic acid (di-n-propylacetate; VA) has been studied after a single oral dose of a solution of 450 mg in 7 patients with alcoholic cirrhosis and in 4 patients recovering from acute hepatitis. The diagnosis was based on biochemical function tests and histological findings. The pharmacokinetic parameters were compared with those reported for healthy volunteers. VA in therapeutic concentration (80 µg/ml) in plasma was less bound to plasma proteins in patients with alcoholic cirrhosis (70.7±11.3%) and in patients recovering from acute hepatitis (78.1±14.1%) than in controls (88.7±5.2%). The reduced binding affected the blood/plasma concentration ratio and the apparent distribution volume Vd(β); the latter was increased from the normal value of 0.14±0.05 l/kg to 0.22±0.09 (p〈0.05) in alcoholic cirrhotics, and to 0.20±0.07 (p=0.056) in patients recovering from acute hepatitis. The half-life of elimination T1/2 (β) (controls=12.2±3.7 h) was significantly (p〈0.05) prolonged in cirrhotics (18.9±5.1 h) and in patients recovering from acute hepatitis (17.0±3.7 h). The plasma $$\overline {Cl} $$ of total drug was not impaired, which can best be explained by the lower plasma protein binding, which might have increased the $$\overline {Cl} $$ of this drug which shows restricted clearance. In addition, the plasma $$\overline {Cl} $$ of free drug was significantly (p〈0.02) reduced in alcoholic cirrhotics. During a two day urine collection no measurable amount of unchanged VA was recovered. There was considerable excretion of VA-conjugates, which could be hydrolyzed either by HCl or by β-glucuronidase/arylsulphatase (4–23% of the dose). These percentages were in the same range as in normals (26.7±16.1%). The study indicates that elimination of VA is slightly impaired in patients with dysfunction of the liver.
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  • 94
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    European journal of clinical pharmacology 13 (1978), S. 267-274 
    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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  • 95
    ISSN: 1432-1041
    Keywords: Phenylbutazone ; pharmacokinetics ; model ; retrospective analysis ; digestive-tract hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Phenylbutazone treatment can cause digestive-tract hemorrhages, but its concentration in the blood at the time of hemorrhage is generally not known. In two patients who had had digestive tract hemorrhages, the variation in the serum phenylbutazone concentration throughout treatment and just before hemorrhage was simulated by a two-compartment model based on assays (gas-liquid chromatography) made after the hemorrhage. Identification of the parameters of the model and simulation of changes in concentration during therapy suggested that the phenylbutazone level in serum at the time of hemorrhage was 101 and 125 µg/ml respectively.
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  • 96
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    European journal of clinical pharmacology 14 (1978), S. 29-37 
    ISSN: 1432-1041
    Keywords: Hydroflumethiazide ; pharmacokinetics ; cardiac failure ; renal drug excretion ; metabolism ; 2,4-disulfamyl-5-trifluoro-methylaniline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydroflumethiazide (HFT) were investigated after single oral doses of 6 µmoles/ per kg body weight in five healthy subjects and in nine patients with moderate cardiac failure. HFT was excreted in urine together with 2,4-disulfamyl-5-trifluoromethylaniline (DTA), which was also present in the blood after administration of HFT. HFT and DTA were determined by TLC and spectrofluorodensitometry. Mean cumulative urinary excretion of HFT was 46.5 and 47.5 per cent of the dose both in healthy subjects and in patients. Distribution half-life (t1/2α) was about 2 h in both groups of subjects, while biological half-life (t1/2β) ranged from 12.4 to 26.9 h (mean 16.6) in healthy subjects, and from 6.3 to 13.7 h (mean 9.6) in patients. Mean renal clearance was 0.33 and 0.211 · h−1 · kg−1 in normal subjects and patients, respectively, and was almost equal to the total body clearance. HFT had a large apparent volume of distribution (Vβ), with mean values of 6.4 and 3.11 · kg−1 in normal subjects and patients. Mean cumulative urinary excretion of DTA was 1.8 and 1.9 per cent in healthy subjects and patients with cardiac failure. The apparent half-life of DTA, determined from urinary excretion rate in eleven subjects, ranged from 16 to 56 h but half-lives in three others were more than 100 h. The results indicate that HFT is partly metabolized in the body to DTA, and DTA and HFT are excreted in urine. The half-life of DTA was longer than that of the parent drug. The apparent volume of distribution, clearance and biological half-life of HFT were lower in patients with cardiac failure than in healthy subjects.
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  • 97
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    European journal of clinical pharmacology 14 (1978), S. 361-366 
    ISSN: 1432-1041
    Keywords: Furosemide ; gestosis of pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 50 mg was administered orally and intravenously to twelve gestotic women for brief periods as a part of a randomized, multicentre clinical trial comparing the efficacy of bed rest and pharmacological treatment. The pharmacokinetic profile was investigated using a gas-liquid chromatographic technique. The plasma half-life after oral and intravenous administration was 115±37.1 and 71.8±26.3 min and plasma clearance was 153±48 and 152±23 ml/min, respectively (mean±SD). Comparative data from healthy pregnant women cannot be obtained for ethical reasons. The results show that gestosis has only a marginal if any effect on the kinetics of furosemide in comparison with published kinetic parameters in healthy volunteers and patients with renal failure. The new-born babies where checked for side effects according to a protocol in use in a larger regional surveillance programme. No clinical side-effects were attributable to furosemide, but the small size of the group does not permit any definitive conclusions about this aspect.
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  • 98
    ISSN: 1432-1041
    Keywords: Phase I clinical trial ; complex protocol ; tolerance ; pharmacokinetics ; praziquantel ; anthelmintic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1×20 mg/kg, 1×50 mg/kg, 3×10 mg/kg and 3×25 mg/kg body weight (τ=4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinicopsychological parameters and subjective comments, the largest daily dose tested (3×25 mg/kg=75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1– h, and the elimination half-life for the period 2–8 h was 1–1.5 h.
    Type of Medium: Electronic Resource
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 13 (1978), S. 119-124 
    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; pharmacokinetics ; hypertension ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml−1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg−1. Non-renal clearance averaged 200 ml · min−1. The renal clearance of bft was significantly lower (p〈0.05) after 5 mg (48 ml · min−1) than after 2.5 mg bft (93 ml · min−1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.
    Type of Medium: Electronic Resource
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